Is cephalexin (a beta-lactam antibiotic) an effective treatment for a patient with a urine culture showing resistance to ampicillin (a beta-lactam antibiotic)?

From the Guidelines

No, cephalexin is not an effective treatment for a patient with a urine culture showing resistance to ampicillin. When bacteria demonstrate resistance to ampicillin, there is often cross-resistance to other beta-lactam antibiotics, including first-generation cephalosporins like cephalexin 1. This cross-resistance occurs because these antibiotics share similar mechanisms of action and are affected by the same bacterial resistance mechanisms, particularly beta-lactamase production.

According to the guidelines, beta-lactam agents, including cephalexin, are less well studied and may have inferior efficacy and more adverse effects compared to other UTI antimicrobials 1. The guidelines recommend that beta-lactams other than pivmecillinam should be used with caution for uncomplicated cystitis.

For patients with ampicillin-resistant urinary tract infections, alternative antibiotics from different classes should be considered, such as:

• Trimethoprim-sulfamethoxazole, if local resistance rates do not exceed 20% 1
• Nitrofurantoin monohydrate/macrocrystals, due to minimal resistance and propensity for collateral damage 1
• Fluoroquinolones, like ciprofloxacin, although they should be reserved for important uses other than acute cystitis due to their propensity for collateral damage 1
• Fosfomycin trometamol, a single-dose therapy with minimal resistance, although it may have inferior efficacy compared to standard short-course regimens 1

The choice of antibiotic should be guided by the complete susceptibility profile from the culture, the patient's medication allergies, renal function, and history of previous antibiotic use. Treating with an antibiotic to which the bacteria has demonstrated resistance can lead to treatment failure and potentially worsen the infection.

From the FDA Drug Label

MIC values should be interpreted according to the following criteria: MIC (mcg/mL)Interpretation ≤ 8Susceptible (S) 16Intermediate (I) ≥ 32Resistant (R) A report of "Resistant" indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected Culture and susceptibility tests should be initiated prior to and during therapy. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy.

The patient's urine culture shows resistance to ampicillin, another beta-lactam antibiotic. Although cephalexin is also a beta-lactam antibiotic, the drug label does not provide direct information on cross-resistance between ampicillin and cephalexin.

• The MIC values for cephalexin are provided, but without knowing the specific MIC value for the patient's organism, it is unclear if cephalexin would be effective.
• The label recommends considering culture and susceptibility information when selecting therapy, but this information is not available for cephalexin in the context of ampicillin resistance.
• Given the potential for cross-resistance between beta-lactam antibiotics, it is uncertain whether cephalexin would be an effective treatment for this patient 2 2.

From the Research

Effectiveness of Cephalexin for Urine Culture Showing Resistance to Ampicillin

• The effectiveness of cephalexin in treating a patient with a urine culture showing resistance to ampicillin is a concern due to both being beta-lactam antibiotics 3.
• A study from 1972 compared the effectiveness of ampicillin, cephalexin, co-trimoxazole, and trimethoprim in treating urinary infections, and found that the overall results for ampicillin and cephalexin were similar, although cephalexin was inferior in treating symptomatic domiciliary infections 3.
• However, another study from 2020 discussed the cross-allergy between penicillins and cephalosporins, and found that the risk of severe cross-allergic reactions to cephalosporins is very low, even in patients with a true penicillin allergy 4.
• A 1987 study compared ciprofloxacin and beta-lactam antibiotics in treating urinary tract infections, and found that ciprofloxacin was more effective in eliminating bacteria from the urine and had a lower relapse rate compared to beta-lactam antibiotics 5.
• A 2023 study compared the outcomes of patients receiving high-dose oral beta-lactam versus standard oral therapy for bacteremia secondary to a urinary tract infection, and found that high-dose oral beta-lactams were as safe and effective as oral fluoroquinolones or trimethoprim-sulfamethoxazole 6.
• Another study from 2009 found that the resistance rates of E. coli isolates to ampicillin were high, and that the empirical use of fluoroquinolones in uncomplicated urinary tract infections should be discouraged due to increased antimicrobial resistance rates 7.

Considerations for Prescribing Cephalexin

• When prescribing cephalexin to a patient with a urine culture showing resistance to ampicillin, it is essential to consider the potential for cross-resistance between the two antibiotics 3, 4.
• The patient's medical history, including any previous allergic reactions to penicillins or cephalosporins, should be carefully evaluated before prescribing cephalexin 4.
• Alternative antibiotic options, such as fluoroquinolones or trimethoprim-sulfamethoxazole, may be considered if the patient's urine culture shows resistance to ampicillin and cephalexin 5, 6, 7.