Penicillins

The one-agent answer to a two-flora problem: beta-lactam/beta-lactamase-inhibitor combinations cover gram-negatives and anaerobes in a single drug — ampicillin-sulbactam for appendicitis, piperacillin-tazobactam as an empiric regimen for perforation with peritonitis. With penicillin/cephalosporin allergy, the fallback is clindamycin plus a fluoroquinolone, gentamicin, or aztreonam.

Amoxicillin-clavulanate — bite prophylaxis. StatPearls: "Prophylactic antibiotics targeting oral flora and skin microbes are warranted for all bites penetrating the epidermis or deeper." "Amoxicillin-clavulanate is the preferred prophylactic antibiotic, with extended-spectrum cephalosporins recommended for patients who are allergic to penicillin." Human bites: "All human bite wounds that pierce the skin should receive amoxicillin-clavulanate prophylaxis for a week." Systemic, joint or intracavitary infection: IV "ampicillin-sulbactam, and hospital admission for further care."

Penicillin is the answer to three separate questions on this page, and the first one is the cleanest: erysipelas is essentially a streptococcal disease, and "penicillin as monotherapy remains the first-line antibiotic used for the treatment of erysipelas." Streptococci remain penicillin-susceptible, which is why the shallowest of these infections gets the narrowest drug, and erysipelas-specific durations belong to the class page. Second, "penicillin is the preferred antibiotic for group A strep," with clindamycin added to suppress toxin. Third, it is the drug for recurrent-cellulitis prophylaxis: the 2014 IDSA guideline, as reported by StatPearls, supports "penicillin or erythromycin twice a day for 4 to 52 weeks or intramuscular benzathine penicillin every 2 to 4 weeks in patients who have 3 to 4 episodes of cellulitis per year." One more member of the class carries the heavy work: piperacillin-tazobactam is the extended-spectrum penicillin in every necrotizing regimen on this page — IDSA's, the StatPearls empiric regimens, and Fournier gangrene management — because type I infection is polymicrobial and needs gram-positive, gram-negative and anaerobic cover at once. Penicillin allergy assessment, cross-reactivity and beta-lactamase mechanics belong to the class page.

Amoxicillin-clavulanate — a first-choice oral regimen when antibiotics are indicated. "Antibiotics should cover gram-negative bacteria and anaerobes. The most commonly prescribed regimens include oral amoxicillin-clavulanate or a combination of an oral fluoroquinolone and metronidazole for 7 to 10 days." Antibiotics are selective, not routine: advised for patients who are frail or have comorbidities, refractory symptoms or vomiting, a CRP above 140 mg/L or a raised white cell count, and strongly advised if immunocompromised.

The first-line beta-lactams for the commonest organisms: penicillin G (or ceftriaxone) for penicillin-susceptible viridans streptococci and S. gallolyticus (4 weeks on a native valve, at least 6 on a prosthetic one), and nafcillin or oxacillin for MSSA — an antistaphylococcal beta-lactam beats vancomycin for MSSA because outcomes are worse with vancomycin, so therapy is de-escalated the moment susceptibilities return. For enterococci, ampicillin or penicillin G is never given alone because beta-lactam monotherapy is not bactericidal against them: it is paired with gentamicin, or with ceftriaxone as an aminoglycoside-sparing double beta-lactam for E. faecalis. Amoxicillin 2 g PO within 60 minutes before the procedure is the AHA dental-prophylaxis agent.

Ampicillin is added at the age extremes — neonates, adults over 50, and the immunocompromised — because those are the patients Listeria monocytogenes targets and the cephalosporins miss it. In neonates, ampicillin plus an aminoglycoside (or an expanded-spectrum cephalosporin) is the empiric regimen, and ampicillin must remain in it to cover GBS and Listeria.

Penicillin G is the treatment of choice for penicillin-sensitive S. aureus and streptococci, and nafcillin for penicillin-resistant (methicillin-sensitive) S. aureus; beta-lactam/beta-lactamase inhibitor combinations are an empiric partner.

The outpatient starting point for CAP in adults without comorbidities is monotherapy — amoxicillin 1 g three times daily, or doxycycline 100 mg twice daily, or a macrolide only where pneumococcal macrolide resistance is under 25% (IDSA/ATS 2019, via StatPearls); with comorbidities it becomes amoxicillin/clavulanate (or a cephalosporin) paired with a macrolide or doxycycline. Ampicillin-sulbactam is a first-choice agent for aspiration pneumonia and an inpatient β-lactam option.

Ampicillin add-on; mastitis first line. StatPearls: "Ampicillin (2 g IV every 6 hours) can be added for better coverage of enterococcus and in patients who are GBS positive, as there is increasing resistance to clindamycin among GBS isolates"; StatPearls (Endometritis) also adds it if "signs and symptoms fail to improve within 48 hours." Mastitis first line (StatPearls, citing ABM): "Dicloxacillin, flucloxacillin, or cephalexin for 10 to 14 days, targeting gram-positive organisms." WHO: penicillin or a first-generation cephalosporin for cesarean prophylaxis.

Penicillin G is first-line for group B streptococcus intrapartum prophylaxis, and the timing is the nursing fact. "Prophylaxis with a beta-lactam antibiotic, preferably penicillin, administered 4 or more hours before delivery, provides highly effective protection against early-onset GBS disease." The regimen is 5 million units as the initial dose, then 2.5 to 3 million units every 4 hours until delivery — which is why the first dose is hung the moment preterm labor is diagnosed rather than after the cervical check. Indications are worth learning as a list: a positive screening culture at 36 0/7 to 37 6/7 weeks, GBS bacteriuria at any point in the current pregnancy, a previous infant with invasive GBS disease, and, when status is unknown, preterm delivery before 37 weeks, membrane rupture for 18 hours or more, an intrapartum temperature of 100.4 °F or higher, or a positive intrapartum NAAT. Ampicillin — a 2 g intravenous loading dose, then 1 g every 4 hours until delivery — is the alternative. With a penicillin allergy, the regimen belongs to the prescriber and the class page. Why this matters so much here: GBS colonization "affects up to one-third of healthy women," and screening with intrapartum prophylaxis cut early-onset neonatal disease from 1.7 cases per 1,000 live births in the early 1990s to 0.22 in 2017. Penicillin pharmacology and allergy cross-reactivity belong to the class page.

The gram-negative/anaerobe backbone of empiric coverage: extended-spectrum piperacillin covers Pseudomonas aeruginosa, Klebsiella, enterococci, and Bacteroides fragilis; piperacillin-tazobactam is one of the antipseudomonal beta-lactams recommended as empiric monotherapy for neutropenic fever (IDSA, as reported by StatPearls). Empiric choice targets the suspected source and is reassessed daily for de-escalation once cultures return.

Penicillin G is first-line for syphilis — that is what the first-line chip on this class refers to — and it is irreplaceable at every stage — quoted: "Penicillin G, administered parenterally, is the preferred drug for treating patients in all stages of syphilis." The disorder-side reason is that Treponema pallidum has never developed penicillin resistance, and the long-acting benzathine formulation maintains treponemicidal levels across the organism's very slow division time, which is why the late-latent course is spaced at weekly intervals. The staging principle is the exam item, and the figures are the lesson: benzathine penicillin G 2.4 million units intramuscularly as a single dose for primary, secondary and early latent syphilis; 7.2 million units total, as three doses of 2.4 million units one week apart, for late latent or latent of unknown duration. The one-year boundary between early and late latent is what moves a patient from one injection to three, which is why an unrecalled chancre costs two extra visits. A missed dose has a stated tolerance in the guideline's latent-syphilis section — 7 to 9 days between doses is preferred and 10 to 14 days is the outer limit, beyond which the sequence restarts. The unit doses belong to the class page. In pregnancy there is no second option: "parenteral penicillin G is the only therapy with documented efficacy for syphilis during pregnancy," and pregnant patients with penicillin allergy "should be desensitized and treated with penicillin." That is the clearest no-alternative statement in the entire guideline, and it is why maternal syphilis patients "should receive the highest priority if penicillin supplies are low." Amoxicillin has one narrow role here — an alternative for chlamydia in pregnancy, where the tetracycline that would otherwise be first-line cannot be used. The regimen belongs to the class page. Allergy cross-reactivity, desensitization mechanics and general penicillin pharmacology belong to the class page.

The sourced indication on this page is the bite wound, and the agent is specific: "amoxicillin-clavulanate is the preferred prophylactic antibiotic," with a 7-day course recommended for closed wounds. The disorder-side reason it is amoxicillin-clavulanate rather than amoxicillin is the flora: bites carry mixed aerobes and anaerobes — Pasteurella multocida from cats, Pasteurella canis from dogs, staphylococci, streptococci, anaerobes, and Capnocytophaga canimorsus in immunocompromised patients — and the beta-lactamase inhibitor is what covers them. The organism list is the justification for the drug. The risk figures explain why prophylaxis is worth giving at all: cat bites are infected about 30% of the time, nearly 33% of hand bites become infected, and cat-bite infections declare themselves fast, typically within 12 to 18 hours after injury. For penicillin allergy the sourced alternatives are "extended-spectrum cephalosporins," or doxycycline or trimethoprim-sulfamethoxazole plus metronidazole or clindamycin. Two non-drug rules travel with the prescription and are easy to get wrong: deep puncture wounds and wounds involving joint spaces are not closed, and cat bites are "inherently high-risk and typically left open" — while uncomplicated wounds "can be safely closed after extensive cleaning and debridement if presenting within 8 hours of injury." Penicillin pharmacology, allergy cross-reactivity and beta-lactamase mechanics belong to the class page.

β-lactam cousins of penicillin, organized by generation — each generation trades some gram-positive reach for broader gram-negative coverage.

Powerful, broad-spectrum DNA-synthesis blockers — but a boxed warning for disabling tendon, nerve, and CNS effects means they’re reserved when alternatives exist.

Suppress viral replication rather than kill viruses outright. The nursing essentials: hydrate with acyclovir, start early (flu within 48 h), and remember most antivirals suppress — they don’t cure.

Powerful IV drugs for serious Gram-negative infection — but nephrotoxic and ototoxic. Levels matter.

Broad, generally safe protein-synthesis inhibitors — a penicillin-allergy alternative. Watch QT and CYP3A4.

Broad-spectrum 30S inhibitors. Generally avoided in pregnancy and in children 8 or younger (permanent tooth staining) unless the infection is serious — doxycycline is still first-line for Rocky Mountain spotted fever at any age — and kept apart from dairy/antacids.