Systematic Review of Plasmid AmpC Type Resistances in Escherichia coli and Klebsiella pneumoniae and Preliminary Proposal of a Simplified Screening Method for ampC

Abstract

Beta-lactamase (BL) production is a major public health problem. Although not the most frequent AmpC type, AmpC-BL is increasingly isolated, especially plasmid AmpC-BL (pAmpC-BL). The objective of this study was to review information published to date on pAmpC-BL in Escherichia coli and Klebsiella pneumoniae, and on the epidemiology and detection methods used by clinical microbiology laboratories, by performing a systematic review using the MEDLINE PubMed database. The predictive capacity of a screening method to detect AmpC-BL using disks with cloxacillin (CLX) was also evaluated by studying 102 Enterobacteriaceae clinical isolates grown in CHROMID ESBL medium with the addition of cefepime (FEP), cefoxitin (FOX), ertapenem (ETP), CLX, and oxacillin with CLX. The review, which included 149 publications, suggests that certain risk factors (prolonged hospitalization and previous use of cephalosporins) are associated with infections by pAmpC-BL-producing microorganisms. The worldwide prevalence has increased over the past 10 years, with a positivity rate ranging between 0.1 and 40%, although AmpC was only detected when sought in a targeted manner. CMY-2 type has been the most prevalent pAmpC-BL-producing microorganism. The most frequently used phenotypic method has been the double-disk synergy test (using CLX disks or phenyl-boronic acid and cefotaxime [CTX] and ceftazidime) and the disk method combined with these inhibitors. In regard to screening methods, a 1-µg oxacillin disk with CLX showed 88.9% sensitivity, 100% specificity, 100% positive predictive value (PPV), 98.9% negative predictive value (NPV), and 98.9% validity index (VI). This predictive capacity is reduced with the addition of extended-spectrum beta-lactamases, showing 62.5% sensitivity, 100% specificity, 100% PPV, 93.5% NPV, and 94.1% VI. In conclusion, there has been a worldwide increase in the number of isolates with pAmpC-BL, especially in Asia, with CMY-2 being the most frequently detected pAmpC-BL-producing type of microorganism. Reduction in its spread requires routine screening with a combination of phenotypic methods (with AmpC inhibitors) and genotypic methods (multiplex PCR). In conclusion, the proposed screening technique is an easy-to-apply and inexpensive test for the detection of AmpC-producing isolates in the routine screening of multidrug-resistant microorganisms.

Prevalence and distribution of ampc beta-lactamase producing escherichia coli and klebsiella pneumoniae isolates obtained from urine samples at a tertiary care hospital in the caribbean

“…Cefoxitin screening however helps to eliminate unnecessary tests which is important for resource limited settings. Thus far, there are several confirmatory phenotypic tests for detection including Disc Potentiation Test, Double Disc Synergy Test, AmpC Disc Test, Disc Approximation Test (DAT), along with the incorporation of inhibitors such as boronic acid or cloxacillin ( Rodríguez-Guerrero et al., 2022 ). The cefoxitin screened isolates in our study underwent DAT and four had inconclusive results.…”

“…A recent systematic review identified an increase in the worldwide prevalence of pAmpC BLs in the Gram negative organisms Escherichia coli and Klebsiella pneumoniae over the past ten years ( Rodríguez-Guerrero et al., 2022 ). However data from the Caribbean was not represented in this study ( Rodríguez-Guerrero et al., 2022 ).…”

“…A recent systematic review identified an increase in the worldwide prevalence of pAmpC BLs in the Gram negative organisms Escherichia coli and Klebsiella pneumoniae over the past ten years ( Rodríguez-Guerrero et al., 2022 ). However data from the Caribbean was not represented in this study ( Rodríguez-Guerrero et al., 2022 ). In a study commissioned among the Caribbean Public Health Agency member countries, AmpC BL genes were detected among the included isolates and the authors suggested a need for further studies to determine the prevalence of this mechanism of resistance in the region, as well as its effect on carbapenem sensitivity ( Heinz et al., 2019 ).…”

Analysis of Extended Spectrum Beta Lactamase Frequency in Klebsiella spp Isolates

“…Previous treatment with third-generation cephalosporins was the only independent risk factor (p=0.008). A similar study found the use of antibiotics containing oxyimino ring for K. pneumoniae strains as a risk factor for ESBL production [25,26]. According to one view, the reason for the differences in terms of risk factors in other studies, as in our study, is; The retrospective character of the study is seen as insufficient number of patients, lack of consensus in distinguishing colonization from real infection, insufficient data on antibiotic use of patients before admission to hospital or infection, and isolates were collected only from certain services [27].…”

Antibiotic Resistances of Enterobacteriaceae with Chromosomal Ampc in Urine Cultures: Review and Experience of a Spanish Hospital

“…However, there is increasing interest in a group of Enterobacteriaceae responsible for 10% of nosocomial and community UTIs, known as the CESPM group ( Citrobacter freundii , Klebsiella aerogenes , Enterobacter cloacae , Serratia marcescens , Providencia stuartii , and Morganella morganii ). They are characterized by naturally producing chromosomal AmpC-inducible beta-lactamases [ 6 , 7 , 8 ], unlike Enterobacteriaceae which produce plasmid-origin AmpC beta-lactamases, for which various diagnostic methods are available [ 9 ].…”