scholarly journals Mechanisms of Resistance in Gram-Negative Urinary Pathogens: From Country-Specific Molecular Insights to Global Clinical Relevance

Diagnostics ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 800
Author(s):  
Branka Bedenić ◽  
Tomislav Meštrović
Keyword(s):  
Clinical Importance ◽  
Resistance Mechanisms ◽  
Bacterial Strains ◽  
Mechanisms Of Resistance ◽  
Gram Negative ◽  
Beta Lactamases ◽  
Resistance Determinants ◽  
Genes Encoding ◽  
Extended Spectrum Beta Lactamases ◽  
Tract Infections

Urinary tract infections (UTIs) are the most frequent hospital infections and among the most commonly observed community acquired infections. Alongside their clinical importance, they are notorious because the pathogens that cause them are prone to acquiring various resistance determinants, including extended-spectrum beta-lactamases (ESBL); plasmid-encoded AmpC β-lactamases (p-AmpC); carbapenemases belonging to class A, B, and D; qnr genes encoding reduced susceptibility to fluoroquinolones; as well as genes encoding enzymes that hydrolyse aminoglycosides. In Escherichia coli and Klebsiella pneumoniae, the dominant resistance mechanisms are ESBLs belonging to the CTX-M, TEM, and SHV families; p-AmpC; and (more recently) carbapenemases belonging to classes A, B, and D. Urinary Pseudomonas aeruginosa isolates harbour metallo-beta-lactamases (MBLs) and ESBLs belonging to PER and GES families, while carbapenemases of class D are found in urinary Acinetobacter baumannii isolates. The identification of resistance mechanisms in routine diagnostic practice is primarily based on phenotypic tests for the detection of beta-lactamases, such as the double-disk synergy test or Hodge test, while polymerase chain reaction (PCR) for the detection of resistance genes is mostly pursued in reference laboratories for research purposes. As the emergence of drug-resistant bacterial strains poses serious challenges in the management of UTIs, this review aimed to appraise mechanisms of resistance in relevant Gram-negative urinary pathogens, to provide a detailed map of resistance determinants in Croatia and the world, and to discuss the implications of these resistance traits on diagnostic approaches. We summarized a sundry of different resistance mechanisms among urinary isolates and showed how their prevalence highly depends on the local epidemiological context, highlighting the need for tailored interventions in the field of antimicrobial stewardship.

scholarly journals Cedecea lapagei An Extremely Rare Uropathogen: A Case Report and Review of the Literature

2021 ◽  
Author(s):  
Abdikarim Hussein Mohamed ◽  
Hussein Ali Mohamud
Keyword(s):  
Renal Failure ◽  
Case Report ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Beta Lactam ◽  
Gram Negative ◽  
Beta Lactamases ◽  
Extended Spectrum ◽  
Extended Spectrum Beta Lactamases ◽  
Tract Infections

Abstract Background: Gram-negative enterobacteria are the most common cause of urinary tract infections. Cedecea is a new separate genus in the family enterobacteriaceae, and it is a very rare pathogen that was primarily found in the respiratory tract. Cedecea lapagei is a very rare pathogen of urinary tract infections. To the best of our knowledge, this is the first case report in the world reported in English literature. Case presentation: A 55 years old man with chronic renal failure, poorly controlled diabetes mellitus, and hypertension presented with acute exacerbations of renal failure and irritative voiding symptoms. After stabilization and empirical antibiotic therapy with Ceftriaxone, the patient’s condition was not improved and deteriorated progressively. After the request of urine culture, the culture was isolated, an extremely rare uropathogen recently recognized by the Centers for Disease Control and Prevention (CDC); the Cedecea lapagei. Cedecea lapagei identification had been done using Eosin methylene blue agar (EMB). Gram-negative lipase positive bacteria with bacillus in shape, motile in nature that is non-spore-forming, and non-encapsulated enterobacteria with the final result of >100,000 colony-forming units per ml of Cedecea lapagei were isolated. Mueller-Hinton agar had been used to perform antimicrobial sensitivity and resistance. The pathogen was extensively resistant to the extended-spectrum beta-lactamases antibiotics and extended-spectrum beta-lactam inhibitors while carbapenems, fluoroquinolones, aminoglycosides, and Trimethoprim-sulfamethoxazole showed a higher sensitivity rate. Conclusion: The treatment of Cedecea lapagei infections represents a challenging issue due to its multi-drug resistant and extensive drug resistance patterns to a variety of antimicrobial classes, such as extended-spectrum beta-lactamases, cephalosporins, and beta-lactam inhibitors. Antimicrobial treatment should be aligned with the culture findings once available.

scholarly journals Extended Spectrem Beta Lactamases among Multi Drug Resistant Gram Negetive Bacilli Causing Urinry Tract Infection

2019 ◽  
Vol 5 (1) ◽  
pp. 25-28
Author(s):  
Ganga Sagar Bhattarai ◽  
Dipendra , Shrestha ◽  
Bishnu Raj Tiwari
Keyword(s):  
Urinary Tract ◽  
Tract Infection ◽  
Diffusion Method ◽  
Gram Negative ◽  
Beta Lactamases ◽  
Extended Spectrum ◽  
The Status ◽  
Extended Spectrum Beta Lactamases ◽  
Tract Infections ◽  
Esbl Producers

Extended Spectrum Beta Lactamases (ESBL), the main cause of resistance to broad spectrum β-lactams, among uropathogenic bacteria have increased over time raising a global concern in the therapeutic management of infections caused by these organisms. The study was carried out in Janamaitri Hospital, Kathmandu between December 2012 to May 2013 with an objective to determine the status of ESBL producing Gram negative bacilli isolated from the urine sample, collected from patients suspected of urinary tract infection. Gram negative bacilli isolated were tested for the presence of ESBL by combined disk and antibiotic susceptibility by Kirby Bauer disc diffusion method following Clinical and Laboratory Standard Institute guidelines. Among the total 1105 mid-stream urine samples, 256 Gram negative bacilli were isolated. By screening test using third generation cephalosporins, 156 isolates were screened as ESBL producers and 91 isolates were positive for ESBL test by combined disk method. Among the 91 (35.55%) ESBL producers, 70 (39.32%) Escherichia coli, 16 (44.44%) Klebsiella pneumoniae, and 5 (33.33%) Pseudomonas aeruginosa were found to be ESBL producers. Majority of ESBL producer showed resistance to ampicillin, co-trimoxazole, norfloxacin followed by ofloxacin. imipenem, amikacin and nitrofurantoin seemed to be the agent of choice for urinary tract infections when ESBL producers are susceptible to it. ESBL production found in these Gram negative bacilli with resultant microbial resistance to available cephalosporins and other agents may pose difficulties with the choice of therapeutic options for the treatment of severe infections. Keywords: UTI, Extended Spectrum Beta Lactamases, Gram negative bacilli

scholarly journals 1273. Activity of Ceftolozane/Tazobactam and Comparators Against Enterobacterales and P. aeruginosa Isolates from Pediatric Patients—SMART United States 2017-2019

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S725-S725
Author(s):  
Sibylle Lob ◽  
Meredith Hackel ◽  
C Andrew DeRyke ◽  
Kelly Harris ◽  
Katherine Young ◽  
...  
Keyword(s):  
United States ◽  
Pediatric Patients ◽  
Bloodstream Infections ◽  
The United States ◽  
Resistance Mechanisms ◽  
Surveillance Program ◽  
Independent Contractor ◽  
Gram Negative ◽  
Genes Encoding ◽  
Tract Infections

Abstract Background Ceftolozane/tazobactam (C/T) is an antipseudomonal cephalosporin combined with a β-lactamase inhibitor approved by FDA and EMA for complicated urinary tract (cUTI) and complicated intraabdominal infections (cIAI), as well as hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP) in patients ≥18 years. Clinical trials studying the use of C/T for pediatric patients with cUTI and cIAI are completed, and HABP/VABP pediatric studies are underway. We evaluated the antimicrobial activity of C/T against gram-negative isolates collected from patients ≤17 years in the United States (US) as part of the global SMART surveillance program. Methods In 2017-2019, 27 US clinical labs each collected up to 250 consecutive gram-negative pathogens per year. A total of 1336 isolates were collected from pediatric patients. MICs were determined using CLSI broth microdilution and breakpoints. C/T-nonsusceptible Enterobacterales (Ebact) and P. aeruginosa were screened for genes encoding β-lactamases. Results Among the 944 collected Ebact and 220 P. aeruginosa isolates, 40.7% and 76.4%, respectively, were collected from patients with respiratory tract infections, 37.0% and 10.0% from UTI, 13.7% and 8.2% from IAI, and 8.3% and 5.0% from bloodstream infections. The table shows antimicrobial susceptibility of Ebact, P. aeruginosa, and select phenotypes. C/T was active against 98% of Ebact, including 50 of 51 and 12 of 13 ESBL-non-CRE phenotype E. coli and K. pneumoniae, respectively. Among P. aeruginosa, C/T was active against 95% of isolates, 9-21 percentage points higher than the comparator β-lactams, and it maintained activity against 71-75% of P. aeruginosa isolates nonsusceptible to commonly used β-lactams. Among the 21 C/T-nonsusceptible Ebact, 2 isolates carried KPC and ESBL and 3 isolates carried only ESBL; in 16 isolates no β-lactamases were detected, of which 15 were species with intrinsic AmpC. Among 12 C/T-nonsusceptible P. aeruginosa, no acquired β-lactamases were detected, likely indicating chromosomally-mediated resistance mechanisms. Results Table Conclusion C/T could be a potential new treatment option for US pediatric patients with infections caused by Ebact and P. aeruginosa, including resistant phenotypes. Disclosures Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) C. Andrew DeRyke, PharmD, Merck & Co., Inc. (Employee, Shareholder) Kelly Harris, PharmD, BCPS, Merck & Co. Inc (Employee) Katherine Young, MS, Merck (Employee) Mary Motyl, PhD, Merck & Co., Inc. (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)

scholarly journals Quinolone resistance in different uropathogens isolated from urine cultures in patients with urinary tract infection

2020 ◽  
Author(s):  
Jorge Angel Almeida Villegas ◽  
Iris Mellolzy Estrada Carrillo ◽  
Rodolfo Garcia Contreras ◽  
Silvia Patricia Peña
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Urinary Tract Infections ◽  
Gram Positive ◽  
Gram Negative ◽  
Beta Lactamases ◽  
Extended Spectrum ◽  
Extended Spectrum Beta Lactamases ◽  
Tract Infections

AbstractObjectiveTo identify patterns of resistance against quinolones in various uropathogens in urinary tract infections in the population of the Toluca valley, MexicoIntroductionQuinolones are antibiotics with a spectrum of activity for both gram-positives and gram-negatives and are antibiotics used for the empirical treatment of urinary tract infections. Recently, a high index of resistance to quinolones has been reported due to different mechanisms on the part of bacteria, however the one that has taken the greatest importance is the presence of extended spectrum beta-lactamasesMethods155 samples were collected from patients with suspected urinary tract infection without exclusion criteria such as age or gender. Automated equipment was used for the identification of the etiological agent and sensitivity tests to quinolones.ResultsThe results positives were divided to evaluate which of the two antibiotics studied had greater resistance. For ciprofloxacin there are 27 resistant strains 37%, 1 strain with intermediate resistance 1% and 45 susceptible strains 62%. For levofloxacin 26 strains are resistant 36%, 41 strains are sensitive 56% and 6 strains show intermediate sensitivity 8%.ConclusionDifferent microorganisms, both gram-positive and gram-negative, were isolated and it can be observed that gram-negative strains are the ones with the greatest resistance against quinolones, mainly Escherichia coli, which produces extended-spectrum beta-lactamases, in the case of gram-positive resistance patterns are variable with a tendency towards sensitivity.

scholarly journals Evaluation of eazyplex® SuperBug CRE Test for Beta-Lactamase Genes Detection in Klebsiella spp. and P. aeruginosa Strains

2019 ◽  
Vol 77 (1) ◽  
pp. 99-103 ◽  
Author(s):  
Alicja Sękowska ◽  
Tomasz Bogiel ◽  
Eugenia Gospodarek-Komkowska
Keyword(s):  
Drug Resistance ◽  
Resistance Mechanisms ◽  
Multi Drug Resistance ◽  
Lamp Method ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Gram Negative ◽  
Beta Lactamases ◽  
Genes Encoding ◽  
Klebsiella Spp

AbstractThe multi-drug resistance of Gram-negative rods is one of the most important issues of present medicine. In recent years, more and more strains resistant to the majority or to all possible therapeutic options have been isolated—especially Klebsiella spp. and Pseudomonas spp. representatives. It is very important to detect strains with these phenotypes as quickly and reliably as possible. The aim of the study was to evaluate the usefulness of eazyplex® SuperBug CRE test (Amplex Diagnostics) for the detection of the most important beta-lactam resistance genes. eazyplex® SuperBug CRE test is based on the loop-mediated isothermal amplification (LAMP) method, and detects genes for the following beta-lactamases: KPC, NDM-1, VIM, OXA-48, CTX-M1, CTX-M9 and OXA-181. The study involved 87 strains. For all of the positive strains in the LAMP method, additional PCR were performed to increase the spectrum of ESBLs detected by the genes encoding for enzymes belonging to TEM and SHV families. The results obtained by the tested method and standard PCR were consistent for all Klebsiella spp. strains. The discrepancy between the evaluated test and PCR results was observed for one P. aeruginosa strain. The eazyplex® SuperBug CRE test can be used for quick detection of the most important beta-lactam resistance mechanisms amongst Gram-negative rods.

scholarly journals The evaluation of eazyplexÒ SuperBug CRE test usefulness for the detection of ESBLs and carbapenemases genes directly from urine samples and positive blood cultures

2021 ◽  
Author(s):  
Alicja Sękowska ◽  
Tomasz Bogiel
Keyword(s):  
Genetic Material ◽  
Modern Medicine ◽  
Blood Cultures ◽  
Urine Samples ◽  
Gram Negative ◽  
Beta Lactamases ◽  
Study Results ◽  
Genes Encoding ◽  
Extended Spectrum Beta Lactamases ◽  
Drug Resistant Strains

Abstract Background. An increasing antimicrobial resistance of Gram-negative rods is an important diagnostic, clinical and epidemiological problem of a modern medicine. Therefore, it is important to detect multi-drug resistant strains as quickly as possible. The aim of this study was to evaluate eazyplex® SuperBug CRE test for beta-lactamases genes detection among Gram-negative rods, directly from urine samples and positive blood cultures. Methods. Eazyplex® SuperBug CRE test is based on isothermal amplification of a genetic material and allows for the detection of a selection genes encoding carbapenemases, i.e. KPC, NDM, VIM, OXA-48, OXA-181 and extended-spectrum beta-lactamases from the CTX-M-1 and CTX-M-9 groups. A total of 120 clinical specimens were included in the study. Results. The test gave valid results for 58 (96.7%) urine samples and 57 (95.0%) positive blood cultures. ESBL and/or carbapenemase enzymes genes were detected in 56 urine and 55 blood samples, respectively. Conclusions. Eazyplex® SuperBug CRE test can be used for a rapid detection of the most important genes encoded for resistance to beta-lactams in Gram-negative rods also without the necessity of bacterial culture.

scholarly journals Antibiotic Resistance of Uropathogens Isolated from Patients Hospitalized in District Hospital in Central Poland in 2020

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 447
Author(s):  
Barbara Kot ◽  
Agata Grużewska ◽  
Piotr Szweda ◽  
Jolanta Wicha ◽  
Urszula Parulska
Keyword(s):  
Antibiotic Resistance ◽  
Multidrug Resistant ◽  
Diffusion Method ◽  
Disk Diffusion Method ◽  
Beta Lactamases ◽  
E Coli ◽  
Central Poland ◽  
Resistance Patterns ◽  
Extended Spectrum Beta Lactamases ◽  
Tract Infections

The aim of this study was to determine antibiotic resistance patterns and the prevalence of uropathogenes causing urinary tract infections (UTIs) in patients hospitalized in January–June 2020 in central Poland. Antimicrobial susceptibility testing was performed using the disk-diffusion method. Escherichia coli (52.2%), Klebsiella pneumoniae (13.7%), Enterococcus faecalis (9.3%), E. faecium (6.2%), and Proteus mirabilis (4,3%) were most commonly isolated from urine samples. E. coli was significantly more frequent in women (58.6%) (p = 0.0089) and in the age group 0–18, while K. pneumoniae was more frequent in men (24.4%) (p = 0.0119) and in individuals aged 40–60 and >60. Gram-negative species showed resistance to ampicillin. K. pneumoniae were resistant to amoxicillin plus clavulanic acid (75.0%), piperacillin plus tazobactam (76.2%), cefotaxime (76.2%), cefuroxime (81.0%), ciprofloxacin (81.0%), and trimethoprim plus sulphamethoxazole (81.0%). Carbapenems were effective against all E. coli and P. mirabilis. Some K. pneumoniae (13.6%) produced metallo-β-lactamases (MBLs). E. coli (22.6%), K. pneumoniae (81.8%), and all E. faecium were multidrug-resistant (MDR). Some E. coli (26.2%), K. pneumoniae (63.6%), and P. mirabilis (14.3%) isolates produced extended-spectrum beta-lactamases (ESBL). Vancomycin-resistant E. faecium was also found. This study showed that the possibilities of UTIs therapy using available antibiotics become limited due to the increasing number of antibiotic-resistant uropathogens.

scholarly journals Resistance Mechanisms of Multiresistant Pseudomonas aeruginosa Strains from Germany and Correlation with Hypermutation

2007 ◽  
Vol 51 (11) ◽  
pp. 4062-4070 ◽  
Author(s):  
B. Henrichfreise ◽  
I. Wiegand ◽  
W. Pfister ◽  
B. Wiedemann
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Efflux Pump ◽  
Acquired Resistance ◽  
Resistance Mechanisms ◽  
Type Ii ◽  
Mechanisms Of Resistance ◽  
Resistance Determinants ◽  
Class 1 ◽  
Mutator Strains ◽  
Multiresistant Strains

ABSTRACT In this study, we analyzed the mechanisms of multiresistance for 22 clinical multiresistant and clonally different Pseudomonas aeruginosa strains from Germany. Twelve and 10 strains originated from cystic fibrosis (CF) and non-CF patients, respectively. Overproduction of the efflux systems MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM was studied. Furthermore, loss of OprD, alterations in type II topoisomerases, AmpC overproduction, and the presence of 25 acquired resistance determinants were investigated. The presence of a hypermutation phenotype was also taken into account. Besides modifications in GyrA (91%), the most frequent mechanisms of resistance were MexXY-OprM overproduction (82%), OprD loss (82%), and AmpC overproduction (73%). Clear differences between strains from CF and non-CF patients were found: numerous genes coding for aminoglycoside-modifying enzymes and located, partially in combination with β-lactamase genes, in class 1 integrons were found only in strains from non-CF patients. Furthermore, multiple modifications in type II topoisomerases conferring high quinolone resistance levels and overexpression of MexAB-OprM were exclusively detected in multiresistant strains from non-CF patients. Correlations of the detected phenotypes and resistance mechanisms revealed a great impact of efflux pump overproduction on multiresistance in P. aeruginosa. Confirming previous studies, we found that additional, unknown chromosomally mediated resistance mechanisms remain to be determined. In our study, 11 out of 12 strains and 3 out of 10 strains from CF patients and non-CF patients, respectively, were hypermutable. This extremely high proportion of mutator strains should be taken into consideration for the treatment of multiresistant P. aeruginosa.

scholarly journals Prevalence Of Extended Spectrum Beta-Lactamases (ESBLs)-Producing Escherichia Coli Isolated From UTI Patients Attending some Selected Hospitals In Minna, Nigeria

2021 ◽  
Vol 37 (2) ◽  
pp. 56-73
Author(s):  
F Iseghohi ◽  
J.C Igwe ◽  
M Galadima ◽  
A.F Kuta ◽  
A.M Abdullahi ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Multidrug Resistance ◽  
Urine Samples ◽  
Antibiotics Resistance ◽  
Healthy Individuals ◽  
Beta Lactamases ◽  
E Coli ◽  
Extended Spectrum ◽  
Extended Spectrum Beta Lactamases ◽  
Tract Infections

Globally, urinary tract infections are one of the most common infections in need of urgent clinical attention. The prevalence of extended spectrum beta-lactamases (ESBL)- producing Escherichia coli isolated from urine samples of some UTI patients and s of apparently healthy individuals in Minna, Nigeria, is investigated. Standard microbiological techniques were used to conduct this study. A total of 170 catch midstream urine samples submitted to the Medical Microbiology Laboratories of 4 different hospitals (and samples from healthy individuals) were randomly collected for 5 months and examined for microbial growths. Female patients (65.9%) submitted more urine samples for UTI test than their male counterpart (34.1%). The age ranges of 21 -30 (26.5%) and 31 - 40 (25.3%) had the highest percentages of infection rate while those within the ages 1- 10 (3.5%) and ≥ 71 (2.3%) were the least infected. This study observed a prevalence of 23.5% of E. coli in Minna metropolis and a significant number (30%) of healthy individuals (HI) was observed to harbor the E. coli in their urine. The isolates were highly susceptible to Gentamicin (65%), Ofloxacin (65%), Tetracycline (62.5%), Cotrimoxazole (62.5%), and Streptomycin (57.5%). Mildly susceptible to Pefloxacin (37.5%), Chloramphenicol (37.5%), and Ciprofloxacin (35%). There were significant resistance to most of the beta-lactames tested [Cefuroxime (80%), Amoxicillin (42.5%), Augmentin (40), Cefotaxime (20%) and Ceftaxidime (7.5%)]. Two of the isolates were resistant to all the 13 antibiotics tested; 70% (28) of the isolates had multiple antibiotics resistance index (MARI) ≥0.3. Multidrug resistance was expressed in 37.5% of the isolates tested. The study showed a vast resistant pool in the environment. Only 25% of the E. coli isolated from the urine samples produced beta-lactamases phenotypically, most of which expressed resistance to more than 5 of the antibiotics tested and had MARI of ≥ 0.5. Further evaluation showed that 25% (10/40) of the E. coli isolated from the UTI patients in Minna, Nigeria, were ESBL- producers and could harbor one or two of the genes. TEM gene was expressed in 70% (7) of the isolates that produced ESBL phenotypically, 60% 6) harbored CTXM gene, 20% (2) had the OXA gene while none of the bacteria harbored the SHV gene. The study established a 5.9% ESBL prevalence among the E. coli isolated from UTI in the environment studied. This study established that E. coli is one of the prevalent bacteri urea majorly isolated from UTI patients in Minna. The prevalent E. coli are multidrug resistant and could harbor more than one ESBL gene . keywords: Escherichia coli, Minna, UTI, ESBL, Multidrug resistance

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