What is the coverage for Gram-negative rods in the urine?

From the Guidelines

For coverage of gram-negative rods in the urine, empiric therapy with fluoroquinolones (ciprofloxacin 500mg orally twice daily or levofloxacin 750mg orally once daily for 5-7 days) is often recommended as first-line treatment. Alternatively, trimethoprim-sulfamethoxazole (TMP-SMX) 160/800mg orally twice daily for 3-5 days can be effective if local resistance patterns permit 1. For more severe infections or hospitalized patients, intravenous options include ceftriaxone 1-2g daily, gentamicin 5mg/kg daily, or piperacillin-tazobactam 3.375g every 6 hours. The choice of antibiotic should be guided by local antibiogram data, as resistance patterns vary geographically. Once culture results are available, therapy should be narrowed to the most appropriate agent.

Key Considerations

• Gram-negative rods commonly causing urinary tract infections include Escherichia coli, Klebsiella, Proteus, and Pseudomonas species.
• These organisms possess an outer membrane that makes them resistant to many antibiotics, necessitating specific antimicrobial agents that can penetrate this barrier or target unique bacterial processes.
• Adequate hydration and completion of the full antibiotic course are essential for successful treatment.
• A recent study published in 2024 found that a 7-day treatment course is sufficient for gram-negative bacteremia from a urinary source, as long as source control has been addressed 1.

Treatment Options

• Fluoroquinolones: ciprofloxacin 500mg orally twice daily or levofloxacin 750mg orally once daily for 5-7 days
• Trimethoprim-sulfamethoxazole (TMP-SMX): 160/800mg orally twice daily for 3-5 days
• Intravenous options: ceftriaxone 1-2g daily, gentamicin 5mg/kg daily, or piperacillin-tazobactam 3.375g every 6 hours

Important Notes

• Local resistance patterns should be considered when choosing an antibiotic.
• Culture results should be used to guide therapy and narrow down the treatment options.
• Adequate hydration and completion of the full antibiotic course are crucial for successful treatment.

From the FDA Drug Label

Fosfomycin (the active component of fosfomycin tromethamine) has in vitro activity against a broad range of gram-positive and gram-negative aerobic microorganisms which are associated with uncomplicated urinary tract infections Fosfomycin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section: Aerobic gram-negative microorganisms Escherichia coli The following in vitro data are available, but their clinical significance is unknown entrations (MIC’s) of 64 mcg/mL or less against most (≥ 90%) strains of the following microorganisms; Aerobic gram-negative microorganisms Citrobacter diversus Citrobacter freundii Enterobacter aerogenes Klebsiella oxytoca Klebsiella pneuomoniae Proteus mirabilis Proteus vulgaris Serratia marcescens

Coverage for gram-negative rods in the urine: Fosfomycin has in vitro activity against a broad range of gram-negative aerobic microorganisms, including Escherichia coli, Citrobacter diversus, Citrobacter freundii, Enterobacter aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, and Serratia marcescens. The drug achieves therapeutic concentrations in the urine, with a mean urine concentration of 706 mcg/mL within 2 to 4 hours after a single oral 3-gm dose. Key points include:

• Gram-negative coverage: Fosfomycin is active against multiple gram-negative microorganisms.
• Urinary concentrations: The drug achieves high concentrations in the urine, which are likely to be effective against gram-negative rods.
• MIC values: The MIC values for fosfomycin against gram-negative microorganisms are generally low, indicating that the drug is likely to be effective against these organisms 2.

From the Research

Coverage for Gram-Negative Rods in the Urine

• Gram-negative rods are a common cause of urinary tract infections (UTIs), and the increasing resistance to antibiotics is a growing concern 3, 4.
• The recommended first-line empiric therapies for acute uncomplicated bacterial cystitis in otherwise healthy adult nonpregnant females include nitrofurantoin or fosfomycin tromethamine 3.
• Second-line options for UTIs include fluoroquinolones and β-lactams, such as amoxicillin-clavulanate 3.
• For UTIs caused by AmpC-β-lactamase-producing organisms, treatment options include fosfomycin, nitrofurantoin, fluoroquinolones, cefepime, piperacillin-tazobactam, and carbapenems 3.
• For UTIs caused by ESBL-producing Enterobacteriaceae, treatment options include nitrofurantoin, fosfomycin, fluoroquinolones, cefoxitin, piperacillin-tazobactam, carbapenems, ceftazidime-avibactam, ceftolozane-tazobactam, and aminoglycosides 3.

Antibiotic Resistance Patterns

• A study found that gram-negative rods causing UTIs showed resistance to amoxicillin (61.7%), trimethoprim (36.2%), nitrofurantoin (13.2%), ciprofloxacin (25.6%), and fosfomycin (10.7%) 4.
• Another study highlighted the increasing demand for further research to advance diagnostics and treatment options for UTIs, particularly in the context of rising antimicrobial resistance 5.

Treatment Options for Resistant Strains

• For UTIs caused by carbapenem-resistant Enterobacteriaceae (CRE), treatment options include ceftazidime-avibactam, colistin, polymixin B, fosfomycin, aztreonam, aminoglycosides, and tigecycline 3.
• For UTIs caused by multidrug-resistant (MDR) Pseudomonas spp., treatment options include fluoroquinolones, ceftazidime, cefepime, piperacillin-tazobactam, carbapenems, aminoglycosides, colistin, ceftazidime-avibactam, and ceftolozane-tazobactam 3.
• Newer β-lactam agents, such as cefiderocol, ceftazidime-avibactam, and ceftolozane-tazobactam, have shown activity against difficult-to-treat gram-negative infections, including those causing meningitis 6.