Antimicrobial Drugs

Antimicrobials are the only drugs we give that are aimed at something that is not the patient. Everything else in the medication room — the beta blocker, the insulin, the opioid — changes the person in the bed. An antibiotic is meant to kill an invader while leaving that person untouched, and how well it manages that trick is the difference between a cure and a kidney injury. This chapter walks through how these drugs pick their target, how they are grouped by the machinery they break, why the microbes are learning to shrug them off, and what the nurse does at the bedside to make the whole thing work safely. Learn the classes as families and the details stop being memorization — they start being predictions you can make.

Section 1Principles of antimicrobial therapy

Selective toxicity: the whole game

Selective toxicity is the principle that makes antimicrobial therapy possible: the drug attacks a structure the microbe has and the patient does not. Bacteria build a peptidoglycan cell wall; your cells build no wall at all, so a drug that sabotages wall construction is nearly invisible to you. Bacteria run 70S ribosomes assembled from 30S and 50S subunits; your cells run 80S ribosomes, so a drug shaped to jam the bacterial one mostly ignores yours. Bacteria have to synthesize their own folate from scratch; you eat yours, so a drug that blocks the synthesis pathway starves the bacterium and skips you entirely.

Read that list backwards and you have predicted the side effects. Selective toxicity is never perfect. Human mitochondria carry ribosomes that resemble bacterial ones — which is exactly why linezolid suppresses bone marrow and why aminoglycosides damage the hair cells of the inner ear. The narrower the gap between microbe and host, the more toxic the drug. That is the single sentence that explains why penicillin is safe enough to give a toddler and amphotericin B has a nickname involving rigors.

Spectrum, and cidal versus static

Narrow-spectrum drugs hit a limited range of organisms; broad-spectrum drugs hit many. Students often assume broad is better. It is not. Broad-spectrum therapy clear-cuts the patient's normal flora along with the pathogen, opening the door to superinfection — Clostridioides difficile colitis, Candida thrush, vaginal yeast — and it applies selection pressure across a far wider bacterial population. Broad is a starting guess, not a goal. The goal is always the narrowest drug that covers the actual organism.

Bactericidal drugs kill outright (beta-lactams, aminoglycosides, fluoroquinolones, vancomycin, metronidazole). Bacteriostatic drugs stall replication and let the immune system finish the job (tetracyclines, macrolides, clindamycin, sulfonamides, linezolid). The distinction matters most when the immune system cannot help — endocarditis, meningitis, neutropenia — where a cidal drug is generally required.

Culture and sensitivity, and the empiric window

A culture and sensitivity (C&S) has two halves. The culture identifies the organism. The sensitivity panel exposes it to a series of drugs and reports the minimum inhibitory concentration (MIC) — the lowest concentration that stops growth — then labels each drug susceptible, intermediate, or resistant. A low MIC number alone does not mean "best drug"; the interpretation next to it does, because it factors in what concentration the drug actually reaches at the site of infection.

Cultures take 24 to 72 hours. A septic patient does not have 72 hours. So we start empiric therapy — an educated, broad guess based on the suspected site, the likely organisms for that site, the local antibiogram, and the patient's recent exposures. Then, when the C&S returns, therapy is de-escalated to a narrow drug that the organism is actually susceptible to. Empiric therapy is a bridge, not a destination, and a broad antibiotic still running on day five with a susceptibility report on the chart is a stewardship failure.

Section 2Antibiotics by mechanism

Cell wall inhibitors: break the box

Bacteria live under enormous internal osmotic pressure and are held together by a peptidoglycan mesh. Interrupt the cross-linking and the cell swells and bursts. All of these drugs are therefore bactericidal, and because human cells have no wall, the beta-lactams are among the safest antimicrobials we own. That mechanism-based safety belongs to the beta-lactams, not to the whole wall-active group: vancomycin attacks wall synthesis too but is nephrotoxic and ototoxic and needs trough/AUC levels with serial creatinine, and daptomycin needs weekly CPK.

The beta-lactams — named for the four-membered beta-lactam ring they share — include penicillins, cephalosporins, carbapenems, and the monobactam aztreonam. They bind the penicillin-binding proteins that do the cross-linking. Penicillins run from narrow (penicillin G, for strep and syphilis) to broader (amoxicillin, ampicillin) to antipseudomonal (piperacillin-tazobactam). Cephalosporins climb through generations — cefazolin (first, the classic surgical prophylaxis drug), ceftriaxone (third, meningitis and pneumonia), cefepime (fourth, Pseudomonas), ceftaroline (fifth, active against MRSA). Carbapenems (meropenem, ertapenem, imipenem-cilastatin) are the heavy artillery reserved for resistant gram-negatives. Aztreonam covers gram-negatives only and is the escape hatch for a patient with true penicillin anaphylaxis.

The non-beta-lactam wall drugs matter too. Vancomycin, a glycopeptide, blocks wall building at a different step and is a workhorse for MRSA. Daptomycin is a lipopeptide that punches holes in the gram-positive membrane rather than the wall; it is inactivated by lung surfactant, so it is never the answer for pneumonia.

Protein synthesis inhibitors: jam the ribosome

The bacterial 70S ribosome is a target with two halves, and the drugs sort by which half they grab. Hitting the 30S subunit: aminoglycosides (gentamicin, tobramycin, amikacin) and tetracyclines (doxycycline, minocycline). Hitting the 50S subunit: macrolides (azithromycin, erythromycin, clarithromycin), clindamycin, linezolid, and chloramphenicol. A useful mnemonic: "buy AT 30, CELL at 50" — Aminoglycosides and Tetracyclines at 30S; Chloramphenicol, Erythromycin/macrolides, Lincosamides (clindamycin), and Linezolid at 50S.

This is where selective toxicity gets thin, and the toxicities are the reason. Aminoglycosides are nephrotoxic and ototoxic — the hearing loss can be permanent — so they demand peak and trough levels and daily creatinine. Tetracyclines chelate calcium: prolonged or repeated courses stain developing teeth, so avoid them under age 8 and in pregnancy — with one exception that matters enormously, because doxycycline is first-line at any age for suspected tick-borne rickettsial illness (Rocky Mountain spotted fever, ehrlichiosis, anaplasmosis), where a short course (under 21 days) does not cause clinically significant staining and withholding the drug can be fatal. They are also inactivated if the patient swallows them with milk, antacids, or an iron pill. Macrolides prolong the QT interval. Clindamycin is the classic C. difficile offender. Linezolid, working on a ribosome that looks like the one in your mitochondria, causes thrombocytopenia, optic and peripheral neuropathy, and — because it is a weak MAO inhibitor — serotonin syndrome when stacked on an SSRI.

Nucleic acid and metabolic inhibitors: break the blueprint, starve the factory

Fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin) poison DNA gyrase and topoisomerase IV, the enzymes that untangle bacterial DNA. They are potent, oral, and carry more boxed warnings than almost anything else on the shelf: tendinitis and tendon rupture (Achilles, worse over 60, on steroids, or post-transplant), aortic aneurysm and dissection, peripheral neuropathy, CNS effects, QT prolongation, and blood glucose swings. Rifampin blocks bacterial RNA polymerase, turns urine, sweat, and tears orange (stains contact lenses), is hepatotoxic, and is a ferocious CYP450 inducer that can quietly defeat oral contraceptives and warfarin. Metronidazole is activated inside anaerobes and protozoa where it shreds DNA; it produces a metallic taste and a disulfiram-like reaction with alcohol.

The metabolic inhibitors starve the bacterium of folate. Sulfamethoxazole blocks dihydropteroate synthase and trimethoprim blocks dihydrofolate reductase — two sequential steps in one pathway, which is why the combination (TMP-SMX) is synergistic and bactericidal. Watch for rash that could become Stevens-Johnson syndrome, hyperkalemia, crystalluria (push fluids), photosensitivity, and a sharp rise in the INR of anyone on warfarin. That same folate mechanism closes a loop in pregnancy: because trimethoprim antagonizes folate, TMP-SMX is avoided in the first trimester (neural tube and other structural defects — folic acid supplementation is advised if it must be used) and again at term, where the sulfonamide displaces bilirubin and risks kernicterus in the newborn. Isoniazid, a first-line TB drug, blocks mycolic acid synthesis and causes peripheral neuropathy — which is why it is co-prescribed with pyridoxine (vitamin B6) — and hepatitis.

Section 3Resistance and stewardship

How resistance arises

Antibiotics do not create resistance. They select for it. In any large bacterial population a few cells already carry a gene that happens to blunt the drug — through random mutation, or borrowed wholesale from a neighbor. Give the antibiotic and you kill the susceptible majority, which is exactly the outcome you wanted, but you also hand the survivors an empty room with no competition. They multiply. This is ordinary natural selection running at bacterial speed, and every unnecessary dose accelerates it.

Bacteria are also promiscuous with DNA. Horizontal gene transfer lets a resistance gene jump between organisms that are not even related: conjugation passes a plasmid through a direct bridge, transformation scoops up free DNA from a dead cell, and transduction ferries genes by bacteriophage. One gut organism can donate a resistance plasmid to a passing pathogen overnight.

The mechanisms themselves come in four shapes, and you can read them straight off the resistance figure. Enzymatic inactivation — beta-lactamases chew open the beta-lactam ring; extended-spectrum beta-lactamases (ESBLs) chew a wider menu; carbapenemases chew even carbapenems. Target modification — MRSA's mecA gene builds an altered penicillin-binding protein (PBP2a) that ordinary beta-lactams cannot grip; VRE's vanA gene rebuilds the wall precursor so that its terminal D-alanine-D-alanine becomes D-alanine-D-lactate, which vancomycin can no longer bind. Efflux pumps bail the drug back out before it works. Reduced permeability shuts the porin doors so the drug never gets in.

The organisms you will meet

MRSA is Staphylococcus aureus that has become immune to the entire traditional beta-lactam class at once — not just methicillin — because PBP2a ignores penicillins, cephalosporins, and carbapenems alike. That single gene knocks out the safest, cheapest drugs you had and forces a move to vancomycin, linezolid, daptomycin, or ceftaroline — the one beta-lactam specifically engineered to bind PBP2a anyway. VRE pushes further, defeating the drug we reached for when MRSA appeared. ESBL-producing gram-negatives push therapy toward carbapenems; CRE defeat the carbapenems and leave a genuinely thin bench. And C. difficile, while not a resistance mechanism itself, is the price of collateral damage: the antibiotic wipes out the gut community and C. diff blooms in the vacancy.

Stewardship and the nurse

Antimicrobial stewardship is the coordinated effort to use these drugs only when needed, and then in the right drug, dose, route, and duration. It is often described as a pharmacy-and-physician program, which badly understates the nurse's role — the nurse is the person who actually gets the culture, notices the report, gives the dose, and hears the patient's story.

Concretely: get the cultures before the first dose. Take a real allergy history — "penicillin gave me an upset stomach at age six" is not an allergy, and roughly 9 in 10 people labeled penicillin-allergic are not, so that label costs them broader, more toxic, more expensive drugs for decades. Flag day 3: is the culture back, and is the patient still on the broad empiric drug? Push the IV-to-PO switch when the patient is eating and stable (linezolid, fluoroquinolones, metronidazole, doxycycline, and fluconazole are all essentially fully absorbed orally). Question the duration — evidence keeps shortening courses. Teach the patient that antibiotics do nothing for a cold, that leftovers are not to be saved or shared, and that the prescribed course should be taken as directed rather than stopped the moment they feel better. And do the unglamorous thing that prevents more resistant infections than any drug decision: wash your hands.

Section 4Antifungals and antivirals

Antifungals: a much smaller gap

Fungi are eukaryotes. Their cells are built like yours — nucleus, 80S ribosomes, similar membranes — which means the pool of microbe-only targets is small and antifungal drugs are, as a group, markedly more toxic than antibacterials. Almost every antifungal exploits one of two genuine differences: fungal membranes use ergosterol where yours uses cholesterol, and fungal cell walls contain beta-(1,3)-D-glucan, which you do not make at all.

Amphotericin B (a polyene) binds ergosterol directly and rips pores in the membrane. It is powerful, and it is rough: infusion-related fevers, rigors, and shaking chills earned it the nickname "shake and bake," plus dose-limiting nephrotoxicity with potassium and magnesium wasting. Liposomal formulations are considerably gentler — and this is a genuine safety trap, because the conventional and liposomal doses are very different and are not interchangeable. Verify the formulation on the label against the order. The azoles (fluconazole, itraconazole, voriconazole, posaconazole, isavuconazole) block lanosterol 14-alpha-demethylase, the enzyme that makes ergosterol; they are the mainstay of oral therapy but bring hepatotoxicity, QT prolongation, and heavy CYP450 interactions with warfarin and statins. Voriconazole adds a distinctive transient visual disturbance — blurred or bright-tinged vision — and photosensitivity. The echinocandins (caspofungin, micafungin, anidulafungin) attack the beta-glucan wall, a target humans simply do not have, and are correspondingly well tolerated; they are first-line for invasive candidemia but are IV-only. Terbinafine treats nail and skin fungus over long courses — monitor liver function and warn about taste changes. Nystatin is topical: swish and swallow for thrush, and teach the patient to hold it in the mouth before swallowing.

Antivirals: the narrowest gap of all

A virus replicates using your cellular machinery, so there is almost nothing to attack that is not also yours. Antivirals work by targeting the handful of enzymes the virus brings itself — a viral polymerase, a protease, an integrase, a neuraminidase. They also suppress rather than cure most of the time, and they are time-sensitive: the earlier the start, the more the drug can do — though in severe or high-risk illness a late start is still worth making.

Acyclovir and its better-absorbed prodrug valacyclovir treat herpes simplex and varicella-zoster. The elegance is in the activation: acyclovir must be phosphorylated by viral thymidine kinase before it works, so it is essentially inert in an uninfected cell. IV acyclovir crystallizes in renal tubules, so hydrate the patient well and infuse over at least an hour. Ganciclovir and valganciclovir handle CMV and are bone-marrow suppressive. Oseltamivir blocks influenza neuraminidase and gives its greatest benefit when started within about 48 hours of symptom onset in uncomplicated outpatient flu; hospitalized, severe, progressive, or high-risk patients are treated no matter how long symptoms have lasted. For HIV, antiretroviral therapy combines drug classes — NRTIs (tenofovir, emtricitabine, abacavir), NNRTIs (efavirenz), protease inhibitors (usually boosted with ritonavir), and integrase inhibitors (dolutegravir, bictegravir), which are now first-line. Two nursing points dominate: abacavir requires HLA-B*5701 screening before the first dose because a positive result predicts a potentially fatal hypersensitivity reaction, and adherence is not a soft outcome — missed doses let the virus mutate into resistance. Hepatitis C is now curable in most patients with 8–12 weeks of direct-acting antivirals such as sofosbuvir-based or glecaprevir-pibrentasvir regimens; screen for hepatitis B first, since these drugs can reactivate it.

Section 5Antiparasitics and nursing care

Antiprotozoals

Protozoa are eukaryotes too, so once again the safety margin is narrow and the drugs are chosen around the parasite's life stage rather than just its name. Malaria is the clearest example. Artemisinin-based combination therapy (artemether-lumefantrine) is first-line for uncomplicated P. falciparum and should be taken with fatty food, which dramatically improves absorption. Atovaquone-proguanil and doxycycline serve for prophylaxis; chloroquine still works where resistance is absent, and long-term use risks irreversible retinopathy. The critical piece is the dormant liver form, the hypnozoite, of P. vivax and P. ovale: treating the blood stage alone leaves it in place and the patient relapses months later. Clearing it requires primaquine or tafenoquine — and both cause severe hemolysis in G6PD deficiency, so screen G6PD before the dose, without exception.

Beyond malaria, metronidazole or tinidazole covers giardiasis, amebiasis, and trichomoniasis. For trichomoniasis, treat the partner too or the patient simply gets it back — and reinforce the alcohol warning, since these are the drugs behind the disulfiram-like reaction. Nitazoxanide covers Giardia and Cryptosporidium. TMP-SMX remains the drug of choice for Pneumocystis pneumonia (an organism reclassified as a fungus but still taught alongside this group), with pentamidine as an alternative that can cause severe hypoglycemia followed by hyperglycemia.

Anthelmintics

Worms are animals, and the drugs against them are mostly aimed at neuromuscular or cytoskeletal machinery the worm depends on. Albendazole and mebendazole block the worm's microtubule assembly, starving it; albendazole is absorbed far better with a fatty meal. Ivermectin opens glutamate-gated chloride channels, paralyzing the parasite — mammals have no such channels at all, and the blood-brain barrier keeps the drug away from the similar channels in the human CNS — it treats strongyloidiasis, onchocerciasis, and scabies. Praziquantel makes the tegument of flukes and tapeworms leak calcium, causing paralysis; take with food and warn about dizziness. Pyrantel pamoate is the over-the-counter pinworm option.

The teaching matters as much as the drug. Pinworm is a household diagnosis: treat all household members, repeat the dose in two weeks to catch newly hatched eggs, wash bed linens and underwear in hot water, cut and scrub fingernails, and collect the diagnostic tape test first thing in the morning before bathing. That set of instructions prevents more reinfection than any second prescription.

Nursing care that applies to every antimicrobial

Strip away the class differences and the same nursing spine holds up all of it. Before: take a real allergy history, get the culture, check renal and hepatic function against the drug and the dose, review interactions, and confirm pregnancy status where it matters. During: give doses on schedule and evenly spaced around the clock so blood levels stay above the MIC — a "late" antibiotic is not a trivial late medication. Stay with the patient for the first dose of anything new. Draw troughs immediately before the next dose and peaks at the specified interval after it, and chart the exact times, because a level drawn at the wrong moment is worse than no level at all: it will be acted upon. After: watch for the response you expect (fever curve, white count, the wound), for the toxicity you were warned about (creatinine, CBC, LFTs, hearing, tendons, QT), and for the superinfection you invited — new diarrhea, white patches in the mouth, vaginal itching.

ReferenceWords worth knowing

The vocabulary of antimicrobial therapy — skim it now, then come back whenever a term on a culture report or a drug label stops you.

Aminoglycoside

A bactericidal class (gentamicin, tobramycin, amikacin) that binds the 30S ribosomal subunit; nephrotoxic and ototoxic, requiring peak and trough monitoring.

Anthelmintic

A drug that kills or expels parasitic worms, e.g., albendazole, ivermectin, praziquantel.

Antimicrobial stewardship

The coordinated effort to use antimicrobials only when indicated, and then in the right drug, dose, route, and duration.

Bactericidal

Kills bacteria outright; required when host defenses are unavailable (endocarditis, meningitis, neutropenia).

Bacteriostatic

Inhibits bacterial replication and relies on the immune system to clear the organism.

Beta-lactam

Any drug built around the beta-lactam ring — penicillins, cephalosporins, carbapenems, and the monobactam aztreonam — that blocks cell wall cross-linking.

Beta-lactamase

A bacterial enzyme that inactivates beta-lactam drugs by opening the ring; extended-spectrum forms (ESBLs) inactivate a much wider range.

Broad-spectrum

Active against a wide range of organisms; useful empirically but destroys normal flora and drives resistance.

Culture and sensitivity (C&S)

A laboratory test that identifies the organism and reports which drugs inhibit it, with susceptible/intermediate/resistant interpretations.

De-escalation

Narrowing therapy from an empiric broad-spectrum drug to a targeted one once the culture and sensitivity result returns.

Empiric therapy

Treatment started before results are available, based on the likely organisms for that site and patient.

Ergosterol

The sterol in fungal cell membranes (humans use cholesterol); the target of polyenes and the azoles' synthesis pathway.

Methicillin-resistant Staphylococcus aureus (MRSA)

S. aureus carrying mecA, which builds an altered penicillin-binding protein (PBP2a) so that every traditional beta-lactam fails at once; the anti-MRSA cephalosporins ceftaroline (and ceftobiprole) are engineered to bind PBP2a and remain active.

Minimum inhibitory concentration (MIC)

The lowest drug concentration that prevents visible growth of an organism in vitro.

Narrow-spectrum

Active against a limited range of organisms; the goal once the pathogen is identified.

Nephrotoxicity

Drug-induced kidney injury; a signature risk of vancomycin, aminoglycosides, amphotericin B, and colistin.

Ototoxicity

Drug-induced damage to hearing or balance, classically from aminoglycosides; may be permanent, so report tinnitus or vertigo at once.

Peak and trough

Serum drug levels drawn at the expected maximum (peak) and immediately before the next dose (trough) to keep therapy effective and non-toxic.

Prophylaxis

Giving an antimicrobial to prevent infection rather than treat it, e.g., cefazolin within 60 minutes before surgical incision.

Selective toxicity

Harming the microbe while sparing the patient by attacking a structure the microbe has and human cells lack.

Superinfection

A new infection that appears during antimicrobial therapy because the protective normal flora were destroyed, e.g., C. difficile colitis or thrush.

Vancomycin-resistant Enterococcus (VRE)

Enterococcus that has altered the D-alanine binding site vancomycin depends on; usually treated with linezolid or daptomycin.