# Antibiotic Mechanisms & Coverage Chart (USMLE)

> How do antibiotics work and what does each class cover on USMLE?

Every antibiotic class by target, the buy AT 30, CCEL at 50 ribosome mnemonic, a bug-by-bug coverage chart, resistance mechanisms and the newest US approvals.

Antibiotics hit five targets: cell wall synthesis (beta-lactams, vancomycin), the 30S or 50S ribosome (aminoglycosides, tetracyclines, macrolides, clindamycin, linezolid), nucleic acids (fluoroquinolones, rifampin, metronidazole), the cell membrane (daptomycin, polymyxins) and folate synthesis (TMP-SMX). The target predicts coverage: vancomycin and daptomycin treat only gram-positive bacteria, and aminoglycosides are useless against anaerobes.

## How do antibiotics work and what does each class cover on USMLE?

Every antibiotic question tests one chain: the target decides which bacteria are vulnerable, distribution decides whether the drug reaches the infection, and signature toxicities decide what goes wrong.

Coverage starts with the envelope, explained in [gram-positive vs gram-negative bacteria](/blog/gram-positive-vs-gram-negative-bacteria-usmle): vancomycin is too large to cross an outer membrane, small hydrophilic drugs enter gram-negatives through porins, and periplasmic beta-lactamases intercept beta-lactams before they reach their targets. The [Infectious Disease](/topics/infectious-disease) hub collects the related organism guides.

| Class | Target | Cidal or static | Best coverage | Classic gap or limit |
| --- | --- | --- | --- | --- |
| Penicillin G and V | PBPs; block cross-linking | Cidal | Streptococci, meningococci, syphilis | Penicillinase-producing *S. aureus* |
| Nafcillin, oxacillin | PBPs; penicillinase-stable | Cidal | MSSA | MRSA, enterococci |
| Ampicillin, amoxicillin | PBPs | Cidal | Enterococci, *Listeria*, *E. coli*, *H. influenzae* without beta-lactamase | Beta-lactamase producers |
| Piperacillin-tazobactam | PBPs plus an inhibitor | Cidal | *Pseudomonas*, *B. fragilis*, most gram-negatives | MRSA; invasive ESBL infection |
| Cephalosporins, cefazolin to cefepime | PBPs | Cidal | Varies by generation; ceftazidime and cefepime cover *Pseudomonas* | Enterococci, *Listeria*, atypicals |
| Ceftaroline, ceftobiprole | PBPs, including PBP2a | Cidal | MRSA, pneumococci | ESBL producers |
| Carbapenems | PBPs; resist ESBL and AmpC enzymes | Cidal | ESBL producers, anaerobes, *Pseudomonas* (not ertapenem) | MRSA, *E. faecium*, *Stenotrophomonas* |
| Aztreonam | PBPs of gram-negatives | Cidal | Aerobic gram-negatives, *Pseudomonas* | Gram-positives, anaerobes |
| Vancomycin | D-Ala-D-Ala of wall precursors | Cidal | Gram-positives, MRSA; oral form for *C. difficile* | All gram-negatives |
| Daptomycin | Membrane depolarization | Cidal | *S. aureus* bacteremia, skin infection; VRE off-label | Gram-negatives, pneumonia |
| Polymyxins | LPS of the outer membrane | Cidal | Multidrug-resistant *Pseudomonas* and *Acinetobacter* | *Proteus*, *Serratia*, gram-positives |
| Aminoglycosides | 30S ribosome | Cidal | Aerobic gram-negative rods | Anaerobes |
| Tetracyclines | 30S ribosome | Static | Rickettsiae, *Borrelia*, *Chlamydia*, *Mycoplasma*, community MRSA | Tooth staining under age 8, except short doxycycline courses |
| Macrolides | 50S ribosome | Static | Atypicals | QT prolongation |
| Clindamycin | 50S ribosome | Either | Streptococci, many MRSA, mouth anaerobes | *C. difficile*; unreliable for *B. fragilis* |
| Linezolid | 50S ribosome | Static; cidal for streptococci | MRSA, VRE | Gram-negatives |
| Chloramphenicol | 50S ribosome | Mostly static | Broad | Marrow toxicity |
| Fluoroquinolones | DNA gyrase, topoisomerase IV | Cidal | Gram-negatives and *Pseudomonas* (ciprofloxacin, levofloxacin); pneumococci and atypicals (levofloxacin, moxifloxacin) | Boxed warning |
| Rifampin | RNA polymerase | Cidal | Tuberculosis; add-on for staphylococcal device infection | Rapid resistance if used alone |
| Metronidazole | DNA damage by free radicals | Cidal | Anaerobes, *Giardia*, *Entamoeba*, *Trichomonas* | Aerobes |
| TMP-SMX | Two sequential folate steps | Often cidal | Cystitis, community MRSA, *Pneumocystis*, *Nocardia* | *Pseudomonas*, anaerobes |

## Buy AT 30, CCEL (sell) at 50: the protein synthesis mnemonic

Protein synthesis inhibitors sort by ribosomal subunit with one mnemonic, **buy AT 30, CCEL (sell) at 50**: **A**minoglycosides and **T**etracyclines bind the 30S subunit, while **C**hloramphenicol, **C**lindamycin, **E**rythromycin (standing in for all macrolides) and **L**inezolid bind the 50S subunit.

| Letter | Drug | Action | Cidal or static | Classic toxicity |
| --- | --- | --- | --- | --- |
| A | Aminoglycosides | 30S; misreading of mRNA | Cidal | Nephrotoxicity, ototoxicity, neuromuscular blockade |
| T | Tetracyclines, including tigecycline | 30S; block aminoacyl-tRNA at the A site | Static | Tooth staining, photosensitivity, pill esophagitis |
| C | Chloramphenicol | 50S; inhibits peptidyltransferase | Mostly static | Aplastic anemia, gray baby syndrome |
| C | Clindamycin | 50S; blocks peptide bond formation | Either, by organism | *C. difficile* colitis |
| E | Erythromycin and other macrolides | 50S; block translocation | Static | QT prolongation, GI upset, infant pyloric stenosis |
| L | Linezolid | 50S; blocks the 70S initiation complex | Static; cidal for streptococci | Thrombocytopenia, neuropathy, serotonin syndrome |
| Add-on | Lefamulin, a pleuromutilin | 50S peptidyl transferase center | Varies by organism | QT prolongation |

Aminoglycosides are the reliably bactericidal group, and their killing rises with peak concentration, so one large daily dose is preferred for most indications. Their uptake needs an oxygen-dependent transport step that anaerobes lack, and paired with ampicillin or vancomycin they become bactericidal against enterococci. Tetracyclines chelate calcium, magnesium, aluminum and iron, so dairy, antacids and supplements block absorption; doxycycline is excreted mainly through the gut and needs no dose reduction in renal failure. Tigecycline, a minocycline derivative, misses *Pseudomonas* and *Proteus*.

On the 50S side, methylation of 23S rRNA lowers binding of macrolides and clindamycin together, and the D-zone test screens macrolide-resistant staphylococci and beta-hemolytic streptococci for inducible clindamycin resistance. Chloramphenicol is now rarely used in the US because of its toxicity, and FDA lists the injection as discontinued, yet dose-related marrow suppression, idiosyncratic aplastic anemia and gray baby syndrome remain testable. Lefamulin, approved in 2019 for community-acquired bacterial pneumonia, is the add-on: it covers pneumococci, *H. influenzae* and atypicals but not Enterobacterales or *Pseudomonas*.

## Antibiotic coverage chart: MRSA, Pseudomonas, anaerobes and resistant gram-negatives

Bedside coverage questions reduce to about a dozen organisms, each with a short list of reliable drugs and a predictable wrong answer.

| Organism or pattern | Reliable choices | Wrong answers |
| --- | --- | --- |
| MRSA | Vancomycin, daptomycin (not for pneumonia), linezolid, tedizolid, ceftaroline, ceftobiprole; oral TMP-SMX, doxycycline or clindamycin for susceptible skin infection | Nafcillin, cefazolin, a beta-lactam plus inhibitor |
| *Pseudomonas aeruginosa* | Piperacillin-tazobactam, ceftazidime, cefepime, meropenem, imipenem, aztreonam, ciprofloxacin, levofloxacin, aminoglycosides | Ceftriaxone, ertapenem, moxifloxacin, tigecycline |
| *B. fragilis* and other gut anaerobes | Metronidazole, carbapenems, beta-lactam plus beta-lactamase inhibitor combinations | Aminoglycosides, aztreonam; clindamycin, cefoxitin and cefotetan are less predictable |
| Mouth anaerobes: lung abscess, empyema, oropharyngeal infection | Clindamycin, amoxicillin-clavulanate | Penicillin alone, if penicillin-resistant anaerobes are likely |
| Atypicals: *Mycoplasma*, *Chlamydia*, *Legionella* | Macrolides, doxycycline, levofloxacin, moxifloxacin, lefamulin | Any beta-lactam |
| *Enterococcus faecalis* | Ampicillin; for endocarditis, ampicillin plus ceftriaxone or gentamicin; vancomycin | Cephalosporins alone, ertapenem, TMP-SMX |
| Vancomycin-resistant enterococci | Linezolid, tedizolid, daptomycin; nitrofurantoin or fosfomycin for cystitis | Vancomycin |
| *Listeria monocytogenes* | Ampicillin, sometimes with an aminoglycoside; TMP-SMX if penicillin-allergic | Any cephalosporin |
| ESBL-producing Enterobacterales | A carbapenem for invasive infection; nitrofurantoin, TMP-SMX or a newer oral agent for cystitis | Piperacillin-tazobactam or cefepime for invasive infection |
| KPC-producing CRE | Ceftazidime-avibactam, meropenem-vaborbactam | Tigecycline for bacteremia or UTI |
| NDM-producing CRE | Aztreonam-avibactam, cefiderocol | Ceftazidime-avibactam alone |
| Carbapenem-resistant *Acinetobacter* | Sulbactam-durlobactam plus imipenem or meropenem | Standard-dose ampicillin-sulbactam alone |

**Does daptomycin cover Pseudomonas?** No. Daptomycin acts only on gram-positive bacteria. Pulmonary surfactant also inactivates the drug, which is why it fails in pneumonia, MRSA pneumonia included. Its labeled uses are complicated skin infections and *S. aureus* bacteremia, including right-sided endocarditis; VRE is an off-label use.

**Which antibiotics cover Pseudomonas?** The antipseudomonal beta-lactams (piperacillin-tazobactam, ceftazidime, cefepime, meropenem, imipenem, aztreonam), ciprofloxacin and levofloxacin, the aminoglycosides and, for multidrug-resistant strains, polymyxins. For difficult-to-treat resistant strains, IDSA's 2026 guidance prefers newer agents such as ceftolozane-tazobactam, its first choice for pneumonia, or ceftazidime-avibactam. Practice the clue pattern in this [Pseudomonas question breakdown](/blog/2026-05-21-q-bank-breakdown-pseudomonas-aeruginosa-why-every-answer-choice-matters).

**Does aspiration pneumonia need anaerobic coverage?** Classic stems pair aspiration with clindamycin, but the 2019 ATS/IDSA guideline on community-acquired pneumonia, which IDSA still lists as current, suggests not routinely adding anaerobic coverage for suspected aspiration pneumonia unless a lung abscess or empyema is suspected.

> **Coverage in one pass:** gram-positive only means vancomycin, daptomycin and linezolid; gram-negative only means aztreonam and the polymyxins; anaerobes mean metronidazole, a carbapenem or a beta-lactamase inhibitor combination; atypicals mean a macrolide, doxycycline or a respiratory fluoroquinolone; and *Pseudomonas* never means ceftriaxone or ertapenem.

## How bacteria resist antibiotics

Resistance questions name a mechanism and ask which drugs it defeats.

| Mechanism | Signature example | Drugs defeated |
| --- | --- | --- |
| Beta-lactamase | Staphylococcal penicillinase; ESBL and AmpC enzymes; KPC, NDM and OXA-48 carbapenemases | Penicillins, cephalosporins; carbapenems when a carbapenemase is present |
| Altered penicillin-binding protein | PBP2a from *mecA* in MRSA | All beta-lactams except ceftaroline and ceftobiprole |
| Altered wall precursor | D-Ala-D-Lac in vancomycin-resistant enterococci | Vancomycin |
| Ribosomal methylation | 23S rRNA methylation; *cfr* in staphylococci | Macrolides with clindamycin; linezolid with *cfr* |
| Drug-modifying enzymes | Acetylation, phosphorylation or adenylation | Aminoglycosides |
| Efflux pumps | Energy-dependent export | Tetracyclines, macrolides, clindamycin, fluoroquinolones |
| Porin loss | OprD (D2) porin loss in *Pseudomonas* | Imipenem |
| Target mutation | Altered DNA gyrase or topoisomerase IV; 23S point mutations | Fluoroquinolones; linezolid |

Clavulanate, sulbactam and tazobactam block penicillinases and some ESBLs in vitro but not AmpC enzymes or carbapenemases, and they are unreliable against ESBL producers in practice; avibactam blocks ESBLs, most KPCs, AmpC and some OXA enzymes but cannot block metallo-beta-lactamases such as NDM. Aztreonam resists metallo-beta-lactamases, but many NDM producers also carry enzymes that hydrolyze it, so aztreonam-avibactam covers what each partner misses, and IDSA's 2026 guidance lists it as a preferred option for NDM producers.

MRSA teaches the opposite lesson: *mecA* encodes PBP2a, which binds beta-lactams poorly, so adding an inhibitor changes nothing and only ceftaroline and ceftobiprole bind it well enough to kill. In enterococci, vancomycin resistance swaps the D-Ala-D-Ala terminus of wall precursors for D-Ala-D-Lac, which vancomycin no longer binds; [Enterococcus for USMLE](/blog/2026-05-21-everything-you-need-to-know-about-enterococcus-for-step-1) covers the treatment choices.

## Newer antibiotics approved in the US since 2023

Five antibiotics approved by the FDA between May 2023 and December 2025 fill specific resistance gaps, and Drugs@FDA lists all five as marketed in October 2026.

| Drug | FDA approval | Class | Labeled use |
| --- | --- | --- | --- |
| Sulbactam-durlobactam | May 2023 | Beta-lactam plus beta-lactamase inhibitor | Hospital-acquired or ventilator-associated pneumonia from *Acinetobacter baumannii-calcoaceticus* complex in adults |
| Ceftobiprole | April 2024 | Anti-MRSA cephalosporin | *S. aureus* bacteremia, including right-sided endocarditis; skin infection; community-acquired pneumonia in adults and children 3 months and older |
| Aztreonam-avibactam | February 2025 | Monobactam plus beta-lactamase inhibitor | Complicated intra-abdominal infection, with metronidazole, when options are limited |
| Gepotidacin | March 2025; gonorrhea added December 2025 | Triazaacenaphthylene topoisomerase inhibitor | Uncomplicated UTI in females 12 and older; urogenital gonorrhea when options are limited |
| Zoliflodacin | December 2025 | Spiropyrimidinetrione topoisomerase inhibitor | One 3 g oral dose for uncomplicated urogenital gonorrhea, age 12 and older |

CDC's gonorrhea treatment page, last reviewed in September 2022, still recommends one 500 mg intramuscular dose of ceftriaxone (1 g at 150 kg or more) and does not yet list either oral drug. Oral urinary options also grew: pivmecillinam (April 2024) treats uncomplicated UTI in women, sulopenem etzadroxil-probenecid (October 2024) does so when oral options are limited, and in June 2026 FDA approved oral tebipenem pivoxil for complicated UTI, including pyelonephritis, in adults with limited or no oral alternatives. Drugs@FDA lists cefepime-enmetazobactam, approved in February 2024, as discontinued, and in January 2020 FDA asked manufacturers to withdraw bacitracin for injection because of nephrotoxicity and anaphylaxis; topical bacitracin remains.

## Toxicities, interactions and C. difficile risk

Most toxicity questions hinge on one signature effect per drug, and several carry FDA boxed warnings.

**Fluoroquinolones** carry a boxed warning for disabling and potentially irreversible tendinitis and tendon rupture, peripheral neuropathy and central nervous system effects, plus worsening of myasthenia gravis. The label reserves them for patients without alternatives when treating uncomplicated cystitis, acute sinusitis or acute exacerbations of chronic bronchitis. Tendon risk rises over age 60, with corticosteroids and after kidney, heart or lung transplant, and separate warnings cover QT prolongation, aortic aneurysm or dissection and blood glucose disturbances. Other boxed warnings include aminoglycosides (nephrotoxicity, ototoxicity and neurotoxicity), clindamycin (*C. difficile*), tigecycline (higher all-cause mortality), chloramphenicol (fatal blood dyscrasias) and metronidazole (carcinogenic in rodents).

- **Vancomycin:** rate-related flushing and rash of the face, neck and upper torso, formerly called red man syndrome, managed by prolonging the infusion; AUC-guided monitoring is preferred for severe MRSA infection.
- **Daptomycin:** myopathy with rising CPK (check weekly, take care with statins) and eosinophilic pneumonia.
- **Linezolid:** thrombocytopenia with longer courses, optic and peripheral neuropathy mainly beyond 28 days, lactic acidosis, and serotonin syndrome because it is a reversible, nonselective MAO inhibitor.
- **Macrolides:** QT prolongation and motilin-driven GI upset; erythromycin and clarithromycin inhibit CYP3A4, azithromycin does not.
- **TMP-SMX:** hyperkalemia, a creatinine rise from blocked tubular secretion rather than true kidney injury, macrocytic anemia and a stronger warfarin effect.
- **Metronidazole:** metallic taste and a disulfiram-like reaction, so no alcohol until 3 days after the last dose.
- **Rifampin:** orange-red body fluids and CYP450 induction that weakens hormonal contraceptives, warfarin and protease inhibitors; antiretroviral interactions are in [HIV antiretroviral drugs](/blog/hiv-antiretroviral-drugs-usmle).
- **Beta-lactams:** hypersensitivity; ceftriaxone is avoided in hyperbilirubinemic preterm neonates, cefotetan can cause a disulfiram-like reaction, and imipenem can provoke seizures.

Antibiotics alter colonic flora and let *C. difficile* overgrow. CDC singles out fluoroquinolones, third- and fourth-generation cephalosporins, clindamycin and carbapenems, and the clindamycin label warns that colitis can appear more than 2 months after antibiotic exposure; see [C. difficile for Step 1](/blog/2026-05-21-everything-you-need-to-know-about-clostridium-difficile-for-step-1) and the ranked [high-yield drug side effects](/blog/high-yield-drug-side-effects-usmle).

## Special populations and the site of infection

Pregnancy, allergy, age and infection site change the right answer more often than the organism does.

**Pregnancy:** penicillins, cephalosporins and erythromycin are among the safest choices. Avoid tetracyclines (fetal teeth), TMP-SMX in the first trimester and near term, nitrofurantoin at term and, when alternatives exist, fluoroquinolones; aminoglycosides carry a fetal ototoxicity risk documented with streptomycin. CDC nonetheless advises doxycycline for suspected Rocky Mountain spotted fever at any age, including during pregnancy.

**Penicillin allergy:** about 10% of US patients report one, but fewer than 1% are truly allergic when evaluated, so CDC recommends a risk assessment, then penicillin skin testing or, for low-risk patients, a supervised oral amoxicillin challenge. Cephalosporin cross-reactivity is about 2% and tracks shared side chains, and aztreonam rarely cross-reacts except with ceftazidime or cefiderocol, which share its side chain. Pregnant patients with syphilis and a penicillin allergy are desensitized and given penicillin G.

**Children:** short doxycycline courses of 5 to 10 days did not stain permanent teeth in the study CDC cites, so a child under 8 with suspected Rocky Mountain spotted fever still gets doxycycline. Fluoroquinolones were traditionally avoided in children because of cartilage concerns.

**Site:** among cephalosporins, only ceftriaxone, cefotaxime, ceftazidime and cefepime reach meningitis-level CSF concentrations; nitrofurantoin reaches therapeutic levels only in urine; moxifloxacin is eliminated mainly in bile; daptomycin fails in the lung. Age-based empiric regimens are in [bacterial, viral and fungal meningitis](/blog/meningitis-bacterial-viral-fungal-usmle).

## How USMLE tests antibiotics

Stems pair a patient, a drug and a new finding, and the answer sits where the three meet.

- **ESBL *E. coli* bacteremia reported susceptible to piperacillin-tazobactam:** choose a carbapenem anyway.
- **Positive D-zone test on a macrolide-resistant staphylococcus:** inducible clindamycin resistance; pick another drug.
- **VRE cystitis versus VRE bacteremia:** nitrofurantoin or fosfomycin for the bladder, daptomycin or linezolid for the blood.
- **NDM-producing *Klebsiella*:** aztreonam-avibactam or cefiderocol; ceftazidime-avibactam alone fails because avibactam cannot block metallo-beta-lactamases.

## Common wrong-answer traps

- **Adding clavulanate to cover MRSA.** Methicillin resistance comes from PBP2a, an altered target that no inhibitor can fix.
- **Choosing ertapenem for *Pseudomonas*.** It is the carbapenem without antipseudomonal activity.
- **Treating cystitis with moxifloxacin.** Biliary elimination leaves too little drug in urine.
- **Using tigecycline for bacteremia.** Blood levels are low, and the label warns of excess mortality.
- **Treating MRSA pneumonia with daptomycin.** Surfactant inactivates it; use vancomycin or linezolid.

## Worked vignette: VRE, sertraline and new neuromuscular signs

A 62-year-old woman who takes sertraline for depression is discharged on an oral antibiotic for a wound infection caused by vancomycin-resistant *Enterococcus faecium*. Two days later she is agitated and diaphoretic, with a temperature of 38.9 °C, tremor, myoclonus and brisk reflexes. The antibiotic most likely responsible has which mechanism of action?

- **A.** Binds the D-Ala-D-Ala terminus of cell wall precursors
- **B.** Inserts into the cell membrane in a calcium-dependent way and depolarizes it
- **C.** Binds 23S rRNA of the 50S subunit and blocks formation of the 70S initiation complex
- **D.** Inhibits DNA gyrase and topoisomerase IV
- **E.** Binds the 30S subunit and blocks aminoacyl-tRNA at the A site

**Answer: C, linezolid.** An oral drug for VRE points to an oxazolidinone, and linezolid is labeled for vancomycin-resistant *E. faecium* infections. Linezolid is also a reversible, nonselective MAO inhibitor, so with sertraline it can trigger serotonin syndrome: agitation, sweating, fever, tremor, myoclonus and hyperreflexia. Vancomycin (A) cannot treat VRE by definition, and daptomycin (B) is given only intravenously and causes myopathy and eosinophilic pneumonia rather than serotonin toxicity. Neither a fluoroquinolone (D) nor a tetracycline (E) explains serotonin toxicity in a patient taking an SSRI. Stop the serotonergic drugs, give supportive care and finish VRE treatment with another active agent such as daptomycin.

## Sources

- IDSA: [2026 Guidance on the Treatment of Antimicrobial-Resistant Gram-Negative Infections](https://www.idsociety.org/practice-guideline/amr-guidance/), [ATS/IDSA guideline on community-acquired pneumonia in adults (2019)](https://www.idsociety.org/practice-guideline/community-acquired-pneumonia-cap-in-adults/)
- StatPearls (NCBI Bookshelf): [daptomycin](https://www.ncbi.nlm.nih.gov/books/NBK470407/), [linezolid](https://www.ncbi.nlm.nih.gov/books/NBK539793/), [clindamycin](https://www.ncbi.nlm.nih.gov/books/NBK519574/), [tetracycline](https://www.ncbi.nlm.nih.gov/books/NBK549905/), [quinolones](https://www.ncbi.nlm.nih.gov/books/NBK557777/), [vancomycin](https://www.ncbi.nlm.nih.gov/books/NBK459263/), [macrolides](https://www.ncbi.nlm.nih.gov/books/NBK551495/), [metronidazole](https://www.ncbi.nlm.nih.gov/books/NBK539728/), [MRSA](https://www.ncbi.nlm.nih.gov/books/NBK482221/)
- CDC: [C. difficile clinical overview](https://www.cdc.gov/c-diff/hcp/clinical-overview/index.html), [Rocky Mountain spotted fever clinical care](https://www.cdc.gov/rocky-mountain-spotted-fever/hcp/clinical-care/index.html), [clinical features of penicillin allergy](https://www.cdc.gov/antibiotic-use/hcp/clinical-signs/index.html), [gonococcal infections in adults](https://www.cdc.gov/std/treatment-guidelines/gonorrhea-adults.htm)

Mechanism, coverage and toxicity fade fast without spaced review: [Drill antibiotic pharmacology with StepGenie flashcards](https://dashboard.stepgenie.app/sign-up).

## Frequently asked questions

### Does daptomycin cover Pseudomonas?

No. Daptomycin is active only against gram-positive bacteria, so it has no role against Pseudomonas aeruginosa or any other gram-negative organism. Its labeled uses are complicated skin infections and Staphylococcus aureus bacteremia, including right-sided endocarditis, and it is used off-label for vancomycin-resistant enterococci. Pulmonary surfactant inactivates daptomycin, so it is not used for pneumonia. For Pseudomonas, choose an antipseudomonal beta-lactam, ciprofloxacin or levofloxacin, or an aminoglycoside.

### Which antibiotics cover Pseudomonas aeruginosa?

Antipseudomonal drugs include piperacillin-tazobactam, ceftazidime, cefepime, meropenem, imipenem, aztreonam, ciprofloxacin, levofloxacin and the aminoglycosides, with polymyxins kept for multidrug-resistant strains. Ceftriaxone, ertapenem, moxifloxacin and tigecycline do not reliably cover it. For difficult-to-treat resistant strains, the 2026 IDSA guidance prefers newer beta-lactams such as ceftolozane-tazobactam, its first choice for pneumonia, or ceftazidime-avibactam, with cefiderocol as an alternative outside the urinary tract.

### What does the mnemonic buy AT 30, CCEL at 50 mean?

The mnemonic sorts protein synthesis inhibitors by ribosomal subunit. Aminoglycosides, which are bactericidal and cause misreading of messenger RNA, and Tetracyclines, which are bacteriostatic and block aminoacyl-tRNA at the A site, bind the 30S subunit. Chloramphenicol, Clindamycin, Erythromycin with the other macrolides, and Linezolid bind the 50S subunit; CCEL is read as sell. The newer pleuromutilin lefamulin, approved for community-acquired pneumonia, also binds the 50S subunit.

### Which antibiotics cover MRSA?

Serious MRSA infections are treated with vancomycin, daptomycin (never for pneumonia, because surfactant inactivates it), linezolid, or one of the two cephalosporins that bind PBP2a, ceftaroline and ceftobiprole. Uncomplicated community-acquired skin infections can be treated orally with TMP-SMX, doxycycline or clindamycin when the strain is susceptible, and tedizolid is labeled for skin infections. Beta-lactamase inhibitors do not help, because methicillin resistance comes from PBP2a, encoded by the mecA gene, an altered target that inhibitors cannot change.

### Which antibiotics cover anaerobes?

Metronidazole, the carbapenems and beta-lactam/beta-lactamase inhibitor combinations such as piperacillin-tazobactam, ampicillin-sulbactam and amoxicillin-clavulanate reliably cover gut anaerobes, including Bacteroides fragilis. Clindamycin, cefoxitin and cefotetan are less predictable against B. fragilis, although clindamycin or amoxicillin-clavulanate suits mouth anaerobes in a lung abscess or empyema; ATS/IDSA guidance does not routinely add anaerobic coverage for suspected aspiration pneumonia. Aminoglycosides never work against anaerobes, because their uptake requires an oxygen-dependent transport step, and aztreonam has no anaerobic activity.

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Canonical page: [Antibiotic Mechanisms & Coverage Chart (USMLE)](https://www.stepgenie.app/blog/antibiotic-mechanisms-coverage-usmle)
Topic hub: [Infectious Disease](https://www.stepgenie.app/topics/infectious-disease)