Cephalosporins generally have a broader spectrum of activity than penicillins. Based on structural modifications over time, they are divided into five generations, with the fifth generation being the newest.

• First generation: mostly effective against gram-positive bacteria and include cephalexin (Keflex), cefadroxil (Duricef), and cefazolin (Ancef).
• Second generation: active against some gram-negative bacteria as well. They include cefaclor, cefoxitin, cefprozil, and cefuroxime (Zinacef).
• Third generation: broader spectrum than the first and second generations and include cefotaxime (Claforan), ceftriaxone (Rocephin), cefixime (Suprax), cefpodoxime and ceftazidime (Fortaz, Tazicef). Third generation agents are active against some drug resistant gram-negative and gram-positive bacteria.
• Fourth generation: cefepime (Maxipime) is the only available option.
• Fifth generation: includes ceftaroline (Teflaro).

Carbapenems are broad spectrum bactericidal antibiotics effective against gram positive bacteria, gram negative bacteria, and anaerobes. Examples include meropenem (Merrem), imipenem-cilastatin (Primaxin), doripenem (Doribax) and ertapenem (Invanz).

Monobactams are effective against aerobic gram negative bacteria only. Aztreonam (Azactam, Cayston) is most commonly used.

Glycopeptides inhibit cell wall synthesis by binding to D-alanyl D-alanine, a component of the peptide chain. They include vancomycin (Vancocin, Firvanq).

Bacitracin is a polypeptide antibiotic that inhibits cell wall synthesis by binding to and blocking a carrier molecule involved in transporting polysaccharides, peptidoglycans, and lipopolysaccharides to the growing bacterial cell wall. It is sold individually as Baci-IM and in combination with other antibiotics, polymyxin and neomycin, as Neosporin.

Cell membrane active agents: Colistin and polymyxin B disrupt the bacterial cell membrane. They are cationic polypeptides that bind to anionic lipopolysaccharide in the outer membrane of gram negative bacteria, leading to displacement of Ca++ and Mg++ ions.

Antibiotics inhibiting bacterial protein synthesis: Some antibiotics inhibit protein synthesis at bacterial ribosomes. Bacterial ribosomes have two subunits: 50S and 30S.

• Antibiotics that act on the 30S subunit include aminoglycosides, tigecycline, and tetracyclines.
• Antibiotics that act on the 50S subunit include chloramphenicol, linezolid, clindamycin, and macrolides.

Common aminoglycosides include gentamicin (Garamycin), streptomycin, amikacin (Amikin), tobramycin (Tobi, Kitabis Pak, Bethkis), and paromomycin (Humatin). Tetracyclines include tetracycline (Ala-tet), doxycycline (Adoxa, Doryx), minocycline (Dynacin, Minocin, Solodyn), and demeclocycline. Tigecycline is available as Tygacil.

Macrolides are wide spectrum bacteriostatic drugs that include azithromycin (Zithromax), erythromycin (EES Granules, Ery-tab,Erythrocin, Eryped), fidaxomicin (Dificid) and clarithromycin (Biaxin XL). Linezolid is sold as Zyvox. Clindamycin is sold as Cleocin, ClindaMax and Clindesse.

Inhibitors of DNA synthesis: These antibiotics inhibit DNA synthesis or replication and include quinolones, sulfonamides, and trimethoprim.

• Fluoroquinolones inhibit the enzyme DNA gyrase, also known as topoisomerase IV.
• Sulfonamides and trimethoprim inhibit different steps in folate synthesis. Sulfonamides are competitive inhibitors of dihydropteroate synthase, while trimethoprim inhibits dihydrofolate reductase.

Quinolones include ciprofloxacin (Cipro), levofloxacin (Levaquin), gemifloxacin (Factive), moxifloxacin (Avelox) and ofloxacin (Floxin). The sulfonamide sulfamethoxazole is sold in combination with trimethoprim as Bactrim and Bactrim DS. Trimethoprim (Primsol) is also used alone in certain infections.

Metronidazole: Metronidazole forms free radicals within the bacterial cell that damage bacterial DNA. It is useful against anaerobic bacteria. It is sold as Flagyl, Flagyl ER and Likmez.

Nitrofurantoin: Nitrofurantoin is sold under the brand names Macrobid, Macrodantin and Furadantin. Nitrofurantoin affects bacterial metabolism through intermediary metabolites and is effective against both gram-positive and gram-negative bacteria in the treatment of lower urinary tract infections (UTIs).

Adverse effects include nausea, heartburn, gas, headache, hair loss, and rarely liver and lung dysfunction and peripheral neuropathy. Nitrofurantoin may cause false test results in urine glucose tests and may change urine color to dark yellow or brown. It is contraindicated in patients with a history of cholestatic jaundice and G6PD deficiency.

Adverse effects of antibiotics: Nausea, gastrointestinal upset, and diarrhea are common adverse effects of antibiotics. Some unique adverse effects are discussed below.

Aminoglycosides: Nephrotoxicity, muscle weakness and paralysis, hearing loss.

Fluoroquinolones: Tendinitis, bone and cartilage anomalies like Achilles tendon rupture, prolongation of QTc, pseudomembranous colitis, photosensitivity.

Chloramphenicol: Aplastic anemia, “gray baby” syndrome due to severe inhibition of red blood cell production in the bone marrow.

Macrolides: Hypersensitivity reactions, erythromycin and clarithromycin have highest risk of QTc prolongation, cholestatic jaundice, tinnitus and deafness; clarithromycin and erythromycin are potent inhibitors of liver enzymes cyt P450.

Colistin and Polymyxin B: Nephrotoxicity

Tetracyclines: Yellowing of teeth, dizziness, vertigo, pseudomembranous colitis, photosensitivity, fatty liver, risk of esophageal ulcerations

Trimethoprim plus sulfamethoxazole: Stevens-Johnson syndrome, crystalluria, kernicterus (severe jaundice in neonates), renal failure, sulfa allergies.

Metronidazole: Neuropathy, headache, seizures, alcohol withdrawal syndrome with severe nausea, vomiting, dizziness, sweating, etc when taken with alcohol.

Clindamycin: Pseudomembranous colitis, esophageal ulcers

Imipenem: Seizures

Cephalosporins: Pseudomembranous colitis, hypersensitivity reactions, leukopenia, thrombocytopenia, Coombs positive hemolytic anemia

Penicillins: Hypersensitivity reactions, rashes, anaphylaxis, urticaria, angioedema, serum sickness, exfoliative dermatitis, seizures, nephritis, pseudomembranous colitis, Coombs positive hemolytic anemia, leukopenia, thrombocytopenia. Patients who are allergic to penicillin may show 2-10% cross reactivity to cephalosporins.

Vancomycin: Hypersensitivity reactions like rash, fever, neutropenia, phlebitis, and “red man” syndrome due to histamine release on rapid intravenous infusion.

Bacteria use several mechanisms to become resistant to antibiotics. They can also transfer resistance to other bacterial species through plasmids and transposons. Resistance mechanisms include:

• Decreased uptake of antibiotic (for example, by reducing the number of porins in the bacterial cell membrane)
• Pumping the antibiotic out using efflux pumps
• Modifying the target site to prevent antibiotic binding
• Enzymatic inactivation of the antibiotic

Methicillin resistant Staphylococcus aureus or MRSA: These are highly resistant Staphylococci that are resistant to penicillins, cephalosporins and carbapenems. They can cause skin infections, systemic infections, and sepsis. MRSA is treated with vancomycin, linezolid, trimethoprim-sulfamethoxazole, clindamycin, daptomycin and doxycycline.