What antibiotic do I choose for a patient with a urinary tract infection (UTI) caused by Enterococcus and Klebsiella that is resistant to penicillin, macrolide, and clindamycin?

From the Guidelines

For a patient with a UTI caused by both Enterococcus and Klebsiella with resistance to penicillin, macrolides, and clindamycin, I recommend fosfomycin (3g single oral dose) as the first-line option, as it is effective against both Enterococcus and Klebsiella, and has been recommended by recent guidelines 1. If the infection is more severe or involves the upper urinary tract, intravenous therapy with a carbapenem, such as meropenem-vaborbactam, may be considered, as recommended by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines 1.

Before starting treatment, it is essential to obtain a urine culture with susceptibility testing to confirm the specific antibiotic sensitivities of both organisms. The recommended antibiotics work through different mechanisms, making them effective against these resistant organisms. For complicated infections or patients with impaired renal function, dosage adjustments may be necessary. Ensure adequate hydration during treatment and advise the patient to complete the full course of antibiotics even if symptoms improve quickly.

Some key points to consider:

• Fosfomycin has been shown to be effective against Enterococcus and Klebsiella, including strains resistant to other antibiotics 1.
• Carbapenems, such as meropenem-vaborbactam, are recommended for severe or complicated UTIs caused by Enterobacterales, including Klebsiella 1.
• Vancomycin may be considered for Enterococcus infections, but its use should be guided by susceptibility testing and clinical judgment 1.
• Aminoglycosides, such as plazomicin, may be considered as an alternative regimen for patients with cUTI due to CRE, but their use should be guided by susceptibility testing and clinical judgment 1.

Overall, the choice of antibiotic should be guided by the results of susceptibility testing, the severity of the infection, and the patient's underlying medical conditions.

From the FDA Drug Label

Levofloxacin tablets are indicated for the treatment of complicated urinary tract infections due to Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis [see Clinical Studies (14.7)]. Levofloxacin tablets are indicated for the treatment of complicated urinary tract infections (mild to moderate) due to Enterococcus faecalis, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, or Pseudomonas aeruginosa [see Clinical Studies (14.8)]. Ciprofloxacin Tablets USP, 250 mg, 500 mg and 750 mg is indicated for the treatment of infections caused by susceptible strains of the designated microorganisms in the conditions and patient populations listed below: Urinary Tract Infections caused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, Proteus mirabilis, Providencia rettgeri, Morganella morganii, Citrobacter diversus, Citrobacter freundii, Pseudomonas aeruginosa, methicillin-susceptible Staphylococcus epidermidis, Staphylococcus saprophyticus, or Enterococcus faecalis

Antibiotic Choice: For a patient with a urinary tract infection (UTI) caused by Enterococcus and Klebsiella that is resistant to penicillin, macrolide, and clindamycin, consider using levofloxacin or ciprofloxacin as both are indicated for the treatment of complicated urinary tract infections due to these organisms 2 3.

• Key Considerations:
  • Resistance patterns
  • Local epidemiology
  • Patient-specific factors (e.g., renal function, potential drug interactions) It is essential to consult the latest clinical guidelines and susceptibility data to ensure the chosen antibiotic is effective against the specific strains of Enterococcus and Klebsiella involved.

From the Research

Treatment Options for UTI caused by Enterococcus and Klebsiella

The patient has a urinary tract infection (UTI) caused by Enterococcus and Klebsiella that is resistant to penicillin, macrolide, and clindamycin. The following treatment options can be considered:

• For Enterococcus:
  • Nitrofurantoin 4
  • Fosfomycin 4
  • Fluoroquinolones 4
  • Daptomycin (for pyelonephritis and complicated UTIs) 4
  • Linezolid (for pyelonephritis and complicated UTIs) 4
  • Quinupristin-dalfopristin (for pyelonephritis and complicated UTIs) 4
• For Klebsiella:
  • Fosfomycin 5, 6
  • Nitrofurantoin 5
  • Fluoroquinolones 5
  • Cefepime 5, 6
  • Piperacillin-tazobactam (for ESBL-producing Klebsiella) 5
  • Carbapenems (for ESBL-producing Klebsiella) 5
  • Ceftazidime-avibactam 5
  • Ceftolozane-tazobactam 5
  • Aminoglycosides (including plazomicin) 5
  • Tigecycline 6
  • Colistin 6

Considerations for Treatment

When choosing a treatment option, consider the following:

• Local susceptibility patterns 7, 5
• Severity of the infection 7, 5
• Presence of underlying comorbidities 4
• Potential for resistance development 5, 8
• Need for combination therapy or synergy using polymyxin 6