From the Guidelines
For urinary tract infections caused by gram-negative rods, the most appropriate empiric treatment is trimethoprim-sulfamethoxazole (TMP-SMX) 160/800mg twice daily for 7 days, as recommended by the most recent guidelines 1.
Key Considerations
- The choice of antibiotic should be guided by local resistance patterns and susceptibility testing results.
- For uncomplicated cystitis, alternative options include nitrofurantoin 100mg twice daily for 5-7 days, ciprofloxacin 250-500mg twice daily for 3-7 days, or fosfomycin 3g single dose.
- For more severe infections like pyelonephritis, initial IV therapy with ceftriaxone 1-2g daily or an aminoglycoside may be necessary before transitioning to oral therapy.
Treatment Duration
- A treatment duration of 7 days is recommended for gram-negative bacteremia from a urinary source, as supported by multiple RCTs 1.
- The choice of drug and dose should be optimized for the patient and the urinary focus of infection.
Important Factors
- Adequate hydration is crucial during treatment, and symptoms should improve within 48-72 hours.
- If symptoms persist, reevaluation with possible urine culture and different antibiotic therapy is warranted.
- Local resistance patterns should guide empiric choices, as E. coli and other gram-negative organisms have increasing resistance to fluoroquinolones and TMP-SMX in many regions 1.
From the FDA Drug Label
Gentamicin Injection, USP is indicated in the treatment of serious infections caused by susceptible strains of the following microorganisms: Pseudomonas aeruginosa, Proteus species (indole-positive and indole-negative), Escherichia coli, Klebsiella-Enterobacter-Serratia species, Citrobacter species and Staphylococcus species (coagulase-positive and coagulase-negative) Aminoglycosides, including gentamicin, are not indicated in uncomplicated initial episodes of urinary tract infections unless the causative organisms are susceptible to these antibiotics and are not susceptible to antibiotics having less potential for toxicity Gentamicin may be active against clinical isolates of bacteria resistant to other aminoglycosides. Antibacterial Activity Gentamicin has been shown to be active against most of the following bacteria, both in vitro and in clinical infections: Gram-Negative Bacteria Citrobacter species, Enterobacter species, Escherichia coli, Klebsiella species, Proteus species, Serratia species, Pseudomonas aeruginosa
The appropriate antibiotics for a urinary tract infection caused by a Gram-negative rod are:
- Gentamicin (IV) 2, which is effective against Gram-negative bacteria such as Pseudomonas aeruginosa, Proteus species, Escherichia coli, Klebsiella-Enterobacter-Serratia species, and Citrobacter species.
- Levofloxacin (PO) 3 may also be considered, as it has been shown to be effective against Gram-negative bacteria such as Escherichia coli and Klebsiella species.
It is essential to note that the choice of antibiotic should be based on the results of susceptibility tests and the severity of the infection. If the causative organisms are resistant to gentamicin or levofloxacin, other appropriate therapy should be instituted.
From the Research
Appropriate Antibiotics for Urinary Tract Infections Caused by Gram-Negative Rods
The choice of antibiotics for urinary tract infections (UTIs) caused by Gram-negative rods depends on various factors, including the severity of the infection, the presence of underlying medical conditions, and the susceptibility of the causative organism to different antibiotics.
- First-line empiric therapies for acute uncomplicated bacterial cystitis in otherwise healthy adult nonpregnant females include:
- A 5-day course of nitrofurantoin
- A 3-g single dose of fosfomycin tromethamine 4
- Second-line options include:
- Fluoroquinolones
- β-lactams, such as amoxicillin-clavulanate 4
- For UTIs caused by AmpC-β-lactamase-producing organisms, treatment options include:
- Fosfomycin
- Nitrofurantoin
- Fluoroquinolones
- Cefepime
- Piperacillin-tazobactam
- Carbapenems 4
- For UTIs caused by ESBL-producing Enterobacteriaceae, treatment options include:
- Nitrofurantoin
- Fosfomycin
- Fluoroquinolones
- Cefoxitin
- Piperacillin-tazobactam
- Carbapenems
- Ceftazidime-avibactam
- Ceftolozane-tazobactam
- Aminoglycosides 4
- For UTIs caused by carbapenem-resistant Enterobacteriaceae (CRE), treatment options include:
- Ceftazidime-avibactam
- Colistin
- Polymyxin B
- Fosfomycin
- Aztreonam
- Aminoglycosides
- Tigecycline 4
- Novel combinations, such as betalactam or carbapenem and betalactamase inhibitor, ceftazidime/avibactam and meropenem/vaborbactam, are effective for infections caused by KPC-carbapenemase-producing pathogens 5
- Imipenem/relebactam, another carbapenem/betalactamase inhibitor combination, has been approved for the treatment of cUTI, but data on its efficacy against carbapenem-resistant pathogens is still limited 5
- Ceftolozane/tazobactam is mainly used for the treatment of MDR Pseudomonas aeruginosa infections 5
- For the treatment of cUTI caused by extended-spectrum betalactamases producing Enterobacterales, aminoglycosides or intravenous fosfomycin should be considered 5
- Ciprofloxacin is a broad-spectrum fluoroquinolone antibacterial agent that is effective against Gram-negative bacteria, but its use should be restricted due to increased rates of resistance 6
- Resistance to gram-negative rods causing urinary tract infection is increasing, with a particular concern being increased resistance to beta-lactams, trimethoprim, and quinolones 7
- Recent advances in pharmacotherapy and medical microbiology are modernizing how these urinary tract infections are treated, including the development and approval of novel antibiotics and the re-examination of the potential role of legacy antibiotics 8