Application of Precision Medicine Concepts in Ambulatory Antibiotic Management of Acute Pyelonephritis

Abstract

Acute pyelonephritis (APN) is a relatively common community-acquired infection, particularly in women. The early appropriate antibiotic treatment of this potentially life-threatening infection is associated with improved outcomes. The international management guidelines for complicated urinary tract infections and APN recommend using oral antibiotics with <10% resistance among urinary pathogens. However, increasing antibiotic resistance rates among Escherichia coli and other Enterobacterales to fluoroquinolones, trimethoprim-sulfamethoxazole (TMP-SMX), and beta-lactams has left patients without reliable oral antibiotic treatment options for APN. This narrative review proposes using precision medicine concepts to improve empirical antibiotic therapy for APN in ambulatory settings. Whereas resistance rates to a particular antibiotic class may exceed 10% at the population-based level, the predicted antibiotic resistance rates based on patient-specific risk factors fall under 10% in many patients with APN on the individual level. The utilization of clinical tools for the prediction of fluoroquinolones, TMP-SMX, and third-generation cephalosporin resistance improves the ambulatory antibiotic management of APN. It may also reduce the need to switch antibiotic therapy later based on the in vitro antibiotic susceptibility testing results of bacterial isolates in urinary cultures. This approach may mitigate the burden of increasing antibiotic resistance in the community by ensuring that the initial antibiotic prescribed has the highest likelihood of treating APN appropriately.

Keywords: acute pyelonephritis; antibiotic resistance; outpatient antibiotic stewardship; precision medicine; transitions of care.

Figure 1

Guideline-based therapy of acute pyelonephritis [3]. ¹ [3]. ² Oral ciprofloxacin 500 mg twice daily for 7 days or levofloxacin 750 mg daily for 5 days in patients not requiring hospitalization. ³ IV Ceftriaxone 1G or consolidated 24 h dose of an aminoglycoside. For SMX-TMP: not recommended unless susceptibilities are known. If TMP-SMX is used empirically, an initial dose of IV ceftriaxone 1G or consolidated 24 h dose of aminoglycoside is recommended. Oral beta-lactam agents are less effective than other available agents. If an oral beta-lactam is used empirically, an initial dose of IV ceftriaxone 1G or consolidated 24 h dose of aminoglycoside is recommended. For beta-lactams: duration of 10–14 days.

Figure 2

Precision-medicine-based therapy of acute pyelonephritis. ¹ See fluoroquinolone risk score in Table 1. ² Low risk of fluoroquinolone resistance defined as fluoroquinolone resistance score < 2. ³ Levofloxacin 750 mg PO Q24 h or ciprofloxacin 500 mg PO Q12 h for 5–7 days. ⁴ Moderate risk of fluoroquinolone resistance defined as risk score of 2. ⁵ Parenteral agents to include: IV/IM ceftriaxone 1G or consolidated 24 h dose of tobramycin or amikacin. ⁶ See TMP-SMX risk score in Table 2. ⁷ Low risk of TMP-SMX resistance defined as risk score < 1. ⁸ High risk of TMP-SMX resistance defined as risk score ≥ 1. ⁹ 1 Double-strength TMP-SMX PO Q12 h × 14 days. ¹⁰ High risk of fluoroquinolone resistance defined as fluoroquinolone resistance score > 2. If there is a high risk of fluoroquinolone resistance and a high risk of TMP-SMX resistance, consider evaluating for risk of ESBL (Table 3) and Pseudomonas aeruginosa. If there is concern for Pseudomonas aeruginosa, consider utilizing anti-pseudomonal agent such as meropenem, piperacillin/tazobactam, cefepime, tobramycin, or amikacin. If ESBL prediction score is <3, and there is no concern for P. aeruginosa, utilize IV/IM ceftriaxone. If ESBL prediction score is ≥3, utilize IV/IM ertapenem or an aminoglycoside. Tobramycin or amikacin are the only recommended aminoglycosides due to the recent change in recommendations by CLSI to not utilize gentamicin as a treatment option for P. aeruginosa [27].