scholarly journals 1445. Antimicrobial Activity of Novel β-Lactamase Inhibitor Combinations Tested against Organisms Causing Complicated Urinary Tract Infections in United States Medical Centers

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S527-S528
Author(s):  
Helio S Sader ◽  
Cecilia G Carvalhaes ◽  
Dee Shortridge ◽  
Michael D Huband

Abstract Background High-dose extended-infusion cefepime-tazobactam (FEP-TAZ) is in clinical development at 2g/2g q8 hours administered over 90 minutes. We evaluated the potency and spectrum of activity of FEP-TAZ, ceftolozane–tazobactam (C-T), ceftazidime–avibactam (CAZ-AVI), and comparators tested against gram-negative bacilli (GNB) causing complicated urinary tract infections (cUTIs) in United States (US) hospitals. Methods In 2018, 3,023 GNBisolates (1/patient) were consecutively collected and susceptibility tested against FEP-TAZ (TAZ at fixed 8 mg/L) and comparators by reference broth microdilution methods. Percentage of isolates inhibited at ≤8 mg/L (CLSI, cefepime high dose) and at ≤16 mg/L (pharmacokinetic/pharmacodynamic [PK/PD] susceptible [S] breakpoint based on extended infusion and high dosage) were evaluated. Results FEP-TAZ (99.9% inhibited at ≤16 mg/L; Table), CAZ-AVI (99.9%S), and meropenem (MEM; 99.5%S) were the most active agents against Enterobacterales (ENT). An ESBL phenotype (CLSI criteria) was observed in 12.5%, 12.9%, and 3.6% of E. coli (EC), K. pneumoniae (KPN), and P. mirabilis (PM), respectively. FEP-TAZ and CAZ-AVI exhibited complete activity against EC, whereas C-T and piperacillin–tazobactam (PIP-TAZ) were active against 91.5% and 88.1% of ESBL-phenotype EC isolates, respectively. The most active agents against KPN were FEP-TAZ (99.6% inhibited at ≤16 mg/L), CAZ-AVI (100.0%S), and amikacin (AMK; 99.4%S). All PM isolates were S to FEP-TAZ (highest MIC, 0.12 mg/L), C-T, CAZ-AVI, MEM, PIP-TAZ and AMK. FEP-TAZ was highly active against E. cloacae (n = 94; MIC90, 0.5 mg/L; 98.9% inhibited at ≤16 mg/L) and Citrobacter spp. (n = 91; MIC90, 0.12 mg/L; highest MIC, 0.5 mg/L). Against P. aeruginosa (PSA), FEP-TAZ inhibited 97.6% of isolates at ≤16 mg/L, with spectrum of activity similar to CAZ-AVI (96.4%S), C-T (99.4%S) and AMK (97.6%S), and greater than MEM (85.5%S) and PIP-TAZ (87.3%S). Conclusion FEP-TAZ showed potent activity against ENT and PSA isolated in US hospitals in 2018, with overall spectrum (ENT + PSA) similar to CAZ-AVI and greater than C-T, PIP-TAZ, and MEM when FEP-TAZ proposed PK/PD S breakpoint of ≤16 mg/L was applied. FEP-TAZ may represent a valuable option for treating cUTIs caused by resistant GNB. Disclosures All authors: No reported disclosures.

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S823-S823
Author(s):  
Kendra Foster ◽  
Linnea A Polgreen ◽  
Brett Faine ◽  
Philip M Polgreen

Abstract Background Urinary tract infections (UTIs) are one of the most common bacterial infections. There is a lack of large epidemiologic studies evaluating the etiologies of UTIs in the United States. This study aimed to determine the prevalence of different UTI-causing organisms and their antimicrobial susceptibility profiles among patients being treated in a hospital setting. Methods We used the Premier Healthcare Database. Patients with a primary diagnosis code of cystitis, pyelonephritis, or urinary tract infection and had a urine culture from 2009- 2018 were included in the study. Both inpatients and patients who were only treated in the emergency department (ED) were included. We calculated descriptive statistics for uropathogens and their susceptibilities. Multi-drug-resistant pathogens are defined as pathogens resistant to 3 or more antibiotics. Resistance patterns are also described for specific drug classes, like resistance to fluoroquinolones. We also evaluated antibiotic use in this patient population and how antibiotic use varied during the hospitalization. Results There were 640,285 individuals who met the inclusion criteria. Females make up 82% of the study population and 45% were age 65 or older. The most common uropathogen was Escherichia Coli (64.9%) followed by Klebsiella pneumoniae (8.3%), and Proteus mirabilis (5.7%). 22.2% of patients were infected with a multi-drug-resistant pathogen. We found that E. Coli was multi-drug resistant 23.8% of the time; Klebsiella pneumoniae was multi-drug resistant 7.4%; and Proteus mirabilis was multi-drug resistant 2.8%. The most common antibiotics prescribed were ceftriaxone, levofloxacin, and ciprofloxacin. Among patients that were prescribed ceftriaxone, 31.7% of them switched to a different antibiotic during their hospitalization. Patients that were prescribed levofloxacin and ciprofloxacin switched to a different antibiotic 42.8% and 41.5% of the time, respectively. Conclusion E. Coli showed significant multidrug resistance in this population of UTI patients that were hospitalized or treated within the ED, and antibiotic switching is common. Disclosures All Authors: No reported disclosures


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S305-S305
Author(s):  
Michael D Huband ◽  
Michael A Pfaller ◽  
Jennifer M Streit ◽  
Helio S Sader ◽  
Robert K Flamm

Abstract Background Omadacycline (OMC) was FDA approved to treat acute bacterial skin and skin structure infection (ABSSSI) and community-acquired bacterial pneumonia (CABP) for indicated organisms in 2018. Phase 2 OMC clinical trials for uncomplicated urinary tract infection (uUTI; NCT03425396) and acute pyelonephritis (NCT03757234) are ongoing. OMC is active against bacterial isolates expressing common tetracycline, penicillin, fluoroquinolone, and macrolide resistance mechanisms. Methods Isolates (14,000) were collected in 2018 from 31 medical centers located in the United States and 38 medical centers in Europe, including 3,458 staphylococci, 1,551 streptococci, 746 enterococci, 574 Haemophilus spp., and 5,690 Enterobacterales isolates. One isolate per patient infection episode was tested. Identifications were confirmed by MALDI-TOF MS and susceptibility testing was performed using CLSI broth microdilution methods. Results OMC (MIC50/90, 0.12/0.25 mg/L) was highly active against S. aureus isolates from skin and skin structure infection (SSSI; 99.3% susceptible [S]) including MRSA (97.7%S) and MSSA (99.9%S) (table). Similarly, OMC demonstrated potent activity against S. aureus isolates from respiratory tract infection (RTI; MIC50/90, 0.12/0.25 mg/L) including MSSA (98.2%S). All S. lugdunensis isolates from SSSI were S (100.0%) to OMC. All Streptococcus anginosus group (100.0%) and 97.6% of S. pyogenes isolates from SSSI were S to OMC as were 98.0% of S. pneumoniae from RTI. No streptococci were resistant (R) to OMC. OMC (MIC50/90 0.12/0.25 mg/L) had potent activity against E. faecalis isolates from SSSI (99.0%S). OMC S against E. cloacae and K. pneumoniae isolates from SSSI was 92.1% S and 89.4% S, respectively. Similarly, 86.2% of K. pneumoniae isolates from RTI were S to OMC. Susceptibility of H. influenzae isolates from RTI to OMC was 99.8%S (no isolates were R). ≥90.0% of E. coli (MIC50/90, 1/2 mg/L) and K. pneumoniae (MIC50/90, 2/4 mg/L) UTI isolates were inhibited by ≤4 mg/L of OMC. Conclusion OMC was highly active against bacterial pathogens associated with ABSSSI, CABP, and UTI including staphylococci (97.7%-100.0%S), streptococci (97.6%-100.0%S), E. faecalis (99.0%S). E. cloacae (92.1%S), K. pneumoniae (86.2%-89.4%S), and E. coli. Disclosures All authors: No reported disclosures.


2020 ◽  
Vol 41 (S1) ◽  
pp. s182-s183
Author(s):  
Larissa Grigoryan ◽  
Melanie Goebel ◽  
Samuel Willis ◽  
Lisa Danek ◽  
Jennifer Matas ◽  
...  

Background: Outpatients with uncomplicated urinary tract infections (UTIs) are often treated empirically without culture, whereas urine cultures are typically collected from patients with complicated UTI. Susceptibilities for fosfomycin (a first-line agent) are not routinely performed or reported in the antibiogram. Understanding the prevalence of antibiotic resistance for UTI is critical for empiric treatment and antibiotic stewardship in primary care. Methods: We developed a UTI-focused antibiogram from a prospective sample of outpatients (women and men) with UTIs from 2 public family medicine clinics in an urban area with a diverse, international population (November 2018 to present). During the study period, providers ordered a urine culture for any adult patient presenting with UTI symptoms, including uncomplicated and complicated infections. We estimated the prevalence of resistance to UTI-relevant antibiotics in the overall study population and compared it between patients born in the United States and other countries. Results: We collected 678 urine cultures from 644 unique patients (79% female). Of these cultures, 158 (23.3%) had no growth, 330 (48.7%) grew mixed urogenital flora, and 190 (28.0%) were positive (>10,000 CFU/mL). Patients with positive cultures were mostly female (88.2%), and their mean age was 46.6 ± 14.8 years. Among patients with positive cultures, 42.7% were born in the United States and 57.3% were born Mexico or Central America. Escherichia coli was the most commonly isolated organism (Fig. 1). Susceptibility results for E. coli and all gram-negative organisms combined are presented in Fig. 2. Susceptibility of uropathogens to TMP-SMX was significantly higher in patients born in the United States compared to patients from Mexico or Central America (82% vs 61%; P = .03). Susceptibility to ciprofloxacin was similar in patients born in the United States and other countries (79% vs 72%; P = .50). Of 77 E. coli isolates, 11 (14%) were positive for extended-spectrum β-lactamase production, including 8 isolates from patients whose country of origin was Mexico or a Central American country. Conclusions: More than 20% of outpatients presenting with UTI symptoms had a negative urine culture. Among outpatients with uncomplicated and complicated UTI, uropathogens had a high prevalence of resistance to ciprofloxacin and TMP-SMX, but susceptibility to fosfomycin (restricted in our system) was 100%. Resistance rates for TMP-SMX were higher in patients from Mexico and Central America. Our findings question whether TMP-SMX should remain a first-line agent in US primary-care settings.Funding: This project was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number UM1AI104681.Disclosures: None


2018 ◽  
pp. 100-108
Author(s):  
Dinh Khanh Le ◽  
Dinh Dam Le ◽  
Khoa Hung Nguyen ◽  
Xuan My Nguyen ◽  
Minh Nhat Vo ◽  
...  

Objectives: To investigate clinical characteristics, bacterial characteristics, drug resistance status in patients with urinary tract infections treated at Department of Urology, Hue University Hospital. Materials and Method: The study was conducted in 474 patients with urological disease treated at Department of Urology, Hue Universiry Hospital from July 2017 to April 2018. Urine culture was done in the patients with urine > 25 Leu/ul who have symptoms of urinary tract disease or infection symptoms. Patients with positive urine cultures were analyzed for clinical and bacterial characteristics. Results: 187/474 (39.5%) patients had symptoms associated with urinary tract infections. 85/474 (17.9%) patients were diagnosed with urinary tract infection. The positive urine culture rate was 45.5%. Symptoms of UTI were varied, and no prominent symptoms. E. coli accounts for the highest proportion (46.67%), followed by, Staphycoccus aureus (10.67%), Pseudomonas aeruginsa (8,0%), Streptococcus faecali and Proteus (2.67%). ESBL - producing E. coli was 69.23%, ESBL producing Enterobacter spp was 33.33%. Gram-negative bacteria are susceptible to meropenem, imipenem, amikacin while gram positive are vancomycin-sensitive. Conclusions: Clinical manifestations of urinary tract infections varied and its typical symptoms are unclear. E.coli is a common bacterium (46.67%). Isolated bacteria have a high rate of resistance to some common antibiotics especially the third generation cephalosporins and quinolones. Most bacteria are resistant to multiple antibiotics at the same time. Gram (+) bacteria are susceptible to vancomycin, and gram (-) bacteria are susceptible to cefoxitin, amikacin, and carbapenem. Key words: urinary tract infection


2021 ◽  
Vol 11 (9) ◽  
pp. 4315
Author(s):  
Emanuel Vamanu ◽  
Laura Dorina Dinu ◽  
Cristina Mihaela Luntraru ◽  
Alexandru Suciu

Bioactive compounds and phenolic compounds are viable alternatives to antibiotics in recurrent urinary tract infections. This study aimed to use a natural functional product, based on the bioactive compounds’ composition, to inhibit the uropathogenic strains of Escherichia coli. E. coli ATCC 25922 was used to characterize the IVCM (new in vitro catheterization model). As support for reducing bacterial proliferation, the cytotoxicity against a strain of Candida albicans was also determined (over 75% at 1 mg/mL). The results were correlated with the analysis of the distribution of biologically active compounds (trans-ferulic acid-268.44 ± 0.001 mg/100 g extract and an equal quantity of Trans-p-coumaric acid and rosmarinic acid). A pronounced inhibitory effect against the uropathogenic strain E. coli 317 (4 log copy no./mL after 72 h) was determined. The results showed a targeted response to the product for tested bacterial strains. The importance of research resulted from the easy and fast characterization of the functional product with antimicrobial effect against uropathogenic strains of E. coli. This study demonstrated that the proposed in vitro model was a valuable tool for assessing urinary tract infections with E. coli.


Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1348
Author(s):  
Lívia Slobodníková ◽  
Barbora Markusková ◽  
Michal Kajsík ◽  
Michal Andrezál ◽  
Marek Straka ◽  
...  

Urinary tract infections (UTIs) are among the events that most frequently need medical intervention. Uropathogenic Escherichia coli are frequently their causative agents and the infections are sometimes complicated by the presence of polyresistant nosocomial strains. Phage therapy is a tool that has good prospects for the treatment of these infections. In the present study, we isolated and characterized two bacteriophages with broad host specificity against a panel of local uropathogenic E. coli strains and combined them into a phage cocktail. According to genome sequencing, these phages were closely related and belonged to the Tequatrovirus genus. The newly isolated phages showed very good activity on a panel of local clinical E. coli strains from urinary tract infections. In the form of a two-phage cocktail, they were active on E. coli strains belonging to phylogroups B2 and D, with relatively lower activity in B1 and no response in phylogroup A. Our study is a preliminary step toward the establishment of a national phage bank containing local, well-characterized phages with therapeutic potential for patients in Slovakia.


mBio ◽  
2014 ◽  
Vol 5 (2) ◽  
Author(s):  
Dana Willner ◽  
Serene Low ◽  
Jason A. Steen ◽  
Narelle George ◽  
Graeme R. Nimmo ◽  
...  

ABSTRACTUrinary tract infections (UTIs) are one of the most commonly acquired bacterial infections in humans, and uropathogenicEscherichia colistrains are responsible for over 80% of all cases. The standard method for identification of uropathogens in clinical laboratories is cultivation, primarily using solid growth media under aerobic conditions, coupled with morphological and biochemical tests of typically a single isolate colony. However, these methods detect only culturable microorganisms, and characterization is phenotypic in nature. Here, we explored the genotypic identity of communities in acute uncomplicated UTIs from 50 individuals by using culture-independent amplicon pyrosequencing and whole-genome and metagenomic shotgun sequencing. Genus-level characterization of the UTI communities was achieved using the 16S rRNA gene (V8 region). Overall UTI community richness was very low in comparison to other human microbiomes. We strain-typedEscherichia-dominated UTIs using amplicon pyrosequencing of the fimbrial adhesin gene,fimH. There were nine highly abundantfimHtypes, and each UTI sample was dominated by a single type. Molecular analysis of the corresponding clinical isolates revealed that in the majority of cases the isolate was representative of the dominant taxon in the community at both the genus and the strain level. Shotgun sequencing was performed on a subset of eightE. coliurine UTI and isolate pairs. The majority of UTI microbial metagenomic sequences mapped to isolate genomes, confirming the results obtained using phylogenetic markers. We conclude that for the majority of acute uncomplicatedE. coli-mediated UTIs, single cultured isolates are diagnostic of the infection.IMPORTANCEIn clinical practice, the diagnosis and treatment of acute uncomplicated urinary tract infection (UTI) are based on analysis of a single bacterial isolate cultured from urine, and it is assumed that this isolate represents the dominant UTI pathogen. However, these methods detect only culturable bacteria, and the existence of multiple pathogens as well as strain diversity within a single infection is not examined. Here, we explored bacteria present in acute uncomplicated UTIs using culture-independent sequence-based methods.Escherichia coliwas the most common organism identified, and analysis ofE. colidominant UTI samples and their paired clinical isolates revealed that in the majority of infections the cultured isolate was representative of the dominant taxon at both the genus and the strain level. Our data demonstrate that in most cases single cultured isolates are diagnostic of UTI and are consistent with the notion of bottlenecks that limit strain diversity during UTI pathogenesis.


2011 ◽  
Vol 32 (8) ◽  
pp. 748-756 ◽  
Author(s):  
Deron C. Burton ◽  
Jonathan R. Edwards ◽  
Arjun Srinivasan ◽  
Scott K. Fridkin ◽  
Carolyn V. Gould

Background.Over the past 2 decades, multiple interventions have been developed to prevent catheter-associated urinary tract infections (CAUTIs). The CAUTI prevention guidelines of the Healthcare Infection Control Practices Advisory Committee were recently revised.Objective.To examine changes in rates of CAUTI events in adult intensive care units (ICUs) in the United States from 1990 through 2007.Methods.Data were reported to the Centers for Disease Control and Prevention (CDC) through the National Nosocomial Infections Surveillance System from 1990 through 2004 and the National Healthcare Safety Network from 2006 through 2007. Infection preventionists in participating hospitals used standard methods to identify all CAUTI events (categorized as symptomatic urinary tract infection [SUTI] or asymptomatic bacteriuria [ASB]) and urinary catheter–days (UC-days) in months selected for surveillance. Data from all facilities were aggregated to calculate pooled mean annual SUTI and ASB rates (in events per 1,000 UC-days) by ICU type. Poisson regression was used to estimate percent changes in rates over time.Results.Overall, 36,282 SUTIs and 22,973 ASB episodes were reported from 367 facilities representing 1,223 adult ICUs, including combined medical/surgical (505), medical (212), surgical (224), coronary (173), and cardiothoracic (109) ICUs. All ICU types experienced significant declines of 19%–67% in SUTI rates and 29%–72% in ASB rates from 1990 through 2007. Between 2000 and 2007, significant reductions in SUTI rates occurred in all ICU types except cardiothoracic ICUs.Conclusions.Since 1990, CAUTI rates have declined significantly in all major adult ICU types in facilities reporting to the CDC. Further efforts are needed to assess prevention strategies that might have led to these decreases and to implement new CAUTI prevention guidelines.


2021 ◽  
Vol 17 (1) ◽  
pp. 119-129
Author(s):  
R.H. Bello ◽  
Y.K.E. Ibrahim ◽  
B.O. Olayinka ◽  
A.A.G. Jimoh ◽  
N.B. Afolabi-Balogun ◽  
...  

Background: The emergence of multidrug- resistance Enterobacteriaceae especially in E. coli bacteria  associated with Urinary Tract Infections (UTIs) in pregnancy is a serious menace globally posing health challenges and confounding successful empirical treatment as well as increasing pregnancy – related  complications.Objectives: The aim of this study is to determine the phenotypic and genotypic characteristics of Extended Spectrum Beta – Lactamases (ESBLs) producing E. coli (ESBLs – EC) isolates in pregnant women attending ante – natal clinics within Ilorin - Kwara State, Nigeria.Materials and methods: A total of 53 non - repeated E. coli isolates from urine samples of pregnant women were presumptively identified using standard bacteriological method and confirmed by commercially available Microgen® Identification Kits. Phenotypic detection of ESBLs was determined using antibiotics susceptibility test and double disc synergy Method for screening and confirmation respectively. Polymerase Chain Reaction (PCR) was further used for the genotypic detection of ESBLs genes.Results: A total 88.67% (47/53) of E. coli exhibited resistance to the cephalosporins of which aztreonam was the highest (75.47%) and the least was cefpodoxime (35.84%) while 85.10% were confirmed positive for ESBL production. The genotypic detection showed the most occurring genotype was blaTEM (50%) blaOXA (27.7%), blaGES (22.5%), blaSHV (15%), blaCTXM and blaVEB (7.5%) while sixty – four (64%) of isolates co – harbored two or more gene. BlaTEM and blaOXA were dominant.Conclusion: This study showed high resistance of E. coli to the third generation cephalosporins harboring different ESBL genes which increases UTIs complexity and limit therapeutic options in pregnancy. Therefore, continuous monitoring of resistance in E. coli, effective appraisal of antibiotic control policies and rational use of antibiotics is therefore encouraged.


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