Dr. Mike Ren also contributed to this post.
We’ve tried to condense the introductory microbiology content for Step 1 into a single post, but the microbial universe had other plans! Heck, even squeezing it down to two posts feels like a major feat. There are details left out, but our goal here is to offer the highest-yield material.
(If you’re just joining us, make sure to check out Part 1 on bacteria and viruses before diving in!)
High-Yield Microbiology Topics for USMLE Step 1: Antibiotics & Opportunistic Infections
Diarrhea (7.5)
Everyone gets it, and for your Step 1 exam, you need to know more than just the misery it can cause. A high yield point to learn about is how to distinguish ETEC from EHEC, and practice sorting organisms into those that cause bloody versus watery diarrhea. That alone is a high-yield test favorite and simply knowing it can often lead to the correct answer, or at the very least, eliminating 2 or 3 incorrect choices.
But don’t forget—not all diarrhea is infectious. Be prepared to consider osmotic causes (like lactose intolerance), inflammatory bowel disease, or even drug-related etiologies that will rear its ugly head. Whether it’s a sick kid in pediatrics or a hospitalized adult, diarrhea has plenty of clinical overlap to be worth your time.
When your patient has diarrhea – ask about immune status: Diarrhea in immunocompromised patients (e.g., HIV/AIDS, transplant recipients, chemotherapy patients) raises concern for opportunistic infections and atypical pathogens.
Think beyond the usual suspects: Common pathogens in the general population (e.g., C. difficile, Salmonella, Shigella) still apply, but also consider:
- HIV/AIDS patients (CD4 <200): Cryptosporidium, Microsporidia, Isospora belli, CMV colitis (especially if bloody diarrhea).
- Post-transplant patients: CMV, Norovirus, Adenovirus, GVHD (in HSCT).
- Neutropenic patients: Consider typhlitis (neutropenic enterocolitis)—look for abdominal pain and fever with diarrhea.
Don’t forget medication causes of diarrhea: Many immunocompromised patients are on antibiotics, antivirals, or immunosuppressants that can also cause diarrhea (e.g., MMF, ART).
Tailor treatment to immune status: Immunosuppressed patients may need longer or more aggressive therapy, and empiric treatment may be warranted while awaiting results.
Red flags: Fever, bloody stools, dehydration, severe abdominal pain, and weight loss should prompt more urgent workup and management
Pneumonias (8)
Pneumonia is a cornerstone topic for both Step 1 and your clinical rotations—especially internal medicine. Know your bugs, but even more important: understand the clinical presentations and chest X-ray findings.
- Streptococcus pneumoniae? Often unilateral lobar consolidation and abrupt onset.
- Atypicals (like Mycoplasma or Chlamydia)? More indolent symptoms, diffuse bilateral infiltrates.
- CAP community acquired vs HCAP hospital acquired
- And just like with diarrhea, you want to assess immune status of the patient
- Pneumocystis Pneumonia (PCP) common in CD4 <200
- In advanced HIV (CD4 <100): consider Cryptococcus, Histoplasma, CMV
In terms of treatment:
- Outpatients usually get azithromycin or a respiratory fluoroquinolone (like levofloxacin).
- Inpatients should receive IV ceftriaxone + azithromycin.
- Concerned about Pseudomonas (e.g., in ventilator-associated pneumonia)? Make sure your antibiotics have Pseudomonal coverage (e.g., cefepime, piperacillin-tazobactam).
Vaginal Infections (7)
Welcome to the trio of trouble: bacterial vaginosis (BV), Trichomonas, and Candida.
Approach: Vaginal infections often present with discharge, odor, itching, or irritation. Diagnosis hinges on pH, microscopy, and discharge characteristics.
These three are test question regulars, and Step 1 loves to ask about discharge characteristics, symptoms, and treatment:
1. Bacterial Vaginosis (BV)
- Cause: Overgrowth of Gardnerella vaginalis, disrupted normal flora.
- Discharge: Thin, gray-white, fishy odor.
- pH: >4.5
- Clue Cells: Squamous epithelial cells studded with bacteria on wet mount.
- Whiff Test: Positive (fishy smell with KOH).
- Treatment: Metronidazole
2. Candidiasis (Yeast Infection)
- Cause: Candida albicans (yeast overgrowth).
- Discharge: Thick, white, “cottage cheese-like,” no odor.
- pH: Normal (≤4.5)
- Microscopy: Pseudohyphae and budding yeast on KOH prep.
- Risk Factors: Antibiotic usage, diabetes, immunosuppression, pregnancy.
- Treatment: Fluconazole (oral) or topical azoles.
3. Trichomoniasis
- Cause: Trichomonas vaginalis (flagellated protozoan).
- Discharge: Frothy, green-yellow, foul-smelling.
- pH: >4.5
- Microscopy: Motile, flagellated protozoa on wet mount.
- Associated Findings: Strawberry cervix (punctate hemorrhages).
- Treatment: Metronidazole (treat both patient and sexual partner).
Step 1 Tips:
- pH >4.5 = BV or Trich; Normal pH suggests Candida
- Clue cells = BV | Motile protozoa = Trich | Pseudohyphae = Candida
- KOH Whiff Test: Positive in BV
- All can cause discharge, but texture, odor, and pH are key to diagnosis.
- BV or Trichomonas → metronidazole treats
- Candida → an azole antifungal (typically fluconazole) treats
TORCHes Infections (7)
TORCH infections refer to a group of congenital infections that can be transmitted from mother to fetus across the placenta, often during the first trimester of pregnancy. These infections are particularly dangerous because they may cause severe fetal complications such as growth restriction, developmental delays, miscarriage, or stillbirth.
The infections are your go-to differential when a newborn presents with congenital abnormalities like jaundice, hepatosplenomegaly, or growth restriction. Many of them have overlapping features, so rely heavily on maternal history to help you distinguish.
Here’s a rapid-fire pearl for each:
Toxoplasmosis
Caused by the protozoan Toxoplasma gondii. Think about the mother’s exposure to cat feces or undercooked meat—the mother is generally fine but the baby gets hydrocephalus, chorioretinitis and intracranial calcifications.
Varicella-Zoster Virus (VZV)
VZV can cause limb hypoplasia and microcephaly, particularly if the infection occurs in early pregnancy.
Parvovirus B19
Parvovirus B19, known for causing “slapped cheek” rash in children, can lead to fetal hydrops, severe anemia, and miscarriage due to its effect on fetal erythroid precursors.
Rubella
Caused by a toga virus– causes congenital cataracts, sensorineural deafness, and congenital heart defects (patent ductus arteriosus PDA and septal defects). Can be prevented with vaccination (MMR vaccine).
CMV
Most common congenital viral infection. Mother will have flu-like symptoms while baby can have seizures, a blueberry muffin rash, periventricular calcifications and sensorineural hearing loss.
HIV
Presents as immunodeficiency in infants.
Herpes Simplex Virus
Typically transmitted perinatally during vaginal delivery rather than transplacentally. Infected neonates may present with skin, eye, and mouth vesicles, encephalitis, or disseminated disease, especially if the mother had a primary infection near the time of delivery. Look for vesicular lesions or seizures.
Syphilis –Treponema pallidum
Can cross the placenta at any stage. For congenital syphilis, think saddle nose, snuffles, maculopapular rash, Hutchinson teeth, and saber shins.
Antibiotics & Anti-Infectives (10)
This section is a beast, and for good reason. Antibiotics show up everywhere—from Step 1 to the wards. Spaced repetition and flashcards are your best friends here, but let’s go over the top priorities.
Penicillins (PCNs)
- Penicillins are β-lactam antibiotics that inhibit bacterial cell wall synthesis.
- While plain penicillin is less common, its derivatives are used frequently.
- Beware of resistant microbes
Notable usages:
- Listeria monocytogenes = Ampicillin, especially in neonates and immunocompromised
- MSSA = Think nafcillin, oxacillin (“naf for staph”).
- Syphilis treatment = Penicillin G (even in pregnancy!)
- Patients can get a rash with ampicillin if they have mono (EBV) – not an allergy!
Antipseudomonal Penicillins
- Piperacillin, ticarcillin – as the name implies, go-to options for Pseudomonas.
Cephalosporins – β-lactam antibiotics, similar to penicillins
- Inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs) → block peptidoglycan cross-linking → cell lysis.
- 1st gen (cefazolin) – great for skin flora like S. aureus.
- 3rd gen (ceftriaxone) – adds gram-negative coverage; ceftazidime covers Pseudomonas.
- 4th gen (cefepime) – also covers Pseudomonas; commonly used in hospitals.
Notable side effects:
- Autoimmune hemolytic anemia (rare but notable)
- Disulfiram-like reaction (esp. cefotetan, cefoperazone) with alcohol
- Associated with Vitamin K deficiency – bleeding risk
- Ceftriaxone: causes biliary sludging in neonates (avoid!)
Carbapenems
β-lactam antibiotics known for their extremely broad spectrum and resistance to most β-lactamases, making them “big guns” reserved for serious or resistant infections. Use sparingly due to their power and potential for side effects.
When to use:
- Life-threatening infections with multi-drug resistant bacteria
- ESBL+ Enterobacteriaceae
- Not first-line unless patient is critically ill
Vancomycin
Binds directly to D-Ala-D-Ala terminal of peptidoglycan precursors → prevents cross-linking. Is used for Gram positive bacteria only, does not have gram negative or anaerobic coverage
Gram-positive expert, especially for MRSA.
Other usages:
- IV Vancomycin use for MRSA infections (pneumonia, osteomyelitis, endocarditis, sepsis)
- Oral Vancomycin use for C. difficile colitis
- Monitor for nephrotoxicity and Red Man Syndrome
Red Man Syndrome
- Histamine-mediated reaction that occurs during or shortly after the infusion of vancomycin when infused too quickly. It’s not an allergic reaction, but rather a response to the release of histamine from mast cells.
- Flushing, erythema (redness), and itching (pruritus), most commonly on the upper body, neck, and face.
- Can progress to hypotension, tachycardia, and shortness of breath if severe.
- Typically occurs within 5-10 minutes of starting the infusion, but may develop during or shortly after the infusion.
- Symptoms resolve rapidly after the infusion is stopped or slowed down.
Aminoglycosides
Gentamicin is the one to know.
Uses: gram-negative infections (e.g., sepsis, pneumonia, meningitis, urinary tract infections)
Monitoring: Peak and trough levels (for nephrotoxicity and ototoxicity), renal function (creatinine), and hearing tests.
Tetracyclines
Uses: gram-positive and gram-negative organisms, as well as atypical bacteria. They are bacteriostatic and work by inhibiting bacterial protein synthesis.
Doxycycline is your staple.
Wide coverage, including:
- Gram-positive cocci: Staphylococcus aureus, Streptococcus pneumoniae, and others
- Gram-negative: Haemophilus influenzae, Moraxella catarrhalis, and more (but not Pseudomonas or Proteus)
- Atypical pathogens: Chlamydia, Mycoplasma pneumoniae, Rickettsia (e.g., Rocky Mountain spotted fever), and Treponema pallidum (syphilis), Borrelia burgdorferi (Lyme disease)
Side effect profile:
- Gastrointestinal upset: nausea, vomiting, diarrhea (take with food to reduce GI upset)
- Photosensitivity – Increased risk of sunburn
- Teeth discoloration – Permanent staining of teeth in children < 8 years, fetal bone development issues in pregnancy
- Hepatotoxicity – in pregnant women
Macrolides
Bacteriostatic antibiotics that inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit. They are commonly used to treat respiratory infections and atypical bacteria.
- Azithromycin is the common one
- Used for atypical pneumonias and STIs and bordetella pertussis.
- Can cause QT prolongation and torsades de pointes.
- Also CYP450 inhibition, which interacts with various drugs such as warfarin and statins.
Metronidazole
Broad-spectrum antibiotic and antiprotozoal agent used primarily for anaerobic infection
- Excellent for anaerobes in addition to Giardia, C. difficile, Trichomonas, H pylori, and BV.
Other side effects to note:
- “Disulfiram-like reaction”: Avoid alcohol during treatment (causes flushing, nausea, vomiting).
- “Metallic taste”: Common side effect of metronidazole.
- “Dark urine”: Harmless side effect related to drug metabolism.
Antifungals
- Azoles are antifungal agents that inhibit the synthesis of ergosterol, a vital component of fungal cell membranes.
- Azoles (like fluconazole) handle non-invasive fungal infections like candida and aspergillus.
- Can cause elevated liver enzymes and hepatitis (especially with ketoconazole and itraconazole)
- Amphotericin B – reserved for life-threatening mycoses, but comes with significant toxicity.
- “Visual disturbances”: Associated with voriconazole (e.g., color vision changes, blurred vision).
Antivirals
Antiviral drugs work by inhibiting specific stages in the viral life cycle. These stages include viral attachment, penetration, uncoating, replication, assembly, and release. Different classes of antiviral agents target different steps in the process, and they are used to treat infections caused by DNA viruses, RNA viruses, and retroviruses.
- -cyclovirs for herpes viruses.
- Neuraminidase inhibitors such as Oseltamivir are used for Influenza A and B, preventing viral release
- Protease inhibitors such as sofosbuvir used for Hepatitis C treatment
- Interferons can be used for treatment of Hepatitis B and Hepatitis C
- Be familiar with HIV regimens, especially integrase inhibitors and NRTIs as well as PREP drugs
Final Thoughts
We know—we barely scratched the surface. But that’s the challenge when aiming for the highest-yield coverage in limited space!
For even more microbiology topics, check out these other posts on the blog:
