What are the common Gram‑negative bacilli and the recommended empiric antibiotic regimens for infections they cause (e.g., urinary‑tract infection, intra‑abdominal infection, hospital‑acquired pneumonia, bloodstream infection, wound infection)?

Gram-Negative Bacilli: Common Pathogens and Empiric Antibiotic Regimens

Most Common Gram-Negative Bacilli

Escherichia coli is by far the most common gram-negative bacillus across all infection types, accounting for 45-71% of isolates, followed by Klebsiella species (12-21%), Pseudomonas aeruginosa (11-14%), and Acinetobacter species (13.8%). 1, 2, 3

Distribution by Infection Site

• Urinary tract infections: E. coli dominates at 68.4%, with Klebsiella species at 14% and Proteus mirabilis at 5% 2, 4
• Intra-abdominal infections: E. coli (46-57%), Klebsiella pneumoniae (12-17%), P. aeruginosa (12-14%), and Bacteroides fragilis (35%) 1, 4, 5
• Respiratory tract infections: Acinetobacter baumannii and K. pneumoniae are the predominant pathogens 2
• Bloodstream infections: E. coli (39.9%), followed by Klebsiella and Acinetobacter species 2
• Wound/soft tissue infections: E. coli (37%), Staphylococcus aureus, and Streptococcus pyogenes 2

Empiric Antibiotic Regimens by Infection Type

Community-Acquired Intra-Abdominal Infections (Mild-to-Moderate)

For mild-to-moderate community-acquired intra-abdominal infections, use narrow-spectrum agents: ticarcillin-clavulanate, cefoxitin, ertapenem, moxifloxacin, or tigecycline as monotherapy, OR metronidazole combined with cefazolin, cefuroxime, ceftriaxone, cefotaxime, levofloxacin, or ciprofloxacin. 1

Key Coverage Requirements

• Must cover enteric gram-negative aerobic and facultative bacilli (primarily E. coli) 1
• Must cover enteric gram-positive streptococci 1
• Must cover obligate anaerobic bacilli (especially Bacteroides fragilis) for distal small bowel, appendiceal, and colon-derived infections 1

Agents to AVOID

• Ampicillin-sulbactam: High resistance rates among community-acquired E. coli (43-54% ESBL production) 1, 4
• Cefotetan and clindamycin: Increasing resistance among Bacteroides fragilis group 1
• Aminoglycosides: Not recommended for routine use due to nephrotoxicity and ototoxicity when less toxic alternatives exist 1

High-Severity Community-Acquired Intra-Abdominal Infections

For patients with APACHE II scores ≥15, prolonged hospital stay (≥5 days), or significant comorbidities, use broad-spectrum regimens: meropenem, imipenem-cilastatin, doripenem, piperacillin-tazobactam, OR ciprofloxacin/levofloxacin plus metronidazole, OR ceftazidime/cefepime plus metronidazole. 1

Critical Considerations

• Quinolones should NOT be used unless local surveillance shows ≥90% E. coli susceptibility (fluoroquinolone resistance reaches 53-61% in many regions) 1, 2
• Empiric enterococcal coverage IS recommended for high-severity infections 1
• Aztreonam plus metronidazole is an alternative, but add an agent for gram-positive cocci 1

Healthcare-Associated Intra-Abdominal Infections

For healthcare-associated infections (developing >48 hours post-admission, recent hospitalization within 90 days, or long-term care facility residents), use multidrug regimens with expanded gram-negative activity including anti-pseudomonal coverage. 1

Recommended Regimens

• Carbapenems (meropenem, imipenem-cilastatin, doripenem) 1
• Piperacillin-tazobactam 1
• Cefepime or ceftazidime PLUS metronidazole 1, 6
• Cefepime dosing: 2 g IV every 8-12 hours for complicated intra-abdominal infections (combined with metronidazole) 6

Mandatory Coverage

• Pseudomonas aeruginosa: Generally recommended for all healthcare-associated infections 1
• Enterococcus species: Empiric coverage required, particularly for postoperative infections, patients with prior cephalosporin exposure, immunocompromised patients, and those with valvular heart disease 1
• ESBL-producing Enterobacteriaceae: Consider in regions with high prevalence (36-54% in some areas) 4, 5

Urinary Tract Infections (Complicated/Pyelonephritis)

For severe complicated UTI or pyelonephritis, use cefepime 2 g IV every 12 hours OR a carbapenem (ertapenem, meropenem, imipenem). 6

For mild-to-moderate complicated UTI, use cefepime 0.5-1 g IV every 12 hours for 7-10 days. 6

Important Caveats

• Fluoroquinolones show high resistance (ciprofloxacin 61%, levofloxacin 54% against E. coli) and should be reconsidered as first-line empiric therapy 2
• Amikacin and carbapenems maintain low resistance rates (~2% for E. coli) 2, 3
• ESBL rates in UTI-associated E. coli reach 43-54% in some regions 4, 5

Hospital-Acquired/Ventilator-Associated Pneumonia

For gram-negative HAP/VAP, use anti-pseudomonal beta-lactams (piperacillin-tazobactam, cefepime, ceftazidime, meropenem, or imipenem) as empiric therapy. 1

Cefepime dosing for pneumonia: 1-2 g IV every 8-12 hours for 10 days; for P. aeruginosa specifically, use 2 g IV every 8 hours 6

Dual Gram-Negative Coverage

• Critically ill patients with recent colonization or infection with multidrug-resistant gram-negative pathogens require TWO antimicrobial agents of different classes with gram-negative activity 1
• De-escalate to single appropriate antibiotic once culture results available 1

Bloodstream Infections

For suspected gram-negative bacteremia in critically ill patients, those with sepsis, neutropenia, femoral catheter, or known gram-negative focus, provide empirical coverage with anti-pseudomonal agents. 1

• Consider dual therapy initially if recent MDR gram-negative colonization/infection 1
• Carbapenems maintain excellent activity (>98% susceptibility) against Enterobacteriaceae bloodstream isolates 3

Regional Resistance Patterns and Special Considerations

Extended-Spectrum Beta-Lactamase (ESBL) Producers

In settings with high ESBL prevalence (>10-15%), carbapenems (ertapenem, meropenem, imipenem) should be first-line empiric therapy for community-acquired infections. 1

• ESBL rates: E. coli 7-54%, Klebsiella species 13-56%, Enterobacter species 18% 4, 3, 5
• CTX-M-15 is the most prevalent ESBL type 4
• Carbapenem-sparing alternatives: Ceftolozane-tazobactam plus metronidazole OR ceftazidime-avibactam plus metronidazole for ESBL infections 1

Carbapenem-Resistant Enterobacteriaceae (CRE)

For suspected CRE infections, use polymyxins, tigecycline (avoid in bacteremia), ceftazidime-avibactam, or ceftolozane-tazobactam based on local susceptibility patterns. 1

• Carbapenem resistance prevalence: 1.6% overall but rapidly increasing 4
• OXA carbapenemases most common (71.4% of carbapenemase-producing isolates) 7
• KPC producers emerging as major threat worldwide 1

Multidrug-Resistant Non-Fermenters

Acinetobacter baumannii shows >70% resistance to fluoroquinolones, beta-lactam/beta-lactamase inhibitors, ceftazidime, cefepime, and carbapenems; consider polymyxins or tigecycline. 2

• MDR rates: A. baumannii 60-80%, XDR rates 45-55% 2
• P. aeruginosa: Consider ceftolozane-tazobactam for multidrug-resistant strains 1

Antibiotic Stewardship Principles

Spectrum Narrowing

• Avoid routine use of broad-spectrum agents (anti-pseudomonal carbapenems, fourth-generation cephalosporins) for community-acquired infections 1
• Discourage extended cephalosporin use due to selective pressure for ESBL production 1
• Limit fluoroquinolone use due to selective pressure for ESBLs and MRSA 1

De-escalation Strategy

• Adjust therapy based on culture results within 48-72 hours 1
• De-escalation associated with lower mortality in ICU patients 1
• Total antibiotic duration: 4-7 days after adequate source control 8

ICU vs. Non-ICU Considerations

• Resistance rates significantly higher in ICU settings across all major gram-negative bacilli (p<0.05) 2
• ICU patients require broader initial coverage with planned de-escalation 2

Duration of Therapy

Antibiotics should be continued for 4-7 days after adequate source control, until resolution of fever and normalization of white blood cell count. 8

• Complicated intra-abdominal infections: 7-10 days 6
• Complicated UTI/pyelonephritis: 7-10 days 6
• Pneumonia: 10 days (P. aeruginosa may require longer) 6
• Febrile neutropenia: 7 days or until resolution of neutropenia 6