Carbapenem-resistant Infections Research Articles

Efficacy and Safety of Ceftazidime–Avibactam Alone versus Ceftazidime–Avibactam Plus Fosfomycin for the Treatment of Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia: A Multicentric Retrospective Study from the SUSANA Cohort

Hospital-acquired pneumonia (HAP) and ventilation-associated pneumonia (VAP) are challenging clinical conditions due to the challenging tissue penetrability of the lung. This study aims to evaluate the potential role of fosfomycin (FOS) associated with ceftazidime/avibactam (CZA) in improving the outcome in this setting. We performed a retrospective study including people with HAP or VAP treated with CZA or CZA+FOS for at least 72 h. Clinical data were collected from the SUSANA study, a multicentric cohort to monitor the efficacy and safety of the newer antimicrobial agents. A total of 75 nosocomial pneumonia episodes were included in the analysis. Of these, 34 received CZA alone and 41 in combination with FOS (CZA+FOS). People treated with CZA alone were older, more frequently male, received a prolonged infusion more frequently, and were less frequently affected by carbapenem-resistant infections (p = 0.01, p = 0.06, p < 0.001, p = 0.03, respectively). No difference was found in terms of survival at 28 days from treatment start between CZA and CZA+FOS at the multivariate analysis (HR = 0.32; 95% CI = 0.07–1.39; p = 0.128), while prolonged infusion showed a lower mortality rate at 28 days (HR = 0.34; 95% CI = 0.14–0.96; p = 0.04). Regarding safety, three adverse events (one acute kidney failure, one multiorgan failure, and one urticaria) were reported. Our study found no significant association between combination therapy and mortality. Further investigations, with larger and more homogeneous samples, are needed to evaluate the role of combination therapy in this setting.

Cefepime-taniborbactam and CERTAIN-1: Can we treat carbapenem-resistant infections?

Wagenlehner and colleagues1 demonstrated non-inferiority and superiority with respect to a primary endpoint of composite success (microbiological plus clinical) of cefepime/taniborbactam vs. meropenem in treating complicated urinary tract infections and acute pyelonephritis caused by carbapenem-susceptible gram-negative bacteria in adults. A major area of interest in real-world application of cefepime/taniborbactam is its potential role in treating carbapenem-resistant infections, which deserves further investigation.

A systematic review and meta-analysis of carbapenem resistance and its possible treatment options with focus on clinical Enterobacteriaceae: Thirty years of development in Pakistan

BackgroundCarbapenem resistance is epidemic worldwide, these last resort antimicrobials are listed in the WHO ‘watch group’ with higher resistance potential. During the years 2017-18 Pakistan Antimicrobial Resistance Surveillance System reported an increase in carbapenem resistance. However, a comprehensive information on prevalence and molecular epidemiology of carbapenem resistance in Pakistan is not available. This systematic review and meta-analysis is aimed to report the current carbapenem resistance situation in Pakistan and its treatment options. MethodsIn this systematic review and meta-analysis, we investigated the pooled prevalence (PPr) of carbapenem resistance in Enterobacteriaceae and non-Enterobacteriaceae by organizing available data, from Web of Science and PubMed by April 2, 2020, in various groups and subgroups including species, years, provinces, extended spectrum β-lactamase production, clinical presentation, carbapenemase and metallo-β-lactamase production, and New Delhi metallo-β-lactamase (NDM) prevalence. Literature review was updated for the studies publisehd by December 07, 2023. Moreover, we descriptively reviewed the molecular epidemiology of carbapenem resistance in Enterobacteriaceae and non-Enterobacteriaceae in Pakistan. Lastly, we statistically explored different treatment options available for carbapenem resistant infections. We used R package ‘metafor’ for performing meta-analysis and influence diagnostics and determining treatment options. ResultsFrom two academic databases Web of Science and PubMed we identified 343 studies. Eighty-eight studies were selected for the systematic review and meta-analysis. Seventy-four studies were selected for phenotypic analysis, 36 for genotypic analysis, and 31 for available treatment options. PPr-ID of 12% [0.12 (0.07, 0.16)] was observed for phenotypic carbapenem resistance in Enterobacteriaceae with more prevalence recorded in Klebsiella pneumoniae 24% [0.24 (0.05, 0.44)] followed by 9% [0.09 (−0.03, 0.20)] in Escherichia coli. During the last two decades we observed a striking increase in carbapenem resistance PPr i.e., from 0% [0.00 (−0.02, 0.03)] to 36% [0.36 (0.17, 0.56)]. blaNDM with PPr 15% [0.15 (0.06, 0.23)] in naive isolates was found to be the fundamental genetic determinant for carbapenem resistance in Enterobacteriaceae in Pakistan. Polymyxin B, colistin, tigecycline, and fosfomycin were identified as the suggested treatment options available for multidrug resistant infections not responding to carbapenems. Various studies reported carbapenem resistance from human, animal, and environment sources. ConclusionIn conclusion, we found that NDM-1 producing carbapenem resistant Enterobacteriaceae are increasing in Pakistan. Meta-analysis showed that metallo-β-lactamases producing E. coli ST405 and K. pneumoniae sequence type11 are the major resistant clones. Number of reported studies in various subgroups and inconsistency in following CLSI guidelines are the potential limitations of this meta-analysis. A National antimicrobial resistance (AMR) surveillance strategy based on One Health is urgently needed to check any future AMR crisis in Pakistan.

Exploring the Prevalence, Predictors, and Impact of Bacterial Infections to Guide Empiric Antimicrobial Decisions in Cirrhosis (EPIC-AD)

BackgroundThis study delved into cirrhosis-related infections to unveil their epidemiology, risk factors, and implications for antimicrobial decisions. MethodsWe analyzed acutely decompensated cirrhosis patients (n=971) from North India between 2013-2023 at a tertiary center. Microbiological and clinical features based on infection sites (EASL criteria) and patient outcomes were assessed. ResultsMedian age was 45 years; 87% were males with 47% having alcoholic hepatitis. Of these, 675 (69.5%) had infections; 305 (45%) were culture-confirmed. Notably, 71% of confirmed cases were MDRO-related, chiefly carbapenem-resistant (48%). MDRO prevalence was highest in pulmonary (80.5%) and skin-soft-tissue infections (76.5%). Site-specific distribution and antimicrobials were suggested.Predictive models identified prior hospitalization [OR:2.23 (CI:1.58-3.14)], norfloxacin prophylaxis [OR:2.26 (CI:1.44-3.55)], prior broad-spectrum antibiotic exposure [OR:1.61 (CI:1.12-2.30)], presence of SIRS [OR:1.75 (CI: 1.23-2.47)], procalcitonin [OR:4.64 (CI:3.36-6.40)], and HE grade [OR:1.41 (CI:1.04-1.90)], with an AUC of 0.891 for infection prediction. For MDRO infection prediction, second infection [OR: 7.19 (CI: 4.11-12.56)], norfloxacin prophylaxis [OR: 2.76 (CI: 1.84-4.13)], CLIF-C OF [OR: 1.10 (CI: 1.01-1.20)], prior broad-spectrum antibiotic exposure [OR: 1.66 (CI: 1.07-2.55)], rifaximin [OR: 040 (0.22-0.74)] multisite [OR: 3.67 (CI: 1.07-12.56)], and polymicrobial infection [OR: 4.55 (CI: 1.45-14.17)] yielded an AUC of 0.779 and 93% specificity. Norfloxacin prophylaxis, multisite infection, mechanical ventilation, prior broad-spectrum antibiotic exposure, and infection as acute precipitant predicted carbapenem-resistant infection (AUC: 0.821).Infections (culture-proven or probable), MDROs, carbapenem/pan-drug resistance, and second infections independently linked with mortality (p<0.001), adjusted for age, leucocytosis, and organ failures. A model incorporating age [HR:1.02 (CI: 1.01-1.03), infection [HR:1.52 (CI: 1.05-2.20)], prior hospitalization [HR:5.33 (CI: 3.75-7.57)], norfloxacin [HR:1.29 (CI: 1.01-1.65)], multisite infection [HR:1.47 (CI:1.06-2.04)], and CLIF-C OF [HR:1.17 (CI: 1.11-1.23)] predicted mortality with C-statistics of 0.782 (p<0.05). ConclusionHigh MDRO burden, especially carbapenem-resistant, necessitates urgent control measures in cirrhosis. Site-specific epidemiology and risk models can guide empirical antimicrobial choices in cirrhosis management. Lay summaryOur study delved into infections among hospitalized cirrhosis patients, investigating their occurrence, distribution, risks, and consequences. Notably, infections affected almost 70% of patients, with nearly half of them being confirmed through culture. Most concerning was the identification of multidrug-resistant organisms (MDROs) in 71% of culture-proven cases, particularly carbapenem-resistant bacteria (48%). Pulmonary and skin-soft-tissue infections were the hardest hit. We developed predictive models to foresee infections and particularly drug-resistant and carbapenem-resistant bacterial infections and their mortality. Thus, highlighting the urgent need for measures to counter the substantial impact of MDRO infections in cirrhosis patients. Our findings underscore the importance of targeted antimicrobial therapy guided by site-specific epidemiological insights.

An Emerging Issue: Carbapenem-Resistant Enterobacteriaceae in Solid-Organ Transplantation.

Bloodstream infections caused by carbapenem-resistant bacteria have increased globally. Solid-organ transplant recipients are more prone to these infections. This study aimed to compare the clinical courses of carbapenem-susceptible and carbapenem-resistant Enterobacteriaceae bloodstream infections and to identify risk factors for carbapenem resistance in solid-organ transplant recipients. For this retrospective descriptive study, data for solid-organ transplant recipients (age ≥18) treated from 2015 to 2022 were obtained from medical records. Enterobacteriaceaepositive blood culture was screened from laboratory data. Among 72 patients, there were 100 bacteremia episodes. Patients included 40 kidney (55.6%), 21 liver (29.2%), 7 heart (9.7%), and 4 combined liver and kidney (5.6%) transplant recipients. Fifty-seven bacteremia episodes were recorded between 2015 and 2020, and 43 bacteremia episodes were recorded between 2020 and 2022. Carbapenem resistance was reported in 15.8% of patients before 2020, whereas this rate increased to 39.5% after 2020 (P = .007). Pitt bacteremia score ≥4 (P < .001), Charlson comorbidity index ≥4 (P = .021), chronic liver disease (P = .015), septic shock at admission (P = .001), hypotension at admission (P = .006), bacteremia episodes 48 hours after hospitalization (P = .004), hospitalization in the past 3 months (P = .004), and prior invasive procedure (P = .043) were significant factors for carbapenem resistance. Logistic regression analysis showed that bacteremia 48 hours after hospitalization (P = .002) and hospitalization in the past 3 months (P = .006) were independent risk factors. Carbapenem resistance increased significantly over the years. Bacteremia 48 hours after hospitalization and hospitalization within the past 3 months were determined to be risk factors for carbapenem resistance. Carbapenem-resistant infections are still nosocomial infections. Patients should be hospitalized for as a short time as possible, and both patients and their physicians should follow infection control and prevention methods.

The Natural Ficus carica L. (fig) Extract as an Effective Prophylactic Antibacterial Agent for Inflammation-Related Infections.

Klebsiella pneumoniae (K. pneumoniae) is a multidrug-resistance Gram-negative organism responsible for carbapenem-resistant infections. These challenges have inspired studies on the use of natural products as alternatives to conventional drugs. The aim of this study was to analyze the antibacterial and antioxidant effects of Ficus carica L. (fig) branch extracts and to perform in vivo animal experiments to better understand the absorption mechanisms of the antibacterial components during the digestion process after oral administration. The antibacterial components of the fig branch extracts were analyzed via gas chromatography-mass spectrometry (GC-MS). An in vivo animal study and liquid chromatography-triple quadrupole-tandem mass spectrometry (LC-QQQ-MS/MS) analyses were performed to analyze the deacetylation reactions of the fig extracts after oral administration in mice. Ultimately, the antibacterial effects of the fig extracts increased with the fractional distillation time. The fig extracts showed excellent antibacterial effects against K. pneumoniae, as well as Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and Pseudomonas aeruginosa (P. aeruginosa). The three antibacterial and antioxidant components of the fig extracts were revealed to be eugenol, acetyleugenol, and psoralen. Interestingly, in this study, we identified acetyleugenol in the phenolic compounds of the fig extract for the first time. Through in vivo animal testing, we observed the deacetylation reaction of acetyleugenol to eugenol in the fig extract as digestion proceeded in the internal organs of the mice after oral administration. The results of this study suggest the use of natural fig extract as an effective therapeutic and prophylactic antibacterial agent for inflammation-related infections with a wide variety of biomedical applications.

Efficacy and nephrotoxicity of polymyxin B in elderly patients with carbapenem resistant bacterial infection

BackgroundTo study the efficacy and nephrotoxicity of polymyxin B in the treatment of elderly patients with carbapenem-resistant organism (CRO) infection.MethodsThe clinical and microbiological data of patients with CRO-infected sepsis treated with polymyxin B were retrospectively analyzed. The effective rate, bacterial clearance, incidence and recovery rate of acute renal injury (AKI) and prognosis-related indicators in AKI at different stages were compared.ResultsThe effective rate of 215 elderly patients with CRO infection treated with polymyxin was 50.7%. The total bacterial clearance rate was 44.2%, the total incidence of AKI was 37.2%, the recovery rate of AKI was 35%, and the incidence range of polymyxin B-related AKI was 10.2–37.2%. Logistic multivariate regression analysis showed that the predictors of AKI in elderly patients were high APACHE II score, long duration of polymyxin, chronic renal insufficiency and ineffective outcome; the ROC curve showed that the cutoff value for predicting AKI was a serum creatinine concentration of 73 mmol/L before polymyxin B use, and the AUC was 0.931.ConclusionsRational use of polymyxin B is safe and effective in elderly patients with CRO infection, and its effective outcome can improve the recovery rate of AKI.

Prevalence of Carbapenem-Resistant Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa in a Tertiary Care Hospital in Eastern India: A Pilot Study

In recent years, a wide range of clinical infections are being caused by carbapenem-resistant Enterobacterales, Acinetobacter baumannii and Pseudomonas aeruginosa. This is a matter of great concern, as carbapenem-resistant infections have fewer treatment options. The Enterobacterales comprises a large group of bacterial species commonly causing infections in healthcare settings. The most common bacteria are Escherichia coli and Klebsiella pneumoniae, which can cause both nosocomial and community-acquired infections. This study aimed to determine the prevalence of carbapenem-resistant Enterobacterales, P. aeruginosa, and A. baumannii, in a tertiary care center in India. The study was conducted over a period of seven months, from May 2022 to November 2022. The specimens were processed at the Microbiology Laboratory of Kalinga Institute of Medical Sciences- Pradyumna Bal Memorial Hospital, Bhubaneswar. Standard procedures were used to process the clinical specimens brought to the laboratory. Carbapenem-resistant isolates were screened according to the CLSI 2022 guidelines. This study included 3,006 isolates of Enterobacterales, A. baumannii, and P. aeruginosa. Of these, 29.40% (n = 844) were found to be carbapenem resistant. The breakup is as follows: 689 (77.94%) were Enterobacterales, 108 (12.21%) were A. baumannii, and 87 (9.84%) were P. aeruginosa. Thus, our investigation revealed an overall prevalence of carbapenem-resistant Enterobacterales, A. baumannii, and P. aeruginosa of 29.40%, which corresponds to previous studies in India. Early patient screening, isolation, and contact prevention measures will help reduce infection transmission. Further, larger multi-centric studies are required to obtain a wider perspective regarding this issue.

Molecular epidemiological investigation of carbapenem resistant Klebsiella pneumoniae isolated from intensive care unit patients of six geographical regions of Turkey.

Klebsiella pneumonia causes serious infections in hospitalized patients. In recent years, carbapenem-resistant infections increased in the world. The molecular epidemiological investigation of carbapenem-resistant K. pneumoniae isolates was aimed in this study. Fifty carbapenem-resistant K. pneumoniae isolates from six geographical regions of Turkey between September 2019-2020 were included in the study. The disk diffusion method was used for the antibiotic susceptibility testing. The microdilution confirmed colistin susceptibility. Genetic diversity was investigated by MLST (Multi-Locus Sequence Typing). The resistance rates were as follows: 49 (98%) for meropenem, 47 (94%) imipenem, 50 (100%) ertapenem, 30 (60%) colistin and amoxicillin-clavulanate, 49 (98%) ceftriaxone, 48 (96%) cefepime, 50 (100%) piperacillin-tazobactam, 47 (94%) ciprofloxacin, 40 (80%) amikacin, 37 (74%) gentamicin. An isolate resistant to colistin by disk diffusion was found as susceptible to microdilution. ST 2096 was the most common (n:16) sequence type by MLST. ST 101 (n:7), ST14 (n:6), ST 147 and ST 15 (n:4), ST391 (n:3), ST 377 and ST16 (n:2), ST22, ST 307, ST 985, ST 336, ST 345, and ST 3681 (n:1) were classified in other isolates. In İstanbul and Ankara ST2096 was common. Among Turkey isolates, the most common clonal complexes (CC) were CC14 (n:26) and CC11 (n = 7). In Turkey, a polyclonal population of CC14 throughout the country and inter-hospital spread were indicated. The use of molecular typing tools will highlight understanding the transmission dynamics.

Carbapenem resistant Acinetobacter baumannii in ICU patients in a tertiary care hospital: A retrospective study highlighting their demographic and clinical profile, impact on ICU stay and mortality

: was considered as a leading cause of nosocomial respiratory infection and bacteremia in many hospitals all over the world. However, there was a still a debates whether colonization and/or infection with , increases morbidity and mortality independently of the effect of other risk factors.Aim of the study was to isolate among ICU patients, to detect carbapenem resistant among ICU patients with infections and to determine specific risk factors and outcome of the infections due to CRAB isolates. : A retrospective study was carried out at Vydehi Institute of Medical Sciences and RC in Bangalore, in the ICU department from June 2021 to May 2022.Among all the patients carbapenem resistance was detected more in patients above 60 years of age, males were predominant than females, most of the patients were on ventilation and in sepsis and mortality rate was high with the increased duration of ICU stays. is a highly prevalent microorganism among ICU patients, while its potential to acquire resistance toward commonly used antibiotics represents it as a grave threat to the health care industry. Therefore, signifying the need for its regular monitoring in the health care setups. VAP due to CRAB and excess use of intravascular devices are the most important risk factors for CRAB bacteremia in our ICU. Early implementation of appropriate antimicrobial therapy, particularly in critically ill ICU patients with Carbapenem resistant infections, with two or more co morbidities, can be crucial for survival.

Exploring the views of infection consultants in England on a novel delinked funding model for antimicrobials: the SMASH study.

A novel 'subscription-type' funding model was launched in England in July 2022 for ceftazidime/avibactam and cefiderocol. We explored the views of infection consultants on important aspects of the delinked antimicrobial funding model. An online survey was sent to all infection consultants in NHS acute hospitals in England. The response rate was 31.2% (235/753). Most consultants agreed the model is a welcome development (69.8%, 164/235), will improve treatment of drug-resistant infections (68.5%, 161/235) and will stimulate research and development of new antimicrobials (57.9%, 136/235). Consultants disagreed that the model would lead to reduced carbapenem use and reported increased use of cefiderocol post-implementation. The presence of an antimicrobial pharmacy team, requirement for preauthorization by infection specialists, antimicrobial stewardship ward rounds and education of infection specialists were considered the most effective antimicrobial stewardship interventions. Under the new model, 42.1% (99/235) of consultants would use these antimicrobials empirically, if risk factors for antimicrobial resistance were present (previous infection, colonization, treatment failure with carbapenems, ward outbreak, recent admission to a high-prevalence setting).Significantly higher insurance and diversity values were given to model antimicrobials compared with established treatments for carbapenem-resistant infections, while meropenem recorded the highest enablement value. Use of both 'subscription-type' model drugs for a wide range of infection sites was reported. Respondents prioritized ceftazidime/avibactam for infections by bacteria producing OXA-48 and KPC and cefiderocol for those producing MBLs and infections with Stenotrophomonas maltophilia, Acinetobacter spp. and Burkholderia cepacia. The 'subscription-type' model was viewed favourably by infection consultants in England.

Clinical spectrum and outcomes of carbapenem resistant infections in patients with acute leukaemia: A clinical study from a tertiary oncology centre in India.

e19020 Background: The prevalence of carbapenem resistant organisms (CRO) are increasing worldwide and associated with grave implications in patients with hematological malignancies. Data on such infections in patients with acute leukemia are scarce, especially from the developing world. The aim of this study was to evaluate characteristics and outcomes of bacteremia with CRO in patients treated for acute leukemia with aggressive chemotherapy regimens. Methods: This prospective observational study was conducted in a tertiary oncology centre in South India. Data on Carbapenem resistant bloodstream infection (CRBSI) in patients with acute leukemia (ALL and AML) aged 14-60 years, from March 2017 to February 2018 were prospectively collected. The final outcome was determined as survival and all-cause death due to CRBSI. Results: Out of 334 patients treated for acute leukemia, 49 patients developed infections with CRO (14.6%). The patients included 27 males (55%) and 22 females (45%), with age ranging from 14 year to 58 years (median age: 42 years). The most common isolates were Klebsiella species (63%) and E.coli (25%). All carbapenem resistant isolates were sensitive to Colistin and 74% were sensitive to Tigecycline. The case-fatality rate was 69% (34/49) in our cohort. Acute kidney injury, shock, septicemia and an initial procalcitonin value &gt; 1mcg/L were predictor of mortality. Disease in remission and neutrophil count recovery post chemotherapy were favorable factors associated with the outcome. There was no statistically significant difference in mortality in patients treated with single agent antibiotics versus combination antibiotics sensitive against CRO. Conclusions: Carbapenem resistant infections in patients with acute leukaemia are associated with a high mortality rate. The factors associated with improved outcome were disease in remission and neutrophil count recovery, post chemotherapy. The presence of acute kidney injury, shock, sepsis and a procalcitonin value more than 1 mcg/L were significant predictor of mortality.

Prevalence of Carbapenem-Resistant Enterobacteriaceae and the Genes Responsible for Carbapenemase Production in a Tertiary Care Hospital in South India

Introduction: Carbapenem resistance in Gram-negative bacilli (GNB) is a major concern in the management of resistant infections. The mechanism of carbapenem resistance is most commonly mediated by carbapenemases. The five most common genes (NDM, KPC, VIM, OXA, and IMP) are responsible for carbapenemase production. Knowledge of these genes is important for the management of the disease. Objective: To estimate the prevalence of different genes responsible for carbapenemase production in GNB at a tertiary healthcare centre in South India. Method: In this retrospective study, samples were collected over 16 months. Carbapenem-resistant GNB underwent to Xpert Carba-R assay (Cepheid, Sunnyvale, California, USA) for the detection of five important genes responsible for carbapenemase production: NDM, KPC, VIM, OXA, and IMP. Results: Out of 184 carbapenem-resistant GNB, 20 samples were not included in this study. The rest of the 164 samples grew Klebsiella pneumoniae (152), Escherichia coli (10), and Enterobacter (2). OXA-48 and NDM were the most common genes responsible, with 137 (84.5%) and 95 (58.6%), respectively. Among them, 70 (43.2%) showed the presence of both genes, and 1 (0.6%) showed the presence of OXA-48, NDM, and VIM. Individually, 66 (40.7%) of OXA-48, 24 (14.8%) of NDM, and one (0.6%) of VIM. In this study, the authors did not find the presence of IMP or KPC genes. Conclusion: As a result of limited options and the higher cost of antibiotics for carbapenem-resistant infections, knowledge of these genes helps in the selection and rational use of antibiotics reduces the cost of management and will prevent mortality and morbidity from these infections.

Prevention of Acute Respiratory Failure Due to Administration of Polymyxins by Intravenous Calcium Gluconate in Critically Ill Patients for Treating Carbapenem Resistant Infections in Acute Medicine Unit: A Quality Improvement Project (Qip)

Background: Polymyxin B and colistin are most potent antibiotics for treating carbapenem resistant infections due tomultidrugs resistant organisms that are currently rising remarkably and alarm signs for global health. These are last resorts options for bacteremia during crisis time when pathogens are only sensitive to polymyxins. Most common life threatening complication is respiratory muscle paralysis due to neuromuscular blockage that lead to apnea, acute type 2 respiratory failure and death. Main aim of this quality Improvement project (QIP)was to demonstrate therapeutic effectiveness and outcomes of I/V calcium gluconate during administration of polymyxins. Methods: This QIP was conducted at acute medicine and HDU of a tertiary care hospital for 2 months in Bangladesh. Patients who got I/V calcium gluconate with polymyxins in January and February, 2023 were compared with similar data without calcium gluconate for prior 4 months. Data analysis and interpretation done by unpaired t test. Results: Primary outcome shows statistically significant decrease dintubation and mechanical ventilation due to sudden respiratory failure and ICU transfer after getting I/V calcium gluconate during polymyxins(30.8%,n=13 and 88.9% ,n=9 and p= &lt;0.005). Conclusion: This study showsstrongly visible positive outcome in prevention of acute respiratory failure by polymyxins in critically ill patients. We feel that all physicians may practice this study in acute medicine and critical care setup. Bangladesh J Medicine 2023; Vol. 34, No. 2(1) Supplement: 216

What to Do with the New Antibiotics?

Multidrug-resistant Gram-negative bacteria-related infections have become a real public health problem and have exposed the risk of a therapeutic impasse. In recent years, many new antibiotics have been introduced to enrich the therapeutic armamentarium. Among these new molecules, some are mainly of interest for the treatment of the multidrug-resistant infections associated with Pseudomonas aeruginosa (ceftolozane/tazobactam and imipenem/relebactam); others are for carbapenem-resistant infections associated with Enterobacterales (ceftazidime/avibactam, meropenem/vaborbactam); and finally, there are others that are effective on the majority of multidrug-resistant Gram-negative bacilli (cefiderocol). Most international guidelines recommend these new antibiotics in the treatment of microbiologically documented infections. However, given the significant morbidity and mortality of these infections, particularly in the case of inadequate therapy, it is important to consider the place of these antibiotics in probabilistic treatment. Knowledge of the risk factors for multidrug-resistant Gram-negative bacilli (local ecology, prior colonization, failure of prior antibiotic therapy, and source of infection) seems necessary in order to optimize antibiotic prescriptions. In this review, we will assess these different antibiotics according to the epidemiological data.

A Clinico-Microbiological Study of Blood Stream Infections in a Tertiary Referral Hospital: Colistin Resistance &amp; Challenges

Carbapenems, frequently used for the treatment of infections caused by Multidrug-resistant (MDR) Gram-negative bacteria (GNB) are being reported with increased resistance rate. Colistin with other antibiotics has emerged as a saviour but inappropriate reporting of colistin susceptibility is a serious clinical concern. To detect the antimicrobial resistance of GNB isolates obtained from blood samples, further, colistin Minimum Inhibitory Concentration (MIC) testing of carbapenem-resistant isolates was done by the Broth Micro-dilution Method (BMD). This prospective study was done in the Department of Microbiology from January 2020 to December 2020. The GNB isolated from blood samples were identified &amp; antimicrobial-susceptibility testing was performed by the Vitek 2 system. Colistin MIC of carbapenem-resistant isolates was done by the BMD method. The data were statistically analysed using SPSS 21. Growth was obtained in 5% of blood samples and 546 (75.8%) of these were GNB including predominantly E.coli, Klebsiella spp &amp; Acinetobacter spp. Carbapenem-resistant infections 246 (48.5%) showed significant association with ICU admission, resistance to other classes of antibiotics &amp; mortality. Among the carbapenem-resistant isolates, only seven (2.9%) were found resistant to colistin by the BMD test. Most of these were Klebsiella spp. (71.4%) &amp; obtained predominantly from ICU patients (85.7%). All the carbapenem-resistant isolates were found intermediate sensitive to colistin by the VITEK-2 system. The isolates of GNB were characterized as MDR 323 (59.2%), XDR 164 (30%) and PDR 2 (0.4%). Use of, colistin, should be guided by BMD, the reference method for MIC testing to avoid erroneous reporting of colistin resistance.

Baicalein inhibits plasmid-mediated horizontal transmission of the blaKPC multidrug resistance gene from Klebsiella pneumoniae to Escherichia coli.

Carbapenem-resistant bacterial infections pose an urgent threat to public health worldwide. Horizontal transmission of the β-lacatamase Klebsiella pneumoniae carbapenemase (blaKPC) multidrug resistance gene is a major mechanism for global dissemination of carbapenem resistance. Here, we investigated the effects of baicalein, an active ingredient of a Chinese herbal medicine, on plasmid-mediated horizontal transmission of blaKPC from a meropenem-resistant K. pneumoniae strain (JZ2157) to a meropenem-sensitive Escherichia coli strain (E600). Baicalein showed no direct effects on the growth of JZ2157 or E600. Co-cultivation of JZ2157 and E600 caused the spread of meropenem resistance from JZ2157 to E600. Baicalein at 40 and 400 μg/mL significantly inhibited the spread of meropenem resistance. Co-cultivation also resulted in plasmid-mediated transmission of blaKPC from JZ2157 to E600, which was inhibited by baicalein. Therefore, baicalein may be used in clinical practice to prevent or contain outbreaks of carbapenem-resistant infections by inhibiting the horizontal transfer of resistance genes across bacteria species.

P23 The SMASH survey: Subscription Models for Antibiotics in Hospital—preliminary results

Abstract Objectives On 1 July 2022 NHS England launched a novel delinked ‘subscription-type’ payment model for two new antimicrobials, ceftazidime/avibactam and cefiderocol. The SMASH survey (Subscription Models for AntibioticS in Hospitals) aims to capture the views of Infectious Diseases and Microbiology Consultants on key knowledge gaps around the implementation and impact of this model in the NHS. Methods A novel questionnaire was developed and piloted for this survey (https://www.surveymonkey.co.uk/r/SMASHsurvey). The target audience included Consultants in Infectious Diseases and/or Medical Microbiology working at least 1 day per week (2 Programmed activities or equivalent) in an NHS acute hospital in England. The questionnaire was distributed to all eligible Consultants in England using a network of local investigators in 35 key locations around the country. The SMASH survey was sponsored by the London School of Hygiene and Tropical Medicine (REC Reference No 28161/RR/29296) and funded by an independent research grant from Shionogi B.V. Results A total of 111 complete responses were received within the first 21 days of the survey launch. Most responders (55.9%, 62/111) had a CCT in Microbiology or Infectious Diseases and Medical Microbiology (26.1%, 29/111). Only 57.6% (64/111) reported having heard of the new funding model before completing the survey, yet the majority (72.1%, 80/111) agreed that it is a welcome development in the management of drug-resistant infections. Some Consultants reported that cost is a significant consideration when using specific antimicrobials (46.8% Agree or Strongly Agree), while other Consultants were unsure (19.8% Neither Agree or Disagree) or disagreed with this statement (33.4% Disagree or Strongly Disagree). Using a 5-point scoring system and other antimicrobials for carbapenem-resistant infections as comparators, responders indicated that they believed ceftazidime/avibactam and cefiderocol had high insurance (4.28/5 and 4.16/5 respectively) and diversity value (4.11/5 and 4.07/5), moderate enablement (3.37/5 and 3.15/5) and transmission value (3.12/5 and 3.00/5) and low spectrum value (2.13/5 and 2.16/5). Meropenem recorded the highest score for enablement value (3.77/5) and transmission value (3.31/5), while Fosfomycin the highest score for spectrum value (3.06/5). With regards to antimicrobial stewardship, only 20.7% (23/111) of Consultants agreed that the new funding model will lead to reduced use of carbapenems. 46% of responders (51/111) would consider using the two newly introduced antibiotics empirically, when risk factors for antimicrobial resistance are present, while the rest would only use them in microbiologically confirmed carbapenem-resistant infections. The most important resistance risk factors that would justify empirical use were previous infection with carbapenem-resistant bacteria (81.1%), current colonisation with carbapenem-resistant bacteria (73.9%), ward outbreak of carbapenem-resistant bacteria (68.5%), clinical treatment failure of carbapenems (63.1%) and recent admission to high prevalence hospital for carbapenem-resistant bacteria (46.9%). Conclusions The ‘subscription type’ payment model for antimicrobials was introduced in England 5 months ago, yet many infection specialists have not been informed about it. Its effect on stewardship is currently uncertain and introduced antimicrobials are likely to be used empirically. Infection specialists in England agree that new antimicrobials have benefits beyond the treatment of an individual patient, especially in terms of insurance and diversity value.

An Investigation on The Use of Colistin in Critically Ill Patients at A Teaching Hospital in Ho Chi Minh City

Colistin is reintroduced into therapeutic protocols as one of the last resort antibiotics against multidrug-resistant (MDR) pathogens. In February 2019, the International Consensus Guidelines (ICG 2019) on optimizing the administration of colistin has for the first time stipulated an official recommendation for higher colistin dosing regimen based on pharmacokinetic/pharmacodynamic (PK/PD) modeling data. This study aimed at assessing the current dosing of colistin at University Medical Center (UMC) of Ho Chi Minh City (HCMC) and to identify rates and risk factors of colistin-induced nephrotoxicity. A cross sectional study was conducted on patients admitted to Intensive Care Unit (ICU), being treated for severe infection with at least 5 days of colistin IV administration from April 2018 to April 2019. KDIGO criteria were used to evaluate nephrotoxicity during treatment. Colistin-resistance was detected in 4 cases during the study period. The majority (n=104, 87.4%) of patients was diagnosed with pneumonia due to mainly Acinetobacter baumannii. Rational dosing according to PK/PD approach, EMA, FDA was observed in 33 cases (27.8%), 39 cases (32,8%), and 44 cases (38,2%), respectively. 85 cases (71,4%) were evaluated as rational dosing in accordance with at least one of the three guidelines. Clinical efficacy was recorded in 59 infected patients (49.6%). Lower average maintenance dose was observed in patients with treatment failure (p = 0.002). KDIGO-defined acute kidney injury (AKI) developed in 70 patients (58,8%). Multivariate analysis showed that concomitant administration of vasopressors (OR = 16.52; 95% CI 5.3750.83; p = 0.001), furosemide (OR = 5.24; 95% CI 1.89–14.55; p = 0.001) and hypoalbuminemia (&lt; 25 g/l) (OR = 6.24; 95% CI 2.17–17.93; p = 0.001) were significantly associated with nephrotoxicity. Consistent with previous studies, due to a very modest clinical cure rate with a high frequency of colistin-induced AKI and the development of colistin-resistant strains, alternative agents such as new beta-lactam/beta-lactamase inhibitor combinations with favourable safety data are strongly preferred for the treatment of carbapenem-resistant infection.

669. Real World Use of Ceftazidime/Avibactam for the Treatment of Multidrug Resistant Gram Negative Bacilli Infections: A Real World Experience from Two Centers in Mexico

Abstract Background Ceftazidime-avibactam (C-A) is effective against many carbapenem resistant Enterobacteriaceae (CRE) and some carbapenem resistant Pseudomonas aeruginosa (CRPsa), indicated in complicated urinary tract infections (cUTI), complicated intra-abdominal infections (cIAI), and hospital-acquired pneumonia. To our knowledge, in Mexico, there is no data regarding the clinical efficacy (clinical cure) of its use in the treatment of cIAI, cUTI, hospital-acquired pneumonia, and the treatment of CRE and CRPsa. Methods this is a descriptive, observational, retrospective study, including infections in which ceftazidime avibactam was the definitive therapy for CRE and CRPsa, and empiric treatment of cUTI, cIAI, Hospital-acquired pneumonia. The study includes patients from 2 centers, between April 2019 and february 2020. Demographic, clinical and microbiological data were obtained. Clinical cure was defined as the absence of fever, leukocytosis, tachycardia, systolic pressure &amp;lt; 90mmHg or use of vasopressors, and lowering of C-reactive protein by at least 60% after 5 days of treatment. Results Seventy patients in which C-A was the definitive antimicrobial treatment were evaluated. UTI accounts for 24 cases (34.2%), followed by primary and secondary peritonitis (28.5%), soft tissue infection (12.8%), bacteremia (12.8%) and hospital-acquired pneumonia (11.4%). Of all infections 39.9% were secondary to CRPsa, and 60.1% were due to CRE (30.3% Klebsiella pneumoniae, 21.2% Escherichia coli and 6% for Klebsiella oxytoca, Enterobacter cloacae and Proteus mirabilis). Clinical cure was achieved in 64 patients (91.4%). Six patients died, but only one was associated to CRPsa infection. Conclusion To the best of our knowledge, this is the first study of Mexican experience with C-A. Our study brings relevant information on the treatment of carbapenem resistant GNB infections with C-A in our population. More studies, specifically RCTs are needed to prove the antibiotic efficacy in our media. Disclosures All Authors: No reported disclosures.