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Journal of Global Antimicrobial... Jun 2024Hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKp) poses a significant threat to public health. This study reports an infection related to hv-CRKp in a...
OBJECTIVES
Hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKp) poses a significant threat to public health. This study reports an infection related to hv-CRKp in a premature infant and reveals its colistin resistance and evolutionary mechanisms within the host.
METHODS
Three KPC-producing CRKp strains were isolated from a patient with sepsis and CRKp osteoarthritis who had been receiving colistin antimicrobial therapy. The minimum inhibitory concentrations (MICs) of Ceftazidime,Ceftazidime-Avibactam(CAZ-AVI),Meropenem,Imipenem,Tigecycline,Amikacin,Minocycline,Sulfamethoxazole/Trimethoprim,Ciprofloxacin,Levofloxacin,Aztreonam,Cefepime,Cefoperazone/Sulbactam,Piperacillin/Tazobactam and colistin were determined using the microbroth dilution method.The whole-genome sequencing analysis was conducted to determine the STs, virulence genes, and antibiotic resistance genes of three CRKp strains.
RESULTS
Whole-genome sequencing revealed that all three CRKp strains belonged to the sequence type (ST) 11 clone and carried a plasmid encoding blaKPC-2. The three strains all possessed the iucABCDiutA virulence cluster, peg-344 gene, and rmpA/rmpA2 genes, defining them as hv-CRKp. Further experiments and whole-genome analysis revealed that a strain of Kp has developed resistance to colistin. The mechanism found to be responsible for the colistin resistance was a deletion mutation of approximately 9000 bp including mgrB gene.
CONCLUSION
This study characterizes the colistin resistance of ST11 clone hv-CRKp during colistin treatment and its rapid evolution within the host.
PubMed: 38849114
DOI: 10.1016/j.jgar.2024.05.021 -
Journal of the Canadian Association of... Jun 2024Updated 2016 consensus guidelines recommend treatment for 14 days with concomitant therapy (proton-pump inhibitor (PPI)-amoxicillin-metronidazole-clarithromycin (PAMC)...
BACKGROUND
Updated 2016 consensus guidelines recommend treatment for 14 days with concomitant therapy (proton-pump inhibitor (PPI)-amoxicillin-metronidazole-clarithromycin (PAMC) or bismuth-based quadruple therapy (PPI-bismuth-metronidazole-tetracycline, PBMT)) as first line, PBMT or PPI-amoxicillin-levofloxacin (PAL) as second or third line, and PPI-amoxicillin-rifabutin (PAR) as fourth line for 10 days.
OBJECTIVES
This was a retrospective cohort study to describe and compare the efficacy of anti- treatment regimens over the periods 2007-2015 and 2016-2021 as well as antibiotic resistance.
METHODS
A modified intention-to-treat (mITT) analysis was used to analyze the success rate of therapies. mITT includes all patients who were prescribed treatment and had at least one follow-up test-of-cure. This included patients who could not complete treatment or were non-adherent with treatment. Risk factors for treatment failures were analyzed by univariate and multivariate logistic regression. Resistance testing was done in a small subset of patients.
RESULTS
-positive patients who received treatment in Edmonton, Alberta were included in a mITT analysis: 334/387(86%) from 2007 to 2015 and 193/199 (97%) from 2016 to 2021. During 2016-2021, 78% (150/193) of patients underwent cumulative guideline-based treatment with a successful cure in 80% (120/150) of patients. In those who were newly diagnosed, the cure rate was 88% (52/59) versus those with previous treatment failure 75% (68/91) ( < 0.05, risk difference [RD] 14%, 95% confidence interval [CI] 1.7-26.3%). The most effective first-line regimens were PAMC for 14 days (87% [45/52]) in 2016-2021 and sequential therapy in 2007-2015 (83% [66/80]) ( = 0.535, RD 4%, 95% CI -8.5-16.5%). When other treatments failed, success with PAR was 50% (2/4) from 2007 to 2015 and 57% (21/37) from 2016 to 2021. Recent (2016-2021) resistance rates to clarithromycin and metronidazole are high at 78% (50/64) and 56% (29/52), respectively. From 2007 to 2015, clarithromycin and metronidazole resistance rates were 80% (36/45) and 83% (38/46), respectively. Levofloxacin resistance increased significantly from 2007-2015 to 2016-2021 (28% [13/46] to 61% [35/57], < 0.05, RD 33%, 95% CI 11.6-54.4%).
CONCLUSIONS
Algorithmic treatment with PAMC first line followed by PBMT, PAL, and PAR cures in 88% of newly diagnosed patients. PAR therapy shows suboptimal cure rates (50-57% success) but can be considered as third instead of fourth line given increasing levofloxacin resistance rates. Antibiotic resistance in is common to clarithromycin, metronidazole, and levofloxacin and frequently accounts for treatment failures.
PubMed: 38841147
DOI: 10.1093/jcag/gwad051 -
Scientific Reports Jun 2024This study investigates quercetin complexes as potential synergistic agents against the important respiratory pathogen Streptococcus pneumoniae. Six quercetin complexes...
This study investigates quercetin complexes as potential synergistic agents against the important respiratory pathogen Streptococcus pneumoniae. Six quercetin complexes (QCX1-6) were synthesized by reacting quercetin with various metal salts and boronic acids and characterized using FTIR spectroscopy. Their antibacterial activity alone and in synergism with antibiotics was evaluated against S. pneumoniae ATCC 49619 using disc diffusion screening, broth microdilution MIC determination, and checkerboard assays. Complexes QCX-3 and QCX-4 demonstrated synergy when combined with levofloxacin via fractional inhibitory concentration indices ≤ 0.5 as confirmed by time-kill kinetics. Molecular docking elucidated interactions of these combinations with virulence enzymes sortase A and sialidase. A biofilm inhibition assay found the synergistic combinations more potently reduced biofilm formation versus monotherapy. Additionally, gene-gene interaction networks, biological activity predictions and in-silico toxicity profiling provided insights into potential mechanisms of action and safety.
Topics: Streptococcus pneumoniae; Quercetin; Anti-Bacterial Agents; Biofilms; Molecular Docking Simulation; Microbial Sensitivity Tests; Drug Synergism; Bacterial Proteins; Cysteine Endopeptidases; Aminoacyltransferases; Neuraminidase
PubMed: 38834612
DOI: 10.1038/s41598-024-62782-w -
European Journal of Gastroenterology &... May 2024There has been an increase in resistance to many of the antimicrobials used to treat Helicobacter pylori (H. pylori) nationally and internationally. Primary...
BACKGROUND
There has been an increase in resistance to many of the antimicrobials used to treat Helicobacter pylori (H. pylori) nationally and internationally. Primary clarithromycin resistance and dual clarithromycin and metronidazole resistance are high in Ireland. These trends call for an evaluation of best-practice management strategies.
OBJECTIVE
The objective of this study was to revise the recommendations for the management of H. pylori infection in adult patients in the Irish healthcare setting.
METHODS
The Irish H. pylori working group (IHPWG) was established in 2016 and reconvened in 2023 to evaluate the most up-to-date literature on H. pylori diagnosis, eradication rates and antimicrobial resistance. The 'GRADE' approach was then used to rate the quality of available evidence and grade the resulting recommendations.
RESULTS
The Irish H. pylori working group agreed on 14 consensus statements. Key recommendations include (1) routine antimicrobial susceptibility testing to guide therapy is no longer recommended other than for clarithromycin susceptibility testing for first-line treatment (statements 6 and 9), (2) clarithromycin triple therapy should only be prescribed as first-line therapy in cases where clarithromycin susceptibility has been confirmed (statement 9), (3) bismuth quadruple therapy (proton pump inhibitor, bismuth, metronidazole, tetracycline) is the recommended first-line therapy if clarithromycin resistance is unknown or confirmed (statement 10), (4) bismuth quadruple therapy with a proton pump inhibitor, levofloxacin and amoxicillin is the recommended second-line treatment (statement 11) and (5) rifabutin amoxicillin triple therapy is the recommend rescue therapy (statement 12).
CONCLUSION
These recommendations are intended to provide the most relevant current best-practice guidelines for the management of H. pylori infection in adults in Ireland.
PubMed: 38829956
DOI: 10.1097/MEG.0000000000002796 -
Infection and Drug Resistance 2024Qiguiyin decoction (QGYD) is a traditional Chinese medicine (TCM) and its combined application with levofloxacin (LVFX) has been confirmed effective in the clinical...
BACKGROUND
Qiguiyin decoction (QGYD) is a traditional Chinese medicine (TCM) and its combined application with levofloxacin (LVFX) has been confirmed effective in the clinical treatment of multidrug-resistant (MDR PA) infection. This study investigated the therapeutic effect and possible mechanism of QGYD in sensitizing LVFX against MDR PA infection.
MATERIALS AND METHODS
Pulmonary infections were induced in rats by MDR PA. The changes in pharmacokinetics-pharmacodynamics (PK-PD) parameters of LVFX after combined with QGYD were investigated in MDR PA-induced rats. Subsequently, the correlation between PK and PD was analyzed and PK-PD models were established to elucidate the relationship between QGYD-induced alterations in LVFX metabolism and its sensitization to LVFX. Antibody chip technology was used to detect the levels of inflammatory factors, suggesting the relationship between the beneficial effect of immune regulation and the sensitization of QGYD.
RESULTS
QGYD significantly enhanced the therapeutic efficacy of LVFX against MDR PA infection. The combination of QGYD changed the PK parameters of LVFX such as T, t, MRT, V/F, CL/F and PD parameters such as MIC, AUC/MIC. Predicted results from PK-PD models demonstrated that the antibacterial effect of LVFX was significantly enhanced with the combination of QGYD, consistent with experimental findings. Antibody chip results revealed that the combination of QGYD made IL-1 β, IL-6, TNF- α, IL-10, and MCP-1 levels more akin to those of the blank group.
CONCLUSION
These findings indicated that QGYD could change the PK-PD behaviors of LVFX and help the body restore immune balance faster. This implied that a potential drug interaction might occur between QGYD and LVFX, leading to improved clinical efficacy when combined.
PubMed: 38828375
DOI: 10.2147/IDR.S455114 -
The Science of the Total Environment Aug 2024Developing cost-efficient wastewater treatment technologies for safe reuse is essential, especially in developing countries simultaneously facing water scarcity. This...
Developing cost-efficient wastewater treatment technologies for safe reuse is essential, especially in developing countries simultaneously facing water scarcity. This study developed and evaluated a hybrid constructed wetlands (CWs) approach, incorporating tidal flow (TF) operation and utilising local Jordanian zeolite as a wetland substrate for real pharmaceutical industry wastewater treatment. Over 273 days of continuous monitoring, the results revealed that the first-stage TFCWs filled with either raw or modified zeolite performed significantly higher reductions in Chemical Oxygen Demand (COD, 58 %-60 %), Total Nitrogen (TN, 32 %-37 %), and Phosphate (PO, 46 %-64 %) compared to TFCWs filled with normal sand. Water quality further improved after the second stage of horizontal subsurface flow CWs treatment, achieving log removals of 1.09-2.47 for total coliform and 1.89-2.09 for E. coli. With influent pharmaceutical concentrations ranging from 275 to 2000 μg/L, the zeolite-filled hybrid CWs achieved complete removal (>98 %) for ciprofloxacin, ofloxacin, erythromycin, and enrofloxacin, moderate removal (43 %-81 %) for flumequine and lincomycin, and limited removal (<8 %) for carbamazepine and diclofenac. The overall accumulation of pharmaceuticals in plant tissue and substrate adsorption accounted for only 2.3 % and 4.3 %, respectively, of the total mass removal. Biodegradation of these pharmaceuticals (up to 61 %) through microbial-mediated processes or within plant tissues was identified as the key removal pathway. For both conventional pollutants and pharmaceuticals, modified zeolite wetland media could only slightly enhance treatment without a significant difference between the two treatment groups. The final effluent from all hybrid CWs complied with Jordanian treated industry wastewater reuse standards (category III), and systems filled with raw or modified zeolite achieved over 95 % of samples meeting the highest water reuse category I. This study provides evidence of using hybrid CWs technology as a nature-based solution to address water safety and scarcity challenges.
Topics: Wetlands; Wastewater; Waste Disposal, Fluid; Water Pollutants, Chemical; Jordan; Drug Industry; Zeolites; Biological Oxygen Demand Analysis
PubMed: 38823717
DOI: 10.1016/j.scitotenv.2024.173634 -
Journal of Global Antimicrobial... May 2024Trimethoprim-sulfamethoxazole (TMP-SMX) has long been considered the treatment of choice for infections caused by Stenotrophomonas maltophilia. Levofloxacin has emerged...
BACKGROUND
Trimethoprim-sulfamethoxazole (TMP-SMX) has long been considered the treatment of choice for infections caused by Stenotrophomonas maltophilia. Levofloxacin has emerged as a potential option for treating these infections. This study aimed to evaluate the clinical outcomes in patients who received TMP-SMX versus levofloxacin for treating S. maltophilia infections.
METHODS
A retrospective, cohort study was conducted in 4 tertiary centres and included patients who were treated with either TMP-SMX or levofloxacin for infections caused by S. maltophilia. The main study outcomes were overall in-hospital mortality, 30-d mortality, and clinical cure. Safety outcomes were also evaluated. Multivariate analysis using logistic regression was used to control for the effect of the covariables.
RESULTS
We included 371 patients in this study, 316 received TMP-SMX and 55 patients received levofloxacin. A total of 70% were in the intensive care unit and 21% presented with bacteraemia. No statistically significant differences were observed in overall in-hospital mortality (52% vs. 40%; P = 0.113; odd ratio [OR], 1.59; 95% confidence interval [CI], 0.89-2.86), 30-d mortality (28% vs. 25%; P = 0.712; OR, 1.13; 95% CI, 0.59-2.18), or clinical cure (55% vs. 64%; P = 0.237; OR, 0.70; 95% CI, 0.37-1.31). Rates of acute kidney injury were comparable between the two groups (11% vs. 7%; P = 0.413).
CONCLUSION
Patients receiving levofloxacin for the treatment of infections caused by S. maltophilia demonstrated clinical outcomes similar to those receiving TMP-SMX. Our study suggests that levofloxacin can be a reasonable alternative to TMP-SMX to treat these infections.
PubMed: 38821443
DOI: 10.1016/j.jgar.2024.05.016 -
Journal of Infection and Public Health Jul 2024The presence of bacterial and fungal coinfections plays an important role in the mortality of patients with coronavirus 2019 (COVID-19). We compared data from the 3...
BACKGROUND
The presence of bacterial and fungal coinfections plays an important role in the mortality of patients with coronavirus 2019 (COVID-19). We compared data from the 3 years before and 3 years after the COVID-19 pandemic outbreak to evaluate its effect on the traits of bacterial and fungal diseases.
METHODS
We retrospectively collected and analyzed data on positive respiratory tract samples (n = 13,133 samples from 7717 patients) and blood cultures (n = 23,652 from 9653 patients) between 2017 and 2022 from the Clinical Center of the University of Szeged, Hungary. We also evaluated antimicrobial susceptibility test results derived from 169,020 respiratory samples and 549,729 blood cultures to gain insight into changes in antimicrobial resistance.
RESULTS
The most common respiratory pathogen in the pre-COVID era was Pseudomonas aeruginosa, whereas Candida albicans was the most frequent during the pandemic. The number of respiratory isolates of Acinetobacter baumannii was also markedly increased. In blood cultures, Staphylococcus epidermidis, Escherichia coli, and S. aureus were dominant during the study period, and A. baumannii was widespread in blood cultures during the pandemic years. Resistance to ofloxacin, penicillin, piperacillin-tazobactam, ceftazidime, cefepime, imipenem, ceftolozane-tazobactam, and itraconazole increased significantly in the COVID era.
CONCLUSIONS
During the COVID-19 pandemic, there were changes in the prevalence of respiratory and blood culture pathogens at the Clinical Center of the University of Szeged. C. albicans became the predominant respiratory pathogen, and the number of A. baumannii isolates increased dramatically. Additionally, antimicrobial resistance notably increased during this period.
Topics: Humans; COVID-19; Hungary; Tertiary Care Centers; Retrospective Studies; SARS-CoV-2; Coinfection; Microbial Sensitivity Tests; Anti-Bacterial Agents; Mycoses; Bacterial Infections; Bacteria; Respiratory Tract Infections; Drug Resistance, Bacterial
PubMed: 38820897
DOI: 10.1016/j.jiph.2024.05.041 -
Frontiers in Cellular and Infection... 2024The increasing incidence of Klebsiella pneumoniae and carbapenem-resistant Klebsiella pneumoniae (CRKP) has posed great challenges for the clinical anti-infective...
INTRODUCTION
The increasing incidence of Klebsiella pneumoniae and carbapenem-resistant Klebsiella pneumoniae (CRKP) has posed great challenges for the clinical anti-infective treatment. Here, we describe the molecular epidemiology and antimicrobial resistance profiles of K. pneumoniae and CRKP isolates from hospitalized patients in different regions of China.
METHODS
A total of 219 K. pneumoniae isolates from 26 hospitals in 19 provinces of China were collected during 2019-2020. Antimicrobial susceptibility tests, multilocus sequence typing were performed, antimicrobial resistance genes were detected by polymerase chain reaction (PCR). Antimicrobial resistance profiles were compared between different groups.
RESULTS
The resistance rates of K. pneumoniae isolates to imipenem, meropenem, and ertapenem were 20.1%, 20.1%, and 22.4%, respectively. A total of 45 CRKP isolates were identified. There was a significant difference in antimicrobial resistance between 45 CRKP and 174 carbapenem-sensitive Klebsiella pneumoniae (CSKP) strains, and the CRKP isolates were characterized by the multiple-drug resistance phenotype.There were regional differences among antimicrobial resistance rates of K. pneumoniae to cefazolin, chloramphenicol, and sulfamethoxazole,which were lower in the northwest than those in north and south of China.The mostcommon sequence type (ST) was ST11 (66.7% of the strains). In addition, we detected 13 other STs. There were differences between ST11 and non-ST11 isolates in the resistance rate to amikacin, gentamicin, latamoxef, ciprofloxacin, levofloxacin, aztreonam, nitrofurantoin, fosfomycin, and ceftazidime/avibactam. In terms of molecular resistance mechanisms, the majority of the CRKP strains (71.1%, 32/45) harbored blaKPC-2, followed by blaNDM (22.2%, 10/45). Strains harboring blaKPC or blaNDM genes showed different sensitivities to some antibiotics.
CONCLUSION
Our analysis emphasizes the importance of surveilling carbapenem-resistant determinants and analyzing their molecular characteristics for better management of antimicrobial agents in clinical use.
Topics: Klebsiella pneumoniae; Humans; China; Klebsiella Infections; Microbial Sensitivity Tests; Anti-Bacterial Agents; Molecular Epidemiology; Multilocus Sequence Typing; Drug Resistance, Multiple, Bacterial; Male; Carbapenem-Resistant Enterobacteriaceae; Female; Middle Aged; Aged; Hospitalization; Adult; Carbapenems
PubMed: 38817445
DOI: 10.3389/fcimb.2024.1380678 -
Therapeutic Advances in Respiratory... 2024Ukraine remains a high World Health Organization priority country for drug-resistant tuberculosis (TB). Rifampicin-resistant TB (RR-TB) has a more protracted, more... (Observational Study)
Observational Study
Impact of line probe assay-based molecular testing on individualized treatment in patients with rifampicin-resistant tuberculosis: data from the prospective INNOVA4TB cohort study in Ukraine.
BACKGROUND
Ukraine remains a high World Health Organization priority country for drug-resistant tuberculosis (TB). Rifampicin-resistant TB (RR-TB) has a more protracted, more complicated, and more expensive treatment. In 2021, Ukraine reported 4025 RR-TB cases - 5.4 times more (751) than all 30 European Union/ European Economic Area countries together.
OBJECTIVES
The objective of the study was to determine the diagnostic accuracy of line probe assay (LPA), AID Autoimmun Diagnostika GmbH, for detecting resistance to anti-TB drugs and its clinical application for selecting treatment regimens.
DESIGN
A prospective observational cohort study.
METHODS
From May 2019 to June 2020, we consecutively enrolled patients with active TB hospitalized at the Regional Phthisiopulmonology Center (Vinnytsia, Ukraine), aged between 18 and 82 years. The LPA was performed in the Genetic Research Laboratory at National Pirogov Memorial Medical University, Vinnytsia, Ukraine.
RESULTS
A total of 84 clinical specimens and 97 culture isolates from 126 TB patients were tested during the study. Accuracy (95% confidence interval) of LPA for clinical samples in comparison with phenotypic drug susceptibility test (DST) was 80.1 (68.5-89.0) for isoniazid (H), 74.7 (62.4-84.6) for rifampicin (R), 74.4 (62.5-84.1) for ethambutol, 71.4 (41.9-91.6) for streptomycin, 84.6 (62.4-96.5) for prothionamide/ethionamide, and 84.6 (73.6-92.3) for levofloxacin (Lfx), respectively. We found a significantly higher sensitivity of LPA for H, R, and Lfx for the culture isolates compared to clinical specimens ( < 0.05). LPA detected different mutations in 6 out of 17 (35.5%) patients susceptible to R by Xpert. A shorter treatment regimen with an injectable agent demonstrated a low suitability rate of 5% (8/156) in a cohort of RR-TB patients from Ukraine.
CONCLUSION
Initial LPA testing accurately identifies resistance to anti-TB drugs and facilitates the selection of an appropriate treatment regimen, minimizing exposure to empirical therapy.
Topics: Humans; Prospective Studies; Adult; Ukraine; Rifampin; Male; Middle Aged; Tuberculosis, Multidrug-Resistant; Female; Mycobacterium tuberculosis; Young Adult; Aged; Adolescent; Antitubercular Agents; Microbial Sensitivity Tests; Aged, 80 and over; Antibiotics, Antitubercular; Predictive Value of Tests; Precision Medicine; Reproducibility of Results
PubMed: 38817020
DOI: 10.1177/17534666241249841