Diversity And Antibiograms of Secondary Bacterial Isolates From Cutaneous Leishmaniasis Wounds

Background: Leishmaniasis is a vector borne disease caused by an intracellular protozoan parasite. The presence of secondary bacterial infections in cutaneous leishmaniasis wounds exacerbate lesion development and could lead to delay in the healing process. Little is also known about the different bacteria species co-infecting leishmaniasis wounds and their sensitivity patterns in Ghana. This study sought to determine the resistance patterns of bacteria co-infecting cutaneous leishmaniasis wounds from selected communities in the Nkwanta district.Methods: Various bacteria were isolated and characterized from exudates obtained from wound swabs collected with sterile cotton tipped applicators. Confirmation of bacterial identity was done using the analytical profile index and the matrix-assisted laser desorption/ionization time of flight mass spectrometry. Antibiotic susceptibility tests were performed using agar disc diffusion method according to the Clinical and Laboratory Standards Institute breakpoint values.Results: A total of 42 secondary bacteria were isolated from the wounds among which S. aureus was the most predominant (31%). Other pathogenic bacteria that colonized the wounds included Bacillus subtilis (23.8%), Pantoea spp(11.9%), Klebsiella pneumoniea (7.1%), Enterobacter cloacae (7.1%), Aeromonas spp (4.8%), Serratia marcescens (4.8%),Serratia liquefacien (2.4%), Serratia plymutheca (2.4%), Providencia rettgeri (2.4%) and Cronobacter spp (2.4%). Majority of the isolates were obtained from Agoufie (21.4%), Baasare (19%), and Gekrong (16.7%). Most of the isolates were resistant to beta-lactam antibiotics and the third generation cephalosporin. Notably, 84.6% of the S. aureus isolates were methicillin and ciprofloxacin resistant whilst 92.3% were resistant to ampicllin. About sixty-nine percent (69.2%) showed intermediate susceptibility to Erythromycin. Additionally, S. plymutheca was resistant to all the test antibiotics. All the K. pneumoniae and E. cloacae isolates showed resistance to ampicillin, cefotaxime, ceftriaxone, ciprofloxacin, amikacin, aztreonam and meropenem but only 66.7% of these isolates were resistant to piperacillin. All isolates of Providencia rettgeri, Cronobacter spp, S. marcescen, S. liquefacien were resistant to all the beta-lactam antibiotics.Conclusion: This study suggests colonization of cutaneous leishmaniasis wounds with varied bacterial species that are mostly resistant to beta-lactam group of antibiotics.

The Ultra-Broad-Spectrum Beta-lactamase Inhibitor QPX7728 Restores the Potency of Multiple Oral Beta-lactam Antibiotics against Beta-lactamase Producing Strains of Resistant Enterobacterales

QPX7728 is a cyclic boronate ultra-broad-spectrum beta-lactamase inhibitor, with potent activity against both serine and metallo beta-lactamases. QPX7728 can be delivered systemically by the IV or oral route of administration. Oral β-lactam antibiotics alone or in combination with QPX7728 were evaluated for 1) sensitivity to hydrolysis by various common beta-lactamases and inhibition of hydrolysis by QPX7728; 2) the impact of non-beta-lactamase-mediated resistance mechanisms on potency of beta-lactams; and 3) in vitro activity against a panel of clinical strains producing diverse beta-lactamases. The carbapenem tebipenem had stability for many serine beta-lactamases from all molecular classes followed by cephalosporin ceftibuten. Addition of QPX7728 to tebipenem, ceftibuten and mecillinam completely reversed beta-lactamase-mediated resistance in cloned beta-lactamases from serine and metallo enzyme classes; the degree of potentiation of other beta-lactams varied according to the beta-lactamase produced. Tebipenem, ceftibuten and cefixime had the lowest MICs against laboratory strains with various combinations of beta-lactamases and the intrinsic drug-resistance mechanisms of porin and efflux mutations. There was a high degree of correlation between potency of various combinations against cloned beta-lactamases and efflux/porin mutants and the activity against clinical isolates, showing the importance of both inhibition of beta-lactamase along with minimal impact of general intrinsic resistance mechanisms affecting the beta-lactam. Tebipenem and ceftibuten appeared to be the best beta-lactam antibiotics when combined with QPX7728 for activity against Enterobacterales that produce serine or metallo beta-lactamases.

The Pharmacokinetics of Beta-Lactam Antibiotics Using Scavenged Samples in Pediatric Intensive Care Patients: The EXPAT Kids Study Protocol

Background: Emerging evidence supports the importance of optimized antibiotic exposure in pediatric intensive care unit (PICU) patients. Traditional antibiotic dosing is not designed for PICU patients, as the extreme pharmacokinetic (PK) behavior of drugs threatens the achievement of optimal antibiotic treatment outcomes. Scavenged sampling is a sampling strategy which may have positive implications for routine TDM and PK research, as well as monitoring other biomarkers. EXPAT Kids study was designed to analyze whether current empiric dosing regimens of frequently used beta-lactam antibiotics achieve defined therapeutic target concentrations in PICU patients.Methods: A mono-centre, exploratory pharmacokinetic and pharmacodynamic study was designed to assess target attainment of beta-lactam antibiotics. One hundred forty patients will be included within 24 months after start of inclusion. At various time points serum concentration of the study antibiotic (cefotaxime, ceftazidime, ceftriaxone, cefuroxime, flucloxacillin, and meropenem) are determined. In parallel with these sampling moments, residual material is collected to validate the use of blood of scavenged heparinized astrup syringes for the quantification of antibiotic exposure. The primary outcome is the time that the free (unbound) concentration of the study antibiotic remains above one to four the minimal inhibitory concentration during a dosing interval (100%ƒT > MIC and 100%ƒT>4xMIC). Other included outcomes are disease severity, safety, length of stay, and inflammatory biomarkers.Discussion: Potentially, scavenged sampling may enrich the EXPAT Kids dataset, and reduce additional blood sampling and workload for clinical personnel. The findings from the EXPAT Kids study will lead to new insights in the PK parameters of beta-lactams and consecutive effects on target attainment and clinical outcomes. Is there a need for more precision in dosing? Netherlands Trial Register Number: Trial NL9326.

Erratum: E. A. Sokova et al., Risk factors and characteristics of adverse reactions associated with the use of beta-lactam antibiotics in older patients

Sоkоvа Е.А., Arkhipov V.V., Demidova O.A., Mazerkina I.A., Alexandrova T.V., Zhuravleva M.V. Risk factors and characteristics of adverse reactions associated with the use of beta-lactam antibiotics in older patients. Bezopasnost’ i risk farma koterapii = Safety and Risk of Pharmacotherapy. 2021;9(3):128–135. https://doi.org/10.30895/2312-7821-2021-9-3-128-135Dear readers, a technical error was made on page 134, issue 3 of the Safety and Risk of Pharmacotherapy, 2021 (2021;9(3):128–135). The following statement:“Acknowledgements. The study reported in this publication was carried out as part of a publicly funded research project No. 056-00005-21-00 and was supported by the Scientific Centre for Expert Evaluation of Medicinal Products (R&D public accounting No. 121021800098-4)”should read:“Acknowledgements. The study reported in this publication was carried out as part of a publicly funded research project No. 056-00005-21-00 and was supported by the Scientific Centre for Expert Evaluation of Medicinal Products (R&D public accounting No. 121022000154-2)”.The correction did not have any effect on the conclusions made by the authors.The text of the online version of the journal was corrected accordingly.

Conceptual model of adding antibiotics to dialysate fluid during renal replacement therapy

Studies have shown significant variability in antibiotic trough concentrations in critically ill patients receiving renal replacement therapy (RRT). The purpose of this study was to assess whether adding beta-lactam antibiotics to dialysate solution can maintain stable antibiotic concentrations during RRT in experimental conditions. A single compartment model reflecting the patient was constructed and connected to the RRT machine. Dialysate fluid was prepared in three different concentrations of meropenem (0 mg/L; 16 mg/L; 64 mg/L). For each dialysate concentration various combinations of dialysate and blood flow rates were tested by taking different samples. Meropenem concentration in all samples was calculated using spectrophotometry method. Constructed experimental model results suggest that decrease in blood meropenem concentration can be up to 35.6%. Moreover, experimental data showed that antibiotic loss during RRT can be minimized and stable plasma antibiotic concentration can be achieved with the use of a 16 mg/L Meropenem dialysate solution. Furthermore, increasing meropenem concentration up to 64 mg/L is associated with an increase antibiotic concentration up to 18.7–78.8%. Administration of antibiotics to dialysate solutions may be an effective method of ensuring a constant concentration of antibiotics in the blood of critically ill patients receiving RRT.

Beta-lactam antibiotics and extended spectrum beta-lactamases

Extended spectrum beta-lactamases (ESBLs) are enzymes produced by bacteria, mostly members of the family Enterobacteriaceae commonly Escherichia coli and Klebsiella pneumoniae. ESBLs hydrolyze the beta-lactam ring of beta-lactam antibiotics making these antibiotics ineffective therefore rendering the bacteria resistance against beta-lactam antibiotics. The global upsurge of ESBLs producing bacteria causing both hospital and community acquired infections mostly urinary tract infections, pneumonia and bloodstream infections, threatens the effectiveness of infectious diseases treatment. ESBL families; TEM, SHV and CTX-M are globally disseminated and frequently detected in clinical isolates as well as colonization and contamination isolates. Various laboratory detection methods of ESBLs producing Gram negative bacteria are available. These methods; phenotypic methods, automated methods and molecular-based methods are varying in sensitivity and specificity, need of technical expertise, and rapidness. Therefore, they should be clearly understood before being employed for routine or research use for detection of ESBLs production among Enterobacteriaceae. In addition, understanding the mode of action and mechanisms of resistance to beta-lactam antibiotics, and the epidemiology of ESBLs producing bacteria is of paramount.

Investigation of blaKPC and blaNDM genes in enterobacteriaceae received in a public health laboratory

Introduction: KPC and NDM carbapenemases production is an important enzymatic mechanism of resistance to carbapenens in bacteria belonging to the Enterobacteriaceae family. These enzymes degrade virtually all beta-lactam antibiotics and are encoded by the blaKPC and blaNDM genes, which can be in mobile genetic elements such as plasmids and transposons. Objectives: This study evaluated the positivity rate of the presence of blaKPC and blaNDM genes in carbapenem-resistant enterobacteria received at the Instituto Adolfo Lutz (IAL) of São José do Rio Preto, Brazil and determined the epidemiological data related to the patients whose isolates were recovered. Methods: From June 2015 to April 2019, bacterial isolates were obtained from different hospitals located in five municipalities in São José do Rio Preto region. In the bacteriology and molecular biology laboratory, DNA extraction and real-time PCR were performed to investigate the blaKPC and blaNDM genes. Afterwards, epidemiological data were surveyed such as the municipality of origin, age, and gender of the patients whose bacterial isolates were recovered. Results: A total of 934 enterobacteria isolates were recovered from the different hospitals. Of these; 93.4% were positive for blaKPC, with 96.3%, 1.85%, and 1.85% of the isolates belonged to the Klebsiella genus, Enterobacter genus, and Escherichia coli species, respectively. Also, 52.5% and 84.4% of the isolates were obtained from women and elderly patients, respectively. The blaNDM gene was detected only in three isolates, two of which originated from surveillance cultures. Conclusion: Therefore, KPC-producing enterobacteria are widespread in all health units of the five municipalities that were studied, suggesting that the blaKPC-carrying Klebsiella sp. isolates may be endemic in these institutions. Additionally, there is a significant role of surveillance cultures in preventing the spread of resistance genes, as observed for blaNDM in this study.

First Global Report of Plasmid-Mediated mcr-1 and Extended-Spectrum Beta-Lactamase-Producing Escherichia coli from Sheep in Portugal

Resistances to extended-spectrum cephalosporins (ESC) and colistin are One Health issues since genes encoding these resistances can be transmitted between all sectors of the One Health concept, i.e., human, animal, and the environment. Among food-producing animals, sheep farming has long been overlooked. To fill in this knowledge gap, we looked for ESC- and colistin resistance in 21 faecal samples collected from sheep in one farm in the south of Portugal. ESC-resistant isolates were selected on MacConkey agar plates supplemented with cefotaxime. Susceptibility testing was performed by the disk-diffusion method according to CLSI, while colistin MIC was determined by broth microdilution. ESC- and colistin-resistance genes were identified by PCR, and the clonality of all isolates was assessed by XbaI-PFGE. The replicon content was determined by PCR according to the PCR-based replicon typing (PBRT) scheme. Sixty-two non-duplicate ESC-resistant E. coli isolates were identified, which all presented an extended-spectrum beta-lactamase (ESBL) phenotype, mostly due to the presence of CTX-M genes. One CTX-M-1-producing E. coli was concomitantly colistin-resistant and presented the plasmid-mediated mcr-1 gene. Nearly all isolates showed associated resistances to non-beta-lactam antibiotics, which could act as co-selectors, even in the absence of beta-lactam use. The results showed a high proportion of ESBL-producing E. coli in sheep faeces. Their dissemination was very dynamic, with the spread of successful clones between animals, but also a large diversity of clones and plasmids, sometimes residing in the same animal. This study highlights the need for global surveillance in all food-producing sectors, in order to avoid the dissemination of genes conferring resistance to last-resort antibiotics in human medicine.