Treatment and Prophylaxis of Bacterial Infections¶
Chapter 149 | Part 5: Infectious Diseases · Part 5 – Antimicrobial Therapy · Chapter 149
Key Clinical Points¶
- Antimicrobial stewardship is critical to minimize resistance, maximize efficacy, and preserve agent value.
- Bactericidal agents are preferred for patients with impaired host defenses (e.g., neutropenia) or infections at sites with limited defenses (e.g., meningitis).
- Pharmacodynamics (PD) dictate dosing: Concentration-dependent (Cmax/MIC), Time-dependent (T > MIC), and Area under curve (AUC/MIC).
- Pregnancy categories (A, B, C, D, X) guide fetal risk; the PLLR rule applies to drugs approved after 2015.
- Penicillin allergies are often overreported; >90% of patients reporting penicillin allergy may tolerate cephalosporins.
- Empirical therapy should be transitioned to directed therapy once pathogen and susceptibility data are available.
- Site of infection dictates drug selection (e.g., blood-brain barrier penetration for meningitis).
- Aminoglycosides require concentration-dependent dosing targets (Cmax/MIC) and are ineffective under anaerobic conditions.
- Trimethoprim-sulfamethoxazole blocks two sequential steps in folate synthesis.
- Nitrofurantoin and metronidazole have specific activation mechanisms (urinary tract and anaerobic environments, respectively).
1. DEFINITION & OVERVIEW¶
Antimicrobial agents have transformed human health through reduced mortality and improved quality of life. However, their use promotes drug resistance in pathogens and bystander organisms. Antimicrobial stewardship focuses on optimizing efficacy, minimizing adverse effects, and preserving agent value.
1.1 Antimicrobial Stewardship & Resistance¶
• Core Principles: ◦ Avoid broader-spectrum agents than needed to reduce resistant bacterial selection. ◦ Use shorter courses when possible to limit resistance emergence. ◦ Apply pharmacokinetic/pharmacodynamic (PK/PD) principles for optimal dosing. ◦ Leverage microbiologic data to refine therapy. ◦ Adhere to host-specific factors and infection sites for targeted treatment.
2. ETIOLOGY & PATHOPHYSIOLOGY¶
Antimicrobial agents target bacterial structures and metabolic pathways with minimal mammalian toxicity. Bactericidal vs. bacteriostatic effects depend on host defenses and infection sites.
2.1 Inhibition of Cell Wall Synthesis¶
• Mechanism: Bacterial cell wall protects against osmotic lysis; peptidoglycan structure consists of NAG-NAM polymers with cross-bridges. • Beta-Lactams: Target transpeptidase (PBPs) in peptidoglycan cross-linking; β-lactamase inhibitors enhance the spectrum of activity. • Glycopeptides and Lipoglycopeptides: Bind d-alanine residues on stem peptides; Vancomycin also binds lipid II intermediate. Telavancin and dalbavancin have additional membrane binding to increase potency. • Other Cell Wall Agents: ◦ Bacitracin/fosfomycin: Inhibit peptidoglycan precursor synthesis. ◦ Mupirocin: Competes with isoleucine for tRNA synthetase.
2.2 Inhibition of Protein Synthesis¶
• Aminoglycosides (e.g., gentamicin): Bind 30S rRNA, block translocation, and cause misreading. • Tetracyclines: Block aminoacyl-tRNA binding to 30S subunit. • Macrolides/ketolides: Bind 50S rRNA, inhibit translocation. • Linezolid: Binds 50S A site, blocks initiation of protein synthesis. • Pleuromutilin (Lefamulin): Binds 50S ribosome to block protein synthesis.
2.3 Inhibition of Bacterial Metabolism¶
• Sulfonamides: Inhibit DHPS (PABA incorporation). • Trimethoprim: Inhibits DHFR (tetrahydrofolate production). • Nitrofurantoin: Reduced to DNA-damaging derivatives in the urinary tract. • Metronidazole: Activated by anaerobic electron transport systems.
2.4 Inhibition of DNA and RNA Synthesis or Activity¶
• Quinolones: Inhibit DNA gyrase/topoisomerase IV, causing double-strand breaks. • Rifamycins: Bind bacterial RNA polymerase β-subunit.
2.5 Disruption of Membrane Integrity¶
• Polymyxins: Disrupt membranes via LPS binding. • Daptomycin: Forms potassium channels in gram-positive membranes.
3. INVESTIGATIONS & DIAGNOSIS¶
Pharmacokinetics (PK) and pharmacodynamics (PD) guide antimicrobial selection and dosing.
3.1 Pharmacokinetics (Drug Disposition)¶
• Absorption: IV bioavailability = 100%; oral bioavailability affected by food and first-pass effect. • Distribution: V_d determined by lipophilicity, protein binding, and tissue penetration. • Metabolism: Phase I (CYP enzymes) and Phase II; Rifampin induces CYP3A4. • Excretion: Renal clearance (glomerular filtration, tubular secretion); hepatic impairment affects β-lactam dosing.
3.2 Pharmacodynamics (Drug-Pathogen Interaction)¶
• Concentration-dependent killing: Aminoglycosides (C_{max}/MIC). • Time-dependent killing: β-lactams (T > MIC). • Area under curve: Fluoroquinolones and Vancomycin (AUC/MIC). • Postantibiotic effect: Prolongs drug-free intervals for aminoglycosides.
4. MANAGEMENT & TREATMENT¶
Antimicrobial therapy requires integration of host factors, infection site, and local resistance patterns.
4.1 Empirical and Directed Therapy¶
• Empirical Therapy: Based on severity, likely pathogens, prior therapy, and epidemiology. • Directed Therapy: Adjusted after microbiologic data (pathogen/susceptibility) are available. • Combination Therapy: Used for severe infections requiring broad coverage.
4.2 Host Factors¶
• Bactericidal Requirement: Preferred in patients with neutropenia or meningitis. • Organ Impairment: Renal/hepatic impairment affects dosing intervals (e.g., β-lactams). • Pregnancy: Use FDA categories to guide fetal risk assessment.
4.3 Site of Infection¶
• CNS Infections: Require blood-brain barrier penetration (e.g., vancomycin, ceftriaxone). • Urinary Tract: Nitrofurantoin or metronidazole for anaerobes. • Anaerobic Sites: Metronidazole preferred.
4.4 Surgical Prophylaxis¶
- Clean (cardiac, thoracic, neurologic, orthopedic, vascular, plastic): Cefazolin (Vancomycin or Clindamycin for MRSA).
- Clean (ophthalmic): Topical neomycin–polymyxin–gramicidin; topical moxifloxacin.
- Clean-contaminated (head and neck): Cefazolin + metronidazole, ampicillin-sulbactam (clindamycin).
- Clean-contaminated (hysterectomy, gastroduodenal, biliary, urologic): Cefazolin; ampicillin-sulbactam (clindamycin + aminoglycoside, aztreonum, or fluoroquinolone).
- Clean-contaminated (colorectal, appendectomy): Cefazolin + metronidazole, ampicillin-sulbactam, ertapenem (clindamycin + aminoglycoside, aztreonem, or fluoroquinolone).
- Dirty (ruptured viscus): Ceftriaxone + metronidazole; continue for 3–5 days post-procedure.
- Dirty (traumatic wound): Cefazolin (clindamycin ± aminoglycoside, aztreonem, or fluoroquinolone); continue for 3–5 days post-procedure.
4.5 Specific Clinical Scenarios¶
- Recurrent S. aureus skin infections: Mupirocin (intranasal application for 5 days).
- Recurrent cellulitis with lymphatic disruption: Benzathine penicillin IM monthly, or oral penicillin/erythromycin twice daily.
- Recurrent cystitis in women: Nitrofurantoin, TMP-SMX, or fluoroquinolones.
- Bite wounds: Amoxicillin-clavulanate (doxycycline, moxifloxacin) for 3–5 days.
- Recurrent spontaneous bacterial peritonitis (cirrhosis): Fluoroquinolone.
- Pneumococcal meningitis (CSF leak/immune defect): Penicillin.
- Meningococcal exposure: Rifampin (2 days) or Ciprofloxacin (single dose).
- High-risk neutropenia (ANC ≤100/μ m for >7 days): Levofloxacin or ciprofloxacin until resolution; Cefoxitin or cefotetan may be considered.
5. SPECIAL CONSIDERATIONS¶
Antimicrobial use in vulnerable populations requires tailored approaches.
5.1 Pregnancy and Lactation¶
• Pregnancy Risk Assessment: ◦ Compatible (Category B): Cephalosporins, Penicillins, Clindamycin, Erythromycin (except estolate), Azithromycin, Ertapenem, Meropenem/meropenem-vaborbactam, Quinupristin-dalfopristin, Vancomycin, Chloramphenicol, Fluoroquinolones, Imipenem-cilastatin. ◦ Specific Risks: ◦ Nitrofurantoin: Risk in third trimester. ◦ Telavancin: Evidence of teratogenicity in animal studies. ◦ Dalbavancin/Oritavancin: Use only if benefit outweighs risk (animal data show potential harm). ◦ Tetracyclines/Tigecycline: Contraindicated or high risk in 2nd/3rd trimesters. ◦ Cefiderocol: No controlled human data; animal studies no evidence of harm. ◦ Eravacycline: Risk at higher doses in animal studies. ◦ Imipenem-cilastatin-relebactam: Animal studies show increased fetal loss. ◦ Lefamulin: Evidence of fetal harm in animal studies. • Breast-feeding: ◦ Metronidazole: Interrupt for 12–24 h after single 2-g dose; potential toxicity in divided doses. ◦ Ceftazidime-avibactam: Excreted in human milk in low concentrations. ◦ Cefiderocol/Eravacycline: Excreted in animal milk.
6. KEY PEARLS & CLINICAL TRAPS¶
• Aminoglycosides: Ineffective under anaerobic conditions; require concentration-dependent dosing (Cmax/MIC). • Trimethoprim-sulfamethoxazole: Blocks two sequential steps in folate synthesis. • Nitrofurantoin/Metronidazole: Require specific activation (urinary/anaerobic) to be effective. • Penicillin Allergy: Overreported; >90% of patients can safely tolerate cephalosporins. • Adverse Reactions (Table 2): ◦ β-lactams: Hypersensitivity, Neurotoxicity (cefepime, imipenem), Red man syndrome. ◦ Aminoglycosides: Nephrotoxicity (reversible), Ototoxicity (potentially irreversible), Tendinitis, Dysglycemia, Exacerbation of myasthenia gravis. ◦ Rifampin: Hepatotoxicity, Orange discoloration of body fluids, Photosensitivity. ◦ Macrolides: Gastrointestinal distress, QT prolongation (Azithromycin risk in high-risk patients). ◦ Clindamycin: Diarrhea/pseudomembranous colitis, Myelosuppression, Lactic acidosis. ◦ Telavancin: QT prolongation, Interference with coagulation tests, Taste disturbances. ◦ Dalbavancin: Myopathy, Eosinophilic pneumonia. • Drug Interactions (Table 3): ◦ Rifampin: Strong inducer of CYP3A4 (decreases levels of warfarin, ritonavir, cyclosporine, diazepam, verapamil, protease inhibitors, voriconazole); also interacts with CYP2C19, 2C9, 2C8, and 2B6 substrates. ◦ Macrolides/Lefamulin: Risk of cardiotoxicity when used with QT-prolonging drugs. ◦ TMP-SMX: Increases effects of warfarin; increases levels of phenytoin and methotrexate.
Reference Tables¶
TABLE 149-1 Risks Associated with Use of Antibacterial Drugs in Pregnancy and Lactation¶
Harrison's 22e, p.1169
| PREGNANCY CATEGORYa |
ANTIBACTERIAL DRUG | FETAL RISK RECOMMENDATIONb | BREAST-FEEDING RISK RECOMMENDATIONb |
|---|---|---|---|
| B | Azithromycin | Limited human data. Animal data suggest low risk. | Limited human data; probably compatible |
| Cephalosporins (including cephalexin, cefuroxime, cefixime, cefpodoxime, cefotaxime, ceftriaxone) |
Compatible | Compatible | |
| Ceftazidime-avibactam | No human data; no fetal harm in animal studies | Ceftazidime is excreted into human milk in low concentrations. Avibactam is excreted into the milk of lactating rats; no human studies have been conducted. |
|
| Ceftolozane-tazobactam | Compatible | Unknown | |
| Clindamycin | Compatible | Compatible | |
| Ertapenem | No human data; probably compatible | Limited human data; probably compatible | |
| Erythromycin | Compatible (except for estolate salt) | Compatible | |
| Meropenem and meropenem-vaborbactam |
No human data. Animal data suggest low risk. | No human data; probably compatible | |
| Metronidazole | Human data suggest low risk. | Interrupt breast-feeding for 12–24 h after single 2-g dose. Limited human data; potential toxicity in divided doses |
|
| Nitrofurantoin | Human data suggest risk in third trimester. | Limited human data; probably compatible. Higher risk associated with younger infants and those with G6PD deficiency |
|
| Penicillins (including amoxicillin, ampicillin, cloxacillin) |
Compatible | Compatible | |
| Quinupristin-dalfopristin | Compatible. Maternal benefit must far outweigh risk to embryo/fetus. |
No human data; potential toxicity | |
| Vancomycin | Compatible | Limited human data; probably compatible | |
| Chloramphenicol | Compatible | ||
| Fluoroquinolones | Human data suggest low risk. | ||
| Clarithromycin | Limited human data. Animal data suggest high risk. | ||
| Imipenem-cilastatin | Limited human data. Animal data suggest low risk. | ||
| Linezolid | Compatible. Maternal benefit must far outweigh risk to embryo/fetus. |
||
| Telavancin | No human data. Animal studies have revealed evidence of teratogenicity.c |
||
| Tedizolid | Limited data. Embryo-fetal studies in mice, rats, and rabbits have demonstrated fetal developmental toxicities. Use only if benefit outweighs risk. |
||
| Dalbavancin | Limited human data. At high doses in animal studies, delayed fetal maturation, increased embryo and offspring death. Use only if benefit outweighs risk. |
||
| Oritavancin | Limited human data. Studies in rats and rabbits demonstrated no harm at 25% of recommended human dose. Use only if benefit outweighs risk. |
||
| C/D | Amikacin | Human data suggest low risk. | Compatible |
| Gentamicin | Human data suggest low risk. | Compatible | |
| Kanamycin | Human data suggest risk. | ||
| Streptomycin | Human data suggest risk. | ||
| Sulfonamides | Human data suggest risk in third trimester. | ||
| Tetracyclines | Contraindicated in second and third trimesters | ||
| Tigecycline | Human data suggest risk in second and third trimesters. |
||
| Not assignedd |
Cefiderocol | No controlled data in human pregnancy; animal studies have not provided evidence of fetal harm. |
Unknown if excreted in human milk; excreted in animal milk. |
| Eravacycline | No controlled data in human pregnancy; animal data indicate drug crosses placenta and is associated with risk at higher doses, |
Unknown if excreted in human milk; excreted in animal milk. Not recommended during and for a period after treatment. |
|
| Imipenem-cilastatin-relebactam | No controlled data in human pregnancy; animal studies have not revealed teratogenicity but have shown evidence of increased fetal loss. |
Imipenem and cilastatin are excreted into human milk; no data on relebactam in human milk. Relebactam is excreted in animal milk. No human data regarding potential effect on infant. |
|
| Lefamuline | No controlled data in human pregnancy; animal studies have revealed evidence of fetal harm. |
Unknown if excreted in human milk; excreted in animal milk. Breast-feeding is not recommended during use and for 2 days afterward. |
TABLE 149-2 Common Adverse Reactions to Antibacterial Agents ANTIBACTERIAL(S) β -Lactams¶
Harrison's 22e, p.1171
| ANTIBACTERIAL(S) | POTENTIAL ADVERSE EFFECTS | COMMENTS |
|---|---|---|
| β-Lactams | Hypersensitivity reactions | Ranges from rash to anaphylaxis. Cross-reactivity among β-lactams is related to chemical structure and side chain similarity. |
| Neurotoxicity | More commonly described with cefepime and imipenem, but likely a class effect. Risk is increased in patients with history of seizures, renal impairment, and advanced age. |
|
| Neutropenia/hematologic reactions | May be related to high doses and prolonged duration | |
| Nephrotoxicity | ||
| “Red man syndrome” | ||
| Telavancin | QT prolongation | |
| Interference with coagulation tests | May falsely affect INR, PT, aPTT. Perform these tests before the next dose of telavancin (when serum drug levels are at their nadir). |
|
| Taste disturbances | ||
| Nephrotoxicity | ||
| Interference with coagulation tests | ||
| Gastrointestinal distress | ||
| Dalbavancin | Gastrointestinal distress | |
| Myopathy | ||
| Eosinophilic pneumonia | ||
| Aminoglycosides | Nephrotoxicity | Associated with prolonged use; usually reversible |
| Ototoxicity | Can cause both vestibular and cochlear toxicity. Ototoxicity may be irreversible. | |
| QT prolongation c |
||
| Tendinitis | ||
| Dysglycemia | ||
| Exacerbation of myasthenia gravis | ||
| Rifampin | Hepatotoxicity | Risk is greater when drug is given with other antituberculosis agents. When rifampin is given alone, LFT values may be transiently elevated without symptoms. |
| Orange discoloration of body fluids | ||
| Photosensitivity | ||
| Gastrointestinal distress | ||
| Macrolides | Gastrointestinal distress | Erythromycin is occasionally used as a therapeutic agent for some gastric motility disorders. |
| QT prolongation c |
Azithromycin use is associated with an increased risk of death from cardiovascular causes among patients at high baseline risk. |
|
| Peripheral neuropathy | ||
| Clindamycin | Diarrhea and pseudomembranous colitis | |
| Myelosuppression | ||
| Optic and peripheral neuropathy | ||
| Lactic acidosis | ||
| TMP-SMX | Hypersensitivity reactions | Allergy usually associated with sulfonamide moiety |
| Nephrotoxicity | Associated with high doses | |
| Hematologic effects | Associated with prolonged use | |
| Pneumonitis and other pulmonary reactions |
||
| Peripheral neuropathy | ||
| Fosfomycin | Gastrointestinal effects | |
| Nephrotoxicity | ||
| Neurotoxicity | ||
| Quinupristin- dalfopristin |
Arthralgias and myalgias | |
| Bone marrow suppression | ||
| Pleuromutilin | Gastrointestinal | Diarrhea |
| QT prolongation c |
When used in conjunction with CYP3A4 substrates |
TABLE 149-3 Important Antibacterial Drug Interactions ANTIBACTERIAL(S) Nafcillin Ceftriaxone¶
Harrison's 22e, p.1172
| ANTIBACTERIAL(S) | INTERACTING AGENT(S) | POTENTIAL EFFECT AND MANAGEMENT |
|---|---|---|
| Nafcillin | Warfarin, cyclosporine, tacrolimus | Decreased effects of interacting drug via CYP3A4 induction. Monitor levels of affected drug closely if drugs are given concomitantly. |
| Calcium-containing IV solutions | ||
| Carbapenems | Valproic acid | Diminished levels of valproic acid. Monitor valproic acid levels closely if drugs are given concomitantly and consider alternative therapies. |
| Serotonergic and adrenergic agents (e.g., SSRIs, vasopressors) |
||
| Quinupristin- dalfopristin |
Substrates of CYP3A4 (e.g., warfarin, ritonavir, cyclosporine, diazepam, verapamil) |
Can result in increased levels of interacting drug |
| Theophyllinea | ||
| Sucralfate; antacids containing aluminum, calcium, or magnesium; ferrous sulfate– and zinc-containing multivitamins |
||
| Tizanidinea | ||
| QT-prolonging drugs (e.g. azoles, sotalol, c amiodarone, dofetilide, fluoxetine) |
||
| Rifampin | Substrates of CYP3A4 (e.g., warfarin, ritonavir, cyclosporine, diazepam, verapamil, protease inhibitors, voriconazole) |
Can result in decreased levels of interacting drug. Avoid concomitant use if possible. If giving drugs concomitantly, monitor drug levels if possible. |
| Substrates of CYP2C19 (e.g., omeprazole, lansoprazole) |
||
| Substrates of CYP2C9 (e.g., warfarin, tolbutamide) | ||
| Substrates of CYP2C8 (e.g., repaglinide, rosiglitazone) |
||
| Substrates of CYP2B6 (e.g., efavirenz) | ||
| Hormone therapy (e.g., norethindrone) | Can result in decreased levels of hormone. If oral contraceptive and rifampin are given concomitantly, use alternative or additional forms of birth control. |
|
| Antacids or drugs containing calcium, magnesium, iron, or aluminum |
||
| Warfarin | ||
| Eravacycline: Strong CYP3A4 inducers (e.g., rifampin) |
||
| Macrolidesb | Substrates of CYP3A4 (e.g., warfarin, ritonavir, cyclosporine, diazepam, verapamil, amiodarone) |
Avoid concomitant administration if possible. |
| QT-prolonging agents (e.g., fluoroquinolones, c sotalol) |
Increased risk of cardiotoxicity and arrhythmias. Monitor QT. c |
|
| Protease inhibitors (e.g., ritonavir) | Can result in increased levels of both macrolides and protease inhibitors. Avoid concomitant use if possible. |
|
| Cimetidine | Cimetidine can increase levels of macrolides. | |
| Ethanol | ||
| Warfarin | ||
| TMP-SMX | Warfarin | Increased effect of warfarin. Monitor levels closely if drugs are given concomitantly. |
| Phenytoin | Increased levels of phenytoin. Monitor levels closely if drugs are given concomitantly. | |
| Methotrexate | Increased levels of methotrexate and prolonged exposure. Monitor levels closely if drugs are given concomitantly. |
|
| Substrates of CYP3A4 (e.g., cyclosporine, warfarin) and CYP2D6 (e.g., aripiprazole) Substrates of CYP2C19 (e.g., omeprazole) and CYP2C9 (e.g., warfarin) |
||
| Lefamulin | QT-prolonging drugs (e.g., azoles, sotalol, c amiodarone, dofetilide, fluoxetine) |
Increased risk of cardiotoxicity and arrhythmias. Monitor QT. c |
| Strong CYP3A4 inducers (e.g., rifampin) | Reduced lefamulin efficacy | |
| Strong CYP3A4 strong inhibitors (e.g., ritonavir) | Increased lefamulin exposure |
TABLE 149-4 Drug Indications for Specific Infections, Associated Pathogens, and Sample Susceptibility Rates…¶
Harrison's 22e, p.1173
| ANTIMICROBIAL(S) | INFECTIONS | COMMON PATHOGENS (% SUSCEPTIBLE); RESISTANCE AS NOTEDa |
|---|---|---|
| Penicillin G | Syphilis; yaws; leptospirosis; streptococcal infections; pneumococcal infections; actinomycosis; oral and periodontal infections; meningococcal meningitis and meningococcemia; viridans streptococcal endocarditis; clostridial myonecrosis; tetanus; rat-bite fever; Pasteurella multocida infections; erysipeloid (Erysipelothrix rhusiopathiae) |
Neisseria meningitidis; viridans streptococci (60%); Streptococcus pneumoniae (97% nonmeningitis; 74% meningitis) |
| Salmonellosis; acute otitis media; Haemophilus influenzae meningitis and epiglottitis; Listeria monocytogenes meningitis; Enterococcus faecalis UTI |
||
| Nafcillin, oxacillin | MSSA bacteremia and endocarditis | Staphylococcus aureus (72%); coagulase-negative staphylococci (49%) |
| Intraabdominal infections (facultative enteric gram-negative bacilli and obligate anaerobes); infections caused by mixed flora (aspiration pneumonia, diabetic foot ulcers); infections caused by Pseudomonas aeruginosa |
||
| Cefazolin | E. coli UTI; surgical prophylaxis; MSSA bacteremia and endocarditis | E. coli (80%) |
| Intraabdominal infections and pelvic inflammatory disease | ||
| Ceftriaxone | Gonococcal infections; pneumococcal meningitis; viridans streptococcal endocarditis; salmonellosis and typhoid fever; health care–associated infections caused by nonpseudomonal facultative gram-negative enteric bacilli |
S. pneumoniae (87% meningitis; 99% nonmeningitis); E. coli (88%); Klebsiella pneumoniae (85%) |
| Health care–associated infections caused by facultative gram-negative bacilli and Pseudomonas spp. |
||
| Ceftaroline | CAP caused by S. pneumoniae, MSSA, H. influenzae, K. pneumoniae, Klebsiella oxytoca, and E. coli; acute bacterial skin and skin-structure infections caused by MSSA, MRSA, Streptococcus pyogenes, Streptococcus agalactiae, E. coli, K. pneumoniae, and K. oxytoca |
Mostly susceptible; four strains of MRSA with ceftaroline MICs >4 μg/mL reported in isolates from a single Greek hospitalc; additional case reports, including in patients without prior exposure to ceftarolined,e |
| Complicated UTIs (ceftazidime-avibactam and meropenem-vaborbactam) and complicated intraabdominal infections (ceftazidime-avibactam in combination with metronidazole) caused by resistant gram-negative organisms, including Pseudomonas, and some anaerobes |
||
| Ceftolozane- tazobactam |
Complicated UTIs and complicated intraabdominal infections (in combination with metronidazole) caused by resistant gram-negative organisms, including Pseudomonas, and some anaerobes |
P. aeruginosa (>86% overall; 60–80% of ceftazidime- and meropenem-resistant strains)f MDR Enterobacterales No activity against KPC-producing organisms |
| Intraabdominal infections, infections caused by Enterobacter spp. and ESBL- producing gram-negative bacilli |
||
| Ertapenem | CAP; complicated UTIs, including pyelonephritis; acute pelvic infections; complicated intraabdominal infections; complicated skin and skin-structure infections, excluding diabetic foot infections accompanied by osteomyelitis or caused by P. aeruginosa |
Enterobacter cloacae (88%); K. pneumoniae (98%) |
| Infections caused by facultative gram-negative bacilli and Pseudomonas in penicillin-allergic patients |
||
| Vancomycin | Bacteremia, endocarditis, and other invasive disease caused by MRSA; pneumococcal meningitis; oral formulation for CDAD |
S. aureus (100%); E. faecalis (93%); E. faecium (41%) |
| Health care– and ventilator-associated pneumonia or skin and soft tissue infections caused by MRSA |
||
| Dalbavancin, oritavancin |
Complicated skin and soft tissue infections | S. aureus: rarely reported for dalbavancin.g Rarely reported for oritavancin.h |
| VRE infections; MRSA bacteremia | ||
| Gentamicin, tobramycin, amikacin |
Combined with penicillin for staphylococcal, enterococcal, or streptococcal endocarditis; combined with β-lactam for gram-negative bacteremia; pyelonephritis |
E. coli (gentamicin, 90%); P. aeruginosa (amikacin, 93%; gentamicin, 89%); A. calcoaceticus-baumannii complex (gentamicin, 83%) |
| Legionella, Campylobacter, and Mycoplasma infections; CAP; GAS pharyngitis in penicillin-allergic patients; bacillary angiomatosis; gastric infections due to Helicobacter pylori; MAI infections |
||
| Clindamycin | Severe, invasive GAS infections (with a β-lactam); infections caused by obligate anaerobes; infections caused by susceptible staphylococci |
S. aureus (73%) |
| Acute bacterial exacerbations of chronic bronchitis; granuloma inguinale; brucellosis (with streptomycin); tularemia; glanders; melioidosis; spirochetal infections caused by Borrelia (Lyme disease and relapsing fever; doxycycline); infections caused by Vibrio vulnificus; some Aeromonas infections; infections due to Stenotrophomonas (minocycline); plague; ehrlichiosis; chlamydial infections (doxycycline); granulomatous infections due to Mycobacterium marinum (minocycline); rickettsial infections; mild CAP; skin and soft tissue infections caused by gram-positive cocci (e.g., CA-MRSA infections); leptospirosis; syphilis; and actinomycosis in the penicillin-allergic patient |
TABLE 149-5 Prophylaxis of Bacterial Infections in Adults CONDITION Surgical Clean (cardiac, thoracic, neurologic…¶
Harrison's 22e, p.1180
| CONDITION | ANTIBACTERIAL AGENTSa | TIMING OR DURATION OF PROPHYLAXIS |
|---|---|---|
| Surgical | ||
| Clean (cardiac, thoracic, neurologic, orthopedic, vascular, plastic) |
Cefazolin (vancomycin,b clindamycin) | 1 h before incision; re-dose with long procedures |
| Clean (ophthalmic) | Topical neomycin–polymyxin B–gramicidin, topical moxifloxacin |
Every 5–15 min for 5 doses immediately prior to procedure |
| Clean-contaminated (head and neck) | Cefazolin + metronidazole, ampicillin-sulbactamc (clindamycin) | 1 h before incision; re-dose with long procedures |
| Clean-contaminated (hysterectomy, gastroduodenal, biliary, unobstructed small intestine, urologic) |
Cefazolin, ampicillin-sulbactamc (clindamycin + aminoglycoside, aztreonam, or fluoroquinolone) |
1 h before incision; re-dose with long procedures |
| Clean-contaminated (colorectal, appendectomy) | Cefazolin + metronidazole, ampicillin-sulbactam,c ertapenem (clindamycin + aminoglycoside, aztreonam, or fluoroquinolone) |
1 h before incision; re-dose with long procedures |
| Dirty (ruptured viscus) | Therapeutic regimen directed at anaerobes and gram-negative bacteria (e.g., ceftriaxone + metronidazole) |
1 h before incision; re-dose with long procedures; continue for 3–5 days after procedure |
| Dirty (traumatic wound) | Therapeutic regimen: cefazolin (clindamycin ± aminoglycoside, aztreonam, or fluoroquinolone) |
1 h before incision; re-dose with long procedures; continue for 3–5 days after procedure |
| Nonsurgical | ||
| Amoxicillin PO, ampicillin IM (clindamycin PO, IV) | ||
| Mupirocine | ||
| Benzathine penicillin IM monthly, oral penicillin or erythromycin twice daily |
||
| Nitrofurantoin, TMP-SMX, fluoroquinolone | ||
| Amoxicillin-clavulanate (doxycycline, moxifloxacin) | ||
| Fluoroquinolonef | ||
| Penicillin | ||
| Rifampin, ciprofloxacin | ||
| Levofloxacin or ciprofloxacinf |