The Critical Vector · Empiric Therapy Guide, Part I of II

Board-Tested Infections

Bacterial, fungal, and viral pathogens COMLEX Level 2-CE reliably tests: the classic symptom-triad vignette, the signature lab or imaging finding, and the one empiric regimen the question wants you to name. Companion file covers ED/ICU presentations and rare, time-critical infections.

Regimens reflect standard board-pattern empiric teaching for study and clinical reasoning — confirm against current guidelines and local antibiogram before treating an actual patient. Doses are intentionally omitted; this is a bug/drug/why reference, not a dosing card.

Bacterial

Infection	Abx	Abx Rationale	Symptom Profile	Clinical Result Profile	Notes
Group A Strep Pharyngitis	Penicillin V or amoxicillinAlt: cephalexin, azithromycin if PCN-allergic	S. pyogenes remains universally PCN-sensitive; narrow-spectrum first-line prevents rheumatic fever without broad collateral coverage.	Sudden sore throat, fever, tonsillar exudate, tender anterior cervical nodes, absence of cough/coryza.	Centor criteria 3–4 → rapid strep/culture; (+) rapid antigen or culture confirms.	Treat to prevent rheumatic fever, not primarily to shorten symptoms. Avoid amoxicillin if mono is on the differential (rash).
CAP — Typicaloutpatient, healthy	Amoxicillin (high-dose)Alt: doxycycline	S. pneumoniae is the dominant typical pathogen; narrow coverage preferred in low-risk outpatients per stewardship principles.	Acute fever, productive cough, pleuritic chest pain, rigors.	CXR: lobar consolidation. Elevated WBC with left shift.	CURB-65 to triage site of care. Macrolide monotherapy now limited by rising pneumococcal resistance.
CAP — AtypicalMycoplasma / Chlamydophila / Legionella	Azithromycin or doxycycline	Atypicals lack a cell wall (Mycoplasma) or are intracellular; beta-lactams are ineffective, macrolides/tetracyclines cover intracellular replication.	"Walking pneumonia": gradual onset, dry cough, headache, malaise out of proportion to exam.	CXR: patchy interstitial infiltrate, worse than exam suggests. Cold agglutinins (+) in Mycoplasma.	Legionella: hyponatremia + GI symptoms + confusion is the classic triad; urine antigen test.
Uncomplicated Cystitis	Nitrofurantoin or TMP-SMXAlt: fosfomycin single-dose	Both concentrate in urine with minimal systemic exposure and collateral resistance pressure; first-line per stewardship guidance for uncomplicated lower-tract disease.	Dysuria, urgency, frequency, suprapubic discomfort; afebrile, no flank pain.	UA: leukocyte esterase (+), nitrites (+, E. coli), pyuria.	Avoid nitrofurantoin if suspected early pyelo (poor tissue penetration) or CrCl <30.
Pyelonephritisoutpatient-appropriate	Fluoroquinolone (cipro/levofloxacin)Alt: ceftriaxone (single dose) → oral step-down	Requires an agent with reliable renal parenchymal and blood-level penetration, unlike nitrofurantoin.	Fever, chills, flank pain, CVA tenderness, +/- nausea/vomiting; cystitis symptoms often present.	UA: pyuria, WBC casts (specific for pyelo). Urine culture to confirm/de-escalate.	Admit and use IV therapy if unable to tolerate PO, pregnant, or systemically ill.
Acute Otitis Media	Amoxicillin (high-dose)Alt: amox-clavulanate if recent abx/conjunctivitis	S. pneumoniae, nontypeable H. influenzae, M. catarrhalis; high-dose overcomes intermediate pneumococcal resistance.	Ear pain, fever, irritability (peds); recent URI.	Otoscopy: bulging, erythematous, non-mobile TM; +/- effusion.	Watchful waiting appropriate in select low-risk children per age/severity criteria.
Bacterial Sinusitis	Amoxicillin-clavulanate	Added beta-lactamase coverage over amoxicillin alone addresses H. influenzae/M. catarrhalis co-infection typical of true bacterial sinusitis.	Symptoms >10 days without improvement, "double-worsening," or severe onset with fever >39°C + purulent discharge.	Clinical diagnosis; imaging not routine. CT if complication suspected (orbital, intracranial).	Most sinusitis is viral — reserved for the bacterial criteria above, not routine URI congestion.
Bacterial Meningitisneonate	Ampicillin + cefotaximeor ampicillin + gentamicin	Ampicillin specifically covers Listeria and Group B Strep, unique to the neonatal period; cefotaxime preferred over ceftriaxone (bilirubin displacement risk). Cefotaxime's US availability has been limited; many centers substitute ceftazidime or cefepime.	Fever or hypothermia, poor feeding, lethargy, bulging fontanelle, irritability.	LP: high WBC (neutrophil-predominant), low glucose, high protein.	GBS, E. coli, Listeria monocytogenes are the classic neonatal triad.
Bacterial Meningitischild / adult	Vancomycin + ceftriaxone+ dexamethasone before/with first dose	Vancomycin covers resistant S. pneumoniae; ceftriaxone covers N. meningitidis and susceptible pneumococcus; steroid blunts inflammatory hearing-loss/mortality in pneumococcal disease.	Fever, nuchal rigidity, headache, photophobia, altered mental status; petechial rash if meningococcal.	LP: neutrophilic pleocytosis, glucose <40% of serum, elevated protein, elevated opening pressure.	Add ampicillin if age >50 or immunocompromised (Listeria coverage). Do not delay abx for imaging/LP.
Cellulitis / Erysipelas	Cephalexin or dicloxacillin+ TMP-SMX/doxycycline if MRSA risk or purulence	Non-purulent cellulitis is overwhelmingly streptococcal/MSSA; anti-staphylococcal beta-lactam covers both without unneeded MRSA spectrum unless risk factors present.	Erythema, warmth, tenderness, poorly demarcated (cellulitis) vs. sharply demarcated raised border (erysipelas); +/- fever.	Clinical diagnosis; cultures low-yield unless purulent, abscess, or systemic toxicity.	Erysipelas is classically GAS and more superficial/lymphatic; mark borders to track response.
Lyme Diseaseearly localized	DoxycyclineAlt: amoxicillin, cefuroxime (pregnancy/peds)	Borrelia burgdorferi is exquisitely doxycycline-sensitive; also covers coincident anaplasmosis from the same tick exposure.	Erythema migrans ("bullseye") rash, flu-like symptoms, recent endemic-area tick exposure.	Clinical diagnosis in endemic areas with classic rash; serology (ELISA → Western blot) if uncertain or disseminated.	Late disease (carditis, arthritis, neuroborreliosis) escalates to IV ceftriaxone.
Pertussis	Azithromycin	Macrolide reduces transmissibility and shortens the catarrhal phase if given early; largely supportive once paroxysmal phase established.	Catarrhal (URI-like) → paroxysmal (severe coughing fits, inspiratory "whoop," post-tussive emesis) → convalescent.	NP PCR/culture for Bordetella pertussis; marked lymphocytosis on CBC.	Treatment mainly limits spread once paroxysmal — abx doesn't shorten established cough.
C. difficile Colitis	Oral vancomycin or fidaxomicinMetronidazole reserved for mild disease/low-resource settings	Oral vancomycin acts locally within the gut lumen where C. diff resides — IV vancomycin does not reach the colon in adequate concentration.	Watery diarrhea, abdominal cramping, recent/current antibiotic exposure, fever.	Stool PCR/toxin EIA (+) for C. diff toxin; leukocytosis often marked.	Fulminant disease (ileus, megacolon, shock) → oral + rectal vancomycin + IV metronidazole; surgery eval.
H. pylori	Quadruple: PPI + bismuth + metronidazole + tetracyclineTriple (PPI+amox+clarithro) if low local resistance	Rising clarithromycin resistance has shifted first-line to bismuth quadruple therapy in most regions.	Epigastric pain, peptic ulcer pattern (duodenal: relieved by food; gastric: worsened by food).	Urea breath test or stool antigen (hold PPI ~2wk prior); biopsy with rapid urease test if endoscopy performed.	Confirm eradication with test-of-cure 4+ weeks after completing therapy.
Gonorrhea / Chlamydiacervicitis / urethritis	Ceftriaxone (single IM) + doxycycline	Empiric dual coverage given frequent co-infection; ceftriaxone dose increased given rising gonococcal resistance, doxycycline replaced azithromycin as chlamydia first-line.	Purulent discharge, dysuria; often asymptomatic, especially chlamydia in women.	NAAT of urine/cervical/urethral swab for both organisms.	Treat partners; test for other STIs including HIV/syphilis. Disseminated gonococcemia → migratory polyarthralgia + dermatitis.
Syphilisprimary / secondary / early latent	Benzathine penicillin G (single IM)Late latent/tertiary: weekly x3	Treponema pallidum has no documented penicillin resistance; long-acting benzathine form maintains treponemicidal levels for weeks.	Primary: painless chancre. Secondary: diffuse rash incl. palms/soles, condyloma lata. Tertiary: gummas, aortitis, neurosyphilis.	Nontreponemal (RPR/VDRL) screen → treponemal (FTA-ABS) confirm; titers trend response.	PCN-allergic pregnant patients require desensitization — no substitute is acceptable in pregnancy.

Fungal

Infection	Antifungal	Rationale	Symptom Profile	Clinical Result Profile	Notes
Oropharyngeal / Esophageal Candidiasis	Nystatin swish-and-swallow (mild oral)Fluconazole (systemic) for esophageal disease	Esophageal involvement implies deeper mucosal invasion requiring systemic azole rather than topical polyene.	White plaques scraping off oral mucosa; odynophagia if esophageal extension.	Clinical diagnosis; endoscopy with brushings if refractory to empiric fluconazole.	Esophageal candidiasis in a young patient is AIDS-defining — check HIV status.
Vulvovaginal Candidiasis	Fluconazole (single oral dose)Alt: topical azole (clotrimazole/miconazole)	Fluconazole's oral convenience and reliable efficacy against C. albicans make it first-line for uncomplicated disease.	Thick "cottage cheese" discharge, vulvar pruritus/erythema, dyspareunia.	Wet mount: pseudohyphae/budding yeast; vaginal pH normal (<4.5), distinguishing from BV/trichomonas.	Recurrent disease (≥3/yr, per CDC 2021) warrants evaluation for uncontrolled diabetes.
Invasive Candidiasis / Candidemia	Echinocandin (micafungin/caspofungin)	Echinocandins are fungicidal, active against azole-resistant Candida (incl. glabrata/auris), and preferred empirically in critically ill/ICU patients.	Persistent fever unresponsive to broad-spectrum antibiotics in a line-bearing, ICU, or TPN patient.	Blood cultures (+) for Candida species; dilated eye exam to rule out endophthalmitis.	Remove/exchange central lines when feasible — source control is essential, not optional.
Cryptococcal Meningitis	Liposomal amphotericin B + flucytosine (induction)→ fluconazole consolidation/maintenance	Combination fungicidal induction clears organism burden faster and reduces mortality versus fluconazole monotherapy; maintenance suppresses relapse in ongoing immunosuppression.	Subacute headache, fever, altered mentation in an immunocompromised (classically AIDS, CD4 <100) host.	LP: markedly elevated opening pressure; India ink or cryptococcal antigen (+) in CSF/serum.	Serial therapeutic LPs to manage elevated opening pressure are often as important as the antifungal itself.
Histoplasmosisdisseminated / severe pulmonary	Liposomal amphotericin B → itraconazole step-down	Amphotericin provides rapid fungicidal control in severe/disseminated disease; itraconazole maintains suppression with better tolerability for prolonged courses.	Fever, weight loss, hepatosplenomegaly (disseminated); cough/dyspnea after exposure to bird/bat droppings (caves, Ohio/Mississippi River valleys).	Urine/serum Histoplasma antigen most sensitive; CXR may show diffuse nodular infiltrates or calcifications.	Mild pulmonary disease in immunocompetent hosts is often self-limited and observed.
Coccidioidomycosissevere / disseminated	Fluconazole (or itraconazole)Amphotericin B for severe/disseminated or pregnancy	Azole therapy is generally sufficient given the organism's susceptibility profile; amphotericin reserved for severe/CNS disease or pregnancy (azole teratogenicity).	"Valley fever": fever, cough, arthralgias, erythema nodosum after Southwestern US (San Joaquin Valley) dust exposure.	Serology (complement fixation/EIA) for Coccidioides; CXR may show consolidation, cavitary lesions.	Most cases in immunocompetent hosts are self-limited and don't require antifungals.

Viral

Infection	Antiviral / Mgmt	Rationale	Symptom Profile	Clinical Result Profile	Notes
Influenza	OseltamivirWithin 48h of onset, or any point if hospitalized/high-risk	Neuraminidase inhibition blocks viral release from infected cells, shortening illness most effectively when started early in the replication curve.	Abrupt fever, myalgias, headache, dry cough, prostration — more systemic than typical URI.	Rapid antigen or PCR nasal swab; leukopenia common.	Benefit is greatest within 48h of onset but still indicated later in hospitalized/high-risk patients.
HSVgenital / oral	Valacyclovir or acyclovir	Nucleoside analog terminates viral DNA chain elongation via HSV thymidine kinase activation — no cure, but shortens outbreaks and reduces shedding.	Painful grouped vesicles on erythematous base; primary episode often with fever/lymphadenopathy.	Clinical diagnosis; PCR or viral culture from unroofed vesicle confirms.	Suppressive daily therapy reduces transmission and recurrence frequency in frequent recurrers.
HSV Encephalitis	IV Acyclovir — start empiricallyTreat Before Confirmation	Untreated HSV encephalitis carries ~70% mortality; empiric treatment on suspicion alone is standard given the cost of delay versus the low toxicity of a short acyclovir course.	Fever, altered mental status, focal neuro deficits, seizures — classically temporal lobe.	MRI: temporal lobe edema/hemorrhage. CSF PCR for HSV (may be falsely negative very early).	Start acyclovir before LP/imaging results return if HSV encephalitis is on the differential.
VZVvaricella / zoster	Valacyclovir (within 72h of rash)	Same nucleoside-analog mechanism as HSV; efficacy is time-dependent, so treatment is only meaningfully effective started early in the vesicular phase.	Varicella: diffuse vesicles "in different stages." Zoster: dermatomal, painful vesicular rash, often with prodromal neuralgia.	Clinical diagnosis; Tzanck smear shows multinucleated giant cells (not specific to VZV vs HSV).	Zoster ophthalmicus (nasociliary involvement, Hutchinson's sign) requires urgent ophtho referral.
EBV Mononucleosis	Supportive care — no specific antiviral indicated	EBV is self-limited in immunocompetent hosts; antivirals do not alter course. Management is symptomatic + activity restriction.	Fever, exudative pharyngitis, posterior cervical lymphadenopathy, fatigue, splenomegaly.	Heterophile (Monospot) antibody (+); atypical lymphocytosis on smear; transaminitis common.	Avoid amoxicillin/ampicillin — near-universal morbilliform rash in EBV infection. Avoid contact sports (splenic rupture) x3–4wk.
CMVimmunocompromised: retinitis, colitis	Ganciclovir (or valganciclovir PO)Foscarnet for ganciclovir-resistant disease	Ganciclovir requires viral kinase for activation and is reserved for end-organ disease in immunocompromised hosts, where untreated CMV causes irreversible organ damage (blindness, colitis).	Retinitis: floaters, vision loss (AIDS, CD4 <50). Colitis: diarrhea, abdominal pain in transplant/AIDS patients.	CMV PCR viral load; retinitis diagnosed by dilated fundoscopic exam (granular hemorrhagic pattern).	Immunocompetent CMV mono-like illness is self-limited and does not require treatment.
HIVacute retroviral syndrome	Refer for prompt ART initiation (regimen per specialist)	Early ART initiation reduces viral reservoir size, reduces transmission risk, and improves long-term outcomes — treat as soon as diagnosis is confirmed, regardless of CD4 count.	Mono-like: fever, pharyngitis, diffuse lymphadenopathy, maculopapular rash, myalgias 2–4wk post-exposure.	4th-gen Ag/Ab combo test (detects p24 antigen); confirm with HIV RNA viral load if acute infection suspected (antibody may be falsely negative in the window period).	Consider PEP for any recent high-risk exposure presenting within 72h.
Hepatitis C	Direct-acting antivirals (sofosbuvir-based combinations)	DAAs target specific HCV viral enzymes (NS3/4A protease, NS5A, NS5B polymerase), achieving >95% cure rates versus older interferon-based regimens.	Often asymptomatic acutely; chronic infection may present with fatigue, or incidentally with elevated LFTs.	Anti-HCV antibody screen → HCV RNA (viral load) confirms active infection; pangenotypic regimens mean genotyping is often unnecessary before treatment.	Universal one-time screening now recommended for all adults regardless of risk factors.