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PURPOSE: Predicting infection risk in carbapenem-resistant Acinetobacter baumannii (CRAB) colonized patients may help in improving timely appropriate antibiotic therapy. This study aims to explore risk factors for developing infections in hospitalized patients with previous CRAB colonization. METHODS: We performed an observational retrospective cohort study at ASST Sette Laghi-Varese Hospital between January 2020 and December 2022. All consecutive adult (> 18 years old) hospitalized patients with documented colonization by CRAB at any anatomical site or with CRAB infections preceded by CRAB colonization were included. Univariate and multivariate analyses were performed to investigate infection risk factors. RESULTS: Overall, 144 patients were included in the study: 104 colonized only and 40 infected patients. Colonization and infection rates significantly changed over the years (2020-2022, p < 0.001). The incidence of infections in CRAB carriers was 27.8% (40/144). Median time from colonization to infection was 4 days (IQR 1-8.5). Overall, inhospital mortality was 32.7% and 55.0% in colonized only and infected patients, respectively. At the multivariable logistic regression cardiovascular disease (OR 5.83, 95% CI 1.12-30.43, p = 0.037), COVID-19 (OR 3.72, 95% CI 1.16-11.91, p = 0.027) and intensive care unit (ICU) admission (OR 8.83, 95% CI 2.94-26.51, p < 0.001) were risk factors independently associated with cardiovascular disease CRAB infection after colonization. CONCLUSIONS: We observed an increased infection risk in patients colonized with CRAB with cardiovascular disease, COVID-19 and admitted in ICU setting. Additional evidence is needed to identify predictors of infection in colonized patients.
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Carbapenem-resistant Pseudomonas aeruginosa is a common multidrug-resistant bacterium encountered in clinical practice. This pathogen causes pneumonia, which is difficult to treat owing to the limited choice of antimicrobial drugs, resulting in a relatively high mortality rate. Carrimycin is a new macrolide antibiotic with broad-spectrum antibacterial and potential immunomodulatory effects. Herein, we report a case of severe pneumonia caused by carbapenem-resistant Pseudomonas aeruginosa that presented with septic shock and Acute Respiratory Distress Syndrome (ARDS). Initially, we used piperacillin-tazobactam and ceftazidime-avibactam but without satisfactory results. Finally, we administered carrimycin in combination with piperacillin-tazobactam; the patient's condition improved, and he was successfully weaned off the ventilator. Therefore, the combined use of carrimycin should be considered for patients infected with carbapenem-resistant Pseudomonas aeruginosa who do not respond to conventional anti-infection treatments.
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Antibacterianos , Carbapenémicos , Infecciones por Pseudomonas , Pseudomonas aeruginosa , Humanos , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/aislamiento & purificación , Masculino , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/microbiología , Persona de Mediana Edad , Pruebas de Sensibilidad Microbiana , AncianoRESUMEN
Antimicrobial resistance is increasingly concerning, causing millions of deaths and a high cost burden. Given that carbapenemase-producing Enterobacterales are particularly concerning due to their ability to develop structural modifications and produce antibiotic-degrading enzymes, leading to high resistance levels, we sought to summarize the available data on the efficacy and safety regarding the combination of meropenem-vaborbactam (MV) versus the best available therapy (BAT). Articles related to our objective were searched in the PubMed and Scopus databases inception to July 2024. To assess the quality of the studies, we used the Cochrane risk-of-bias tool, RoB2. The outcomes were pooled as a risk ratio (RR) and a 95% confidence interval (95%CI). A total of four published studies were involved: one retrospective cohort study and three phase 3 trials, including 432 patients treated with MV and 426 patients treated with BAT (mono/combination therapy with polymyxins, carbapenems, aminoglycosides, colistin, and tigecycline; or ceftazidime-avibactam; or piperacillin-tazobactam). No significant difference in the clinical response rate was observed between MV and the comparators at the TOC (RR = 1.29, 95%CI [0.92, 1.80], p = 0.14) and EOT (RR = 1.66, 95%CI [0.58, 4.76], p = 0.34) visits. MV was associated with a similar microbiological response as the comparators at TOC (RR = 1.63, 95%CI [0.85, 3.11], p = 0.14) and EOT assessment (RR = 1.16, 95%CI [0.88, 1.54], p = 0.14). In the pooled analysis of the four studies, 28-day all-cause mortality was lower for MV than the control groups (RR = 0.47, 95%CI [0.24, 0.92], p = 0.03). MV was associated with a similar risk of adverse events (AEs) as comparators (RR = 0.79, 95%CI [0.53, 1.17], p = 0.23). Additionally, MV was associated with fewer renal-related AEs than the comparators (RR = 0.32, 95%CI [0.15, 0.66], p = 0.002). MV was associated with a similar risk of treatment discontinuation due to AEs (RR = 0.76, 95%CI [0.38, 1.49], p = 0.42) or drug-related AEs (RR = 0.56, 95%CI [0.28, 1.10], p = 0.09) as the comparators. In conclusion, MV presents a promising therapeutic option for treating CRE infections, demonstrating similar clinical and microbiological responses as other comparators, with potential advantages in mortality outcomes and renal-related AEs.
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Antibacterianos , Ácidos Borónicos , Enterobacteriaceae Resistentes a los Carbapenémicos , Combinación de Medicamentos , Infecciones por Enterobacteriaceae , Meropenem , Humanos , Enterobacteriaceae Resistentes a los Carbapenémicos/efectos de los fármacos , Meropenem/uso terapéutico , Meropenem/farmacología , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Antibacterianos/efectos adversos , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Infecciones por Enterobacteriaceae/microbiología , Ácidos Borónicos/uso terapéutico , Resultado del Tratamiento , Carbapenémicos/uso terapéutico , Carbapenémicos/farmacología , Compuestos Heterocíclicos con 1 AnilloRESUMEN
Carbapenem-resistant Klebsiella pneumoniae producing metallo-ß-lactamase poses a major public health threat worldwide. Imipenemase often coexists with other resistance genes leading to the formation of multidrug-resistant bacteria. In this study, we describe the microbiological and genomic characteristics of the hypervirulent carbapenem-resistant K. pneumoniae ST20-K23 strain KPN945 harboring blaIMP-4 and qnrS1. The minimum inhibitory concentration of KPN945 against antimicrobials was determined by the broth microdilution method. The virulence of KPN945 was evaluated through string test, serum killing resistance, and Galleria mellonella larvae infection models. The transferability of pKPN945B was assessed using a conjugation test. The genome sequence characteristics of KPN945 were analyzed through whole genome sequencing, and a phylogenetic tree was constructed to evaluate the prevalence of imipenemase. Our findings showed that KPN945 was non-susceptible to ß-lactam antibiotics, highly resistant to serum killing, and highly lethal to G. mellonella larvae. The fusion plasmid pKPN945B carried by the isolate KPN945 belonged to the IncR incompatibility group and harbored multiple drug resistance genes such as blaIMP-4, blaCTX-M-14, qnrS1, and sul2. The most important point is that the IncR plasmid is a novel plasmid that arose by the accretion of parts from different plasmids, making it transferable and with a fitness cost. Globally, blaIMP-4 is the most prevalent imipenemase subtype, with the highest isolation rates in Asia, particularly China. The spread of blaIMP-4, especially the emergence of transferable plasmids, deserves our vigilance and prevention. Additionally, we should pay attention to the formation of hypervirulent K. pneumoniae mediated by non-virulent plasmids. IMPORTANCE: Up to now, IncR replicons carrying blaIMP-4 have not been reported, and the IncR plasmids described in previous studies have been found to be non-transferrable to other bacteria through conjugation. Moreover, there have been no extensive phylogenetic analyses of strains carrying blaIMP in the published papers. The lack of data in these studies is noteworthy because blaIMP appears in the novel transferable fusion plasmid IncR. Although the IncR plasmid has no tra operon, it can still be transferred to Escherichia coli EC600 or Klebsiella pneumoniae ATCC13883 (RIFR) without high fitness cost, but it only affects the MIC of imipenem. blaIMP integrates with other resistance mechanisms leading to the formation of multidrug-resistant strains. Notably, the high prevalence of blaIMP-4 in Asia and the presence of blaIMP-4 on novel transferable IncR plasmids suggest the urgent need to monitor the emergence of such plasmids and control their spread.
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Carbapenem-resistant Enterobacterales, particularly those that produce carbapenemases, pose a significant public health concern due to very limited treatment options. The timely identification of carbapenemase-producing Enterobacterales (CPE) is essential for putting in place efficient infection control measures and selecting appropriate antimicrobial therapies, thereby improving the clinical outcome of the patient. The purpose of this systematic review is to compare the diagnostic accuracy and practicality between two phenotypic tests, namely the modified carbapenem inactivation method (mCIM) and carbapenemase Nordmann-Poirel (Carba NP) test, in detecting carbapenemase production by Enterobacterales and thereby aiding the clinician in making a decision to choose an appropriate test for their phenotypic detection. This systematic review involved combining sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, diagnostic odds ratio with 95% confidence interval (CIs), Forest plot for sensitivity and specificity, and plotting suitable summary receiver operating characteristic curve with the area under the curve. Of the 20 studies included in this review, the overall effect sizes of Carba NP and mCIM with 95% CIs were as follows: sensitivity, 91% (86-96%) and 97% (95-99%); specificity, 93% (88-97%) and 97% (93-100%); PPV, 97% and 98%; NPV, 79% and 90%; accuracy, 93% and 97%; diagnostic odds ratio, 1487.8879 and 8527.5541; and AUC, 0.85 and 1, respectively. In conclusion, the mCIM method showed superior sensitivity (97%), specificity (97%), and accuracy compared to the Carba NP test in detecting carbapenemase production, even though both these methods had a few technical limitations. The Carba NP test is rapid, affordable, and dependable, whereas mCIM is more accurate and cost-effective but time-consuming. We propose that both tests can be reliably used for screening of carbapenemase production in Enterobacterales, as endorsed by the Clinical and Laboratory Standards Institute even in resource-limited clinical laboratories, in the order of prioritizing the mCIM method first and then followed by the Carba NP test when situation demands expedited results.
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Objectives: This study aims to provide lacking data on antibiotics and treatment strategies used in the management of carbapenem-resistant Enterobacteriaceae (CRE) infections in Nigeria. Methods: A cross-sectional study was carried out at the University College Hospital in Ibadan. CRE isolated from routine culture of specimens from hospitalized patients from December 2021 to September 2022 was identified. Treatment information and other data were collected from the patients' medical records. Results: The hospital laboratory isolated CRE from 55 patients during the study period and 27 (49.1%) of them had data available for the study. The most frequently isolated CRE was Klebsiella spp. (13 of 27, 48.1%). Of the 24 patients who received empiric antibiotics, only two (8.3%) of their CRE isolates were susceptible. After receiving culture results, 18 (66.7%) patients were treated with at least one antibiotic, to which resistance was documented. Only three (11.1%) patients overall commenced or remained on an antibiotic, to which their CRE isolate was susceptible. Conclusions: Despite culture data, we found a high prevalence of drug-pathogen mismatch in CRE treatment, including new or persistent use of antibiotics, to which resistance was documented. Antimicrobial stewardship efforts need to be strengthened to specifically address CRE treatment and effective antibiotics need to be made accessible.
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It remains that intracranial infection has an alarming mortality and morbidity. Klebsiella pneumoniae (KP) have increasingly been isolated in ventriculitis and meningitis episodes. Intracranial infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) account for high mortality. To understand its clinical impact and related risk factors accurately are crucial in the management of bacterial intracranial infection. The retrospective study aimed to delineate the clinical risk of death from intracranial infection and analyze the risk factors. A total of 176 Klebsiella pneumoniae intracranial infectious patients were available to divide into CRKP group and carbapenem-susceptive Klebsiella Pneumoniae (CSKP) group. We performed survival analysis and estimate the time-varying effects of CRKP and CSKP infection on 30-day mortality. Infectious patients caused by CSKP was associated with lower mortality than CRKP group. The risk factors associated with death from intracranial infection caused by Klebsiella pneumoniae included SOFA scores, ventilator therapy, CRKP, and heart failure. Longer hospital stays are independently associated with lower mortality rates. Intracranial infection caused by CRKP was associated with excess mortality. Complex comorbidities mean higher mortality. Active supportive treatment is required for complicated patients with intracranial infections caused by carbapenem-resistant Klebsiella pneumoniae.
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Carbapenémicos , Infecciones por Klebsiella , Klebsiella pneumoniae , Humanos , Masculino , Femenino , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/aislamiento & purificación , Infecciones por Klebsiella/mortalidad , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/microbiología , Persona de Mediana Edad , Factores de Riesgo , Estudios Retrospectivos , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico , Anciano , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Adulto , Enterobacteriaceae Resistentes a los Carbapenémicos/efectos de los fármacos , Enterobacteriaceae Resistentes a los Carbapenémicos/aislamiento & purificaciónRESUMEN
Objective: To assess the efficacy and safety of colistin sulfate in treating infections caused by carbapenem-resistant organisms (CRO) and to analyze potential factors impacting its effectiveness. Methods: In this retrospective study, medical records of CRO-infected patients from June 2020 to June 2023 were analyzed, divided into effective and ineffective treatment groups, and compared for clinical outcomes and adverse reactions. Multifactorial logistic regression and ROC curve analysis were used to identify influencing factors. Results: The study included 226 patients, with 124 in the effective treatment group and 102 in the ineffective group. A total of 293 CRO strains were cultured. The clinical efficacy rate of colistin sulfate was 54.87%, the microbiological efficacy rate 46.46%, and the hospital mortality rate 20.80%, with nephrotoxicity observed in 11.50% of patients. Multifactorial analysis identified APACHE II scores and vasoactive drug use as independent predictors of ineffective treatment, while treatment duration and albumin levels predicted effective treatment. ROC analysis indicated that albumin levels >34 g/L, APACHE II scores <13, and treatment duration >10 days correlated with better clinical efficacy. Conclusion: Colistin sulfate is both safe and effective in clinical settings. Factors such as treatment duration, albumin levels, APACHE II scores, and vasoactive drug use independently affect its clinical efficacy, providing valuable guidance for its informed clinical application.
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This research focused on evaluating the clinical results of patients suffering from pneumonia caused by carbapenem-resistant Klebsiella pneumoniae (CRKP), who received treatment with either ceftazidime-avibactam (CZA) alone or in combination with other antibiotics. From January 2020 to December 2023, we retrospectively analyzed CRKP-related pneumonia patients treated in two Chinese tertiary hospitals. Mortality was measured at 14 and 30 days as the primary outcome. Secondary outcomes included the 14-day microbiological cure rate and the 14-day clinical cure rate. Factors contributing to clinical failure were evaluated via both univariate analysis and multivariate logistic regression. To account for confounding factors, propensity score matching (PSM) was utilized. Among the 195 patients with CRKP infections, 103 (52.8 %) received CZA combination therapy, and 92 (47.2 %) patients received CZA monotherapy. The combination therapy group exhibited superior clinical and microbiological cure rates compared to the monotherapy group, with a 14-day clinical cure rate of 60.1 % vs. 45.7 % (P = 0.042) and a 14-day microbiological cure rate of 72.8 % vs. 58.6 % (P = 0.038), respectively. Combination therapy reduced mortality rates at 14 days (7.8 % vs. 17.4 %, P = 0.041), but not at 30 days (14.6 % vs. 25.0 %, P = 0.066). Even after using PSM, the group treated with the CZA combination continued to had a lower mortality rate at 14 days (5.9 % vs. 17.6 %, P = 0.039). The 14-day clinical cure rate for the combination therapy group was 63.2 %, and the 14-day microbial cure rate was 77.9 %. Both of these statistics were notably greater than those observed in the monotherapy group. Furthermore, the multivariate logistic regression model indicated a significant link between combination therapy and a decrease in clinical failure. Carbapenems were noted to be the most effective class of concomitant agents. Our findings indicate that patients with pneumonia due to CRKP benefit from combination treatment of CZA rather than monotherapy; administering carbapenem in combination with CZA in the early stages could provide considerable survival benefits.
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PURPOSE: Infection by carbapenem-resistant Klebsiella pneumoniae (CRKP) has high mortality. There is no clear optimal therapeutic choice for pneumonia caused by CRKP. The aim of this study was to compare the clinical outcomes and safety of the standard doses of polymyxin B-based regimens vs tigecycline-based regimens and to identify risk factors for mortality. METHODS: This retrospective cohort study included patients with pneumonia caused by CRKP between January 1, 2020 and December 31, 2022. The primary outcomes were 7-day bacterial eradication rate and 14- and 28-day all-cause mortality. The secondary outcome was incidence of acute kidney injury. RESULTS: Seventy-three patients were included in this study, 29 in the polymyxin B-based combination therapy group and 44 in tigecycline-based combination therapy group. There were no significant differences between the two groups in terms of the 7-day bacterial eradication rate (31.03% vs 20.45%, p = 0.409), the 14-day all-cause mortality (37.93% vs 22.73%, p = 0.160), and the incidence of acute kidney injury (14.29% vs 6.82%, p = 0.526). The 28-day all-cause mortality in the polymyxin B-based therapy group was higher than in the tigecycline-based group (75.86% vs 45.45%, p = 0.010). Binary logistic regression analysis revealed that male and previous use of carbapenems were independent factors associated with 28-day all-cause mortality for patients treated with polymyxin B (p < 0.05). CONCLUSIONS: Polymyxin B-based combination therapy at the standard dose should be used with caution for patients with CRKP-induced pneumonia, especially for men who used carbapenems prior to CRKP detection.
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Antibacterianos , Quimioterapia Combinada , Infecciones por Klebsiella , Klebsiella pneumoniae , Polimixina B , Tigeciclina , Humanos , Polimixina B/administración & dosificación , Polimixina B/uso terapéutico , Polimixina B/efectos adversos , Masculino , Estudios Retrospectivos , Tigeciclina/administración & dosificación , Tigeciclina/uso terapéutico , Tigeciclina/efectos adversos , Femenino , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/mortalidad , Infecciones por Klebsiella/epidemiología , Infecciones por Klebsiella/microbiología , Anciano , Klebsiella pneumoniae/efectos de los fármacos , Persona de Mediana Edad , Carbapenémicos/uso terapéutico , Carbapenémicos/efectos adversos , Carbapenémicos/administración & dosificación , Resultado del Tratamiento , Enterobacteriaceae Resistentes a los Carbapenémicos/efectos de los fármacos , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/epidemiología , Neumonía Bacteriana/tratamiento farmacológico , Neumonía Bacteriana/microbiología , Neumonía Bacteriana/mortalidadRESUMEN
BACKGROUND: This study aimed to characterize three KPC variants (KPC-33, KPC-100, and KPC-201) obtained from a clinical isolate of Pseudomonas aeruginosa (#700), along with two induced strains C109 and C108. METHODS: Genomic DNAs of #700 (ST235), C109 (ST463), and C108 (ST1076) were sequenced using Illumina and Oxford Nanopore technologies. The transferability and stability of the plasmid was assessed through conjugation experiments and plasmid stability experiments, respectively. Minimum inhibitory concentrations of bacterial strains were determined using broth microdilution methods. In vitro induction was performed using ceftazidime-avibactam (CZA) at concentrations of 6/4⯵g/ml. Linear genomic alignments were visualized using Easyfig, and protein structure modeling of the novel KPC variant (KPC-201) was conducted using PyMol. RESULTS: The plasmids carrying the KPC variants in the three CZA-resistant strains (C109, C108, and #700) had sizes of 39,251â¯bp (KPC-100), 394,978â¯bp (KPC-201), and 48,994â¯bp (KPC-33). All three plasmids belonged to the IncP-like incompatibility (Inc) groups, and the plasmid exhibited relatively high plasmid stability, KPC-33 and KPC-201-harboring plasmids were successfully transferred to the recipient strain P. aeruginosa PAO1rifR. The genetic environments of the three blaKPC genes differed from each other. The mobile elements of the three blaKPC genes were as follows, TnAS1-IS26-ΔISKpn27-blaKPC-33-ISKpn6-IS26, IS6-ΔISKpn27-blaKPC-100-ISKpn6-IS26-Tn3-IS26, and IS6100-ISKpn27-blaKPC-201-ISKpn6-TnAS1. Notably, the length of ΔISKpn27 upstream of the blaKPC-33 and blaKPC-100 genes were remarkably short, measuring 114â¯bp and 56â¯bp, respectively, deviating significantly from typical lengths associated with ISKpn27 elements. Moreover, the novel KPC variant, KPC-201, featured a deletion of amino acids LDR at positions 161-163 in KPC-3, resulting in a looser pocket structure contributing to its avibactam resistance. CONCLUSIONS: KPC-201, identified as a novel KPC variant, exhibits resistance to CZA. The presence of multiple mobile elements surrounding the blaKPC-variant genes on stable plasmids is concerning. Urgent preventive measures are crucial to curb its dissemination in clinical settings.
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Objectives: To summarize the clinical characteristics, outcomes and identify risk factors of Acinetobacter baumannii (AB) meningitis in children. Methods: This was a single-center, retrospective study. Children hospitalized between January 2016 and December 2021 who were diagnosed with AB meningitis were included. The clinical characteristics and outcomes were reviewed. Risk factors were determined using univariate analyses (chi-square and Mann-Whitney U tests). Results: Seventeen patients were included; 15 cases were secondary to neurosurgery, and two were neonates with primary bacterial meningitis. Common symptoms included fever, convulsions and nervous system abnormalities. Cerebrospinal fluid (CSF) tests typically showed increased white blood cell counts dominated by neutrophils, reduced glucose levels and elevated protein levels. Ten patients were successfully treated (successful treatment [ST] group); seven had failed treatment (failed treatment [FT] group). Univariate analyses revealed that mechanical ventilation, routine white cell counts in the peripheral blood, procalcitonin, protein in the CSF, septic shock and carbapenem-resistant AB (CRAB) differed significantly between the groups. Conclusion: AB meningitis in children has a high mortality rate. FT was associated with mechanical ventilation, septic shock, CRAB, lower peripheral leukocyte counts, higher protein levels in the CSF and procalcitonin. Larger studies are needed to identify independent risk factors for adverse outcomes.
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Infecciones por Acinetobacter , Acinetobacter baumannii , Antibacterianos , Meningitis Bacterianas , Centros de Atención Terciaria , Humanos , Femenino , Masculino , Factores de Riesgo , China/epidemiología , Estudios Retrospectivos , Preescolar , Lactante , Infecciones por Acinetobacter/microbiología , Meningitis Bacterianas/microbiología , Meningitis Bacterianas/mortalidad , Antibacterianos/uso terapéutico , Niño , Resultado del Tratamiento , Recién Nacido , Carbapenémicos/uso terapéutico , Recuento de Leucocitos , AdolescenteRESUMEN
BACKGROUND: The dwindling antibiotic reserve owing to augmented drug-resistant bacteria is a major handicap for treating physicians. Klebsiella pneumoniae, a gram-negative encapsulated member of the Enterobacteriaceae family, is one such pathogenic bacteria. Carbapenemase-producing Klebsiella pneumoniae is globally recognized as one of the most critical bacterial threats to public health due to its extremely limited treatment options. Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections pose therapeutic challenges due to simultaneous resistance to various other groups of antibiotics. In this study, we have evaluated the synergistic effect of fosfomycinagainst CRKP isolates when used in combination with colistin by applying the Checkerboard method. METHODS: A laboratory-based prospective study was conducted in the Department of Microbiology, JSS Hospital, Mysuru, for a period of one year after obtaining ethical clearance. Klebsiella pneumoniae isolates obtained from clinical samples were screened for carbapenem resistance by the VITEK-2 compact system (bioMérieux, Marcy-l'Étoile, France). The minimum inhibitory concentration (MIC) of colistin and fosfomycin was individually ascertained by broth microdilution (BMD). Finally, the synergistic activity of the fosfomycin-colistin combination was determined by the BMD-based Checkerboard method. RESULTS: Among the 50 CRKP isolates, 36 (72%) isolates showed synergism, eight (16%) isolates showed indifference and six (12%) isolates showed partial synergism, while none of them showed additivity and antagonism by the Checkerboard method. These results are found to be statistically significant (chi-square value of 116.204 and p-value of < 0.00001). CONCLUSION: This study showed a promising in-vitro synergy between the drugs fosfomycin and colistin by Checkerboard BMD testing protocol. Colistin being a reserve antibiotic, monotherapy comes with the limitations of higher chances of resistance as well as toxicity, which can be overcome by combination therapy, thereby decreasing CRKP-associated mortality rates and delivering holistic patient benefit.
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BACKGROUND: There are multiple antibiotic regimens for the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) in clinical practice. We conducted this meta-analysis to compare the efficacy and safety of cefiderocol-based regimens and colistin-based regimens in the treatment of CRAB infections. METHODS: Two authors independently searched the PubMed, Web of Science, Embase, and Cochrane databases from their establishment to April 15, 2024, to search for randomized controlled trials (RCTs) or cohort studies, and compared the clinical efficacy and safety of cefiderocol-based regimens and colistin-based regimens in the treatment of CRAB infections. The Newcastle Ottawa Scale (NOS) checklist was used to evaluate the quality of the included studies. The primary outcome was all-cause mortality, and subgroup analysis was conducted on the basis of the site of infection and the risk of bias in the studies. Trial sequential analysis (TSA) was then conducted. RESULTS: Six observational studies were included, with 251 cases in the cefiderocol-based group and 372 cases in the colistin-based group. Compared to the colistin-based group, the cefiderocol-based group had lower all-cause mortality (RR = 0.71, 95% CI: 0.54-0.92, P = 0.01) and 30-day mortality (RR = 0.64, 95% CI: 0.43-0.95, P = 0.03). However, for the 14-day and 28-day mortality rates, there was no statistically significant difference between two groups. According to the subgroup analysis, among patients with bloodstream infection (BSI), the cefiderocol-based group had lower all-cause mortality, but it did not reduce the mortality of ventilator-associated pneumonia (VAP) patients. The result of TSA showed that our conclusions are reliable. There was no significant statistical difference in the microbiological cure rate, clinical cure rate, or duration of hospitalization. In addition, the cefiderocol-based group did not have an increased incidence of acute kidney injury (AKI). CONCLUSIONS: Compared with the colistin-based regimens, the cefiderocol-based regimens were significantly associated with a lower risk of mortality in CRAB-infected patients, especially for patients with BSI. However, they did not show any advantages in terms of the clinical cure rate or microbiological cure rate, nor did they reduce the incidence of AKI. PROSPERO REGISTRATION NUMBER: CRD42023487213.
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Infecciones por Acinetobacter , Acinetobacter baumannii , Antibacterianos , Carbapenémicos , Cefiderocol , Colistina , Colistina/uso terapéutico , Colistina/farmacología , Acinetobacter baumannii/efectos de los fármacos , Humanos , Infecciones por Acinetobacter/tratamiento farmacológico , Infecciones por Acinetobacter/mortalidad , Infecciones por Acinetobacter/microbiología , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Carbapenémicos/uso terapéutico , Carbapenémicos/farmacología , Cefalosporinas/uso terapéutico , Farmacorresistencia Bacteriana Múltiple , Resultado del TratamientoRESUMEN
This guideline aims to promote the prudent use of antibacterial agents for managing carbapenem-resistant Enterobacterales (CRE) infections in clinical practice in Korea. The general section encompasses recommendations for the management of common CRE infections and diagnostics, whereas each specific section is structured with key questions that are focused on antibacterial agents and disease-specific approaches. This guideline covers both currently available and upcoming antibacterial agents in Korea.
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Objective: Characterization of the multidrug resistance (MDR) region in P. aeruginosa strain PA59 revealed the presence of antibiotic resistance genes, including blaIMP-45 and blaVIM-2, within a complex genetic landscape of mobile genetic elements. Methods: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) strains were isolated from Shanghai Changhai Hospital. Polymerase chain reaction (PCR) was used to detect the ß-lactamase genes in the isolated strains. Strains carrying two or more genes were subjected to whole-genome sequencing (WGS) and in-depth bioinformatics analysis. Results: A total of 94 CRPA strains were isolated, among which PA59 was determined to carry blaIMP-45 and blaVIM-2 genes. Compared with single-gene positive or other blaIMP and blaVIM dual-gene positive strains reported, PA59 exhibited a broader range of drug resistance. We discovered a multidrug resistant (MDR)-related region composed of various mobile elements in the PA59 chromosome. This region carried many resistance genes, including the target genes blaIMP-45 and blaVIM-2. By further comparing the mobile elements GI13 and Ph08, we speculated that this integron structure carrying blaIMP-45 and blaVIM-2 was initially integrated into the genomic island or prophage, forming a more complex genetic structure, and then further integrated into the PA59 chromosome through plasmids. Phylogenetic tree analysis showed limited sequence similarity between PA59 and other CRPA strains. Conclusions: This study identified PA59 as the first reported P. aeruginosa strain carrying both blaIMP-45 and blaVIM-2 on the chromosome. The assembly and annotation of the PA59 genome provide valuable insights into the genomic diversity and gene content of this clinically important pathogen, aiding the development of effective strategies against antibiotic resistance.
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OBJECTIVES: This study aimed to assess the incidence and risk factors of subsequent CRE infection among rectal carriers, and their association with geographic region and age. METHODS: A meta-analysis of studies investigating incidence and/or risk factors of subsequent CRE infection among rectal carriers was conducted, with subgroup analyses by geographic region and age. PubMed, Embase, Web of Science, and Cochrane Library were searched (published from inception to January 31st, 2024). This study is registered with PROSPERO, CRD42023444420. RESULTS: Of 4459 studies identified, 24 studies with 8188 CRE rectal carriers were included. The pooled incidence of subsequent CRE infection was 20.6% (95% CI 15.9-25.8). The highest incidence was seen in America (23.6%, 95% CI 14.2-34.5), followed by Europe (20.9%, 95% CI 12.5-30.8) and Asia (19.8%, 95% CI 12.7-27.9). Children had a greater incidence (26.7%, 95% CI 21.3-32.3) than adults (19.8%, 95% CI 14.9-25.2). Fourteen factors were associated with subsequent CRE infection. In Asia, the most notable risk factor was gastritis (OR 4.95 95% CI 1.87-13.11). In Europe, admission to ICU was prominent (OR 2.76 95% CI 1.14-6.65). In America, use of a urinary foley catheter (OR 4.33 95% CI 1.06-17.70) was dominant. Admission to ICU was most notable in adult (OR 3.01 95% CI 1.80-5.02), while mechanical ventilation was shown the greatest significance in children (OR 15.61 95% CI 4.39-55.47). CONCLUSIONS: Risk of subsequent CRE infection among rectal carriers was critical. Identifying the risk factors for subsequent infection could help developing more potent prevention and control measures to reduce CRE infection.
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Background: Acinetobacter baumannii (Ab) disease in the United States is commonly attributed to outbreaks of 1 or 2 monophyletic carbapenem resistance (CR) Ab lineages that vary by region. However, there is limited knowledge regarding CRAb epidemiology and population structures in the U.S. Deep South, and few studies compare contemporary CR and carbapenem-susceptible (Cs) Ab, despite relative prevalence of the latter. Methods: We performed a multiyear analysis of 2462 Ab cases in a large healthcare system in Birmingham, AL, and 89 post-2021 Ab isolates were sequenced and phenotyped by antibiotic susceptibility tests. Results: Although the cumulative CR rate was 17.7% in our cohort, rates regularly increased in winter months as result of seasonal changes in case incidence of CsAb, specifically. Genotyped CRAb belonged to clonal group (CG) 1, CG2, CG108, CG250, or CG499, with local clones of CG108, CG250, and CG499 persisting over multiple months. There was no clonal expansion of any CsAb lineage. Among CRAb isolates, levels of ß-lactam antibiotic resistance and the repertoire of related genetic resistance determinants, which included the novel CR-conferring FtsI A515V polymorphism, differed according to CG. CG108 and CG499 isolates displayed specific heteroresistance to sulbactam and trimethoprim/sulfamethoxazole, respectively, which resulted in discrepant susceptibility results in microbroth versus agar-based antibiotic susceptibility tests modalities. Conclusions: We report an unusually high degree of CRAb phylogenetic diversity principally driven by emergent U.S. lineages harboring novel resistance elements that must be incorporated into diagnostic, surveillance, and preclinical research efforts.
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OBJECTIVES: To evaluate the potency of Manuka honey UMF +15 against Carbapenem-resistant Enterobacterales (CRE). Bacterial resistance is a worldwide problem that is increasing year by year, especially Carbapenem resistance. Alternatives to antibiotics are needed to both reduce costs, and to reduce the spread of antibiotic resistance, with the ultimate goal of saving lives. METHODS: The efficacy of Manuka honey UMF +15 was tested by 2 methods; Well diffusion assay and minimum bactericidal concentration (MBC) against twenty Carbapenem-resistant isolates which collected from Makkah city hospitals during three months of study from 1st of September 2023 up to 1st of December 2023. RESULTS: The growth of all isolates of Carbapenem-resistant Enterobacterales (CRE) was severely inhibited by low concentrations of Manuka honey, affecting 25% of isolates at 15% and 75% of isolates at 18% of Manuka honey. In addition, using the honey at different concentrations in a well diffusion assay resulted, as expected, in a variable zone diameter, ranging from large zones(14mm) to small zones (2 mm) according to the concentration of the honey. CONCLUSION: This study shows the remarkable antibacterial activity of Manuka honey and suggests that this natural remedy might be used in the future as an alternative treatment option against Carbapenem-resistant Enterobacterales (CRE); however, further clinical trials should be performed to corroborate our initial findings.
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Antibacterianos , Enterobacteriaceae Resistentes a los Carbapenémicos , Miel , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Enterobacteriaceae Resistentes a los Carbapenémicos/efectos de los fármacos , Carbapenémicos/farmacología , Leptospermum , Humanos , Enterobacteriaceae/efectos de los fármacosRESUMEN
BACKGROUND: Ceftazidime/avibactam is one of the preferred treatment options for carbapenem-resistant Enterobacterales (CRE). However, the benefit of combining ceftazidime/avibactam with another antibiotic remains unclear. OBJECTIVES: To identify variables associated with treatment failure during the use of ceftazidime/avibactam for CRE infections and assess the effect of combining an aminoglycoside with ceftazidime/avibactam. METHODS: This was a retrospective cohort study of patients with a positive CRE culture treated with ceftazidime/avibactam between 2015 and 2021 in 134 Veterans Affairs (VA) facilities. The primary outcome was 30-day mortality and the secondary outcome was in-hospital mortality. A subanalysis in patients who received an aminoglycoside was also performed. RESULTS: A total of 303 patients were included. The overall 30-day and in-hospital mortality rates were 12.5% and 24.1%, respectively. Age (aOR 1.052, 95% CI 1.013-1.093), presence in the ICU (aOR 2.704, 95% CI 1.071-6.830), and receipt of an aminoglycoside prior to initiation of ceftazidime/avibactam (aOR 4.512, 95% CI 1.797-11.327) were independently associated with 30-day mortality. In the subgroup of patients that received an aminoglycoside (n=77), their use in combination with ceftazidime/avibactam had a 30-day mortality aOR of 0.321 (95% CI, 0.089-1.155). CONCLUSIONS: In veterans treated with ceftazidime/avibactam for CRE infections, increased age, receipt of an empiric aminoglycoside, and presence in the ICU at the time of index culture were associated with higher 30-day mortality. Among patients who received an aminoglycoside, their use in combination with ceftazidime/avibactam trended toward protectiveness of 30-day mortality, suggesting a potential role for this combination to treat CRE infections in patients who are more severely ill.