What is the best oral antibiotic option for a patient with a history of Septra (trimethoprim/sulfamethoxazole) and doxycycline allergy, presenting with a recurrent symptomatic Escherichia coli (E. coli) urinary tract infection (UTI) with significant leukocyturia (white blood cells), nitrites, and hematuria (red blood cells), and normal renal function?

From the Guidelines

The best oral antibiotic option for this patient with recurrent pan-sensitive E. coli UTIs and normal renal function would be nitrofurantoin (Macrobid) 100 mg twice daily for 5-7 days. Given her history of multiple UTIs in a short timeframe despite recent treatment with ceftriaxone and cephalexin, nitrofurantoin would be appropriate as it achieves high urinary concentrations and has good efficacy against E. coli while having a different mechanism of action from previously used antibiotics 1. The choice of nitrofurantoin is supported by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases guidelines, which recommend it as a first-line treatment for acute uncomplicated cystitis due to its minimal resistance and propensity for collateral damage 1.

Some key points to consider in this patient's management include:

• The patient's allergies to Septra and doxycycline, which limit the use of certain antibiotics
• The recurrent nature of her infections, suggesting the need for a thorough evaluation for underlying predisposing factors
• The importance of post-treatment cultures to confirm eradication of the infection
• The potential benefits of preventive measures such as increased hydration, urinating after intercourse, and possibly cranberry supplements

Alternatively, fosfomycin (Monurol) 3 grams as a single dose could be considered, especially if compliance is a concern 1. However, it's worth noting that fosfomycin appears to have inferior efficacy compared with standard short-course regimens, according to data submitted to the US Food and Drug Administration (FDA) and summarized in the Medical Letter 1.

The patient's history of recent treatment with ceftriaxone and cephalexin, as well as her allergies, makes it essential to choose an antibiotic with a different mechanism of action to minimize the risk of resistance development. The guidelines from the European Association of Urology & European Society for Paediatric Urology and the American Academy of Pediatrics also support the use of nitrofurantoin as a first-line treatment for uncomplicated urinary tract infections 1.

Overall, the choice of nitrofurantoin for this patient is based on its efficacy, safety profile, and the patient's specific clinical scenario, including her allergies and history of recent antibiotic use 1.

From the FDA Drug Label

The following in vitro data are available, but their clinical significance is unknown: Levofloxacin exhibits in vitro minimum inhibitory concentrations (MIC values) of 2 mcg/mL or less against most (≥ 90%) isolates of the following microorganisms; however, the safety and effectiveness of levofloxacin in treating clinical infections due to these bacteria have not been established in adequate and well-controlled clinical trials Gram-Negative Bacteria Escherichia coli Haemophilus influenzae Haemophilus parainfluenzae Klebsiella pneumoniae Legionella pneumophila Moraxella catarrhalis Proteus mirabilis Pseudomonas aeruginosa Serratia marcescens

The best oral antibiotic option for this patient with normal renal function is levofloxacin.

• Levofloxacin has been shown to be effective against Escherichia coli, which is the pathogen of interest in this case.
• The patient has a history of allergies to Septra and doxycycline, but there is no mention of an allergy to levofloxacin.
• The patient has had recent treatment with iv ceftriaxone and keflex, but levofloxacin is a different class of antibiotic and may still be effective.
• It is essential to note that the patient's recent UTI was treated with keflex, and the current UTI may be a recurrence or a new infection, and levofloxacin may be a suitable option for treatment 2, 2.

From the Research

Patient's Condition

The patient has a history of Septra and doxycycline allergy and has had 3 symptomatic pan-sensitive E.coli UTIs over the past 2 months. She was recently treated with iv ceftriaxone and stepped down to keflex 2 weeks ago and completed the full course. She now has another symptomatic UTI along with significant WBC and nitrites in cloudy urine and a small amount of RBC.

Treatment Options

Considering the patient's normal renal function and allergy to Septra and doxycycline, the following oral antibiotic options can be considered:

• Nitrofurantoin: a 5-day course is recommended for acute uncomplicated bacterial cystitis 3
• Fosfomycin tromethamine: a 3-g single dose is recommended for acute uncomplicated bacterial cystitis 3
• Pivmecillinam: a 5-day course is recommended for acute uncomplicated bacterial cystitis 3
• Amoxicillin-clavulanate: can be considered as a second-line option, but the dosage may need to be adjusted based on the patient's renal function and the severity of the infection 4, 3, 5
• Cephalexin: can be considered as a second-line option, but the patient has already been treated with keflex (a type of cephalexin) recently, so its effectiveness may be reduced

Key Considerations

• The patient's recent treatment with keflex may affect the effectiveness of cephalexin as a treatment option
• The patient's allergy to Septra and doxycycline should be taken into account when selecting an antibiotic
• The patient's normal renal function is an important factor in selecting an antibiotic and determining the dosage
• The use of amoxicillin-clavulanate may be associated with the development of resistance in E.coli, so its use should be carefully considered 6