Dataset Information

Antimicrobial Susceptibility and Cross-Resistance Patterns among Common Complicated Urinary Tract Infections in U.S. Hospitals, 2013 to 2018.

ABSTRACT: In the face of increasing rates of antimicrobial resistance in complicated urinary tract infections (cUTIs), clinicians need to understand cross-resistance patterns among commonly encountered pathogens. We performed a multicenter, retrospective cohort study in the Premier database of approximately 180 hospitals, from 2013 to 2018. Using an ICD-9/10-based algorithm, we identified all adult patients hospitalized with cUTIs and included those with a positive blood or urine culture. We examined the microbiology and susceptibilities to common cUTI antimicrobials (3rd-generation cephalosporin [C3], fluoroquinolones [FQ], trimethoprim-sulfamethoxazole [TMP/SMZ], fosfomycin [FFM], and nitrofurantoin [NFT]) singly and in groups of two. Among 28,057 organisms from 23,331 patients, the 3 most common pathogens were Escherichia coli (41.0%; C3^r, 15.1%), Klebsiella pneumoniae (12.1%; C3^r, 13.2%), and Pseudomonas aeruginosa (11.0%; C3^r, 12.0%). E. coli was most frequently resistant to FQ (43.5%) and least to NFT (6.7%). K. pneumoniae was most frequently resistant to NFT (60.8%) and least to FFM (0.1%). P. aeruginosa was most frequently resistant to FQ (34.4%) and least to TMP/SMZ (4.2%). Of the C3^r E. coli isolates, 87.1% were also FQ^r, 63.7% were TMP/SMZ^r, and 13.3% were NFT^r C3^r K. pneumoniae isolates had a 76.5% chance of being FQ^r, 78.1% were TMP/SMZ^r, and 77.6% were NFT^r C3^r P. aeruginosa coexisted with FQ^r in 47.3%, TMP/SMZ^r in 18.9%, and NFT^r in 28.7%. Among the most common pathogens isolated from hospitalized patients with cUTIs, the rates of single resistance to common treatments and of cross-resistance to these regimens are substantial. Knowing the patterns of cross-resistance may help clinicians tailor empirical therapy more precisely.

SUBMITTER: Zilberberg MD

PROVIDER: S-EPMC7526848 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Antimicrobial Susceptibility and Cross-Resistance Patterns among Common Complicated Urinary Tract Infections in U.S. Hospitals, 2013 to 2018.

Zilberberg Marya D MD Nathanson Brian H BH Sulham Kate K Shorr Andrew F AF

Antimicrobial agents and chemotherapy 20200722 8

In the face of increasing rates of antimicrobial resistance in complicated urinary tract infections (cUTIs), clinicians need to understand cross-resistance patterns among commonly encountered pathogens. We performed a multicenter, retrospective cohort study in the Premier database of approximately 180 hospitals, from 2013 to 2018. Using an ICD-9/10-based algorithm, we identified all adult patients hospitalized with cUTIs and included those with a positive blood or urine culture. We examined the ...[more]

PMID: 32423953

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Project description:BackgroundComplicated urinary tract infection (cUTI) is common among hospitalized patients. Though carbapenems are an effective treatment in the face of rising resistance, overuse drives carbapenem resistance (CR). We hypothesized that resistance to routinely used antimicrobials is common, and, despite frequent use of carbapenems, associated with an increased risk of inappropriate empiric treatment (IET), which in turn worsens clinical outcomes.MethodsWe conducted a retrospective cohort study of patients hospitalized with a culture-positive non-CR cUTI. Triple resistance (TR) was defined as resistance to > 3 of the following: 3rd generation cephalosporins, fluoroquinolones, trimethoprim-sulfamethoxazole, fosfomycin, and nitrofurantoin. Multivariable models quantified the impact of TR and inappropriate empiric therapy (IET) on mortality, hospital LOS, and costs.ResultsAmong 23,331 patients with cUTI, 3040 (13.0%) had a TR pathogen. Compared to patients with non-TR, those with TR were more likely male (57.6% vs. 47.7%, p < 0.001), black (17.9% vs. 13.6%, p < 0.001), and in the South (46.3% vs. 41.5%, p < 0.001). Patients with TR had higher chronic (median [IQR] Charlson score 3 [2, 4] vs. 2 [1, 4], p < 0.001) and acute (mechanical ventilation 7.0% vs. 5.0%, p < 0.001; ICU admission 22.3% vs. 18.6%, p < 0.001) disease burden. Despite greater prevalence of empiric carbapenem exposure (43.3% vs. 16.2%, p < 0.001), patient with TR were also more likely to receive IET (19.6% vs. 5.4%, p < 0.001) than those with non-TR. Although mortality was similar between groups, TR added 0.38 (95% CI 0.18, 0.49) days to LOS, and $754 (95% CI $406, $1103) to hospital costs. Both TR and IET impacted the outcomes among cUTI patients whose UTI was not catheter-associated (CAUTI), but had no effect on outcomes in CAUTI.ConclusionsTR occurs in 1 in 8 patients hospitalized with cUTI. It is associated with an increase in the risk of IET exposure, as well as a modest attributable prolongation of LOS and increase in total costs, particularly in the setting of non-CAUTI.

Project description:Oral fosfomycin is approved in Canada for the treatment of acute uncomplicated cystitis. Several studies have reported "off label" use of oral fosfomycin in the treatment of patients with complicated lower urinary tract infection (cLUTI). This review summarizes the available literature describing the use of oral fosfomycin in the treatment of patients with cLUTI. Collectively, these studies support the use of a regimen of 3 grams of oral fosfomycin administered once every 48 or 72 hours for a total of 3 doses for patients who have previously failed treatment with another agent, are infected with a multidrug-resistant (MDR) pathogen, or cannot tolerate first-line treatment due to intolerance or adverse effects. Additionally, a Phase 2/3 clinical trial, known as the ZEUS study, assessed the efficacy and safety of intravenous (IV) fosfomycin versus piperacillin-tazobactam in the treatment of patients with complicated upper urinary tract infection (cUUTI) or acute pyelonephritis (AP) including in patients with concomitant bacteremia. IV fosfomycin was reported to be noninferior to piperacillin-tazobactam in treating patients with cUUTI and AP; however, when outcomes were independently evaluated according to baseline diagnosis (i.e., cUUTI versus AP), IV fosfomycin was superior to piperacillin-tazobactam in the treatment of patients with cUUTI and demonstrated superior microbiological eradication rates, across all resistant phenotypes including extended-spectrum β-lactamase- (ESBL-) producing Escherichia coli and Klebsiella spp. and carbapenem-resistant (CRE), aminoglycoside-resistant, and MDR Gram-negative bacilli (primarily Enterobacterales). Based on the ZEUS study, IV fosfomycin dosed at 6 grams every 8 hours for 7 days (14 days in patients with concurrent bacteremia) appears to be a safe and effective therapeutic option in treating patients with upper urinary tract infections, particularly those with cUUTI caused by antimicrobial-resistant Enterobacterales.

Project description:The rise in resistant Gram-negative pathogens continues to challenge clinicians treating infections. These resistant infections have inspired the development of new antimicrobial agents, including ceftolozane-tazobactam, a novel ?-lactam/?-lactamase inhibitor combination approved by the US Food and Drug Administration for the treatment of complicated urinary tract infections (cUTIs) and complicated intra-abdominal infections (cIAIs) in combination with metronidazole. Ceftolozane exhibits bactericidal activity by inhibiting penicillin-binding proteins (PBPs), with high affinity for PBP1b, PBP1c, and PBP3. The addition of tazobactam protects ceftolozane from hydrolysis by irreversibly binding to some ?-lactamase enzymes. Ceftolozane-tazobactam is active against a wide range of Gram-negative pathogens, including extended-spectrum ?-lactamase (ESBL)-producing Enterobacteriaceae and multidrug-resistant (MDR) Pseudomonas aeruginosa, several streptococcal species, and Bacteroides fragilis. When anaerobic coverage is needed, it should be used in combination with metronidazole. Ceftolozane demonstrates linear pharmacokinetics, low protein binding, and minimal accumulation with repeated dosing. The major pharmacokinetic/pharmacodynamic index for ceftolozane is the percentage of the dosing interval in which the plasma free drug concentration remains higher than the minimum inhibitory concentration (%T.MIC). Phase III clinical trials for the treatment of cUTIs and cIAIs have been completed, showing that it is an effective and safe alternative for the treatment of these infections. The approved dose for cUTIs and cIAIs is 1.5 g (1 g ceftolozane and 500 mg tazobactam) infused over 1 hour every 8 hours. A higher 3 g dose is currently in Phase III trials for the treatment of ventilated nosocomial pneumonia. Dosage adjustments are necessary for patients with moderate-to-severe renal impairment. Current data suggest that ceftolozane-tazobactam is a promising carbapenem-sparing alternative agent for the treatment of cUTIs and cIAIs, including those caused by ESBL-producing Enterobacteriaceae and MDR P. aeruginosa.

Dataset Information

Antimicrobial Susceptibility and Cross-Resistance Patterns among Common Complicated Urinary Tract Infections in U.S. Hospitals, 2013 to 2018.

Publications

Antimicrobial Susceptibility and Cross-Resistance Patterns among Common Complicated Urinary Tract Infections in U.S. Hospitals, 2013 to 2018.

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