Medical Specialty

Infectious Disease

Every pathogen, syndrome, antimicrobial agent, resistance pattern, empiric regimen, prophylaxis strategy, and management algorithm in one place.

01 Microbiology Fundamentals

Infectious disease medicine rests on a foundation of microbiology — understanding how organisms are classified, how they cause disease, and how they evade host defenses and antimicrobial therapy. The Gram stain remains the single most important rapid diagnostic test in clinical microbiology, dividing bacteria into two major groups based on cell wall structure. Virulence factors determine pathogenicity, while resistance mechanisms dictate treatment choices. Mastery of these fundamentals is essential for rational empiric therapy and antimicrobial stewardship.

Gram Stain Classification

The Gram stain differentiates bacteria by cell wall composition. Gram-positive organisms retain the crystal violet–iodine complex due to a thick peptidoglycan layer (20–80 nm), appearing purple/blue. Gram-negative organisms have a thin peptidoglycan layer (1–3 nm) surrounded by an outer membrane containing lipopolysaccharide (LPS/endotoxin), and stain pink/red with the safranin counterstain.

Category	Morphology	Key Organisms	Clinical Significance
Gram-positive cocci (clusters)	Cocci in clusters	S. aureus (coagulase +), CoNS (coagulase −)	Skin/soft tissue, bacteremia, endocarditis, osteomyelitis
Gram-positive cocci (chains)	Cocci in chains/pairs	S. pyogenes (GAS), S. agalactiae (GBS), Enterococcus	Pharyngitis, cellulitis, neonatal sepsis, UTI, endocarditis
Gram-positive cocci (diplococci)	Lancet-shaped diplococci	S. pneumoniae	Pneumonia, meningitis, otitis media
Gram-positive rods	Rods	Listeria, Clostridium, Corynebacterium, Bacillus	Meningitis (neonates/elderly), C. diff colitis, gas gangrene
Gram-negative cocci	Diplococci (kidney-bean)	N. meningitidis, N. gonorrhoeae, M. catarrhalis	Meningitis, gonorrhea, COPD exacerbation
Gram-negative rods (Enterobacterales)	Rods	E. coli, Klebsiella, Proteus, Enterobacter, Serratia	UTI, bacteremia, intra-abdominal, pneumonia
Gram-negative rods (non-fermenters)	Rods	Pseudomonas aeruginosa, Acinetobacter, Stenotrophomonas	HAP/VAP, burn wound infections, MDR nosocomial infections
Anaerobes	Mixed	Bacteroides fragilis, Clostridium, Fusobacterium, Peptostreptococcus	Intra-abdominal, lung abscess, brain abscess
Atypical bacteria	Not well visualized on Gram stain	Mycoplasma, Chlamydia, Legionella, Rickettsia	Atypical pneumonia, PID, Rocky Mountain spotted fever

Gram stain showing Gram-positive cocci in clusters (purple) among white blood cells — **Figure 1 — Gram Stain.** Gram-positive cocci in clusters (purple) consistent with Staphylococcus species, seen among polymorphonuclear leukocytes. The Gram stain provides rapid identification of bacterial morphology and guides initial empiric therapy within minutes. Source: Wikimedia Commons. Public domain.

Bacterial Cell Wall & Virulence Factors

The cell wall is the primary target of many antibiotics. Peptidoglycan (murein) is the structural scaffold; beta-lactams inhibit its synthesis by binding penicillin-binding proteins (PBPs). Key virulence factors include:

Virulence Factor	Mechanism	Example Organisms
Endotoxin (LPS)	Lipid A triggers TLR4 → cytokine storm → septic shock	All Gram-negative bacteria
Exotoxins	Secreted proteins causing tissue damage	TSST-1 (S. aureus), Shiga toxin (EHEC), tetanospasmin (C. tetani)
Capsule	Antiphagocytic polysaccharide	S. pneumoniae, N. meningitidis, Klebsiella, H. influenzae type b
Biofilm	Sessile community on surfaces; 1000× increased antibiotic resistance	S. epidermidis (prosthetic devices), P. aeruginosa (CF lungs)
Protein A	Binds Fc portion of IgG → prevents opsonization	S. aureus
IgA protease	Cleaves mucosal IgA	N. meningitidis, N. gonorrhoeae, S. pneumoniae, H. influenzae
Pili/fimbriae	Adhesion to mucosal epithelium	E. coli (P fimbriae → pyelonephritis), N. gonorrhoeae

Antimicrobial Resistance Mechanisms

Mechanism	Description	Clinical Examples
Enzymatic inactivation	Bacteria produce enzymes that destroy/modify the antibiotic	Beta-lactamases (ESBLs, AmpC, carbapenemases/KPC), aminoglycoside-modifying enzymes
Target modification	Alteration of the antibiotic binding site	PBP2a in MRSA (mecA gene), vanA/vanB in VRE, 23S rRNA methylation (macrolide resistance)
Efflux pumps	Active removal of antibiotic from cell	Tetracycline resistance, fluoroquinolone resistance in P. aeruginosa
Decreased permeability	Loss of outer membrane porins	Carbapenem resistance in P. aeruginosa (OprD loss), Acinetobacter
Target bypass	Alternative metabolic pathway circumvents inhibited step	Vancomycin resistance (D-Ala-D-Lac replaces D-Ala-D-Ala in VRE)

The "ESKAPE" pathogens — Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. — are the leading causes of nosocomial infections and are increasingly multidrug-resistant. These organisms "escape" the effects of commonly used antibiotics.

When Gram stain shows Gram-negative diplococci in CSF, treat for N. meningitidis immediately. When it shows Gram-positive diplococci, think S. pneumoniae. Gram-positive rods in blood cultures from an elderly or immunocompromised patient should prompt concern for Listeria monocytogenes.

02 The Infectious Disease Assessment

The systematic evaluation of a patient with suspected infection involves identifying the source, the likely pathogen, and the severity of illness. The fever workup, blood culture interpretation, and sepsis screening tools are the cornerstones of ID assessment.

Fever Workup

Fever is defined as a core body temperature ≥38.0°C (100.4°F). In elderly and immunocompromised patients, fever may be absent despite serious infection (hypothermia <36°C may indicate sepsis). A systematic approach to fever includes:

Step	Action	Details
1. History	Characterize the fever	Onset, duration, pattern (continuous, intermittent, relapsing), associated symptoms, travel, exposures, sexual history, IV drug use, immunosuppression
2. Physical exam	Source identification	Skin (rash, wounds, IV sites), lungs (crackles, consolidation), heart (new murmur), abdomen (tenderness, peritonitis), joints, meninges (nuchal rigidity)
3. Basic labs	CBC, CMP, lactate, procalcitonin	Leukocytosis (or leukopenia in sepsis), left shift, thrombocytopenia, elevated lactate, AKI
4. Cultures	Blood cultures (2 sets from separate sites), urine culture, sputum culture	Always obtain BEFORE antibiotics; 2 sets = 4 bottles (2 aerobic + 2 anaerobic)
5. Imaging	CXR, CT as indicated	CXR for pneumonia; CT abdomen/pelvis for intra-abdominal source; CT head for altered mental status

Blood Culture Interpretation

Scenario	Interpretation	Action
2/2 bottles positive for S. aureus	True bacteremia until proven otherwise	Always treat; echo (TTE ± TEE), repeat cultures q48h until negative, source investigation
1/2 bottles positive for CoNS	Likely contaminant (~85% of single-bottle CoNS)	Repeat cultures; if clinical concern, treat and investigate (line infection)
2/2 bottles positive for CoNS	More likely true infection, especially with central line	Treat as line infection; consider line removal
Any bottle positive for S. aureus, S. lugdunensis, or Candida	Always true pathogen	Full workup: repeat cultures, echocardiography, source control
Polymicrobial (GNR + anaerobes)	Suggests GI source (perforation, abscess)	CT abdomen/pelvis, surgical consultation

S. aureus bacteremia (SAB) is never a contaminant. Every patient with SAB requires: (1) repeat blood cultures every 48 hours until clearance, (2) echocardiography (TEE preferred), (3) evaluation for metastatic foci, and (4) a minimum of 2 weeks IV therapy for uncomplicated SAB, 4–6 weeks if complicated (endocarditis, osteomyelitis, deep-seated focus). ID consultation for SAB reduces mortality.

Sepsis Screening — qSOFA

The quick SOFA (qSOFA) is a bedside screening tool for patients with suspected infection outside the ICU. A score ≥2 identifies patients at risk for poor outcomes:

Criterion	Points
Respiratory rate ≥22/min	1
Altered mentation (GCS <15)	1
Systolic blood pressure ≤100 mmHg	1

qSOFA ≥2 has a specificity of ~70% for in-hospital mortality in non-ICU patients with suspected infection. It is a screening tool — the full SOFA score is required for the formal Sepsis-3 definition.

Source Identification by Presentation

Clue	Likely Source	Key Workup
Productive cough, pleuritic pain, hypoxia	Pneumonia	CXR, sputum culture, Legionella/pneumococcal urinary antigens
Dysuria, frequency, CVA tenderness	UTI/pyelonephritis	Urinalysis, urine culture
RUQ pain, jaundice, fever (Charcot triad)	Cholangitis	RUQ ultrasound, MRCP, blood cultures
New murmur, embolic phenomena	Endocarditis	Blood cultures ×3, TTE/TEE
Headache, neck stiffness, photophobia	Meningitis	LP (if no contraindication), blood cultures, CT head first if focal deficits
Erythema/warmth around catheter site	Catheter-related BSI	Paired peripheral and catheter cultures, differential time to positivity
Abdominal pain with peritoneal signs	Intra-abdominal abscess/peritonitis	CT abdomen/pelvis with contrast

03 Key Terminology & Abbreviations

Term	Definition
Bacteremia	Presence of viable bacteria in the bloodstream, confirmed by positive blood culture
Sepsis (Sepsis-3)	Life-threatening organ dysfunction caused by dysregulated host response to infection; SOFA score ≥2
Septic shock	Subset of sepsis with vasopressor requirement to maintain MAP ≥65 AND lactate >2 mmol/L despite adequate fluid resuscitation
Empiric therapy	Initial antibiotic regimen chosen before organism identification, based on suspected source and local resistance patterns
De-escalation	Narrowing antibiotic spectrum once culture and sensitivity results are available
MIC	Minimum inhibitory concentration — lowest concentration of antibiotic that prevents visible bacterial growth
Bactericidal	Antibiotic that kills bacteria (MBC/MIC ratio ≤4); required for endocarditis, meningitis, neutropenic fever
Bacteriostatic	Antibiotic that inhibits bacterial growth without killing; host immune system completes eradication
MDR	Multidrug-resistant — resistant to ≥1 agent in ≥3 antimicrobial categories
ESBL	Extended-spectrum beta-lactamase — enzyme conferring resistance to 3rd-generation cephalosporins; treat with carbapenems
CRE	Carbapenem-resistant Enterobacterales — resistant to carbapenems via carbapenemases (KPC, NDM, OXA-48)

ABxAntibiotics AMSAltered mental status ARTAntiretroviral therapy BCxBlood culture BSIBloodstream infection CAPCommunity-acquired pneumonia CDIClostridioides difficile infection CMVCytomegalovirus CNSCentral nervous system CoNSCoagulase-negative staphylococci CRBSICatheter-related bloodstream infection CRECarbapenem-resistant Enterobacterales CSFCerebrospinal fluid DOTDirectly observed therapy ESBLExtended-spectrum beta-lactamase FMTFecal microbiota transplantation FUOFever of unknown origin GASGroup A Streptococcus GBSGroup B Streptococcus HAPHospital-acquired pneumonia HSVHerpes simplex virus IDInfectious disease IGRAInterferon-gamma release assay INSTIIntegrase strand transfer inhibitor LPLumbar puncture MACMycobacterium avium complex MDRMultidrug-resistant MICMinimum inhibitory concentration MRSAMethicillin-resistant S. aureus MSSAMethicillin-susceptible S. aureus OIOpportunistic infection PCP/PJPPneumocystis jirovecii pneumonia PEPPost-exposure prophylaxis PrEPPre-exposure prophylaxis RIPERifampin, Isoniazid, Pyrazinamide, Ethambutol SABS. aureus bacteremia SOFASequential Organ Failure Assessment SSTISkin and soft tissue infection TBTuberculosis TDMTherapeutic drug monitoring TEETransesophageal echocardiography TMP-SMXTrimethoprim-sulfamethoxazole VAPVentilator-associated pneumonia VREVancomycin-resistant Enterococcus

04 Sepsis & Septic Shock

Sepsis is a medical emergency defined by the Sepsis-3 consensus (2016) as life-threatening organ dysfunction caused by a dysregulated host response to infection. It affects over 1.7 million adults annually in the United States, with a mortality rate of 15–30% for sepsis and 40–50% for septic shock.

Emergency — Hour-1 Sepsis Bundle (Surviving Sepsis Campaign 2021)

All elements should be initiated within 1 hour of sepsis recognition:
1. Measure lactate — remeasure if initial lactate >2 mmol/L
2. Obtain blood cultures before antibiotics (do not delay ABx if cultures cannot be obtained promptly)
3. Administer broad-spectrum antibiotics — each hour of delay increases mortality by ~4%
4. Begin rapid fluid resuscitation — 30 mL/kg crystalloid for hypotension or lactate ≥4 mmol/L
5. Start vasopressors if hypotension persists during or after fluid resuscitation — target MAP ≥65 mmHg

Sepsis-3 Definitions

Term	Definition	Criteria
Sepsis	Infection + organ dysfunction	Suspected or documented infection with acute change in SOFA score ≥2 points
Septic shock	Subset of sepsis with circulatory and metabolic failure	Sepsis + vasopressor requirement to maintain MAP ≥65 mmHg AND serum lactate >2 mmol/L despite adequate volume resuscitation

SOFA Score (Sequential Organ Failure Assessment)

Organ System	0	1	2	3	4
Respiration (PaO2/FiO2)	≥400	<400	<300	<200 with ventilatory support	<100 with ventilatory support
Coagulation (platelets ×10³/µL)	≥150	<150	<100	<50	<20
Liver (bilirubin, mg/dL)	<1.2	1.2–1.9	2.0–5.9	6.0–11.9	>12
Cardiovascular (MAP/vasopressors)	MAP ≥70	MAP <70	Dopamine ≤5 or dobutamine any dose	Dopamine >5 or epi/norepi ≤0.1	Dopamine >15 or epi/norepi >0.1
CNS (GCS)	15	13–14	10–12	6–9	<6
Renal (creatinine mg/dL or UOP)	<1.2	1.2–1.9	2.0–3.4	3.5–4.9 or UOP <500 mL/d	>5.0 or UOP <200 mL/d

Vasopressor Selection in Septic Shock

Agent	Receptor	Role	Dose Range
Norepinephrine	α1 >> β1	First-line vasopressor	0.01–3 µg/kg/min
Vasopressin	V1	Second-line, added to norepinephrine (catecholamine-sparing)	0.03–0.04 units/min (fixed dose)
Epinephrine	α1, β1, β2	Second/third-line; also for anaphylactic shock	0.01–0.5 µg/kg/min
Phenylephrine	Pure α1	Alternative if tachyarrhythmia limits norepinephrine use	0.5–6 µg/kg/min
Angiotensin II	AT1 receptor	Refractory vasodilatory shock	20–200 ng/kg/min

Lactate-Guided Resuscitation

Serum lactate reflects tissue hypoperfusion and anaerobic metabolism. A target of lactate clearance ≥20% every 2 hours (or normalization <2 mmol/L) guides adequacy of resuscitation. Persistently elevated lactate despite resuscitation suggests ongoing tissue hypoperfusion, mesenteric ischemia, hepatic dysfunction, or catecholamine excess.

Do not delay antibiotics for imaging or procedures. In septic shock, every hour of delayed antibiotic administration increases mortality by approximately 4–8%. Draw blood cultures first, but if venipuncture will take time, start antibiotics immediately and draw cultures as soon as possible thereafter.

Corticosteroids in Septic Shock

The Surviving Sepsis Campaign (2021) suggests IV hydrocortisone 200 mg/day (50 mg q6h or continuous infusion) for patients with septic shock who remain vasopressor-dependent despite adequate fluid resuscitation. The ADRENAL and APROCCHSS trials showed modest reduction in time to shock reversal but inconsistent mortality benefit. Consider initiating when norepinephrine dose reaches ≥0.25 µg/kg/min.

05 Bloodstream Infections & Bacteremia

Catheter-Related Bloodstream Infections (CRBSI)

Central venous catheters account for ~250,000 BSIs annually in the U.S. Diagnosis requires differential time to positivity (DTP) — blood cultures drawn through the catheter turn positive ≥2 hours before peripheral cultures, suggesting the catheter as the source.

Pathogen	Frequency	Line Removal?	Treatment
CoNS	~35%	Try salvage with lock therapy if uncomplicated	Vancomycin 7–14 days
S. aureus	~15%	Always remove the line	Nafcillin/cefazolin (MSSA) or vancomycin (MRSA) × 4–6 weeks
Enterococcus	~10%	Remove if possible	Ampicillin (if susceptible) or vancomycin × 7–14 days
Gram-negative rods	~20%	Remove if possible	Directed therapy × 7–14 days
Candida spp.	~10%	Always remove the line	Echinocandin × 14 days after first negative BCx + ophthalmologic exam

Candidemia

Candida in blood cultures is never a contaminant. Management: (1) remove all central venous catheters, (2) start echinocandin empirically (micafungin 100 mg IV daily or caspofungin 70 mg load then 50 mg daily), (3) obtain ophthalmologic exam to evaluate for endophthalmitis, (4) repeat blood cultures daily until clearance, (5) treat for 14 days after first negative blood culture. Fluconazole can be used for step-down if the species is susceptible (C. albicans, C. parapsilosis) and the patient is clinically stable.

C. auris is an emerging multidrug-resistant Candida species that is often resistant to fluconazole, variably resistant to amphotericin B, and occasionally resistant to echinocandins. It persists on surfaces and skin, causing nosocomial outbreaks. Contact precautions and aggressive environmental cleaning are essential.

S. aureus Bacteremia — Mandatory Workup

Component	Details
Repeat blood cultures	Every 48 hours until negative; duration of therapy starts from first negative culture
Echocardiography	TEE preferred (sensitivity 90–95% vs TTE 50–70% for vegetations); TTE acceptable if low-risk
Source investigation	CT/MRI for metastatic foci (vertebral osteomyelitis, epidural abscess, splenic abscess)
ID consultation	Shown to reduce mortality by 50% and improve adherence to evidence-based care
Uncomplicated SAB	Removable focus + negative TEE + negative follow-up cultures at 48–72h + no metastatic infection + no prosthetic material → 2 weeks IV therapy
Complicated SAB	Any of: positive follow-up cultures at 72h, endocarditis, metastatic infection, prosthetic material → 4–6 weeks IV therapy

06 Fever of Unknown Origin

Fever of unknown origin (FUO) was classically defined by Petersdorf and Beeson (1961) as fever >38.3°C on multiple occasions, lasting >3 weeks, with no diagnosis after 1 week of inpatient evaluation. Modern definitions allow outpatient workup. The etiology falls into four major categories: infections (~30%), malignancy (~20%), autoimmune/inflammatory (~15%), and undiagnosed (~25%).

FUO Categories

Type	Definition	Common Etiologies
Classic FUO	Fever >3 weeks, no diagnosis after appropriate workup	TB, endocarditis, intra-abdominal abscess, lymphoma, adult Still disease, temporal arteritis
Nosocomial FUO	Hospitalized ≥24h, fever developing after admission, no infection at admission	C. difficile, catheter-related infection, drug fever, DVT/PE, sinusitis (intubated), acalculous cholecystitis
Neutropenic FUO	ANC <500/µL with fever ≥38.3°C, no identifiable source after 3 days	Invasive Aspergillus, Candida, resistant bacteria (VRE, ESBL), viral reactivation (HSV, CMV)
HIV-associated FUO	HIV-positive with fever >4 weeks (outpatient) or >3 days (inpatient)	MAC (CD4 <50), CMV, PJP, lymphoma, TB, histoplasmosis

Diagnostic Approach to Classic FUO

Phase	Investigations
Initial	CBC with differential, CMP, ESR, CRP, LDH, ferritin, blood cultures ×3, urinalysis/culture, CXR, HIV test, ANA, RF
Directed	CT chest/abdomen/pelvis, TTE/TEE (if murmur or risk factors), peripheral smear, serum protein electrophoresis
Advanced	FDG-PET/CT (excellent for localizing occult infection or malignancy), bone marrow biopsy, temporal artery biopsy (if age >55 with elevated ESR), liver biopsy

FDG-PET/CT has become a valuable tool in FUO workup, with a diagnostic yield of 40–70% in identifying the source when conventional imaging is negative. It is particularly useful for detecting large-vessel vasculitis, occult abscesses, and lymphoma.

Drug fever should always be considered in hospitalized patients with FUO. Classic culprits include beta-lactams, sulfonamides, anticonvulsants, and allopurinol. The patient may appear "inappropriately well" with relative bradycardia and eosinophilia. The fever typically resolves within 48–72 hours of drug discontinuation.

07 Community-Acquired Pneumonia

Community-acquired pneumonia (CAP) is the leading infectious cause of death worldwide. The 2019 ATS/IDSA guidelines emphasize severity-based empiric therapy, covering typical and atypical pathogens, with risk stratification using validated scoring systems.

Common Pathogens

Pathogen	Frequency	Key Features
S. pneumoniae	Most common overall	Rust-colored sputum, lobar consolidation, rapid onset
H. influenzae	Common in COPD	Purulent sputum, bronchopneumonia pattern
Mycoplasma pneumoniae	Most common atypical	Young adults, gradual onset, dry cough, extrapulmonary manifestations (rash, hemolytic anemia)
Legionella pneumophila	~5%	GI symptoms, hyponatremia, high fevers, water exposure; positive urinary antigen (serogroup 1 only)
Chlamydophila pneumoniae	~5–10%	Gradual onset, hoarseness, biphasic illness
Respiratory viruses	~25% (often co-infection)	Influenza, RSV, SARS-CoV-2, rhinovirus
Klebsiella pneumoniae	Alcoholism, aspiration	"Currant jelly" sputum, cavitation, upper lobe (aspiration), bulging fissure sign

CURB-65 Score

Criterion	Points
Confusion (new-onset)	1
Uremia (BUN >20 mg/dL or >7 mmol/L)	1
Respiratory rate ≥30/min	1
Blood pressure (SBP <90 or DBP ≤60 mmHg)	1
Age ≥65	1

0–1: outpatient | 2: consider short inpatient stay or close outpatient follow-up | 3–5: inpatient (4–5 consider ICU)

Empiric Therapy by Severity (ATS/IDSA 2019)

Setting	Regimen	Notes
Outpatient, no comorbidities	Amoxicillin 1 g TID OR doxycycline 100 mg BID OR azithromycin 500 mg then 250 mg daily (if local resistance <25%)	Duration 5 days minimum (afebrile ≥48h + 1 sign of stability)
Outpatient, comorbidities	Amoxicillin-clavulanate 875/125 mg BID or cephalosporin PLUS macrolide or doxycycline; OR respiratory fluoroquinolone alone	Comorbidities: CLD, DM, chronic heart/liver/renal disease, alcoholism, asplenia, immunosuppression
Inpatient (non-ICU)	Beta-lactam (ampicillin-sulbactam 3 g q6h, ceftriaxone 1–2 g q24h, or cefotaxime) PLUS macrolide (azithromycin 500 mg daily); OR respiratory FQ alone	Duration 5–7 days
ICU (severe CAP)	Beta-lactam (ceftriaxone or ampicillin-sulbactam) PLUS macrolide; OR beta-lactam PLUS respiratory FQ	Add vancomycin + piperacillin-tazobactam if MRSA/Pseudomonas risk factors

ATS/IDSA 2019 no longer recommends routine MRSA or Pseudomonas coverage for CAP unless the patient has risk factors (prior respiratory isolation of these organisms, recent hospitalization with parenteral antibiotics). Always obtain cultures and procalcitonin before starting antibiotics when possible.

Chest X-ray showing right lower lobe consolidation consistent with community-acquired pneumonia — **Figure 2 — Chest X-ray: Pneumonia.** Right lower lobe consolidation with air bronchograms, consistent with bacterial pneumonia. CXR remains the first-line imaging modality for suspected CAP. Source: Wikimedia Commons. Licensed under CC BY-SA 3.0.

08 Hospital-Acquired & Ventilator-Associated Pneumonia

Hospital-acquired pneumonia (HAP) develops ≥48 hours after hospital admission and was not incubating at the time of admission. Ventilator-associated pneumonia (VAP) develops ≥48 hours after endotracheal intubation. Both carry mortality rates of 20–50%.

Risk Factors for MDR Pathogens

MRSA Risk Factors	Pseudomonas Risk Factors
Prior MRSA isolation	Prior Pseudomonas isolation
IV antibiotic use within 90 days	IV antibiotic use within 90 days
High MRSA prevalence unit (>20%)	Structural lung disease (bronchiectasis, CF)
Hemodialysis	Prolonged mechanical ventilation

Empiric Therapy (ATS/IDSA 2016)

Risk Category	Regimen
HAP/VAP, no MDR risk, low mortality risk	Piperacillin-tazobactam 4.5 g q6h OR cefepime 2 g q8h OR meropenem 1 g q8h
HAP/VAP with MRSA risk	Above PLUS vancomycin (trough 15–20 µg/mL or AUC/MIC 400–600) OR linezolid 600 mg q12h
HAP/VAP with Pseudomonas risk	2 anti-pseudomonal agents from different classes (e.g., pip-tazo + tobramycin, or cefepime + ciprofloxacin)
HAP/VAP with both MRSA + Pseudomonas risk	Anti-pseudomonal beta-lactam + anti-pseudomonal agent from 2nd class + MRSA coverage

VAP prevention bundle: head-of-bed elevation 30–45°, daily sedation vacation and spontaneous breathing trial, oral chlorhexidine, DVT and stress ulcer prophylaxis, daily assessment for extubation readiness. These measures together reduce VAP rates by 40–70%.

VAP Diagnostic Criteria

Clinical diagnosis: new or progressive infiltrate on CXR plus ≥2 of: fever >38°C, leukocytosis (>12,000) or leukopenia (<4,000), purulent secretions. The Clinical Pulmonary Infection Score (CPIS) ≥6 suggests VAP. Obtain lower respiratory tract cultures (endotracheal aspirate with semi-quantitative culture or BAL with quantitative culture ≥10&sup4; CFU/mL) before changing antibiotics.

09 Tuberculosis

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a leading infectious killer globally, with ~10 million new cases and 1.5 million deaths annually. One-quarter of the world's population is latently infected. In the United States, TB disproportionately affects foreign-born individuals, people experiencing homelessness, and the immunocompromised.

Latent TB Infection (LTBI) vs Active TB

Feature	Latent TB (LTBI)	Active TB
Symptoms	None	Cough >2–3 weeks, hemoptysis, night sweats, weight loss, fever
Infectivity	Not infectious	Infectious (pulmonary/laryngeal)
CXR	Normal (or old granuloma/calcification)	Upper lobe infiltrates, cavitation, miliary pattern
AFB smear/culture	Negative	Positive (smear positive = highly infectious)
TST/IGRA	Positive	Usually positive (may be negative if severely immunosuppressed)
Treatment goal	Prevent reactivation	Cure infection, prevent transmission

Screening: TST vs IGRA

Test	Mechanism	Advantages	Limitations
TST (Mantoux/PPD)	Intradermal injection of purified protein derivative; read at 48–72 hours	Inexpensive, widely available	Cross-reacts with BCG and NTM; requires return visit; reader variability
IGRA (QuantiFERON, T-SPOT)	Measures interferon-gamma release from T cells stimulated by TB-specific antigens (ESAT-6, CFP-10)	Single blood draw; not affected by BCG; more specific	More expensive; may have indeterminate results in immunosuppressed

TST interpretation (induration cutoffs): ≥5 mm = positive in HIV, close contacts, immunosuppressed, CXR with old TB. ≥10 mm = recent immigrants, IVDU, healthcare workers, high-risk congregate settings. ≥15 mm = no known risk factors.

Active TB Treatment — Standard 4-Drug RIPE Regimen

Drug	Abbreviation	Daily Dose	Duration	Key Toxicity
Rifampin	R	10 mg/kg (max 600 mg)	6 months (entire course)	Hepatotoxicity, orange discoloration (urine, tears, sweat), potent CYP450 inducer (drug interactions!)
Isoniazid	H/I	5 mg/kg (max 300 mg)	6 months (entire course)	Hepatotoxicity (#1 cause of drug-induced liver injury), peripheral neuropathy (give pyridoxine/B6 25–50 mg daily)
Pyrazinamide	Z	25 mg/kg (max 2 g)	First 2 months only	Hepatotoxicity, hyperuricemia/gout, arthralgias
Ethambutol	E	15–20 mg/kg	First 2 months only (or until susceptibilities confirmed)	Optic neuritis (red-green color discrimination — baseline and monthly visual acuity testing)

Standard regimen: 2 months RIPE (intensive phase) → 4 months RI (continuation phase) = 6 months total. Extend to 9 months if cavitary disease AND positive 2-month sputum culture.

All patients with active TB should be on respiratory isolation (airborne precautions: negative-pressure room, N95 respirator for healthcare workers). Isolation can be discontinued after clinical improvement, 3 consecutive negative AFB sputum smears collected 8–24 hours apart, and a reliable treatment plan in place.

LTBI Treatment Regimens

Regimen	Duration	Dosing	Notes
3HP (preferred)	3 months (12 doses)	Isoniazid + rifapentine weekly (DOT)	Highest completion rates; not for HIV on PIs or children <2y
4R	4 months	Rifampin daily	Good alternative; fewer hepatotoxicity than 9H
9H	9 months	Isoniazid daily	Older standard; low completion rates

MDR-TB & XDR-TB

MDR-TB: resistant to at least isoniazid + rifampin. XDR-TB: MDR-TB + resistance to a fluoroquinolone + at least one injectable agent (or bedaquiline/linezolid). Treatment requires 4–6 drugs for 18–20 months (newer regimens with bedaquiline, pretomanid, and linezolid [BPaL] allow shorter 6–9 month courses). ID and public health involvement is mandatory.

10 Fungal Pneumonia & Opportunistic Infections

Pneumocystis jirovecii Pneumonia (PJP)

PJP occurs in severely immunocompromised patients, classically HIV with CD4 <200 cells/µL. Presentation: gradual-onset dyspnea, dry cough, fever, bilateral ground-glass opacities on CT. Elevated LDH and (1,3)-beta-D-glucan support diagnosis. Confirmed by silver stain or DFA of induced sputum or BAL.

Severity	Treatment	Adjunctive Therapy
Mild-moderate (PaO2 >70, A-a gradient <35)	TMP-SMX 15–20 mg/kg/day (TMP component) PO divided q8h × 21 days	None required
Moderate-severe (PaO2 ≤70 or A-a gradient ≥35)	TMP-SMX 15–20 mg/kg/day IV divided q6–8h × 21 days	Prednisone 40 mg BID × 5d, then 40 mg daily × 5d, then 20 mg daily × 11d (reduces mortality if started within 72h)

Invasive Aspergillosis

Occurs in prolonged neutropenia (ANC <500 for >10 days), solid organ/stem cell transplant, high-dose corticosteroids. Classic CT finding: halo sign (early) and air crescent sign (recovery phase, ~2–3 weeks). Diagnose with serum/BAL galactomannan antigen and culture. Treatment: voriconazole 6 mg/kg IV q12h × 2 doses, then 4 mg/kg IV q12h (target trough 2–5.5 µg/mL). Alternative: isavuconazole or liposomal amphotericin B.

Endemic Mycoses

Organism	Geography	Key Features	Treatment
Histoplasma capsulatum	Ohio/Mississippi River valleys, Central America	Cave/chicken coop exposure; acute pulmonary, chronic cavitary, or disseminated (HIV); mediastinal lymphadenopathy; calcified granulomas	Mild: itraconazole. Severe/disseminated: liposomal amphotericin B → itraconazole step-down
Coccidioides immitis	Southwestern US, Mexico (desert "Valley fever")	Pulmonary nodules, erythema nodosum, arthralgias; meningitis (complement fixation in CSF); eosinophilia	Mild: fluconazole. Severe/disseminated/meningitis: fluconazole 400–800 mg daily (lifelong for meningitis)
Blastomyces dermatitidis	Great Lakes, Ohio/Mississippi valleys	Verrucous skin lesions, lytic bone lesions, pulmonary infiltrates; broad-based budding yeast on microscopy	Mild-moderate: itraconazole. Severe: amphotericin B → itraconazole
Cryptococcus neoformans	Worldwide (pigeon droppings)	Meningitis in HIV (CD4 <100); elevated opening pressure on LP; India ink (encapsulated yeast), serum/CSF CrAg	Induction: liposomal amphotericin B + flucytosine × 2 weeks. Consolidation: fluconazole 400 mg × 8 weeks. Maintenance: fluconazole 200 mg daily

In HIV patients with cryptococcal meningitis, elevated intracranial pressure is the primary cause of early mortality. Therapeutic lumbar punctures should be performed daily to maintain opening pressure <20 cm H2O. Serial large-volume (20–30 mL) LPs or a lumbar drain may be necessary. Do NOT start ART immediately — wait 4–6 weeks to reduce risk of immune reconstitution inflammatory syndrome (IRIS).

11 Bacterial Meningitis

Emergency — Bacterial Meningitis

Bacterial meningitis is a medical emergency with mortality of 15–25% and neurologic sequelae in 30–50% of survivors. If suspected: blood cultures → empiric antibiotics + dexamethasone → lumbar puncture (in that order). Do NOT delay antibiotics for LP or CT. CT head before LP only if: immunocompromised, history of CNS disease, new-onset seizure, papilledema, altered consciousness, or focal neurologic deficit.

CSF Analysis in Meningitis

Parameter	Normal	Bacterial	Viral	TB/Fungal
Opening pressure	10–20 cm H2O	>25 (often >30)	Normal or mildly elevated	Elevated
WBC (/µL)	<5	1,000–10,000+ (neutrophil predominant)	50–1,000 (lymphocyte predominant)	50–500 (lymphocyte predominant)
Glucose (mg/dL)	45–80 (CSF/serum ratio ≥0.6)	<40 (ratio <0.4)	Normal	Low
Protein (mg/dL)	15–45	>250	50–200	100–500
Gram stain	No organisms	Positive in 60–90%	Negative	AFB smear sensitivity ~10–40% (TB); India ink ~50% (Crypto)

Empiric Antibiotic Therapy by Age Group

Age Group	Common Pathogens	Empiric Regimen
Neonates (<1 month)	GBS, E. coli, Listeria	Ampicillin + gentamicin (or cefotaxime)
Infants/children (1 mo–18 y)	S. pneumoniae, N. meningitidis, H. influenzae type b	Vancomycin + ceftriaxone (or cefotaxime)
Adults (18–50 y)	S. pneumoniae, N. meningitidis	Vancomycin + ceftriaxone
Elderly (>50 y) or immunocompromised	S. pneumoniae, N. meningitidis, Listeria, GNR	Vancomycin + ceftriaxone + ampicillin (for Listeria coverage)

Adjunctive Dexamethasone

Dexamethasone 0.15 mg/kg IV q6h × 4 days, given 15–20 minutes BEFORE or with the first dose of antibiotics. Proven to reduce mortality and hearing loss in S. pneumoniae meningitis in adults (de Gans trial, NEJM 2002). Continue only if Gram stain or culture confirms pneumococcal meningitis. Discontinue if another organism is identified.

N. meningitidis Chemoprophylaxis

Close contacts of patients with meningococcal meningitis require prophylaxis within 24 hours:

Agent	Dose	Notes
Rifampin	600 mg PO q12h × 2 days	Not for pregnant women
Ciprofloxacin (preferred for adults)	500 mg PO × 1 dose	Single dose, most convenient
Ceftriaxone	250 mg IM × 1 dose	Preferred in pregnancy and children

The index patient treated with ceftriaxone does NOT need additional chemoprophylaxis (ceftriaxone eradicates nasopharyngeal carriage). If treated with penicillin, the patient should also receive chemoprophylaxis before discharge.

12 Viral Encephalitis

HSV Encephalitis

HSV-1 encephalitis is the most common cause of sporadic fatal encephalitis in the United States. It classically involves the temporal lobes (bilateral but asymmetric). Presentation: acute onset fever, headache, altered mental status, seizures, focal neurologic deficits, personality changes.

Emergency — HSV Encephalitis

Start IV acyclovir 10 mg/kg q8h immediately upon clinical suspicion — do not wait for LP or MRI results. Untreated mortality is ~70%; with early acyclovir, mortality drops to 20–30%. Continue for 14–21 days.

Diagnostic Test	Finding
CSF analysis	Lymphocytic pleocytosis (10–500 WBC), elevated protein, normal glucose, RBCs may be present (hemorrhagic necrosis)
CSF HSV PCR	Gold standard; sensitivity ~98%, specificity ~99%. May be negative in first 24–72 hours — if high suspicion, repeat LP in 3–7 days
MRI brain	T2/FLAIR hyperintensity in medial temporal lobes (bilateral but asymmetric), insular cortex, orbitofrontal regions; may show hemorrhage
EEG	Periodic lateralized epileptiform discharges (PLEDs) in temporal region

Other Viral Encephalitides

Virus	Key Features	Diagnosis	Treatment
West Nile virus	Summer/fall, mosquito-borne; meningoencephalitis, acute flaccid paralysis, tremor; elderly at highest risk	CSF WNV IgM	Supportive care only
Enterovirus	Summer/fall; children; aseptic meningitis more than encephalitis	CSF enterovirus PCR	Supportive
VZV	Immunocompromised; may occur without rash; vasculopathy, cerebellitis	CSF VZV PCR, VZV IgG	IV acyclovir 10–15 mg/kg q8h
CMV	HIV with CD4 <50; ventriculoencephalitis	CSF CMV PCR	Ganciclovir + foscarnet
Rabies	Animal bite exposure; hydrophobia, aerophobia, encephalitic or paralytic form; almost uniformly fatal once symptomatic	Nuchal skin biopsy (DFA), saliva PCR	Post-exposure prophylaxis (PEP): wound care + rabies immunoglobulin + vaccine series

13 Brain Abscess & Epidural Abscess

Brain Abscess

Brain abscess arises from contiguous spread (sinusitis, otitis, dental infection), hematogenous dissemination (endocarditis, lung abscess, IVDU), or post-neurosurgical/trauma. Classic triad (present in <50%): headache, fever, focal neurologic deficit. Organisms depend on source: contiguous — Streptococcus, anaerobes; hematogenous — S. aureus, Streptococcus; immunocompromised — Toxoplasma, Nocardia, Aspergillus.

Feature	Details
Imaging	MRI with contrast (gold standard): ring-enhancing lesion with restricted diffusion on DWI (differentiates from tumor)
Empiric therapy	Ceftriaxone 2 g IV q12h + metronidazole 500 mg IV q8h ± vancomycin (if post-surgical or MRSA risk). Duration: 6–8 weeks IV
Surgical drainage	Indicated if abscess >2.5 cm, mass effect, intraventricular rupture, or no improvement on antibiotics
LP	Contraindicated — risk of herniation. Diagnosis is imaging-based.

Spinal Epidural Abscess

A neurosurgical emergency. Risk factors: IVDU, epidural catheter, spinal procedures, diabetes, immunosuppression. Classic triad: back pain, fever, neurologic deficit (progressive weakness, sensory level, bowel/bladder dysfunction). Most common organism: S. aureus (~65%).

Component	Details
Imaging	MRI with gadolinium of entire spine (gold standard); sensitivity >90%
Treatment	Emergent surgical decompression + drainage + IV antibiotics (vancomycin + ceftriaxone). Medical management alone only if: no neurologic deficit, stable imaging, organism identified, and close follow-up
Duration	4–6 weeks IV antibiotics minimum; 6–8 weeks if associated osteomyelitis/discitis

The key to outcome in spinal epidural abscess is early diagnosis. Once paralysis develops, it is often irreversible. Any patient with fever + back pain + risk factors (IVDU, DM, recent spinal procedure) should receive an urgent MRI of the entire spine, not just the symptomatic region — skip lesions occur in up to 15% of cases.

14 Infective Endocarditis

Infective endocarditis (IE) is an infection of the endocardial surface of the heart, usually involving one or more heart valves. The diagnosis relies on the modified Duke criteria (2023 update), integrating clinical, microbiologic, imaging, and pathologic data.

Modified Duke Criteria (2023 Update)

Major Criteria	Definition
Blood cultures	Typical organism from ≥2 separate cultures (viridans streptococci, S. bovis, HACEK, S. aureus, Enterococcus without a primary focus); OR persistently positive cultures (≥2 positive >12 hours apart, or 3/3 or majority of ≥4 cultures positive)
Imaging	Vegetation, abscess, pseudoaneurysm, or new dehiscence on echocardiography; OR abnormal activity on FDG-PET/CT or radiolabeled leukocyte SPECT/CT (prosthetic valve, implanted device)

Minor Criteria	Definition
Predisposition	IVDU, prosthetic valve, prior IE, structural heart disease, cardiac device
Fever	≥38.0°C
Vascular phenomena	Arterial emboli, septic pulmonary infarcts, mycotic aneurysm, Janeway lesions, conjunctival hemorrhage
Immunologic phenomena	Glomerulonephritis, Osler nodes, Roth spots, positive rheumatoid factor
Microbiologic evidence	Positive blood culture not meeting major criteria; serologic evidence of active infection with organism consistent with IE

Definite IE: 2 major, OR 1 major + 3 minor, OR 5 minor criteria. Possible IE: 1 major + 1 minor, OR 3 minor criteria.

Empiric Therapy

Valve Type	Regimen	Duration
Native valve (acute)	Vancomycin 15–20 mg/kg q8–12h + ceftriaxone 2 g q24h	Pending cultures; adjust based on organism
Native valve — viridans streptococci (MIC ≤0.12)	Penicillin G or ceftriaxone × 4 weeks; or 2-week course with gentamicin	4 weeks (or 2 weeks with aminoglycoside if uncomplicated)
Native valve — S. aureus (MSSA)	Nafcillin/oxacillin 2 g IV q4h	6 weeks
Native valve — S. aureus (MRSA)	Vancomycin (AUC/MIC 400–600) or daptomycin 8–10 mg/kg IV daily	6 weeks
Prosthetic valve	Vancomycin + gentamicin × 2 weeks + rifampin (after blood culture clearance) × ≥6 weeks	6+ weeks total
IVDU, right-sided (tricuspid)	Nafcillin/oxacillin (if MSSA); consider 2-week course if uncomplicated right-sided MSSA IE	2–6 weeks

Indications for Surgery in IE

Indication	Timing
Heart failure due to valve dysfunction	Emergent/urgent
Uncontrolled infection (persistent bacteremia >7 days, abscess, fistula)	Urgent
Large vegetation (>10 mm) with embolic event or high embolic risk	Urgent
Prosthetic valve endocarditis with dehiscence or obstruction	Urgent
Fungal or highly resistant organism	Urgent

The POET trial (NEJM 2019) demonstrated that in clinically stable patients with left-sided endocarditis, switching from IV to oral antibiotics after at least 10 days of IV therapy is non-inferior to completing the full IV course. This applies only to streptococcal, enterococcal, S. aureus, or CoNS endocarditis with documented clinical response and no abscess.

15 Osteomyelitis

Osteomyelitis is infection of bone, classified by mechanism: hematogenous (bacteremia seeding bone, common in children and vertebral bodies in adults), contiguous (direct spread from adjacent soft tissue, trauma, or surgery), and vascular insufficiency (diabetic foot). The most common pathogen across all types is S. aureus.

Classification by Mechanism

Type	Typical Location	Common Organisms	Key Features
Hematogenous	Vertebral bodies (adults); metaphysis of long bones (children)	S. aureus, coagulase-negative Staphylococci, Streptococcus; GNR (IVDU, UTI source); Salmonella (sickle cell disease)	Insidious back pain with elevated ESR/CRP; children: limp, refusal to bear weight
Contiguous (post-surgical/traumatic)	Site of surgery or open fracture	S. aureus, Pseudomonas, polymicrobial	Hardware loosening, wound drainage, non-healing fracture
Vascular insufficiency	Diabetic foot (metatarsals, calcaneus)	Polymicrobial: S. aureus, Streptococcus, Enterococcus, GNR, anaerobes	Chronic non-healing ulcer overlying bone

Diagnosis

Modality	Sensitivity/Specificity	Role
Plain radiographs	Low sensitivity early (<40% at 2 weeks)	May show periosteal elevation, cortical destruction, sequestrum (late findings)
MRI	Sensitivity 90–100%, specificity 80–90%	Gold standard imaging; shows bone marrow edema, soft tissue extent, abscess
Bone biopsy + culture	Gold standard for organism identification	Required before prolonged antibiotic therapy; avoid swab cultures of wound surface (unreliable)
Probe-to-bone test	Sensitivity ~89%, specificity ~56% (diabetic foot ulcers)	If sterile metal probe reaches bone through ulcer, osteomyelitis is likely
ESR/CRP	Elevated in >90%	Useful for monitoring treatment response (CRP normalizes faster than ESR)

Treatment

Scenario	Antibiotic	Duration
Native vertebral osteomyelitis (MSSA)	Nafcillin/oxacillin 2 g IV q4h or cefazolin 2 g IV q8h	6 weeks IV
Native vertebral osteomyelitis (MRSA)	Vancomycin (AUC/MIC 400–600)	6 weeks IV
Contiguous osteomyelitis with debridement	Culture-directed IV therapy	4–6 weeks (from last debridement)
Prosthetic joint infection with DAIR	IV pathogen-directed + rifampin (after wound closure)	6 weeks IV, then oral suppressive therapy × 3–6 months
Diabetic foot osteomyelitis	Culture-directed therapy; consider ampicillin-sulbactam or ertapenem for polymicrobial	6 weeks if no amputation; shorter if all infected bone resected

16 Septic Arthritis

Septic arthritis is a joint space infection that constitutes an orthopedic emergency — delayed treatment leads to irreversible cartilage destruction. The most common organism is S. aureus in adults and N. gonorrhoeae in sexually active young adults.

Synovial Fluid Analysis

Parameter	Normal	Non-inflammatory	Inflammatory	Septic
Appearance	Clear, colorless	Clear, yellow	Translucent, yellow	Opaque, purulent
WBC (/µL)	<200	<2,000	2,000–50,000	>50,000 (often >100,000)
PMN %	<25%	<25%	>50%	>75%
Gram stain	Negative	Negative	Negative	Positive in 50–75%
Culture	Negative	Negative	Negative	Positive in 80–90% (if not pretreated)

Gonococcal vs Non-Gonococcal Septic Arthritis

Feature	Gonococcal (DGI)	Non-Gonococcal
Population	Young, sexually active	Elderly, RA, prosthetic joint, DM, immunocompromised
Presentation	Migratory polyarthralgias → tenosynovitis + dermatitis (pustular skin lesions) → septic arthritis (usually monoarticular)	Acute monoarticular arthritis (knee most common); fever; limited ROM
Organism	N. gonorrhoeae	S. aureus (~55%), Streptococcus (~20%), GNR (~10%)
Culture yield	Synovial fluid culture positive in only ~25–50%; blood cultures positive in ~10%; NAAT of urine/genital swab is more sensitive	Synovial fluid culture positive in 80–90%
Treatment	Ceftriaxone 1 g IV daily × 7–14 days + azithromycin 1 g PO × 1 (for possible co-infection with Chlamydia)	Vancomycin (empiric MRSA coverage) ± ceftriaxone; adjust to cultures; 3–4 weeks (native joint), 6 weeks (prosthetic)
Joint drainage	Daily arthrocentesis or arthroscopic washout	Repeated arthrocentesis or surgical drainage; surgical washout for hip joint (cannot aspirate easily), prosthetic joint, or failure to improve

Always send synovial fluid for crystal analysis (polarized microscopy) in addition to Gram stain and culture. Gout and pseudogout can mimic septic arthritis, but the two can coexist — crystals do not exclude infection. If the clinical picture is concerning for sepsis, treat empirically even if crystals are present.

17 C. difficile Infection

Clostridioides difficile infection (CDI) is the most common cause of healthcare-associated diarrhea. Risk factors: antibiotic exposure (especially fluoroquinolones, clindamycin, broad-spectrum cephalosporins), age >65, hospitalization, PPI use, immunosuppression.

Diagnosis

Test only formed stool specimens from patients with ≥3 unformed stools in 24 hours. The preferred approach is a two-step algorithm: (1) GDH (glutamate dehydrogenase) antigen screen or NAAT, then (2) toxin A/B EIA if NAAT is positive. Alternatively, NAAT alone (high sensitivity but may detect colonization rather than active disease).

Severity Classification & Treatment (IDSA/SHEA 2021 Update)

Severity	Criteria	Treatment
Non-severe (initial episode)	WBC ≤15,000 AND Cr <1.5 mg/dL	Fidaxomicin 200 mg PO BID × 10 days (preferred) OR vancomycin 125 mg PO QID × 10 days
Severe	WBC ≥15,000 OR Cr ≥1.5 mg/dL	Fidaxomicin 200 mg PO BID × 10 days OR vancomycin 125 mg PO QID × 10 days
Fulminant	Hypotension, shock, ileus, megacolon	Vancomycin 500 mg PO/NG QID + vancomycin 500 mg per rectum q6h (if ileus) + metronidazole 500 mg IV q8h. Surgical consultation for colectomy
First recurrence	Recurrence within 2–8 weeks of completing therapy	Fidaxomicin 200 mg BID × 10 days, then every other day × 20 days (extended-pulsed regimen); OR vancomycin taper/pulse
Second or subsequent recurrence	Multiple recurrences	Vancomycin taper/pulse, then fecal microbiota transplantation (FMT) after completing antibiotic course; or bezlotoxumab (anti-toxin B monoclonal antibody) as adjunct

Fidaxomicin is now preferred over oral vancomycin for initial and recurrent CDI because it has a narrower spectrum (less disruption of normal flora), lower recurrence rates (~13% vs ~27% with vancomycin), and achieves high fecal concentrations. The main limitation is cost.

Do NOT test for cure. A positive NAAT can persist for weeks after successful treatment. Repeat testing should only be done if symptoms recur. Also, do NOT use anti-motility agents (loperamide) in CDI as they may precipitate toxic megacolon.

18 Intra-Abdominal Infections

Classification

Type	Examples	Microbiology
Primary peritonitis (SBP)	Spontaneous bacterial peritonitis in cirrhotic ascites	E. coli, Klebsiella, S. pneumoniae (monomicrobial)
Secondary peritonitis	Perforated viscus (appendicitis, diverticulitis, peptic ulcer)	Polymicrobial: Enterobacterales, anaerobes (B. fragilis), Enterococcus
Tertiary peritonitis	Persistent/recurrent infection after adequate treatment of secondary peritonitis	Resistant organisms: VRE, Candida, Pseudomonas
Intra-abdominal abscess	Hepatic, splenic, pancreatic, tubo-ovarian, psoas	Polymicrobial; amoebic liver abscess (E. histolytica)

Spontaneous Bacterial Peritonitis (SBP)

Diagnose by paracentesis: ascitic fluid PMN count ≥250 cells/µL = SBP (culture may be negative in ~40%). Treatment: ceftriaxone 2 g IV daily × 5 days. Albumin 1.5 g/kg at diagnosis and 1 g/kg on day 3 reduces mortality in patients with Cr >1, BUN >30, or bilirubin >4. Prophylaxis: norfloxacin 400 mg daily or TMP-SMX for patients with prior SBP, GI hemorrhage, or ascitic fluid protein <1.5 g/dL with advanced liver disease.

Ascending Cholangitis (Charcot Triad & Reynolds Pentad)

Charcot Triad	Reynolds Pentad
Fever + RUQ pain + jaundice	Charcot triad + altered mental status + hypotension

Treatment: IV antibiotics (piperacillin-tazobactam or ampicillin-sulbactam + metronidazole) + urgent biliary drainage (ERCP preferred). Reynolds pentad suggests suppurative cholangitis requiring emergent decompression.

Empiric Therapy for Secondary Peritonitis

Severity	Regimen Options
Mild-moderate (community-acquired)	Ceftriaxone + metronidazole; OR ertapenem 1 g IV daily; OR ampicillin-sulbactam 3 g IV q6h
Severe (healthcare-associated, post-operative)	Piperacillin-tazobactam 4.5 g IV q6h; OR meropenem 1 g IV q8h; OR cefepime + metronidazole ± vancomycin (if Enterococcus risk)

Source control (surgical repair of perforation, drainage of abscess) is the cornerstone of managing secondary peritonitis. Antibiotics alone are insufficient without adequate source control. CT-guided percutaneous drainage has replaced open surgery for most abscesses.

19 Infectious Diarrhea

Etiology by Mechanism

Type	Organisms	Key Features
Inflammatory (bloody/dysentery)	Shigella, Salmonella, Campylobacter, EHEC (O157:H7), C. difficile, Entamoeba	Fever, bloody diarrhea, fecal leukocytes, tenesmus; invade/damage mucosa
Secretory (watery)	Cholera, ETEC (traveler's diarrhea), Norovirus, Rotavirus, Cryptosporidium	Large-volume watery diarrhea, dehydration; no blood or fecal leukocytes
Toxin-mediated (preformed toxin)	S. aureus, B. cereus, C. perfringens	Vomiting and/or diarrhea within 1–6 hours of ingestion (S. aureus, B. cereus emetic); 8–16 hours (C. perfringens, B. cereus diarrheal)

When to Treat vs Supportive Care

Organism	Treatment	Important Notes
Shigella	Azithromycin 500 mg daily × 3 days or ciprofloxacin 500 mg BID × 3 days	Treat all cases (reduces transmission and duration)
Salmonella (non-typhoidal)	Supportive care in uncomplicated gastroenteritis	Treat only if: bacteremia, age <12 months or >50, immunocompromised, prosthetic joint/valve, sickle cell
Campylobacter	Azithromycin 500 mg daily × 3 days	Treat if severe or if given early (<3 days); Guillain-Barré syndrome may follow (~1/1000)
EHEC (O157:H7)	Do NOT give antibiotics	Antibiotics increase risk of HUS (hemolytic uremic syndrome). Supportive care only
Traveler's diarrhea	Azithromycin 1 g × 1 dose (or 500 mg daily × 3 days); or rifaximin 200 mg TID × 3 days (for non-invasive/non-bloody)	Most common cause: ETEC. Self-limited in 3–5 days. Treat if moderate-severe
Giardia	Metronidazole 250 mg TID × 5–7 days or tinidazole 2 g × 1 dose	Chronic diarrhea, bloating, foul-smelling stools; hikers/campers/daycare; stool O&P or Giardia antigen

Empiric antibiotics for community-acquired bloody diarrhea are generally NOT recommended until EHEC is excluded (stool culture, Shiga toxin testing). However, if the patient is severely ill with dysentery (fever, toxicity), azithromycin is the safest empiric choice while awaiting stool studies, as it covers Shigella and Campylobacter without the theoretical risk of HUS associated with fluoroquinolones in EHEC.

20 UTI & Pyelonephritis

Classification

Type	Definition	Common Pathogens
Uncomplicated cystitis	Lower UTI in non-pregnant, premenopausal woman with normal urinary tract	E. coli (~80%), S. saprophyticus, Klebsiella, Proteus
Complicated UTI	UTI with structural/functional abnormality, pregnancy, male sex, catheter, renal transplant, obstruction	E. coli, Klebsiella, Proteus, Enterococcus, Pseudomonas
Pyelonephritis	Upper UTI with flank pain, fever, CVA tenderness	E. coli, Klebsiella, Proteus; consider MRSA if hematogenous
Catheter-associated UTI (CAUTI)	Symptoms + ≥10³ CFU/mL from catheterized specimen (or new catheter specimen after removal)	E. coli, Enterococcus, Candida, Pseudomonas, Klebsiella

Treatment

Condition	First-Line	Alternatives	Duration
Uncomplicated cystitis	Nitrofurantoin 100 mg BID × 5 days or TMP-SMX DS BID × 3 days (if local resistance <20%)	Fosfomycin 3 g PO × 1 dose	3–5 days
Complicated cystitis	Fluoroquinolone (ciprofloxacin 500 mg BID or levofloxacin 750 mg daily) or TMP-SMX	IV if unable to tolerate PO	7–14 days
Uncomplicated pyelonephritis (outpatient)	Ciprofloxacin 500 mg BID × 7 days or TMP-SMX DS BID × 14 days	Ceftriaxone 1 g IM × 1 dose as bridge	7–14 days
Complicated pyelonephritis / urosepsis	Ceftriaxone 1–2 g IV daily, piperacillin-tazobactam, or meropenem (if ESBL risk)	Add vancomycin if Gram-positive cocci in clusters	10–14 days
CAUTI	Remove or replace catheter + culture-directed therapy	Empiric ceftriaxone or fluoroquinolone	7 days (if prompt response); 10–14 days (if delayed response)

Asymptomatic bacteriuria (ASB) should only be treated in two populations: pregnant women (risk of pyelonephritis and preterm labor) and patients undergoing urologic procedures with anticipated mucosal bleeding. Do NOT treat ASB in elderly patients, catheterized patients, or diabetics — treatment does not improve outcomes and promotes resistance.

21 Sexually Transmitted Infections

Gonorrhea & Chlamydia

Feature	Gonorrhea (N. gonorrhoeae)	Chlamydia (C. trachomatis)
Presentation (male)	Purulent urethral discharge, dysuria (2–5 day incubation)	Mucoid/watery discharge, dysuria (7–21 day incubation); often asymptomatic
Presentation (female)	Cervicitis, PID; often asymptomatic	Cervicitis, PID; most common bacterial STI; often asymptomatic
Diagnosis	NAAT (urine or swab) — test of choice; culture for susceptibility if treatment failure	NAAT (urine or swab) — test of choice
Treatment	Ceftriaxone 500 mg IM × 1 dose (1 g if ≥150 kg). If chlamydia not excluded, add doxycycline 100 mg BID × 7 days	Doxycycline 100 mg PO BID × 7 days (preferred over azithromycin per 2021 CDC STI guidelines)
Partner notification	All sexual partners within 60 days; expedited partner therapy (EPT) where legal	All partners within 60 days; EPT

Syphilis (Treponema pallidum)

Stage	Presentation	Treatment
Primary	Painless chancre (clean-based ulcer) at inoculation site, 10–90 days post-exposure; painless lymphadenopathy	Benzathine penicillin G 2.4 million units IM × 1 dose
Secondary	Diffuse maculopapular rash (including palms and soles), condylomata lata, mucous patches, fever, lymphadenopathy; 6–12 weeks after primary	Benzathine penicillin G 2.4 million units IM × 1 dose
Latent (early <1 yr)	Asymptomatic, positive serology	Benzathine penicillin G 2.4 million units IM × 1 dose
Latent (late >1 yr or unknown duration)	Asymptomatic, positive serology	Benzathine penicillin G 2.4 million units IM weekly × 3 doses
Tertiary	Gummas, aortitis (ascending aortic aneurysm), tabes dorsalis, general paresis	Benzathine penicillin G 2.4 million units IM weekly × 3 doses
Neurosyphilis	Any stage; CSF pleocytosis; meningitis, cranial nerve palsies, tabes dorsalis, Argyll Robertson pupils	IV penicillin G 3–4 million units q4h × 10–14 days

Serologic testing: Screen with non-treponemal test (RPR or VDRL) → confirm with treponemal test (FTA-ABS or TP-PA). Many labs now use reverse algorithm: treponemal screen → reflex RPR. Non-treponemal titers correlate with disease activity and are used to monitor treatment response (4-fold decline = adequate response). The Jarisch-Herxheimer reaction (fever, rigors, hypotension within 24h of treatment) is common in early syphilis and is self-limited.

Genital Herpes (HSV-1 & HSV-2)

Feature	Details
Presentation	Painful vesicles/ulcers on erythematous base; inguinal lymphadenopathy; primary episode is most severe
Diagnosis	HSV PCR (preferred) or viral culture of lesion; type-specific serology (HSV-1 IgG, HSV-2 IgG)
First episode	Valacyclovir 1 g PO BID × 7–10 days or acyclovir 400 mg TID × 7–10 days
Recurrent episodes	Valacyclovir 500 mg BID × 3 days or 1 g daily × 5 days
Suppressive therapy	Valacyclovir 500 mg–1 g PO daily (reduces outbreaks by 70–80% and transmission by 50%)

22 PID & Tubo-ovarian Abscess

Pelvic inflammatory disease (PID) is an ascending infection of the upper female genital tract (endometritis, salpingitis, peritonitis, tubo-ovarian abscess). It is primarily caused by N. gonorrhoeae and C. trachomatis, but is often polymicrobial (anaerobes, GNR, Mycoplasma genitalium).

Diagnosis

Clinical diagnosis: pelvic/lower abdominal pain + one or more of: cervical motion tenderness, uterine tenderness, adnexal tenderness. Additional criteria supporting diagnosis: fever >38.3°C, cervical mucopurulent discharge, elevated WBC, elevated ESR/CRP, laboratory documentation of GC/CT.

Treatment (CDC 2021)

Setting	Regimen
Outpatient (mild-moderate)	Ceftriaxone 500 mg IM × 1 dose + doxycycline 100 mg PO BID × 14 days ± metronidazole 500 mg PO BID × 14 days
Inpatient	Cefotetan 2 g IV q12h + doxycycline 100 mg PO/IV q12h; OR cefoxitin 2 g IV q6h + doxycycline 100 mg PO/IV q12h; OR clindamycin 900 mg IV q8h + gentamicin (loading + maintenance)

Tubo-ovarian Abscess (TOA)

Diagnosed by pelvic ultrasound or CT. Treatment: IV antibiotics (as above for inpatient PID) + image-guided drainage if abscess ≥3 cm or failure to improve in 48–72 hours. Surgical intervention if ruptured (surgical emergency) or unresponsive to medical therapy.

Low threshold to diagnose and treat PID — untreated PID leads to infertility (~15% after one episode, ~35% after two), ectopic pregnancy, and chronic pelvic pain. The clinical diagnosis has low sensitivity and specificity, but the consequences of delayed treatment outweigh the risks of overtreatment. Test all PID patients for HIV and syphilis.

23 HIV Pathophysiology & Natural History

Human immunodeficiency virus (HIV) is a retrovirus that targets CD4+ T lymphocytes, leading to progressive immune deficiency. Without treatment, HIV progresses through well-defined stages over 8–10 years from acute infection to AIDS (CD4 <200 cells/µL or AIDS-defining illness).

Viral Lifecycle

Step	Mechanism	Drug Target
1. Attachment/entry	gp120 binds CD4 receptor → conformational change → gp41 binds CCR5 or CXCR4 coreceptor → membrane fusion	Entry inhibitors (maraviroc = CCR5 antagonist; enfuvirtide = fusion inhibitor)
2. Reverse transcription	Viral RNA → DNA by reverse transcriptase	NRTIs (tenofovir, emtricitabine, abacavir, lamivudine); NNRTIs (efavirenz, rilpivirine, doravirine)
3. Integration	Viral DNA integrates into host genome via integrase	INSTIs (dolutegravir, bictegravir, cabotegravir)
4. Transcription/translation	Host cell machinery produces viral mRNA and polyproteins	—
5. Assembly/budding	Polyproteins assembled into immature virion; budding from cell membrane	—
6. Maturation	Protease cleaves polyproteins into functional proteins	Protease inhibitors (darunavir, atazanavir)

Natural History of Untreated HIV

Stage	Duration	CD4 Count	Viral Load	Features
Acute retroviral syndrome	2–4 weeks post-exposure	Transient drop	Very high (>100,000)	Fever, rash, pharyngitis, lymphadenopathy, myalgia (mono-like illness); 50–90% symptomatic; highest infectivity
Clinical latency	~8–10 years (median)	Gradual decline (~50–80/year)	Steady-state "set point"	Usually asymptomatic; persistent generalized lymphadenopathy
Symptomatic HIV / AIDS	Variable	<200 cells/µL	Rising	Opportunistic infections, wasting, malignancies, death within 2–3 years without ART

Without treatment, median time from HIV infection to AIDS is ~10 years, and median survival after AIDS diagnosis is ~2 years. With modern ART, life expectancy approaches that of the general population when treatment is initiated early and consistently maintained.

24 HIV Testing & Diagnosis

Recommended Testing Algorithm (CDC 2014)

Step	Test	Window Period	Notes
1. Initial screen	4th-generation HIV-1/2 Ag/Ab combo assay	~2 weeks (detects p24 Ag)	Detects both HIV-1/2 antibodies and p24 antigen; replaces older Ab-only tests
2. Confirmatory	HIV-1/HIV-2 antibody differentiation immunoassay	—	Distinguishes HIV-1 from HIV-2
3. If discordant	HIV-1 RNA (viral load/NAAT)	~10–14 days	Detects acute HIV before antibody seroconversion; resolves indeterminate results

Baseline Laboratory Workup (Newly Diagnosed HIV)

Test	Purpose
CD4 count (absolute and %)	Determines immunologic status and need for OI prophylaxis
HIV RNA viral load	Baseline for monitoring ART response; goal is undetectable (<20–50 copies/mL)
HIV genotype (resistance testing)	Guide ART selection; perform before initiating therapy
HLA-B*5701	Screen before abacavir use — if positive, do NOT use abacavir (risk of hypersensitivity reaction)
CBC, CMP, lipid panel, HbA1c	Baseline metabolic assessment; ART metabolic monitoring
Hepatitis B (HBsAg, anti-HBs, anti-HBc), Hepatitis C Ab	Coinfection management; tenofovir-containing regimens treat both HIV and HBV
RPR/VDRL, GC/CT NAAT, Trichomonas	STI screening
TB screening (IGRA or PPD)	Latent TB treatment if positive
Toxoplasma IgG	If positive and CD4 <100, prophylaxis required
G6PD level	Before dapsone or primaquine use

25 Antiretroviral Therapy

ART is recommended for all persons with HIV regardless of CD4 count (treat early). The goal is durable viral suppression (HIV RNA <50 copies/mL), immune reconstitution, reduced transmission, and improved survival. Modern regimens are once-daily, well-tolerated, and highly effective.

Preferred Initial ART Regimens (DHHS 2023)

Regimen	Components	Key Considerations
Bictegravir/emtricitabine/TAF (Biktarvy)	INSTI + 2 NRTIs (single tablet)	High barrier to resistance, minimal drug interactions, once daily. Cannot use if CrCl <30 or with rifampin
Dolutegravir/lamivudine (Dovato)	INSTI + 1 NRTI (2-drug regimen, single tablet)	Only if HBV negative, HIV RNA <500,000, no resistance to either component; once daily
Dolutegravir + emtricitabine/TAF (or TDF)	INSTI + 2 NRTIs	Flexible backbone; dolutegravir has high barrier to resistance
Cabotegravir + rilpivirine (Cabenuva)	Long-acting injectable INSTI + NNRTI	IM injections every 1–2 months; for virally suppressed patients (switch strategy); NOT for initial therapy

Pre-Exposure Prophylaxis (PrEP)

Regimen	Population	Monitoring
Emtricitabine/TDF (Truvada) daily	All at-risk populations	HIV test q3 months, renal function q6–12 months, STI screen q3–6 months
Emtricitabine/TAF (Descovy) daily	MSM, transgender women (≥35 kg); NOT approved for receptive vaginal sex	Same as above; less renal/bone toxicity than TDF
Cabotegravir (Apretude) IM q2 months	All at-risk populations	Superior efficacy to daily oral PrEP in trials; long-acting injectable

Post-Exposure Prophylaxis (PEP)

Initiate within 72 hours of exposure (sooner is better; ideally within 2 hours). Standard regimen: emtricitabine/TDF + dolutegravir (or raltegravir) × 28 days. Test source patient and exposed individual for HIV at baseline, 4–6 weeks, and 12 weeks.

Immune reconstitution inflammatory syndrome (IRIS) can occur within weeks to months of ART initiation, as the recovering immune system mounts an exaggerated inflammatory response against pre-existing opportunistic infections (paradoxical IRIS) or uncovers subclinical infections (unmasking IRIS). Common in patients starting ART with CD4 <50 and high viral load. Treatment: continue ART, treat the underlying OI, add corticosteroids for severe cases. For this reason, in cryptococcal meningitis and TB meningitis, ART initiation should be delayed 4–6 weeks and 2–8 weeks, respectively.

26 Opportunistic Infections in HIV

CD4-Based Risk & Prophylaxis

CD4 Threshold	Opportunistic Infection	Prophylaxis	When to Stop Prophylaxis
<200	Pneumocystis jirovecii (PJP)	TMP-SMX DS daily (also covers Toxoplasma)	CD4 >200 for ≥3 months on ART
<100	Toxoplasma gondii (if IgG positive)	TMP-SMX DS daily	CD4 >200 for ≥3 months on ART
<50	Mycobacterium avium complex (MAC)	Azithromycin 1200 mg weekly (if unable to start ART promptly)	CD4 >100 for ≥3 months on ART; not required if starting ART immediately
<50	CMV retinitis	No primary prophylaxis; regular fundoscopic exams	—
Any CD4	TB (if LTBI positive)	LTBI treatment (3HP, 4R, or 9H)	After completing course

Key Opportunistic Infections

OI	CD4	Presentation	Diagnosis	Treatment
PJP	<200	Subacute dyspnea, dry cough, fever; bilateral GGOs on CT; elevated LDH	Induced sputum/BAL: silver stain, DFA; elevated beta-D-glucan	TMP-SMX × 21 days; prednisone if PaO2 ≤70
Toxoplasmosis	<100	Ring-enhancing brain lesions (multiple), headache, focal deficits, seizures	Serum Toxoplasma IgG (usually positive); MRI: multiple ring-enhancing lesions with edema; clinical response to empiric therapy	Pyrimethamine + sulfadiazine + leucovorin × 6 weeks, then maintenance
MAC	<50	Fever, night sweats, weight loss, diarrhea, hepatosplenomegaly, pancytopenia; elevated alk phos	Blood cultures (mycobacterial); takes 1–2 weeks	Azithromycin 500 mg daily + ethambutol 15 mg/kg daily ± rifabutin
CMV retinitis	<50	"Floaters," vision loss; fundoscopy: "pizza pie" or "cottage cheese and ketchup" appearance (hemorrhages + exudates)	Fundoscopic exam; CMV PCR in blood	Ganciclovir IV or valganciclovir PO × 14–21 days induction, then maintenance until immune reconstitution
Cryptococcal meningitis	<100	Subacute headache, fever, AMS; meningismus often mild/absent	Serum/CSF CrAg (highly sensitive); India ink; opening pressure usually elevated	Amphotericin B + flucytosine × 2 weeks → fluconazole consolidation → maintenance
Kaposi sarcoma (HHV-8)	Any (risk increases with lower CD4)	Violaceous papules/nodules (skin, oral mucosa, visceral)	Biopsy showing spindle cells; HHV-8 immunostain	ART (may regress with immune reconstitution); chemotherapy for advanced (liposomal doxorubicin)

Toxoplasma ring-enhancing brain lesions in HIV must be differentiated from primary CNS lymphoma (typically single lesion, EBV PCR in CSF, thallium SPECT/PET uptake). Empiric treatment for toxoplasmosis with clinical and radiographic reassessment at 2 weeks is the standard approach — biopsy is reserved for patients who do not respond or are Toxoplasma IgG negative.

27 Cellulitis, Abscess & Necrotizing Fasciitis

Purulent vs Non-Purulent SSTI

Type	Organisms	Treatment
Non-purulent cellulitis (no abscess/drainage)	Beta-hemolytic Streptococcus (GAS) most common; MSSA	Cephalexin 500 mg QID, dicloxacillin 500 mg QID, or clindamycin 300–450 mg TID × 5–7 days. Add MRSA coverage only if: penetrating trauma, IVDU, MRSA risk factors, failure of beta-lactam
Purulent cellulitis (abscess, furuncle, carbuncle)	S. aureus (CA-MRSA in many regions)	I&D is primary treatment for abscess; add TMP-SMX DS BID or doxycycline 100 mg BID if: abscess >2 cm, multiple lesions, surrounding cellulitis, immunocompromised, systemic symptoms
Severe (failed oral, rapid progression, systemic toxicity)	S. aureus (including MRSA), Streptococcus	Vancomycin 15–20 mg/kg IV q8–12h + piperacillin-tazobactam (if polymicrobial concern); OR vancomycin + ceftriaxone

Necrotizing Fasciitis

Emergency — Necrotizing Fasciitis

Necrotizing fasciitis is a surgical emergency with mortality of 25–35% (higher if delayed surgery). Clinical features: severe pain out of proportion to exam findings, rapidly spreading erythema, crepitus, bullae/hemorrhagic blisters, skin necrosis, septic shock. Do NOT wait for imaging if clinical suspicion is high. Treatment: emergent surgical debridement + broad-spectrum antibiotics (vancomycin + piperacillin-tazobactam + clindamycin). Clindamycin inhibits toxin production. Serial debridements are typically required.

Type	Microbiology	Risk Factors
Type I (polymicrobial)	Mixed aerobic + anaerobic (GNR, anaerobes, Enterococcus)	Diabetes, peripheral vascular disease, post-surgical, perineal (Fournier gangrene)
Type II (monomicrobial)	Group A Streptococcus (most common) or S. aureus (including CA-MRSA)	Healthy individuals, minor trauma, NSAIDs (may mask symptoms)
Type III	Vibrio vulnificus (saltwater exposure), Aeromonas (freshwater)	Liver disease, raw shellfish consumption, wound exposure to water

LRINEC Score (Laboratory Risk Indicator for Necrotizing Fasciitis)

Variable	Score
CRP ≥150 mg/L	4
WBC 15,000–25,000	1; >25,000 = 2
Hemoglobin 11–13.5 g/dL	1; <11 = 2
Sodium <135 mEq/L	2
Creatinine >1.6 mg/dL	2
Glucose >180 mg/dL	1

Score ≥6 suggests necrotizing fasciitis (PPV ~92%). However, a low score does NOT exclude the diagnosis — clinical suspicion should override the score. If in doubt, take the patient to the operating room.

28 Diabetic Foot Infections

Diabetic foot infections (DFI) occur in ~25% of diabetics over their lifetime, and are the leading cause of non-traumatic lower extremity amputation. Classification guides management.

IWGDF/IDSA Severity Classification

Grade	Severity	Clinical Features	Treatment
1	Uninfected	Wound without signs of infection	Wound care, offloading
2	Mild	Infection limited to skin/subcutaneous tissue, erythema ≤2 cm around ulcer, no systemic signs	Oral antibiotics: cephalexin, amoxicillin-clavulanate, or TMP-SMX + amoxicillin-clavulanate
3	Moderate	Erythema >2 cm, or involving deeper structures (abscess, osteomyelitis, septic arthritis), no SIRS	IV antibiotics: ampicillin-sulbactam, piperacillin-tazobactam, or ertapenem. Consider MRSA coverage
4	Severe	Any foot infection with SIRS/sepsis	Broad-spectrum IV: vancomycin + piperacillin-tazobactam or meropenem. Emergent surgical evaluation

Osteomyelitis in Diabetic Foot

The probe-to-bone (PTB) test is performed by inserting a sterile blunt metal probe through the ulcer: if bone is palpable, osteomyelitis is likely (sensitivity ~89% in patients with high pretest probability). ESR >70 mm/hr has high specificity for osteomyelitis. MRI is the gold standard imaging modality. Bone biopsy with culture provides definitive diagnosis and guides antibiotic therapy — always preferred over wound swab cultures.

Multidisciplinary management (ID, vascular surgery, podiatry, wound care, endocrinology) significantly reduces amputation rates. Always assess peripheral arterial disease (ABI, pulse examination) as revascularization may be needed before infection can heal. Optimize glycemic control concurrently.

29 Antibiotic Spectrum & Selection

Beta-Lactam Antibiotics

Class	Examples	Spectrum	Key Notes
Natural penicillins	Penicillin G, Penicillin V	Streptococcus, Treponema pallidum, Actinomyces	Drug of choice for syphilis; narrow spectrum
Anti-staphylococcal penicillins	Nafcillin, oxacillin, dicloxacillin	MSSA (beta-lactamase stable)	Drug of choice for MSSA; does NOT cover MRSA
Aminopenicillins	Amoxicillin, ampicillin	Streptococcus, Enterococcus, Listeria, some GNR	Ampicillin for Listeria and Enterococcus; susceptible to beta-lactamases
BL/BLI combinations	Amoxicillin-clavulanate, ampicillin-sulbactam, piperacillin-tazobactam	Extended GNR including anaerobes; pip-tazo covers Pseudomonas	Pip-tazo = workhorse for empiric broad-spectrum coverage
1st-gen cephalosporins	Cefazolin, cephalexin	MSSA, Streptococcus, E. coli, Klebsiella, Proteus	Surgical prophylaxis (cefazolin); PO SSTI (cephalexin)
3rd-gen cephalosporins	Ceftriaxone, cefotaxime, ceftazidime	Broad GNR; ceftriaxone = meningitis, pneumonia; ceftazidime covers Pseudomonas	Ceftriaxone: once-daily, excellent CNS penetration
4th-gen cephalosporins	Cefepime	Broad GNR + Pseudomonas, stable to AmpC beta-lactamases	Better against Enterobacter than 3rd-gen (AmpC stable)
5th-gen cephalosporins	Ceftaroline	MRSA + Gram-negative (not Pseudomonas)	Only cephalosporin active against MRSA
Carbapenems	Meropenem, imipenem, ertapenem, doripenem	Broadest beta-lactam spectrum: GPC, GNR, anaerobes. Ertapenem does NOT cover Pseudomonas or Acinetobacter	Reserve for ESBL, serious polymicrobial infections; imipenem lowers seizure threshold

Non-Beta-Lactam Antibiotics

Agent	Spectrum	Key Uses	Major Toxicities
Vancomycin	MRSA, CoNS, Enterococcus (not VRE vanA), C. difficile (PO only)	MRSA infections, febrile neutropenia, C. diff (PO). AUC/MIC-guided dosing (target 400–600)	Nephrotoxicity, red man syndrome (histamine), ototoxicity
Linezolid	MRSA, VRE, Streptococcus	VRE infections, MRSA pneumonia (superior lung penetration), oral bioavailability 100%	Thrombocytopenia, serotonin syndrome (MAO inhibitor), peripheral neuropathy, lactic acidosis (>2 weeks)
Daptomycin	MRSA, VRE (bactericidal)	Bacteremia, endocarditis (right-sided), SSTI	Inactivated by surfactant — do NOT use for pneumonia. CPK elevation/rhabdomyolysis; monitor CPK weekly
Fluoroquinolones	GNR (including Pseudomonas for cipro/levofloxacin), atypical organisms; levo/moxi cover Streptococcus	UTI, pneumonia (respiratory FQ), bone/joint	QTc prolongation, tendon rupture, aortic dissection, C. diff, peripheral neuropathy; FDA black box warning
Aminoglycosides	Aerobic GNR, synergy with beta-lactams for GPC	Synergy in endocarditis; serious GNR infections	Nephrotoxicity (reversible), ototoxicity (irreversible), neuromuscular blockade
Metronidazole	Anaerobes (B. fragilis, C. difficile), protozoa (Giardia, Trichomonas, Entamoeba)	Intra-abdominal infections (with cephalosporin), brain abscess, C. diff (2nd line), trichomoniasis	Disulfiram-like reaction with alcohol, peripheral neuropathy (prolonged use), metallic taste
TMP-SMX	MRSA (CA-MRSA), PJP, Stenotrophomonas, Nocardia, Listeria	PJP treatment/prophylaxis, CA-MRSA SSTI, UTI	Hyperkalemia, myelosuppression, rash (Stevens-Johnson), renal toxicity

"Cidal vs static" matters in specific clinical scenarios. Bactericidal agents are required for meningitis (poor immune penetration to CNS), endocarditis (bacteria within vegetations are shielded), and neutropenic fever (no functioning immune system). Linezolid is bacteriostatic against Enterococcus and Staphylococcus but bactericidal against Streptococcus.

30 Antifungal Agents

Class	Agents	Mechanism	Spectrum	Key Toxicities
Azoles	Fluconazole, voriconazole, itraconazole, posaconazole, isavuconazole	Inhibit 14-α-demethylase (ergosterol synthesis)	Fluconazole: Candida (not C. krusei, variable C. glabrata), Cryptococcus. Voriconazole: Aspergillus (DOC), Fusarium. Itraconazole: Histoplasma, Blastomyces, Sporothrix. Posaconazole: broadest azole (Mucor prophylaxis)	Hepatotoxicity, QTc prolongation, CYP450 inhibition (drug interactions); voriconazole: visual disturbances, photosensitivity, skin cancer (long-term)
Echinocandins	Caspofungin, micafungin, anidulafungin	Inhibit 1,3-beta-D-glucan synthase (cell wall)	Candida (all species including azole-resistant; first-line for candidemia), Aspergillus (salvage). NO activity against Cryptococcus or Mucor	Generally well-tolerated; hepatotoxicity (rare), histamine-related reactions
Polyenes	Amphotericin B deoxycholate, liposomal amphotericin B (AmBisome)	Binds ergosterol → pore formation → cell lysis (fungicidal)	Broadest spectrum: Candida, Aspergillus, Cryptococcus, Mucor/Rhizopus, endemic mycoses. NO activity against Aspergillus terreus	Nephrotoxicity (#1 — lipid formulation less toxic), infusion reactions, hypokalemia, hypomagnesemia, anemia
Flucytosine (5-FC)	Flucytosine	Inhibits DNA/RNA synthesis	Cryptococcus, some Candida; always used in combination (synergy with amphotericin B)	Myelosuppression (dose-dependent), hepatotoxicity, GI toxicity

Mucormycosis (Rhizopus, Mucor) is treated with liposomal amphotericin B + surgical debridement. Risk factors: uncontrolled diabetes (especially DKA), iron overload, deferoxamine therapy, hematologic malignancy. Azoles and echinocandins have NO activity against Mucor (except isavuconazole, which has approval for mucormycosis). Posaconazole is used for step-down therapy.

31 Antiviral Agents

Agent	Mechanism	Indications	Key Notes
Acyclovir / Valacyclovir	Guanosine analog; requires viral thymidine kinase for activation → inhibits viral DNA polymerase	HSV (genital, encephalitis, keratitis), VZV (shingles, varicella)	Dose-adjust for renal impairment; crystalline nephropathy (ensure adequate hydration); valacyclovir is oral prodrug with better bioavailability
Ganciclovir / Valganciclovir	Guanosine analog; inhibits viral DNA polymerase (broader than acyclovir)	CMV retinitis, CMV prophylaxis in transplant	Myelosuppression (neutropenia, thrombocytopenia) — monitor CBC. Valganciclovir = oral prodrug
Foscarnet	Pyrophosphate analog; directly inhibits viral DNA polymerase (no kinase activation needed)	CMV resistant to ganciclovir, acyclovir-resistant HSV/VZV	Nephrotoxicity, electrolyte abnormalities (hypocalcemia, hypokalemia, hypomagnesemia), seizures; requires aggressive IV hydration
Oseltamivir / Zanamivir	Neuraminidase inhibitors	Influenza A and B (treatment and prophylaxis)	Most effective within 48h of symptom onset; benefit in hospitalized patients even if started later. Oseltamivir 75 mg BID × 5 days
Baloxavir marboxil	Cap-dependent endonuclease inhibitor	Influenza A and B	Single oral dose; alternative to oseltamivir
Sofosbuvir-based regimens	NS5B polymerase inhibitor (direct-acting antiviral)	Hepatitis C (all genotypes)	Sofosbuvir/velpatasvir (Epclusa) × 12 weeks = pangenotypic, >95% SVR (cure). Screen all adults for HCV
Remdesivir	Nucleotide analog; inhibits RNA-dependent RNA polymerase	COVID-19 (hospitalized patients requiring supplemental O2; outpatients at high risk within 7 days of symptom onset)	3-day course for outpatients; 5-day course for hospitalized. Hepatotoxicity (monitor LFTs)

32 Antimicrobial Stewardship Principles

Antimicrobial stewardship programs (ASPs) aim to optimize antibiotic use, improve patient outcomes, reduce adverse events (C. difficile, resistance emergence), and decrease healthcare costs. Core strategies include:

Key Stewardship Interventions

Strategy	Description	Impact
Prospective audit and feedback	ID pharmacist/physician reviews antimicrobial orders and provides real-time recommendations	Reduces broad-spectrum use by 20–40%; associated with decreased C. diff and resistance
Formulary restriction & preauthorization	Selected broad-spectrum agents require approval before dispensing	Rapid reduction in targeted antibiotic use; risk of delayed therapy if process is cumbersome
De-escalation	Narrowing empiric broad-spectrum therapy based on culture results	Core principle: "start broad, narrow early." Reduces selection pressure without compromising outcomes
IV-to-PO conversion	Transition from IV to oral antibiotics when patient tolerating PO and clinically improving	Earlier discharge, reduced line-related complications, cost savings. Many antibiotics have excellent oral bioavailability (fluoroquinolones ~100%, linezolid ~100%, metronidazole ~100%, TMP-SMX ~100%)
Procalcitonin-guided therapy	Use serum procalcitonin to guide antibiotic initiation and duration in respiratory infections and sepsis	Procalcitonin <0.25 ng/mL: bacterial infection unlikely; <0.5 or declining by ≥80%: consider stopping antibiotics. Reduces antibiotic exposure by 2–3 days
Therapeutic drug monitoring (TDM)	Measuring drug levels to optimize efficacy and minimize toxicity	Vancomycin: AUC/MIC 400–600 (replace trough-based monitoring). Aminoglycosides: peak and trough. Voriconazole: trough 2–5.5 µg/mL
Duration optimization	Evidence-based shorter courses when data supports	CAP: 5 days. UTI (uncomplicated): 3–5 days. Intra-abdominal (source controlled): 4 days. Cellulitis: 5–6 days. Bacteremia (GNR uncomplicated): 7 days

The IDSA recommends that all hospitals implement an antimicrobial stewardship program. Key elements: physician and pharmacist co-leadership, hospital administration support, real-time access to antibiograms, integration with infection prevention, education, and tracking/reporting of antibiotic use metrics (DOT per 1,000 patient-days).

Antibiotic-associated C. difficile risk (highest to lowest): fluoroquinolones, clindamycin, broad-spectrum cephalosporins, carbapenems, penicillins. Every unnecessary day of broad-spectrum antibiotics increases CDI risk.

33 Imaging in Infectious Disease

Clinical Scenario	Imaging Modality	Key Findings
Community-acquired pneumonia	CXR (PA and lateral)	Lobar consolidation, air bronchograms, pleural effusion; CT if CXR negative but high suspicion
Lung abscess	CT chest with contrast	Thick-walled cavitary lesion with air-fluid level; dependent segments (aspiration)
TB (pulmonary)	CXR, CT chest	Upper lobe infiltrates/cavitation (reactivation), miliary pattern (disseminated), Ghon complex (primary), hilar lymphadenopathy
PJP	CT chest (HRCT)	Bilateral ground-glass opacities (perihilar distribution); cysts may form; CXR may be normal early
Infective endocarditis	TTE, TEE (if TTE negative or prosthetic valve)	Vegetations, abscess, new valvular regurgitation, dehiscence; FDG-PET/CT for prosthetic valve/device
Osteomyelitis	MRI (gold standard)	T1: low signal in bone marrow. T2/STIR: high signal (edema). Contrast enhancement. 3-phase bone scan if MRI contraindicated
Vertebral discitis-osteomyelitis	MRI with gadolinium	Involvement of 2 adjacent vertebral bodies + intervening disc; epidural/paravertebral abscess
Brain abscess	MRI with contrast + DWI	Ring-enhancing lesion with restricted diffusion (bright on DWI, dark on ADC) — differentiates from tumor (no restricted diffusion)
Spinal epidural abscess	MRI with gadolinium (entire spine)	Epidural collection with enhancement, cord compression; image entire spine (skip lesions)
Intra-abdominal abscess	CT abdomen/pelvis with IV contrast	Rim-enhancing fluid collection ± gas; guides percutaneous drainage
Necrotizing fasciitis	CT (if diagnosis uncertain, do NOT delay surgery)	Fascial thickening, fat stranding, gas tracking along fascial planes; MRI more sensitive but takes longer
FUO workup	FDG-PET/CT	Detects occult infection, inflammation, or malignancy with 40–70% diagnostic yield

Chest X-ray showing bilateral upper lobe cavitary infiltrates in pulmonary tuberculosis — **Figure 3 — Chest X-ray: Pulmonary Tuberculosis.** Bilateral upper lobe cavitary infiltrates with surrounding consolidation, characteristic of reactivation pulmonary tuberculosis. Cavitary disease is associated with high bacillary burden and increased infectivity. Source: Wikimedia Commons. Public domain.

34 Classification Systems

Sepsis-3 (2016 Third International Consensus Definitions)

Term	Definition
Sepsis	Life-threatening organ dysfunction caused by a dysregulated host response to infection. Operationalized as suspected infection + acute SOFA score increase ≥2
Septic shock	Sepsis requiring vasopressors to maintain MAP ≥65 mmHg AND lactate >2 mmol/L after adequate volume resuscitation. Hospital mortality >40%
qSOFA	Bedside screen: RR ≥22, AMS, SBP ≤100. Score ≥2 = high risk

CURB-65 (Community-Acquired Pneumonia Severity)

Score	30-Day Mortality	Disposition
0–1	<3%	Outpatient
2	~9%	Consider short inpatient or supervised outpatient
3–5	15–40%	Inpatient; 4–5 = ICU consideration

Modified Duke Criteria for Infective Endocarditis (2023)

Classification	Criteria Required
Definite IE	2 major OR 1 major + 3 minor OR 5 minor; or pathologic criteria (vegetation histology/culture)
Possible IE	1 major + 1 minor OR 3 minor
Rejected	Firm alternative diagnosis, resolution with ≤4 days of antibiotics, no pathologic evidence at surgery/autopsy

WHO Clinical Staging of HIV/AIDS

Stage	Features
1 (Asymptomatic)	Asymptomatic or persistent generalized lymphadenopathy
2 (Mild)	Weight loss <10%, recurrent URIs, herpes zoster, angular cheilitis
3 (Advanced)	Weight loss >10%, chronic diarrhea >1 month, oral candidiasis, pulmonary TB, severe bacterial infections
4 (Severe/AIDS)	HIV wasting, PJP, esophageal candidiasis, extrapulmonary TB, Kaposi sarcoma, CNS toxoplasmosis, cryptococcal meningitis, CMV retinitis, HIV encephalopathy

CDC HIV Classification (Revised 2014)

Stage	CD4 Count	Definition
Stage 0	Any	Early HIV infection (negative/indeterminate test within 6 months before first positive)
Stage 1	≥500 cells/µL	No AIDS-defining condition
Stage 2	200–499 cells/µL	No AIDS-defining condition
Stage 3 (AIDS)	<200 cells/µL	OR presence of AIDS-defining condition regardless of CD4

35 Medications Master Table

Drug	Class	Route	Standard Dose	Renal Adjustment	Key Toxicity / Monitoring
Amoxicillin	Aminopenicillin	PO	500–1000 mg TID	Reduce if CrCl <30	Rash, diarrhea, C. diff
Amoxicillin-clavulanate	BL/BLI	PO	875/125 mg BID	Avoid ER formulation if CrCl <30	Diarrhea, hepatotoxicity (clavulanate)
Ampicillin-sulbactam	BL/BLI	IV	3 g q6h	Reduce frequency if CrCl <30	Rash, diarrhea
Piperacillin-tazobactam	BL/BLI	IV	4.5 g q6h (or extended infusion q8h)	3.375 g q6h if CrCl <40	Thrombocytopenia (especially with vancomycin), hypokalemia
Cefazolin	1st-gen ceph	IV	2 g q8h	Reduce if CrCl <35	Generally well-tolerated; cross-reactivity with penicillin ~1–2%
Ceftriaxone	3rd-gen ceph	IV/IM	1–2 g q24h (meningitis: 2 g q12h)	No renal adjustment needed	Biliary sludging; do not mix with calcium-containing solutions in neonates
Cefepime	4th-gen ceph	IV	2 g q8h	Reduce if CrCl <60; neurotoxicity risk if not adjusted	Neurotoxicity (encephalopathy, seizures — especially in renal impairment)
Meropenem	Carbapenem	IV	1 g q8h (meningitis: 2 g q8h)	Reduce if CrCl <50	Seizures (less than imipenem), C. diff, rash
Ertapenem	Carbapenem	IV/IM	1 g q24h	Reduce if CrCl <30	No Pseudomonas coverage; seizures (rare)
Vancomycin	Glycopeptide	IV	15–20 mg/kg q8–12h (AUC-guided)	Adjust per AUC/MIC or trough; hold if trough >20	Nephrotoxicity, red man syndrome, ototoxicity; AUC/MIC 400–600 target
Linezolid	Oxazolidinone	IV/PO	600 mg q12h	No adjustment (but metabolites accumulate)	Thrombocytopenia (weekly CBC), serotonin syndrome, peripheral neuropathy, lactic acidosis
Daptomycin	Lipopeptide	IV	6 mg/kg q24h (SSTI), 8–10 mg/kg q24h (bacteremia/IE)	q48h if CrCl <30	CPK elevation (check weekly); NOT for pneumonia
Ciprofloxacin	Fluoroquinolone	PO/IV	500 mg PO BID or 400 mg IV q12h	Reduce if CrCl <30	QTc prolongation, tendon rupture, C. diff, aortic dissection
Levofloxacin	Fluoroquinolone	PO/IV	750 mg daily	Reduce if CrCl <50	Same as ciprofloxacin + respiratory coverage (pneumococcus)
Metronidazole	Nitroimidazole	PO/IV	500 mg q8h	No standard adjustment; avoid in severe hepatic impairment	Disulfiram reaction, peripheral neuropathy, metallic taste
TMP-SMX	Folate inhibitor	PO/IV	DS (160/800) BID for UTI/SSTI; 15–20 mg/kg/d (TMP) for PJP	Avoid if CrCl <15 (for treatment doses)	Hyperkalemia, rash/SJS, myelosuppression, renal toxicity
Fluconazole	Azole antifungal	PO/IV	400–800 mg daily (varies by indication)	50% dose reduction if CrCl <50	Hepatotoxicity, QTc prolongation, drug interactions (CYP2C19, CYP3A4)
Voriconazole	Azole antifungal	PO/IV	6 mg/kg q12h ×2 then 4 mg/kg q12h	Avoid IV formulation if CrCl <50 (cyclodextrin vehicle accumulates)	Visual disturbances, photosensitivity, hepatotoxicity, periostitis; TDM: trough 2–5.5
Micafungin	Echinocandin	IV	100 mg daily (candidemia), 150 mg daily (esophageal)	No renal adjustment	Generally well-tolerated; hepatotoxicity (rare)
Acyclovir	Nucleoside analog	PO/IV	IV: 10 mg/kg q8h (encephalitis); PO: 400 mg TID (genital HSV)	Reduce dose/frequency if CrCl <50	Crystalline nephropathy (hydrate), neurotoxicity (tremor, confusion in renal failure)
Oseltamivir	Neuraminidase inhibitor	PO	75 mg BID × 5 days	75 mg daily if CrCl 30–60; 30 mg daily if CrCl <30	Nausea/vomiting; neuropsychiatric events (rare, children)

36 Abbreviations Master List

ABxAntibiotics AFBAcid-fast bacilli AMSAltered mental status ANCAbsolute neutrophil count ARTAntiretroviral therapy ASPAntimicrobial stewardship program AUCArea under the curve BALBronchoalveolar lavage BCGBacillus Calmette-Guérin (TB vaccine) BCxBlood culture BL/BLIBeta-lactam/beta-lactamase inhibitor BSIBloodstream infection CAPCommunity-acquired pneumonia CAUTICatheter-associated urinary tract infection CDIClostridioides difficile infection CFCystic fibrosis CMVCytomegalovirus CNSCentral nervous system CoNSCoagulase-negative staphylococci CrAgCryptococcal antigen CRBSICatheter-related bloodstream infection CRECarbapenem-resistant Enterobacterales CSFCerebrospinal fluid CVACostovertebral angle CXRChest X-ray DAIRDebridement, antibiotics, implant retention DFADirect fluorescent antibody DGIDisseminated gonococcal infection DKADiabetic ketoacidosis DOTDirectly observed therapy DTPDifferential time to positivity DWIDiffusion-weighted imaging EHECEnterohemorrhagic E. coli EIAEnzyme immunoassay ESBLExtended-spectrum beta-lactamase ETECEnterotoxigenic E. coli FMTFecal microbiota transplantation FQFluoroquinolone FTA-ABSFluorescent treponemal antibody absorption FUOFever of unknown origin GASGroup A Streptococcus (S. pyogenes) GBSGroup B Streptococcus (S. agalactiae) GDHGlutamate dehydrogenase GGOGround-glass opacity GNRGram-negative rod GPCGram-positive cocci HACEKHaemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella HAPHospital-acquired pneumonia HBVHepatitis B virus HCVHepatitis C virus HHV-8Human herpesvirus 8 HIVHuman immunodeficiency virus HSVHerpes simplex virus HUSHemolytic uremic syndrome I&DIncision and drainage IDInfectious disease IEInfective endocarditis IGRAInterferon-gamma release assay INSTIIntegrase strand transfer inhibitor IRISImmune reconstitution inflammatory syndrome IVDUIntravenous drug use KPCKlebsiella pneumoniae carbapenemase LPLumbar puncture LRINECLaboratory Risk Indicator for Necrotizing Fasciitis LTBILatent tuberculosis infection MACMycobacterium avium complex MAPMean arterial pressure MDRMultidrug-resistant MICMinimum inhibitory concentration MRSAMethicillin-resistant Staphylococcus aureus MSSAMethicillin-susceptible Staphylococcus aureus NAATNucleic acid amplification test NDMNew Delhi metallo-beta-lactamase NNRTINon-nucleoside reverse transcriptase inhibitor NRTINucleoside reverse transcriptase inhibitor NTMNon-tuberculous mycobacteria OIOpportunistic infection PBPPenicillin-binding protein PEPPost-exposure prophylaxis PIDPelvic inflammatory disease PJPPneumocystis jirovecii pneumonia PMNPolymorphonuclear leukocyte (neutrophil) PPDPurified protein derivative PrEPPre-exposure prophylaxis PTBProbe-to-bone qSOFAQuick Sequential Organ Failure Assessment RIPERifampin, Isoniazid, Pyrazinamide, Ethambutol RPRRapid plasma reagin SABStaphylococcus aureus bacteremia SBPSpontaneous bacterial peritonitis SIRSSystemic inflammatory response syndrome SOFASequential Organ Failure Assessment SSTISkin and soft tissue infection STISexually transmitted infection SVRSustained virologic response (HCV cure) TAFTenofovir alafenamide TBTuberculosis TDFTenofovir disoproxil fumarate TDMTherapeutic drug monitoring TEETransesophageal echocardiography TMP-SMXTrimethoprim-sulfamethoxazole TOATubo-ovarian abscess TP-PATreponema pallidum particle agglutination TSTTuberculin skin test TTETransthoracic echocardiography UTIUrinary tract infection VAPVentilator-associated pneumonia VDRLVenereal Disease Research Laboratory VREVancomycin-resistant Enterococcus VZVVaricella-zoster virus XDRExtensively drug-resistant

37 Empiric Antibiotic Guide

Syndrome / Site	Empiric Regimen	Key Pathogens	Duration
Sepsis / septic shock (unknown source)	Vancomycin + piperacillin-tazobactam (or meropenem if ESBL risk)	S. aureus, GNR, Enterococcus, anaerobes	Narrow based on source and cultures
CAP (inpatient, non-ICU)	Ceftriaxone + azithromycin; or respiratory FQ alone	S. pneumoniae, H. influenzae, atypicals	5–7 days
HAP/VAP (no MDR risk)	Piperacillin-tazobactam or cefepime or meropenem	S. aureus, Pseudomonas, Enterobacterales	7 days
Bacterial meningitis (adult)	Vancomycin + ceftriaxone (± ampicillin if >50y or immunocompromised) + dexamethasone	S. pneumoniae, N. meningitidis, Listeria	10–14 days (varies by organism)
Infective endocarditis (native valve, acute)	Vancomycin + ceftriaxone	S. aureus, Streptococcus, Enterococcus	4–6 weeks
Intra-abdominal infection (community)	Ceftriaxone + metronidazole; or ertapenem	E. coli, B. fragilis, Enterococcus	4 days (if source controlled)
Necrotizing fasciitis	Vancomycin + piperacillin-tazobactam + clindamycin	GAS, S. aureus, polymicrobial	Until source controlled + clinical improvement
Diabetic foot infection (moderate)	Ampicillin-sulbactam or piperacillin-tazobactam ± vancomycin	S. aureus, Streptococcus, GNR, anaerobes	2–4 weeks (soft tissue); 6 weeks (osteomyelitis)
Uncomplicated cystitis	Nitrofurantoin 100 mg BID or TMP-SMX DS BID	E. coli, S. saprophyticus	3–5 days
Pyelonephritis (outpatient)	Ciprofloxacin 500 mg BID or TMP-SMX DS BID	E. coli, Klebsiella, Proteus	7–14 days
Neutropenic fever	Cefepime 2 g q8h or meropenem 1 g q8h or piperacillin-tazobactam 4.5 g q6h	GNR (including Pseudomonas), GPC	Until ANC recovery + afebrile ≥48h
C. difficile (non-severe)	Fidaxomicin 200 mg BID or vancomycin 125 mg PO QID	C. difficile	10 days
PJP (moderate-severe)	TMP-SMX IV (15–20 mg/kg/d TMP) + prednisone	Pneumocystis jirovecii	21 days
Vertebral osteomyelitis	Vancomycin + ceftriaxone (empiric, pending biopsy cultures)	S. aureus, Streptococcus, GNR	6 weeks IV
Septic arthritis (non-gonococcal)	Vancomycin ± ceftriaxone	S. aureus, Streptococcus	3–4 weeks
Brain abscess	Ceftriaxone + metronidazole ± vancomycin	Streptococcus, anaerobes, S. aureus	6–8 weeks IV
PID (outpatient)	Ceftriaxone 500 mg IM ×1 + doxycycline BID × 14d ± metronidazole	N. gonorrhoeae, C. trachomatis, anaerobes	14 days

Scanning electron micrograph of methicillin-resistant Staphylococcus aureus (MRSA) bacteria — **Figure 4 — Staphylococcus aureus (MRSA).** Scanning electron micrograph showing clusters of methicillin-resistant Staphylococcus aureus (MRSA). MRSA remains the most clinically significant resistant pathogen in both community and healthcare settings, causing skin/soft tissue infections, bacteremia, endocarditis, and osteomyelitis. Source: Wikimedia Commons, by CDC/NIAID. Public domain.

Ziehl-Neelsen stain showing acid-fast bacilli (red) of Mycobacterium tuberculosis — **Figure 5 — Acid-Fast Bacilli (Mycobacterium tuberculosis).** Ziehl-Neelsen stain of sputum showing red acid-fast bacilli (AFB) of M. tuberculosis against a blue background. A positive AFB smear indicates high bacillary burden and high infectivity, requiring airborne isolation precautions. Source: Wikimedia Commons. Public domain.

• References

Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801–810.
Evans L, Rhodes A, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Intensive Care Med. 2021;47(11):1181–1247.
Metlay JP, Waterer GW, Long AC, et al. Diagnosis and Treatment of Adults with Community-acquired Pneumonia. ATS/IDSA 2019 Guidelines. Am J Respir Crit Care Med. 2019;200(7):e45–e67.
Kalil AC, Metersky ML, Klompas M, et al. Management of Adults with Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines. Clin Infect Dis. 2016;63(5):e61–e111.
Nahid P, Dorman SE, Alipanah N, et al. Official ATS/CDC/IDSA Clinical Practice Guideline: Treatment of Drug-Susceptible Tuberculosis. Clin Infect Dis. 2016;63(7):e147–e195.
Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice Guidelines for the Management of Bacterial Meningitis. Clin Infect Dis. 2004;39(9):1267–1284.
de Gans J, van de Beek D. Dexamethasone in adults with bacterial meningitis. N Engl J Med. 2002;347(20):1549–1556.
Baddour LM, Wilson WR, Bayer AS, et al. Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications (AHA 2015 Update). Circulation. 2015;132(15):1435–1486.
Fowler VG, Durack DT, Selton-Suty C, et al. The 2023 Duke-ISCVID Criteria for Infective Endocarditis. Clin Infect Dis. 2023;77(4):518–526.
Iversen K, Ihlemann N, Gill SU, et al. Partial oral versus intravenous antibiotic treatment of endocarditis (POET trial). N Engl J Med. 2019;380(5):415–424.
Berbari EF, Kanj SS, Kowalski TJ, et al. IDSA Clinical Practice Guidelines for the Diagnosis and Treatment of Native Vertebral Osteomyelitis. Clin Infect Dis. 2015;61(6):e26–e46.
McDonald LC, Gerding DN, Johnson S, et al. Clinical Practice Guidelines for Clostridioides difficile Infection in Adults and Children: 2017 Update by IDSA/SHEA. Clin Infect Dis. 2018;66(7):e1–e48.
Johnson S, Lavergne V, Skinner AM, et al. Clinical Practice Guideline by the IDSA/SHEA: 2021 Focused Update on Management of CDI in Adults. Clin Infect Dis. 2021;73(5):e1029–e1044.
Gupta K, Hooton TM, Naber KG, et al. International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women: IDSA/ESMID 2011. Clin Infect Dis. 2011;52(5):e103–e120.
Workowski KA, Bachmann LH, Chan PA, et al. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep. 2021;70(4):1–187.
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. Department of Health and Human Services (DHHS). Updated 2023.
Panel on Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. NIH/CDC/IDSA. Updated 2023.
Stevens DL, Bisno AL, Chambers HF, et al. Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by IDSA. Clin Infect Dis. 2014;59(2):e10–e52.
Lipsky BA, Berendt AR, Deery HG, et al. IDSA Clinical Practice Guideline for the Diagnosis and Treatment of Diabetic Foot Infections. Clin Infect Dis. 2012;54(12):e132–e173.
Barlam TF, Cosgrove SE, Abbo LM, et al. Implementing an Antibiotic Stewardship Program: Guidelines by IDSA and SHEA. Clin Infect Dis. 2016;62(10):e51–e77.