Activity of fosfomycin and comparison of several susceptibility testing methods against contemporary urine isolates

Hirsch, Elizabeth B.; Raux, Brian R.; Zucchi, Paola C.; Kim, Yisu; McCoy, Christopher; Wright, Sharon B.; Eliopoulos, George M.

doi:10.1016/j.ijantimicag.2015.08.012

Cited by 63 publications

(65 citation statements)

References 16 publications

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“…A recent study found an overall fosfomycin [21]. Against 91 MDR or extended-spectrum beta-lactamase (ESBL)-confirmed uropathogens from the same isolate collection, fosfomycin was the most active (95% susceptibility) agent compared with 4 oral agents studied (nitrofurantoin, trimethoprim-sulfamethoxazole, ciprofloxacin, and ampicillin) [16].…”

Section: Fosfomycin Tromethaminementioning

confidence: 97%

“…Thus, clinicians need to either ask their microbiology laboratory for specific (disk diffusion) testing (which often results in a delay in receiving results) or use fosfomycin empirically based on existing susceptibility data. The latter approach can be reasonably successful for E. coli isolates (since most are susceptible, even among hospital isolates) but has to be done with caution when treating other gramnegative species since CLSI interpretive criteria exist only for E. coli and Enterococcus faecalis urine isolates [21,30]. Some epidemiologic data have suggested that susceptibility to routinely tested agents like ciprofloxacin or TMP-SMX can be used as a marker for likely susceptibility to fosfomycin, but it is not uniform [5].…”

Section: Fosfomycin Tromethaminementioning

confidence: 99%

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Clinical Management of an Increasing Threat: Outpatient Urinary Tract Infections Due to Multidrug-Resistant Uropathogens: Table 1.

et al. 2016

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Urinary tract infections (UTIs) are among the most commonly treated bacterial infections. Over the past decade, antimicrobial resistance has become an increasingly common factor in the management of outpatient UTIs. As treatment options for multidrugresistant (MDR) uropathogens are limited, clinicians need to be aware of specific clinical and epidemiological risk factors for these infections. Based on available literature, the activity of fosfomycin and nitrofurantoin remain high for most cases of MDR Escherichia coli UTIs. Trimethoprim-sulfamethoxazole retains clinical efficacy, but resistance rates are increasing internationally. Beta-lactam agents have the highest rates of resistance and lowest rates of clinical success. Fluoroquinolones have high resistance rates among MDR uropathogens and are being strongly discouraged as first-line agents for UTIs. In addition to accounting for local resistance rates, consideration of patient risk factors for resistance and pharmacological principles will help guide optimal empiric treatment of outpatient UTIs.

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Section: Fosfomycin Tromethaminementioning

confidence: 97%

Section: Fosfomycin Tromethaminementioning

confidence: 99%

Clinical Management of an Increasing Threat: Outpatient Urinary Tract Infections Due to Multidrug-Resistant Uropathogens: Table 1.

et al. 2016

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“…Notably, these isolates were collected from either hospitalized or ED patients; therefore, it could be presumed that a number of these isolates may have been responsible for complicated UTIs among this population. Recommended methods for fosfomycin susceptibility testing (agar dilution/disk diffusion) are time-consuming and limit its routine testing among clinical microbiology laboratories (10). Our data suggest that fosfomycin may be a useful agent for avoiding broad-spectrum intravenous treatment of UTI for patients with risk of MDR uropathogens.…”

mentioning

confidence: 91%

“…Consecutive, nonduplicate monomicrobial urine cultures of Enterobacteriaceae and Pseudomonas aeruginosa from hospitalized or emergency department (ED) patients were collected between August 2013 and January 2014 from the Beth Israel Deaconess Medical Center (BIDMC) clinical microbiology laboratory as previously described (10). All isolates were collected from unique patients, and those from non-ED outpatient locations were excluded.…”

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confidence: 99%

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Susceptibility of Multidrug-Resistant Gram-Negative Urine Isolates to Oral Antibiotics

Hirsch

Zucchi

Chen

et al. 2016

Antimicrob Agents Chemother

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cIncreasing resistance among Gram-negative uropathogens limits treatment options, and susceptibility data for multidrug-resistant isolates are limited. We assessed the activity of five oral agents against 91 multidrug-resistant Gram-negative urine isolates that were collected from emergency department/hospitalized patients. Fosfomycin and nitrofurantoin were most active (>75% susceptibility). Susceptibilities to sulfamethoxazole-trimethoprim, ciprofloxacin, and ampicillin were <40%; empirical use of these agents likely provides inadequate coverage in areas with a high prevalence of multidrug-resistant uropathogens. Multidrug resistance among Gram-negative bacilli that cause uncomplicated urinary tract infections (UTIs), such as Pseudomonas aeruginosa and Klebsiella pneumoniae, is increasing (1, 2). Such resistance significantly limits patient treatment options (3-6). There is a paucity of published data on current in vitro susceptibility profiles for multidrug-resistant (MDR) urine isolates (7,8). As UTIs are commonly treated in the outpatient setting with oral agents, knowledge of susceptibility patterns in MDR urinary pathogens is critical to guide empirical treatment (9). We therefore assessed the in vitro activity of five oral agents-fosfomycin, nitrofurantoin, sulfamethoxazole-trimethoprim, ciprofloxacin, and ampicillin-against 91 MDR Gram-negative urine isolates.(This research was presented in part at the 25th European Congress of Clinical Microbiology and Infectious Diseases, Copenhagen, Denmark, 25 to 28 April 2015.) Consecutive, nonduplicate monomicrobial urine cultures of Enterobacteriaceae and Pseudomonas aeruginosa from hospitalized or emergency department (ED) patients were collected between August 2013 and January 2014 from the Beth Israel Deaconess Medical Center (BIDMC) clinical microbiology laboratory as previously described (10). All isolates were collected from unique patients, and those from non-ED outpatient locations were excluded. Only MDR isolates, defined as nonsusceptible to Ն1 agent in at least 3 antibiotic classes, were assessed during the study period (11). BIDMC is a 649-bed level 1 trauma center and teaching hospital affiliated with Harvard Medical School. The study was approved by the Institutional Review Boards at BIDMC and Northeastern University.For further characterization of isolates meeting study criteria, those nonsusceptible to carbapenems and third/fourth-generation cephalosporins were screened for extended-spectrum ␤-lactamase (ESBL) production using double-disk testing with cefotaxime (30 g) and ceftazidime (30 g) alone and in combination with clavulanate (10 g) as recommended by the Clinical and Laboratory Standards Institute (CLSI) (12). Isolates that were nonsusceptible to carbapenems were screened for the presence of bla KPC and bla NDM by PCR and gene sequencing (13,14).Antibiotic susceptibility was determined by several methods. Fosfomycin and nitrofurantoin MICs were determined in duplicate on separate days by agar dilution as previously described (10). Ciprofl...

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Parenteral Fosfomycin for the Treatment of Multidrug Resistant Bacterial Infections: The Rise of the Epoxide

2019

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Fosfomycin was initially discovered in 1969 but has recently gained renewed interest for the treatment of multidrug‐resistant (MDR) bacterial infections, particularly in the United States. Its unique mechanism of action, bactericidal activity, broad spectrum of activity, and relatively safe and tolerable adverse effect profile make it a great addition to the dwindling antibiotic armamentarium. Fosfomycin contains a three‐membered epoxide ring with a direct carbon to phosphorous bond that bypasses the intermediate oxygen bond commonly present in other organophosphorous compounds; this structure makes the agent unique from other antibiotics. Despite nearly 50 years of parenteral fosfomycin use in Europe, fosfomycin has retained stable activity against most pathogens. Furthermore, fosfomycin demonstrated in vitro synergy in combination with other cell wall–active antibiotics (e.g., β‐lactams, daptomycin). These combinations may offer respite for severe infections due to MDR gram‐positive and gram‐negative bacteria. The intravenous (IV) formulation is currently under review in the United States, and apropos, this review collates more contemporary evidence (i.e., studies published between 2000 and early 2019) in anticipation of this development. The approval of IV fosfomycin provides another option for consideration in the management of MDR infections. Its unique structure will give rise to a promising epoxide epoch in the battle against MDR bacteria.

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Activity of fosfomycin and comparison of several susceptibility testing methods against contemporary urine isolates

Cited by 63 publications

References 16 publications

Clinical Management of an Increasing Threat: Outpatient Urinary Tract Infections Due to Multidrug-Resistant Uropathogens: Table 1.

Clinical Management of an Increasing Threat: Outpatient Urinary Tract Infections Due to Multidrug-Resistant Uropathogens: Table 1.

Susceptibility of Multidrug-Resistant Gram-Negative Urine Isolates to Oral Antibiotics

Parenteral Fosfomycin for the Treatment of Multidrug Resistant Bacterial Infections: The Rise of the Epoxide

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