- Impact of a Standardized Beta-Lactam Allergy Questionnaire on Aztreonam Use. [Journal Article]
- JPJ Pharm Pract 2018 Jan 01; :897190018758557
- CONCLUSIONS: Utilization of a standardized beta-lactam allergy questionnaire as a pharmacy education tool resulted in a statistically significant decrease in aztreonam utilization, based on doses, days of therapy, and de-escalations.
- Resistance Pattern and Detection of Metallo-beta-lactamase Genes in Clinical Isolates ofPseudomonas aeruginosain a Central Nigeria Tertiary Hospital. [Journal Article]
- NJNiger J Clin Pract 2018; 21(2):176-182
- CONCLUSIONS: The prevalence of MBL-producing strains of P. aeruginosa which poses serious challenge for therapeutics and infection control is currently low in Abuja, North Central, Nigeria. Therefore, rational use of the carbapenems and other antipseudomonal antibiotics, regular surveillance and adequate infection control measures should be instituted to limit further spread.
- Prevalence of Metallo-β-lactamase Producing Non-fermentative Pseudomonas Species from Clinical Isolates in Dhaka, Bangladesh. [Journal Article]
- MMMymensingh Med J 2018; 27(1):89-94
- Antimicrobial drug resistance, a global concern, has been increasing unpredictably in microorganism causing human infections specially among Gram negative non-fermenting Pseudomonas spp. Carbapenems,...
Antimicrobial drug resistance, a global concern, has been increasing unpredictably in microorganism causing human infections specially among Gram negative non-fermenting Pseudomonas spp. Carbapenems, a beta lactam antibiotics, are the most potent and effective drug usually kept reserved for treating the multi-drug resistant Psedomonas spp and other infections caused by organisms producing Extended Spectrum Beta Lactamase (ESBL) and AmpC. Clinical utility of carbapenem will reduce when resistant bacteria evolve due to production of carbapenem hydrolyzing Metallo-β-lactamase (MBL) which confers high-level resistance to all beta-lactam antibiotics except aztreonam. The various reports on the prevalence of MBLs are available from many countries but few from Bangladesh. We investigated the prevalence of MBL production in these Pseudomonads obtained from clinical sources in an uraban setting in Dhaka, Bangladesh. A total of 29,136 specimens were processed for culture from January 2011 and December 2015 from non duplicated patients attending diagnostic unit of icddr,b from different settings of Bangladesh. The specimens included urine 14,323; blood 11,378; other body fluid 2,487; sputum 535 and tracheal aspirate 413. All specimens were processed for culture following standard bacteriological methods and the Pseudomonas spp were identified following defined standard biochemical procedures. Metallo-β-lactamase (MBL) was determined by EDTA disk synergy (EDS) test. Antimicrobial susceptibility test was performed by disk diffusion method and susceptibility pattern was interpreted and reported following Clinical Laboratory Standard Institute (CLSI) guideline. From 29,136 specimens a total of 2,340(8%) were isolated and identified as Pseudomonas spp. Of the identified Pseudomonas spp, 238(57.6%) were from tracheal aspirate, 216(40.4%) from sputum, 902(36.7%) from other body fluids, 463(4.1%) from blood and 521(3.6%) from urine samples. From 2,340 Pseudomonas spp, by selective sampling, imipenem-meropenem resistant and intermediate susceptible 100 strains were tested for MBL production and 92 were found positive. Tracheal aspirate showed 38%, other body fluids 30%, Urine 17%, sputum 4% and blood 3% MBL production respectively. Irrespective of the sources of specimens, Pseudomonas spp showed 71% resistance to cefixime, 70% to ceftriaxone, 64% to gentamicin, 56% to piperecillin+tazobactam, 50% to ciprofloxacin, 49% to amikacin, 46% to netilmicin, 45% to ceftazidime, 30% to meropenem, 26% to imipenem and 19% to polymyxin B. As multi-drug resistant Pseudomonas showed high level of (92%) MBL production, so MBL detection testing facility may be a useful battery to determine MDR producing Pseudomonas from clinical isolates.
- Study of pandrug and heavy metal resistance among E. coli from anthropogenically influenced Delhi stretch of river Yamuna. [Journal Article]
- BJBraz J Microbiol 2018 Feb 12
- Escalating burden of antibiotic resistance that has reached new heights present a grave concern to mankind. As the problem is no longer confined to clinics, we hereby report identification of a pandr...
Escalating burden of antibiotic resistance that has reached new heights present a grave concern to mankind. As the problem is no longer confined to clinics, we hereby report identification of a pandrug resistant Escherichia coli isolate from heavily polluted Delhi stretch of river Yamuna, India. E. coli MRC11 was found sensitive only to tobramycin against 21 antibiotics tested, with minimum inhibitory concentration values >256μg/mL for amoxicillin, carbenicillin, aztreonam, ceftazidime and cefotaxime. Addition of certain heavy metals at higher concentrations were ineffective in increasing susceptibility of E. coli MRC11 to antibiotics. Withstanding sub-optimal concentration of cefotaxime (10μg/mL) and mercuric chloride (2μg/mL), and also resistance to their combinatorial use, indicates better adaptability in heavily polluted environment through clustering and expression of resistance genes. Interestingly, E. coli MRC11 harbours two different variants of blaTEM (blaTEM-116 and blaTEM-1 with and without extended-spectrum activity, respectively), in addition to mer operon (merB, merP and merT) genes. Studies employing conjugation, confirmed localization of blaTEM-116, merP and merT genes on the conjugative plasmid. Understanding potentialities of such isolates will help in determining risk factors attributing pandrug resistance and strengthening strategic development of new and effective antimicrobial agents.
- Treatment of Infections Caused by Extended-Spectrum-Beta-Lactamase-, AmpC-, and Carbapenemase-Producing Enterobacteriaceae. [Review]
- CMClin Microbiol Rev 2018; 31(2)
- Therapy of invasive infections due to multidrug-resistantEnterobacteriaceae(MDR-E) is challenging, and some of the few active drugs are not available in many countries. For extended-spectrum β-lactam...
Therapy of invasive infections due to multidrug-resistantEnterobacteriaceae(MDR-E) is challenging, and some of the few active drugs are not available in many countries. For extended-spectrum β-lactamase and AmpC producers, carbapenems are the drugs of choice, but alternatives are needed because the rate of carbapenem resistance is rising. Potential active drugs include classic and newer β-lactam-β-lactamase inhibitor combinations, cephamycins, temocillin, aminoglycosides, tigecycline, fosfomycin, and, rarely, fluoroquinolones or trimethoprim-sulfamethoxazole. These drugs might be considered in some specific situations. AmpC producers are resistant to cephamycins, but cefepime is an option. In the case of carbapenemase-producingEnterobacteriaceae(CPE), only some "second-line" drugs, such as polymyxins, tigecycline, aminoglycosides, and fosfomycin, may be active; double carbapenems can also be considered in specific situations. Combination therapy is associated with better outcomes for high-risk patients, such as those in septic shock or with pneumonia. Ceftazidime-avibactam was recently approved and is active against KPC and OXA-48 producers; the available experience is scarce but promising, although development of resistance is a concern. New drugs active against some CPE isolates are in different stages of development, including meropenem-vaborbactam, imipenem-relebactam, plazomicin, cefiderocol, eravacycline, and aztreonam-avibactam. Overall, therapy of MDR-E infection must be individualized according to the susceptibility profile, type, and severity of infection and the features of the patient.
- Probing the Mechanism of Inactivation of the FOX-4 Cephamycinase by Avibactam. [Journal Article]
- AAAntimicrob Agents Chemother 2018 Feb 12
- Ceftazidime-avibactam is a "second generation" β-lactam-β-lactamase inhibitor combination that is effective against Enterobacteriaceae expressing class A extended-spectrum β-lactamases, class A carba...
Ceftazidime-avibactam is a "second generation" β-lactam-β-lactamase inhibitor combination that is effective against Enterobacteriaceae expressing class A extended-spectrum β-lactamases, class A carbapenemases and/or class C cephalosporinases. Knowledge of the interactions of avibactam, a diazabicyclooctane with different β-lactamases is required to anticipate future resistance threats. FOX family β-lactamases possess unique hydrolytic properties with a broadened substrate profile to include cephamycins, partly as a result of an isoleucine at position 346, instead of the conserved asparagine found in most AmpCs. Interestingly, a single amino acid substitution at N346 in theCitrobacterAmpC is implicated in resistance to the aztreonam-avibactam combination. In order to understand how diverse active site topologies affect avibactam inhibition, we tested a panel of clinical Enterobacteriaceae isolates producingblaFOXusing ceftazidime-avibactam, determined the biochemical parameters for inhibition using the FOX-4 variant, and probed the atomic structure of avibactam with FOX-4. Avibactam restored susceptibility to ceftazidime for most isolates producingblaFOX; two isolates expressingblaFOX-4orblaFOX-5displayed an MIC of 16 μg/mL for the combination. FOX-4 possessed ak2/Kvalue of 1,800 ± 100 M-1s-1and akoffof 0.0013 ± 0.0003 s-1Mass spectrometry showed that the FOX-4-avibactam complex was stable for 24 hr. Analysis of the crystal structure of FOX-4 with avibactam at a 1.5 Å resolution revealed a unique characteristic of this AmpC β-lactamase. Unlike in the PDC-1 avibactam crystal structure, interactions (e.g., hydrogen bonding) between avibactam and position I346 in FOX-4 are not evident. Furthermore, another residue is not observed to be close enough to compensate for the loss of these critical hydrogen bonding interactions. This observation supports findings from the inhibition analysis of FOX-4; FOX-4 possessed the highestKdvalue (1,600 nM) for avibactam compared to other AmpCs (7-660 nM). Medicinal chemists must consider the properties of extended-spectrum AmpCs, such as the FOX β-lactamases for the design of future diazabicyclooctanes.
- Targeting the nonmevalonate pathway inBurkholderia cenocepaciaincreases susceptibility to certain β-lactam antibiotics. [Journal Article]
- AAAntimicrob Agents Chemother 2018 Feb 12
- The non-mevalonate pathway is the sole pathway for isoprenoid biosynthesis inBurkholderia cenocepaciaand possibly a novel target for the development of antibacterial chemotherapy. The goal of the pre...
The non-mevalonate pathway is the sole pathway for isoprenoid biosynthesis inBurkholderia cenocepaciaand possibly a novel target for the development of antibacterial chemotherapy. The goal of the present study was to evaluate the essentiality ofdxr, the second gene of the non-mevalonate pathway, inB. cenocepaciaand to determine whether interfering with the non-mevalonate increases susceptibility towards antibiotics. To this end, a rhamnose-inducible conditionaldxrknock-down mutant ofB. cenocepaciaK56-2 (B. cenocepaciaK56-2dxr) was constructed, by using a plasmid which enables the delivery of a rhamnose-inducible promotor in the chromosome. Expression ofdxris essential for bacterial growth; this growth defect could be complemented by expressingdxr in transunder control of a constitutive promotor, but not by providing 2-C-methyl-D-erythritol-4-phosphate, the reaction product of DXR.B. cenocepaciaK56-2dxrshowed markedly increased susceptibility to the β-lactam antibiotics aztreonam, ceftazidime and cefotaxime, while susceptibility to other antibiotics was not (or much less) affected, and also this increased susceptibility could be complemented byin transexpression ofdxrA similar increased susceptibility was observed when antibiotics were combined with FR900098, a known DXR inhibitor. Our data confirm that the non-mevalonate pathway is essential inB. cenocepaciaand suggest that combining potent DXR inhibitors with selected β-lactam antibiotics is a useful strategy to combatB. cenocepaciainfections.
- Analysis of Potential β-Lactam Surrogates to PredictIn VitroSusceptibility and Resistance to Ceftaroline for Clinical Isolates ofEnterobacteriaceae. [Journal Article]
- JCJ Clin Microbiol 2018 Feb 07
- Ceftaroline fosamil was approved by the United States Food and Drug Administration in 2010 and by the European Medicines Agency in 2012. As of April 2017, only one commercial antimicrobial susceptibi...
Ceftaroline fosamil was approved by the United States Food and Drug Administration in 2010 and by the European Medicines Agency in 2012. As of April 2017, only one commercial antimicrobial susceptibility testing device offered a gram-negative panel that included ceftaroline. This circumstance is unfortunate as many clinical microbiology laboratories rely solely on commercial devices to generatein vitroantimicrobial susceptibility testing results for common bacterial pathogens. In lieu of device-based testing of clinical isolates ofEnterobacteriaceae, laboratories wishing to test ceftaroline must opt for either disk diffusion testing or use a gradient strip, however, both alternatives interrupt laboratory workflow and require additional labor and expense. Identification of a reliable surrogate β-lactam to predictin vitrosusceptibility to ceftaroline may offer another interim solution as laboratories await availability of ceftaroline for testing on their commercial device. We tested six β-lactams (aztreonam, ceftazidime, ceftriaxone, cefotaxime, cefoxitin, and cefpodoxime) as potential surrogates for ceftaroline against a collection of 543 clinical isolates ofEnterobacteriaceaeselected to approximate the distribution of ceftaroline MICs observed in AWARE global surveillance studies conducted in 2013. All six potential surrogates generated very major error rates of 16.3 to 56.6%, far exceeding the accepted limit of 1.5% set by the Clinical and Laboratory Standards Institute (CLSI) and the United States Food and Drug Administration (FDA) Center for Devices and Radiological Health. Failure to identify a reliable surrogate to predictin vitrosusceptibility and resistance to ceftaroline for clinical isolates ofEnterobacteriaceaeunderscores the need for expedited addition of newer antimicrobial agents to commercial antimicrobial susceptibility testing devices.
- Etiology and antimicrobial resistance patterns in pediatrics with urinary tract infections. [Journal Article]
- PIPediatr Int 2018 Feb 02
- CONCLUSIONS: There is high antibiotic resistance in hospitalized children with UTIs. Susceptibility testing should be carried out on all clinical isolates, and the empirical antibiotic treatment should be altered accordingly. This article is protected by copyright. All rights reserved.
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- Saudi plants as a source of potential β-lactamase inhibitors. [Journal Article]
- PJPak J Pharm Sci 2018; 31(1(Suppl.)):325-332
- This study was performed to assess the potential β-lactamase inhibitory properties of nineteen crude Saudi plant extracts belonging to eight families against extended spectrum β-lactamase (ESβL) stra...
This study was performed to assess the potential β-lactamase inhibitory properties of nineteen crude Saudi plant extracts belonging to eight families against extended spectrum β-lactamase (ESβL) strains of Klebsiella pneumoniae and other medically important pathogens. A total of 276 microbial isolates of pathogenic bacteria were used in this study; only 15 of them showed decreased sensitivity to one or several of ceftazidime, aztreonam, cefotaxime or ceftriaxone, which are deemed to be possible producers of ESβL. Antibacterial activities of plant extracts were carried out against ESβL positive isolates by the disc diffusion method. The potential ESβL suppressing activities of plant extracts and prepared fractions, (chloroform and methanol), with or without antibiotic were studied by disc diffusion method. Results revealed that selected plant extracts showed no antibacterial activity against tested strains; meanwhile, only Echinops viscosus, Pulicaria arabica, Tephrosia nubica, Chrozophora oblongifolia, and Clutia myricoides showed pronounced ESβL inhibitory activities. The extracts were quantified for phenolic compounds and their antioxidant properties. Bio-guided fractionation of the active extracts revealed that the chloroform fraction of C. myricoides possess a promising ESβL inhibitory activity. The separation and the structural elucidation of the active compounds from C. myricoides will offer beneficial leads for developing β-lactamase inhibitors.