What are the IDSA guidelines for treating gram‑negative infections in an adult, non‑pregnant patient with normal renal function?

IDSA Guidelines for Gram-Negative Bacterial Treatment

For adult, non-pregnant patients with normal renal function, broad-spectrum antipseudomonal agents—piperacillin-tazobactam, carbapenems, or antipseudomonal cephalosporins—are recommended as initial therapy for suspected gram-negative infections, with selection guided by infection severity, anatomic site, and local resistance patterns. 1

Empiric Therapy by Clinical Syndrome

Urinary Tract Infections

Uncomplicated Cystitis:

• Nitrofurantoin for 5 days is the preferred first-line agent, sparing broader-spectrum antibiotics 2
• Fluoroquinolones (ciprofloxacin or levofloxacin) for 3 days are acceptable when local resistance is <10% 2, 1
• Trimethoprim-sulfamethoxazole for 3 days is appropriate if susceptibility is confirmed, though contemporary E. coli resistance limits first-line use 2, 1

Pyelonephritis:

• Outpatient: Oral fluoroquinolone (ciprofloxacin 1000 mg ER daily for 7 days or levofloxacin 750 mg daily for 5 days) if local resistance <10% 1
• Hospitalized: IV fluoroquinolone, aminoglycoside ± ampicillin, extended-spectrum cephalosporin ± aminoglycoside, or carbapenem 1
• Duration: 5-7 days for fluoroquinolones; 7 days for β-lactams 2
• High resistance areas (>10%): Administer one IV dose of ceftriaxone 1 g or 24-hour aminoglycoside dose before switching to oral therapy 1

Intra-Abdominal Infections

Mild-to-Moderate Community-Acquired:

• Ampicillin-sulbactam, ertapenem, or third-generation cephalosporin plus metronidazole 2, 1
• These narrow-spectrum regimens are preferable to avoid unnecessary broad coverage 2

Severe Community-Acquired (ICU or high severity):

• Antipseudomonal carbapenem (imipenem-cilastatin or meropenem) or piperacillin-tazobactam as monotherapy 1
• Coverage must include enteric gram-negative aerobic/facultative bacilli and obligate anaerobes for distal small-bowel and colon-derived infections 2

Duration: Individualize based on source control adequacy; postoperative prophylaxis should not exceed 72 hours 1

Respiratory Tract Infections

Community-Acquired Pneumonia (non-ICU):

• Third-generation cephalosporin combined with a macrolide, or respiratory fluoroquinolone monotherapy 1

Severe Pneumonia with Pseudomonas Risk (ICU):

• Antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, ceftazidime, or carbapenem) plus either fluoroquinolone (ciprofloxacin/levofloxacin) or aminoglycoside 1
• Risk factors include severe COPD, structural lung disease, healthcare-associated infection, and immunocompromised status 1

Catheter-Related Bloodstream Infections

Empiric Coverage Indications:

• Critically ill patients, sepsis, neutropenia, femoral catheter, or known gram-negative focus require empiric gram-negative coverage 2
• Patients with recent colonization/infection with multidrug-resistant (MDR) gram-negative pathogens need two antimicrobial agents of different classes initially 2

Management:

• Short-term catheters infected with gram-negative bacilli must be removed 2
• De-escalate to single appropriate antibiotic once susceptibilities available 2
• Duration: 7-14 days for uncomplicated infections; extend beyond 14 days if persistent bacteremia, severe sepsis, or metastatic infection present 2

Necrotizing Soft-Tissue Infections

• Broad-spectrum coverage including anti-MRSA agent (vancomycin, daptomycin, or linezolid) plus antipseudomonal gram-negative coverage (piperacillin-tazobactam, carbapenem, or cefepime) 1

Pathogen-Specific Recommendations

Enterobacteriaceae (E. coli, Klebsiella, Enterobacter)

• First-line: Third-generation cephalosporin 1
• ESBL-suspected: Carbapenem is drug of choice 1
• Alternatives: β-lactam/β-lactamase inhibitor combinations or fluoroquinolones 1
• E. coli causes 75-95% of uncomplicated UTIs and approximately 32% of complicated intra-abdominal infections 1

Pseudomonas aeruginosa

• Dual therapy required: Antipseudomonal β-lactam plus either fluoroquinolone or aminoglycoside 1
• Monotherapy for severe Pseudomonas infections risks resistance emergence and worse outcomes 1
• High-risk groups: severe COPD, structural lung disease, healthcare-associated infection, immunocompromised 1

Acinetobacter species

• First-line: Carbapenem 1
• Alternatives: Cephalosporin-aminoglycoside combination, ampicillin-sulbactam, or colistin when carbapenem contraindicated 1

Resistance-Driven Modifications

Extended-Spectrum Cephalosporin-Resistant Enterobacteriaceae (ESCR-E)

Screening:

• Screen colorectal or liver transplant candidates when local prevalence exceeds 10% 1

Perioperative Prophylaxis:

• Trimethoprim-sulfamethoxazole for non-severe infections 1
• Fosfomycin for urinary procedures 1
• Avoid cephamycins and cefepime due to insufficient evidence 1

Treatment:

• Carbapenems remain drugs of choice 1
• Narrow-spectrum agents should be used when feasible 1
• MDR K. pneumoniae and E. coli with extended-spectrum β-lactamases have poor outcomes when treated with cephalosporins or piperacillin-tazobactam versus carbapenems, even when appearing susceptible in vitro 2

Carbapenem Resistance

• Increasing concern over carbapenemase-producing gram-negative bacilli 2
• No randomized trials exist for polymyxin (colistin) or aminoglycoside therapy in these infections 2

Critical Dosing and Administration

Timing:

• Fluoroquinolones and vancomycin: start ≥120 minutes before surgical incision 1
• All other standard agents: administer ≤60 minutes before incision 1

Aminoglycosides:

• Single daily dosing preferred for patients with stable normal renal function 2
• Monitor drug levels when multiple daily dosing used >24 hours 2
• Monitor drug levels when single-daily dosing used >48 hours 2
• Avoid concomitant nephrotoxic drugs 2, 1
• Limited prostate tissue penetration restricts use in prostate procedures 1
• Nephrotoxicity exacerbated by impaired renal perfusion; administer after fluid resuscitation 2

Dose Adjustments:

• Obesity and renal impairment necessitate individualized dosing 1

De-escalation Strategy

Culture-Guided Narrowing:

• Switch to narrow-spectrum agents (penicillin or amoxicillin) for susceptible isolates 1
• Discontinue unnecessary broad-spectrum coverage once susceptibilities available 2, 1
• Adjust initial regimen to single agent for remainder of therapeutic course, usually 7-14 days 2

Key Pitfalls to Avoid

1. Never use monotherapy for severe Pseudomonas infections—dual coverage reduces resistance emergence and improves outcomes 1

2. Avoid aminoglycosides as first-line unless no suitable alternatives—narrow therapeutic range with ototoxicity and nephrotoxicity risk 2

3. Do not use agents with unnecessary antipseudomonal activity for community-acquired infections—reserve ICU agents to prevent resistance 2

4. β-lactam monotherapy for pyelonephritis is less effective—requires initial parenteral dose if used 1

5. Treatment failure with Enterobacter bacteremia when cephalosporins used—consider alternative agents 2

6. ESCR-E screening without actionable protocols provides no benefit—must link to targeted prophylaxis modifications 1

7. Inappropriate initial antibiotic therapy for MDR gram-negative CRBSI increases morbidity and mortality—risk factors include critical illness, neutropenia, prior antibiotics, and femoral catheter 2