- Faropenem resistance causes in vitro cross resistance to carbapenems in ESBL- producing Escherichia coli.
Faropenem resistance causes in vitro cross resistance to carbapenems in ESBL- producing Escherichia coli.
Int J Antimicrob Agents. 2020 Jan 16;:105902
Authors: Gandra S, Choi J, McElvania E, Green SJ, Harazin M, Thomson RB, Dantas G, Singh KS, Das S
OBJECTIVE: Faropenem is an oral penem drug with activity against facultative gram-positive and gram-negative bacteria including CTX-M-15 type extended spectrum beta-lactamase (ESBL)- producing Enterobacteriales and anaerobic bacteria. Due to structural similarities there is a concern for the development of carbapenem cross-resistance; however, there are no studies confirming this. We examined if in vitro development of faropenem resistance in Escherichia coli isolates would result in cross-resistance to carbapenems.
METHODS: Four well characterized E. coli isolates from the US Centers for Disease Control and Prevention antibiotic resistance isolate bank were utilized. Three isolates (NSF1, NSF2, NSF3) are ESBL producers (CTX-M-15) and one (NSF4) is pan-susceptible. Faropenem minimum inhibitory concentrations (MICs) were determined and resistance was induced by serial passaging in increasing concentrations of faropenem. Susceptibility to carbapenems was determined and whole genome sequencing (WGS) was performed to identify the underlying genetic mechanism leading to carbapenem resistance.
RESULTS: Faropenem MIC increased from 1mg/L to 64mg/L within 10 days for NSF2 and NSF4 isolates, and from 2 mg/L to 64 mg/L within 7 days for NSF1 and NSF3 isolates. Reduced carbapenem susceptibility (ertapenem MIC ≥8 mg/L, doripenem/meropenem ≥2 mg/L, imipenem ≥1 mg/L) developed among three CTX-M-15 producing isolates that were faropenem resistant, but not in NSF4 isolate that lacked ESBL enzyme. WGS analysis revealed non-synonymous changes in ompC gene among three CTX-M-15 producing isolates, and a single nucleotide polymorphism in envZ gene in NSF4 isolate.
CONCLUSION: Induced resistance to faropenem causes cross-resistance to carbapenems among E. coli isolates containing CTX-M-15 type ESBL enzymes.
PMID: 31954833 [PubMed - as supplied by publisher]
- In vitro activity of ceftolozane/tazobactam against phenotypically defined extended-spectrum β-lactamase (ESBL)-positive isolates of Escherichia coli and Klebsiella pneumoniae isolated from hospitalized patients (SMART 2016).
In vitro activity of ceftolozane/tazobactam against phenotypically defined extended-spectrum β-lactamase (ESBL)-positive isolates of Escherichia coli and Klebsiella pneumoniae isolated from hospitalized patients (SMART 2016).
Diagn Microbiol Infect Dis. 2019 Nov 15;:114925
Authors: Karlowsky JA, Kazmierczak KM, Young K, Motyl MR, Sahm DF
The Clinical and Laboratory Standards Institute (CLSI)-defined broth microdilution testing method (M07, 11th edition, 2018) was used to determine MICs for ceftolozane/tazobactam and eight comparator agents against 21,952 isolates of Enterobacteriaceae submitted by 161 clinical laboratories in 51 countries in 2016 as a part of the SMART global surveillance program. MICs were interpreted using CLSI breakpoints (M100 29th edition, 2019). 89.7% of isolates of Enterobacteriaceae were susceptible to ceftolozane/tazobactam, compared to 70.0%, 76.3%, 77.7%, 84.7%, 93.6%, and 96.4%, respectively, for ceftriaxone, ceftazidime, cefepime, piperacillin-tazobactam, ertapenem, and meropenem. 82.4% of isolates of ESBL-positive, carbapenemase-negative Enterobacteriaceae were susceptible to ceftolozane/tazobactam, compared to 1.5%, 7.8%, 20.3%, 71.1%, 94.7%, and 98.7%, respectively, for ceftriaxone, cefepime, ceftazidime, piperacillin-tazobactam, ertapenem, and meropenem. In vitro susceptibility to ceftolozane/tazobactam was >60% higher than susceptibility to other advanced-generation cephalosporins among all Enterobacteriaceae and >10% higher than susceptibility to piperacillin-tazobactam among ESBL-positive Enterobacteriaceae collected globally in 2016.
PMID: 31954597 [PubMed - as supplied by publisher]
- Citrobacter koseri causing osteomyelitis in a diabetic foot with concomitant acute gouty arthritis successfully treated with ertapenem.
Citrobacter koseri causing osteomyelitis in a diabetic foot with concomitant acute gouty arthritis successfully treated with ertapenem.
BMJ Case Rep. 2019 Jul 27;12(7):
Authors: Tinevez D, Knezevic NN
We present an elderly diabetic man with left hallux pain and drainage who was initially diagnosed with acute gouty arthritis using the diagnostic rule for acute gout and monosodium urate crystals presented on synovial fluid analysis. Further investigation with surgical debridement, plain X-ray, MRI and wound culture revealed concomitant Citrobacter koseri septic arthritis with osteomyelitis. C. koseri is considered an opportunistic infection that rarely causes musculoskeletal infections. Acute gouty arthritis and septic arthritis are rarely seen occurring concomitantly in the same joint and are often difficult to differentiate due to similar findings on exam and imaging. The present case illustrates that osteomyelitis with an opportunistic organism can present concomitantly with acute gouty arthritis, and the diagnosis of one should not exclude the other.
PMID: 31352398 [PubMed - in process]