Carbapenem Resistant Gram Research Articles

2759. Cefiderocol vs Best Available Therapy for the Treatment of Carbapenem- Resistant Acinetobacter baumannii

Abstract Background Cefiderocol has been evaluated as a treatment of carbapenem-resistant gram negative infections. However robust data for the optimal approach to treat carbapenem-resistant Acinetobacter baumannii (CRAB) is lacking. The purpose of this study was to evaluate the efficacy of cefiderocol vs best available therapy (BAT) for the treatment CRAB infections. Methods This IRB-approved retrospective observational review was conducted at a three-hospital community health system between June, 2020 to February, 2021. Hospitalized patients were included if they were ≥18 years old and received ≥24 hours of targeted antibiotics for CRAB. Patients were excluded if they were considered to be colonized or were pregnant. Patients in the cefiderocol group were matched with patients in BAT group based on age and source of infection in a 1:3 ratio. The primary endpoint of this study was to assess all-cause inpatient mortality (ACIM) at the end of therapy. The secondary endpoint included clinical cure (CC) at the end of therapy. A subgroup analysis was performed for patients treated with cefiderocol monotherapy, cefiderocol combination therapy, and combination BAT to determine differences in ACIM and CC. Results A total of 60 patients were included in the primary analysis; 15 receiving cefiderocol and 45 receiving BAT. There was no difference in patient age, race, and diagnosis between both groups. Patients in the BAT group had a shorter length of stay vs cefiderocol group (14 vs 19 days. P=0.05). Ampicillin/sulbactam (86.7% vs 57.8%, P=0.06) and minocycline (86.7% vs 22.2%, P=0.0001) non-susceptible CRAB isolates were more common in the cefiderocol group vs BAT group (as seen in Figure 1). No differences were seen in ACIM (27% vs 18%, P=0.47) and CC (53% vs 60%, P=1.0) between both groups. The subgroup analysis revealed cefiderocol combination therapy had a decreased number of patients with ACIM and had favorable CC outcomes compared to cefiderocol monotherapy and combination BAT (as seen in Figure 2). Comparison of Susceptibility Patterns All Cause Inpatient Mortality and Clinical Cure in Subgroup Analysis of Monotherapy vs Combination Therapy Conclusion Cefiderocol seems to be a viable option for treatment of CRAB infections. No differences were seen in ACIM and CC between cefiderocol and BAT. Cefiderocol combination therapy seems to be a preferred therapeutic option for CRAB infections. Disclosures All Authors: No reported disclosures

Efficacy of Colistin with Carbapenems Combination by Checkerboard Assay against Carbapenem Resistant Non Lactose Fermenting Gram Negative Bacteria

Recent emergence of carbapenem resistant non-fermenting Gram negative bacteria (CRNFGNB) predominantly Pseudomonas and Acinetobacter species are responsible for significant proportion of nosocomial infections with increased mortality. Of the various mechanisms known, carbapenemases especially metallo beta lactamase (MBL) mediated resistance is the most concerning because of its easy transmissibility via mobile genetic elements and lack of MBL inhibitors for clinical use. In the present study we determined to estimate the prevalence of carbapenem resistant Pseudomonas and Acinetobacter species, their resistance mechanisms by phenotypic tests and synergistic studies with Colistin and carbapenems combination by checkerboard assay. Carbapenem resistance among these two bacteria is 53.2% being isolated predominantly from pus and endotracheal secretions and from patients within the age group of less than 9 years (44%) and more than 60 years (23%). The incidence of carbapenemase and MBL production in NFGNB is 89.8% and 87.9%, respectively. Only Colistin and Tigecycline show significant antibacterial activity while most of the tested antibiotics were found to be least effective against carbapenem resistant NFGNB. Colistin and Imipenem combination demonstrated synergistic activity in majority of the NFGNB species; however, translation of such in vitro efficacy models into highly variable in vivo conditions could be possible only with strong clinical support.

Prevalence and molecular characterization of carbapenem resistant gram-negative bacilli in a tertiary care hospital in Mumbai

Carbapenem (CR) among gram-negative bacteria is a worldwide problem. It is ranked in the highest priority category in the World Health Organization (WHO) global priority list of pathogens.It is responsible for therapeutic failure in both hospital and community-acquired infections.Identifying and monitoring the local epidemiology of the carbapenem resistant organisms, understanding specific mechanisms underlying the resistance and implementing measures to prevent their spread is the need of the hour.The aim of the study was to determine the prevalence and molecular epidemiology of Carbapenem resistant Gram negative bacilli in this hospital.: A retrospective study was carried out in the Department of Microbiology of a tertiary care Hospital in Mumbai from January to December 2022. All Gram negative bacilli from various specimens were identified and antimicrobial susceptibility was reported using the VITEK2 automated system (BioMerieux, Durham, North Carolina) and interpreted as per CLSI 2022 guidelines. The resistant genes in the isolates were detected by Xpert Carba-R assay (Cepheid, Sunnyvale, CA) on request by a consulting physician.: Out of 2,351 gram negative bacilli isolates, 624 were Carbapenem resistant (26.5%). (59.9%) was the most common CR isolate. Molecular testing was done for 190 of these 624 CR isolates. In which New Delhi Metallo beta lactamase (NDM (33.68%) was the most common resistant gene identified followed by NDM & OXA-48(32.63%). With the prevalence of Carbapenem resistant isolates in the settings, adherence to infection control practices and stringent implementation of antimicrobial stewardship is crucial to curb the rate of infection.

New Insights on the Carbapenem-resistant Gram Negative-associated-Infections: Challenges and Opportunities

New Insights on the Carbapenem-resistant Gram Negative-associated-Infections: Challenges and Opportunities

Multi-drug resistant (MDR) and extensively drug-resistant (XDR) bacteraemia rates among cancer patients in an oncology hospital in eastern India: an 11-year retrospective observational study

Trend analysis of bacteraemias caused by multi-drug resistant (MDR) and extensively drug resistant (XDR) bacteria helps to assess efficacy of infection prevention and control (IPC) practices. Data on the trends of MDR and XDR bacteraemias are lacking from cancer patients in India. To report antibiotic resistance rates over time in bacteraemias and to assess the effect of IPC practices where patient isolation facilities were limited on the rates and trends of MDR and XDR bacteraemias from a cancer centre in eastern India. A retrospective observational study was conducted in a specialist cancer hospital in India from 2011 to 2021. The study included both patients with haematological and solid organ malignancy. Data on blood cultures and surveillance culture samples were analysed. Blood cultures were processed using BACT/ALERT® (bioMérieux, Marcy-l'Étoile, France) and the identification and antibiotic susceptibilities of bacteria were performed using VITEK® 2 (bioMérieux, Marcy-l'Étoile, France). Surveillance cultures for MDR/XDR bacteria were performed on a subset of patients and processed based on a modified method described previously. 3rd-generation cephalosporin-resistant Gram negative bacilli were the commonest cause of MDR bacteraemia (57.6%) followed by carbapenem resistant organisms (CRO) (35.7%). Bacteraemias caused by vancomycin-resistant enterococci (VRE), meticillin-resistant Staphylococcus aureus (MRSA) and colistin-resistant Gram negative bacilli were responsible for 1.3%, 2.3% and 3.0% of laboratory confirmed bloodstream infections (BSI) respectively. The ranges of the rates of MDR/XDR BSI per 1000 in-patients during the study period were: MRSA (1-1.18), VRE (0-0.88), 3rd generation cephalosporin-resistant Gram negative bacilli (10.10-20.32), CRO (5.05-13.07) and colistin-resistant Gram negative bacilli (E.coli, Klebsiella, Pseudomonas aeruginosa, Acinetobacter spp (0-1.3). Surveillance cultures collected from a subset of patients showed ranges of MRSA detection in 0-2.11%, VRE in 1.67%-7.49%, 3rd generation cephalosporin-resistant Gram negative bacilli in 55%-89.91% and carbapenem resistant Gram negative bacilli in 18.33%-31.11% of patients. This is one of few studies providing trend data for MDR/XDR bacteraemia rates among cancer patients in India over a decade. In a high prevalence setting it was possible to keep the rates of MDR/XDR bacteraemia controlled with IPC strategies and without adequate isolation facilities. The results are of potential interest to policy makers, IPC specialists and clinicians.

Risk Factors for Carbapenem Resistant Gram Negative Bacteria (CR-GNB) Carriage Upon Admission to the Gastroenterology Department in a Tertiary First Class Hospital of China: Development and Assessment of a New Predictive Nomogram.

With the increasing number of critically ill patients in the gastroenterology department (GED), infections associated with Carbapenem resistant gram-negative bacteria (CR-GNB) are of great concern in GED. As the turn-around time (TAT) for a positive screening culture result is slow, contact precaution and pre-emptive isolation, cohorting methods should be undertaken immediately on admission for high-risk patients. Accurate prediction tools for CR-GNB colonization in GED can help determine target populations upon admission. And thus, clinicians and nurses can implement preventive measures more timely and effectively. The purpose of the current study was to develop and internally validate a CR-GNB carrier risk predictive nomogram for a Chinese population in GED. Based on a training dataset of 400 GED patients collected between January 2020 and December 2021, we developed a model to predict CR-GNB carrier risk. A rectal swab was used to evaluate the patients' CR-GNB colonization status microbiologically. We optimized features selection using the least absolute shrinkage and selection operator regression model (LASSO). In order to develop a predicting model, multivariable logistic regression analysis was then undertaken. Various aspects of the predicting model were evaluated, including discrimination, calibration, and clinical utility. We assessed internal validation using bootstrapping. The prediction nomogram includes the following predictors: Transfer from another hospital (Odds ratio [OR] 3.48), High Eastern Cooperative Oncology Group (ECOG) performance status (OR 2.61), Longterm in healthcare facility (OR 10.94), ICU admission history (OR 9.03), Blood stream infection history (OR 3.31), Liver cirrhosis (OR 4.05) and Carbapenem usage history within 3 month (OR 2.71). The model demonstrated good discrimination and good calibration. With an estimate of individual risk using the nomogram developed in this study, clinicians and nurses can take more timely infection preventive measures on isolation, cohorting and medical interventions.

Spread of armA 16S rRNA Methylase Gene in a Tertiary Hospital and Errors in Aminoglycoside Susceptibility Results of Rapid Susceptibility Test Systems

Aminoglycosides (AGs) are actively used in combination therapies against carbapenem resistant gram negative species in recent years. Spread of 16S rRNA methylases which can cause high-level resistance to AG antibiotics, limits this treatment choice. Although there are some studies showing that errors in determining AG susceptibility in automated systems may be related to the armA gene, one of the 16S rRNA methylase genes, the exact reason for these errors is not yet known. In our study, we aimed to investigate the relevance of 16S rRNA methylases to the discrepancies between VITEK 2.0 and disc diffusion test results for amikacin (AK) and gentamicin (GEN) susceptibility of Acinetobacter baumannii and Klebsiella pneumoniae isolates. All K.pneumoniae and A.baumannii isolates from 1st January-10th February 2018 were collected prospectively and included in the study. Additionally, two initial isolates from July 2017 (one K.pneumoniae and one A.baumannii isolate) for which first discrepant susceptibility results were determined, were also included. Amikacin and gentamicin susceptibility results of 37 isolates [A. baumannii (n= 20) and K.pneumoniae (n= 17)] were evaluated together with VITEK 2.0 system, disc diffusion and gold standard broth microdilution methods and minor error (mE), major error (ME) and very major error (VME) rates were calculated. The rmtB, rmtC and armA genes in isolates were investigated by polymerase chain reaction (PCR) and the relationship between the presence of 16S rRNA methylases and false susceptibility results were examined. In addition, disc diffusion test results were evaluated at the end of four, six, eight hours and one night incubation periods to examine the effect of the double zone phenotype observed in 13 of the study isolates on rapid susceptibility tests. All disc diffusion test results were found to be compatible with broth microdilution test results. When the VITEK 2.0 system and the broth microdilution test were compared, 10.3% and 12.1% VME and 8.1% and 5.4% mE were detected for AK and GEN susceptibility results, respectively. While rmtB and rmtC genes were not detected in the study isolates, armA gene was positive in eight (47.1%) of 17 K.pneumoniae isolates and in 15 (75%) of 20 A.baumannii isolates. All three VMEs in A.baumannii isolates were detected in AK susceptibility results. Two of those were armA gene positive and one was armA gene negative isolates. All four VMEs in K. pneumoniae isolates were detected in GEN susceptibility results only, and all of these isolates were armA gene positive. No direct correlation was found between the errors detected in the VITEK 2.0 system susceptibility results and the double zone phenotype. When the isolates were evaluated in the 4-16 hours incubation time interval, it was observed that resistant colonies could be detected after a minimum of six hours of incubation period in the inhibition zone surrounding the aminoglycoside discs. To the best of our knowledge this is the first report of armA producing A.baumannii from Turkey. The high rate of armA gene positivity detected in our isolates suggested that the prevalence of armA gene increased in our country or at least in our region, in recent years. In the AG susceptibility results of the VITEK 2.0 system, the rate of VME above the acceptance criterion has shown that the errors occurred were not directly related to armA gene positivity or double zone phenotype. Finally, our study results indicated that AG susceptibility results should be evaluated minimum six hours later of incubation while implementing rapid susceptibility tests.

The epidemiology of bloodstream infection contributing to mortality: the difference between community-acquired, healthcare-associated, and hospital-acquired infections

BackgroundThe epidemiology of bloodstream infection (BSI) is well-established; however, little is known about the contribution of different pathogens to mortality. To understand true burden of BSI, pathogens contributing to mortality were investigated and compared according to where the BSI was acquired.MethodsData from deceased patients in two teaching hospitals in the Republic of Korea were collected. BSI contributing mortality was defined as BSI within 2-weeks before death. Cases were grouped by acquisition sites: community-acquired (CA)-, healthcare-associated (HCA)-, and hospital-acquired (HA)-BSI. Drug resistance, BSI focus, and appropriateness of empirical antimicrobial therapy were also compared.ResultsAmong 1849 deceased patients in the hospitals, 280 (15.1%) patients experienced BSI within 2-weeks before death. In all, 71, 53, and 156 patients in the CA-, HCA-, and HA-BSI groups, respectively, with 316 total isolated pathogens were analyzed. The three most common pathogens were Klebsiella pneumoniae (17.1%), Escherichia coli (16.4%), and Staphylococcus aureus (11.4%). While K. pneumoniae and E. coli were the most common pathogens in CA- and HCA-BSI, Acinetobacter baumannii and Candida species were in HA-BSI. 26.3% (41/156) of patients experienced breakthrough HCA-BSI during administration of carbapenem and/or vancomycin. The proportion of central venous catheter-related infection (0%, 3.4% and 28.3%), carbapenem resistant-Gram negative bacilli (0%, 6.9% and 21.9%), and inappropriate empirical antimicrobial therapy (21.1%, 37.7% and 51.9%; all P < 0.001) were more frequently observed in HA-BSI.ConclusionThe epidemiology of BSI related to mortality had unique characteristics according to the acquisition site. Given the epidemiology of HA-BSI, infection control and antibiotics stewardship programs should be emphasized.

Evaluation of ceftazidime-avibactam efficacy in gram negative bacteria

In recent years, the emergence of multidrug-resistant Enterobacterales and Pseudomonas aeruginosa strains has become a serious problem due to high morbidity/mortality rates and difficulty in treatment.Treatment options are very limited in infections caused by carbapenem-resistant microorganisms.Ceftazidime/avibactam (CZA) is a newly developed cephalosporin/beta-lactamase inhibitor combination for the treatment of infections caused by resistant Gram negative microorganisms.In this study, the in vitro activity of CZAagainst various carbapenem resistant Gram negative microorganisms was evaluated.122 carbapenem-resistant Gram negative bacteria species were included in the study. Identification of the strains and their antimicrobial susceptibility were performed using conventional methods as well as a BD Phoenix (BectonDickinson, MD, USA) fully automated system. Ceftazidime-avibactam susceptibility was determined using the disk diffusion method (Bioanalyse, Ankara, Turkey) and the gradient diffusion test (Liofilchem MIC strip test, Italy).In carbapenem-resistant K. pneumoniae strains, gentamicin/amikacin susceptibility was found in 14 strains (14.3%) and ceftolozane-tazobactam susceptibility was found in only one strain. In P. aeruginosa strains, gentamicin/amikacin susceptibility was seen in 8 strains (33.3%) and piperacillin tazobactam susceptibility was found in 7 strains (29.2%), and other than these all strains were found to be resistant to all the other antibiotics studied. CZA susceptibility rates in carbapenem resistant K. pneumoniae and P. aeruginosa strains were found to be 85.7% and 83.3%, respectively.ESBL production and carbapenemase activity were positive in the strains included in the study.The results obtained from this study show that CZA can be a treatment alternative in carbapenem-resistant Gram negative bacterial infections. More studies are needed in order to monitor the resistance status of these new treatment options against the increasing resistance threat in hospitals and to determine the appropriate treatment option.

POSC116 Economic Evaluation of Cefiderocol in Patients with Confirmed Carbapenem-Resistant Infections in the Italian Healthcare System

Carbapenem-resistant (CR) gram negative pathogens present a particular threat and WHO highlighted three priority pathogens (CR Enterobacterales, CR Pseudomonas aeruginosa, CR Acinetobacter baumannii) which cefiderocol, a new parental antibiotic can target. Here, we determine the cost-effectiveness of cefiderocol compared to colistin and colistin based regimens for treatment of complicated Urinary Tract Infections (cUTI), Pneumonia and Bloodstream infection/sepsis in patients who have confirmed CR pathogen. A decision tree was adopted for the treatment pathway with two separate subgroups of patients; either at high risk of a carbapenem-resistant infection or a confirmed CR infection (determined by microbiological testing). Only confirmed CR population are considered here. Published literature was used for cost inputs and Italian microbiological susceptibility data were used to determine susceptibility to CR pathogen. Treatment effectiveness data for cefiderocol and colistin was inputted from the CREDIBLE – CR trial. No inappropriate therapies could be selected since the pathogen susceptibility was known at the time of intervention and no de-escalation was required. The evaluation was performed from both a healthcare and a societal perspective over a lifetime time horizon, using the ICER annual discount rate of 3%. A probabilistic sensitivity analysis (PSA) was also conducted to account for uncertainty. The cost-effectiveness threshold was set at €40,000. A summary of the base case cost-effectiveness results for the confirmed carbapenem-resistant population are as follows for cefiderocol and colistin respectively: cost per patient is €15,988 vs €12,732; QALYS are 10.20 vs 9.70 and discounted LY per patient are 13.46 vs 12.81. The ICER,€6,515, is below the cost-effectiveness threshold. A PSA was conducted to show a probability of cost-effectiveness of 71.4% (ICER: €5,972). Cefiderocol is estimated to be cost-effective for the treatment of confirmed CR infections in Italy, when compared to colistin and colistin based regimens, but further research is warranted for comparisons to other antibiotics.

Carbapenem Resistant Gram Negative Bacteria in Gut and Correlation with Bacteraemia in a Paediatric Stem Cell Transplant Unit in India.

Carbapenem Resistant Gram Negative Bacteria in Gut and Correlation with Bacteraemia in a Paediatric Stem Cell Transplant Unit in India.

Detection and characterization of carbapenem resistant Gram\u2010negative bacilli isolates recovered from hospitalized patients at Soba University Hospital, Sudan

BackgroundAntimicrobial resistance (AMR) poses a complex threat to global health security and universal health coverage. Recently, nosocomial infections with carbapenemase-producing Gram-negative bacilli (GNB) is increasing worldwide. We report the molecular characterization and detection of genes associated with carbapenemase producing Gram negative bacteria isolated from hospitalized patients at Soba University Hospital (SUH) in Khartoum State, Sudan.ResultsBetween October 2016 and February 2017, a total of 206 GNB clinical specimens were collected from hospitalized patients in SUH. Of 206 carbapenem resistance isolates, 171 (83 %) were confirmed as phenotypically resistant and 121 (58.7 %) isolates harboured one or more carbapenemase genes. New Delhi metallo-β-lactamase (NDM) types were the most predominant genes, blaNDM 107(52 %), followed by blaIMP 7 (3.4 %), blaOXA-48 5(2.4 %) and blaVIM 2 (0.9 %). Co-resistance genes with NDM producing GNB were detected in 87 (81.3 %) of all blaNDM producing isolates. NDM-1 was the most frequent subtype observed in 75 (70 %) blaNDM producing isolates. The highest percentage of resistance was recorded in ampicillin (98 %), cephalexin (93.5 %) amoxicillin clavulanic acid (90 %), cefotaxime (89.7 %), ceftriaxone (88.4 %), ceftazidime (84.2 %), sulfamethoxazole-trimethoprim (78.4 %) and nitrofurantoin (75.2 %), aztreonam (66 %) and temocillin (64 %). A close correlation between phenotypic and carbapenemase genes detection in all GNB was observed.ConclusionsThe frequency of carbapenemase producing bacilli was found to be high in SUH. NDM was found to be the most prevalent carbapenemase gene among clinical isolates. Close surveillance across all hospitals in Sudan is required. The relative distribution of carbapenemase genes among GNB in nosocomial infections in Africa needs to be defined.

Clinical, phenotypic and genotypic profile of carbapenem resistant gram negative infections in intensive care units

Carbapenems are currently the only active beta-lactams effective against the ESBL producing pathogens; this has led to an increase in their use not only for documented infections but also for empirical treatment of acquired infections in ICU patients. Thus, there is a selective pressure for carbapenem resistance in intensive care units of tertiary care hospitals. Carbapenem resistant infections are associated with high morbidity &amp; mortality. 1. To screen for carbapenem resistance among gram negative infections in ICU patients by disc diffusion &amp; confirmation by Vitek 2 system; 2: To detect the carbapenemase production by phenotypic methods; 3: To confirm the presence of resistant gene by PCR; 4: To find out the attributable risk factors from the clinical history of such patients; 5: To follow up &amp; estimate mortality rate in such infections and its statistical correlation A total of 160 gram negative isolates [E.coli(71), Klebsiella(63), Acinetobacter(10), Pseudomonas(9) and Enterobacter(7)] from patients of various intensive care units were screened by disc diffusion out of which 53(33.12%) were carbapenem resistant. Resistant isolates were further tested by Vitek 2 system for determination of MICs, Modified Hodge test(MHT) and Combined Disc test(CDT) for carbapenemase production and subjected to multiplex PCR for detection of resiatant gene i.e., bla NDM-1, bla VIM, bla IMP and bla KPC. Follow up of all the cases till the end of hospital stay was done and mortality rate was calculated.Results: 53 isolates(33.12%) were carbapenem resistant, 17 isolates were MHT positive while 39 were CDT positive. 24 isolates [E.coli(12), Klebsiella(7), Acinetobacter(3), Pseudomonas(1) and Enterobacter(1)] showed the presence of NDM-1 gene on PCR. Gentamicin(35%), Amikacin (45%), Tigecycline(88%) &amp; Colistin(100%) were sensitive for carbapenem resistant GNBs. Mortality in carbapenem sensitive infections in ICUs was 21% whereas resistant infections showed 37% (p value &amp;#60;0.05).Conclusion: 45% of carbapenem resistance is due to presence of NDM-1 gene, E.coli was the commonest isolate. Other mechanisms of resistance such as excessive ESBL production, porin loss may be responsible for resistance in remaining isolates. Effective infection control measures should be taken to prevent the spread of these super bugs in a ICU.

Frequency and associated factors for carbapenem-non-susceptible Bacteroides fragilis group bacteria colonization in hospitalized patients: Case control study in a university hospital in Turkey

PurpuseThe carbapenem-resistant Bacteroides fragilis group (CR-BFG) bacteria have been reported in several countries recently with increasing global attention. The high incidence of CR-BFG isolated from our hospitalized patients has become an important problem. Therefore, we aimed to determine the frequency and associated factors for intestinal colonization by carbapenem-non-susceptible BFG (CNS-BFG) among adult patients hospitalized at intensive care units, neurosurgery and internal medicine wards in our hospital. MethodsRectal swabs (n = 1200), collected from 766 patients between February 2014 and March 2015, were inoculated onto kanamycin-vancomycin-leaked blood agar containing 0.125 mg/L meropenem. The isolates were identified by MALDI-TOF MS. Susceptibility testing was performed by agar dilution method. The carbapenemase gene (cfiA) was detected by PCR. Logistic regression analysis was used to evaluate the associated factors for intestinal colonization by CNS-BFG. ResultsA total 180 non-duplicate BFG isolates were obtained from 164 patients.Ten different species, including Parabacteroides distasonis (n = 46, 25.6%), and Bacteroides fragilis (n = 30; 16.6%), were identified. Twenty-five percent of the isolates were non-susceptible to meropenem (MIC >2 mg/L). The highest prevalence of meropenem resistant strains (MIC >8 mg/L) was detected among B. fragilis (n = 12), followed by Parabacteroides spp. (n = 4). All but one B. fragilis strains were cfiA gene positive. Hospital admission, increasing Charlson score, use of antibiotics; including carbapenems in past three months, colonization with other accompanying carbapenem-resistant Gram negative bacteria (Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa), and having undergone surgical operations were significantly associated with RCS- BFG colonization. ConclusionsThe high carriage rate of CNS-BFG in hospitalized patients may lead to worse clinical outcomes, such as serious infections and mortality, and deserves attention.

Klebsiella pneumoniae Suşlarında OXA-48 ve Alt Türevlerinin Araştırılması ve Fenotipik Yansıma

The number of infections caused by carbapenem-resistant Gram negative bacteria is increasing among nosocomial infections. These bacteria are a serious threat to health because they are usually resistant to other antibiotics. This study was aimed to determine the carbapenemase resistance of OXA-48 and its subderivatives in Klebsiella pneumoniae isolates isolated from various clinical samples by phenotypic and genotypic methods and to investigate the presence of OXA-48 gene region genotypically in isolates without resistance. A total of 127 K.pneumoniae strains isolated from patients treated in various clinics and intensive care units were included in this study from March 2015 to March 2016. The isolates were identified and susceptibilities were tested using BD Phoenix automated system and also with Kirby-Bauer disk diffusion method. The presence of resistance was examined phenotypically with the disk of temosillin, which is considered to indicate the presence of OXA-48 type enzymes. The presence of OXA-48 type enzyme was investigated by “in-house” polymerase chain reaction (PCR) in all isolates and the presence of OXA-48 variant was investigated by DNA sequencing analysis on positive isolates. Carbapenem resistance rate was 35 % and ESBL positivity was determined as 46 %. The sensitivity of temocillin disk method in the identification of OXA-48 gene presence in K. pneumoniae strains was found to be 88 %, and specificity 89 %. Ertapenem was the best carbapenem with sensitivity and specificity balance to detect carbapenem resistance caused by OXA-48. The presence of blaOXA-48 gene region was 80 % in K. pneumoniae isolates detected as resistant to carbapenems by an automated system. All sequences obtained by DNA sequence analysis of 42 OXA-48 positive isolates were OXA-48 and there was no variant OXA-48 gene among the sequences. It was observed that the phenotypic reflection of resistance did not occur immediately in three isolates genotypically having OXA-48 gene region. The presence of blaOXA-48 gene region in carbapenems-resistant K.pneumoniae isolates is common. In addition, in some isolates having OXA-48 gene region, should be kept in mind in patients who do not recover despite treatment, due to phenotypic reflection of resistance does not occur immediately

Hastane genel tuvaletlerinin karbapenem dirençli gram negatif mikroorganizmaların bulaşında katkısı olabilir mi? Sosyal el yıkama gözlemleri ile birlikte değerlendirme

Aim: The goal of our study is to investigate the role that public toilets in hospitals have in spreading and transmitting significant carbapenem resistant Gram negative microorganisms, and potentially compare them to the isolates present in our intensive care units.Materials and Methods: In our study, student groups took samples from the toilets that were actively used, mostly by patient companions, in our hospital. In addition, social hand washing compliance and reliability was observed from the specified toilets.Results: In 85 samples taken from fourteen toilets, Gram negative bacteria accounted for 26% of 115 bacterial growths. However, carbapenem-resistance, which is thought to have epidemiological significance, was not present in Gram negative isolates.Conclusion: It was concluded that no major problem was associated with the transmission of Carbapenem-resistant Gram negative microorganisms from these areas through the hands and peripheral surfaces of patients and their companions.

Detecting Carbapenemase Production amongst Gram Negative Isolates and its Role in Appropriate Antibiotic Selection

Multidrug resistance has been increasing world wide amongst most microrganisms, and adding to increased rate of both hospital and community acquired infections. Of all resistance mechanisms the alarming spread of carbapenemase producers is most worrisome and needs to be tackled head on. The present study was undertaken with the objective of determining the prevalence of carbapenemase producers and its significance in selecting the appropiate antibiotic for clinical use.The study was undertaken by the department of Microbiology and Immunology of SGRRIM&amp;HS, Dehradun over a period of six months. A total of 1918 varied clinical specimens were subjected to Bacterial identification and antibiotic sensitivity determination. Further carbapenemase production was detected phenotypically using modified carbapenemase inactivation method (mCIM) for randomly selected 152 carbapenem resistant gram negative isolates. Total of 58.55% isolates tested mCIM test positive of which the highest percentage (71.4%) were Pseudomonas spp, while 17.2% isolates were not found to be carbapenemase producers i.e mCIM negative. These results substantiate the importance of differentiating the carbapenemase producers from non producers to aid in rational use of antibiotics.

Clinical profile and outcome of carbapenem-resistant gram negative bacteremia in children with cancer in pediatric intensive care unit of a resource-limited country

ObjectiveThe prevalence of Carbapenem-Resistant Gram Negative Blood Stream Infection (CRGN-BSI) is increasing worldwide. However, there is a paucity of data in a vulnerable population “Children with cancer”. The objective of this study is to describe the clinical profile and outcome of children with cancer admitted in PICU with CRGN-BSI. MethodsWe retrospectively reviewed medical record of all children with cancer admitted in PICU who had CRGN-BSI from September 2017 to August 2019. Isolates with meropenem MIC ≤19 mg/dl were considered as Carbapenem Resistant. Responder was defined as negative blood culture in 5 days. Clinical profile and outcomes were obtained. Descriptive statistics were applied. ResultsOut of 1234 PICU admissions, 54 children with cancer developed CRGN-BSI (0.3%). The mean age of CRGN-BSI was 6.97 ± 4 years. 67% (n = 36) of these were male and 54% (n = 29) were malnourished. The primary diagnosis was hematological malignancy in 80% (n = 43) and 76% of the children used ICU therapies (mechanical ventilation [n = 14, 26%] and vasoactive inotropic support [n = 27, 50%]). All of them were neutropenic on admission and 98% patients received blood products. Pending blood culture results, 50% (n = 27) of the patients were started on meropenem. E-coli (n = 30, 56%) and Kelbseilla species (n = 14, 26%) were the most common isolates in our cohort and 46% (n = 25) of the patients were the responders. 18% (n = 10) were community acquired infection and 82% (n = 44) were health-care associated infections. The case-fatality rate was 35% (n = 19). Age, gender, nutritional status and empirical meropenem were not associated with mortality. ConclusionCRGN-BSI in children with underlying malignancy is a serious illness with high mortality. No single factor could determine the mortality in our study. We suggest study with larger sample size, early blood culture testing and rational use of Carbapenem.

Colistin monotherapy versus colistin-based combination therapy for treatment of bacteremia in burn patients due to carbapenem-resistant gram negative bacteria

Carbapenem-resistant gram negative pathogen (CR-GNP) infection in burn patients is a growing concern since treatment options are limited and resistance to the main line of treatment, colistin, is increasing. The goal of this study was to compare treatment outcomes of colistin monotherapy versus colistin-based combination therapy for CR-GNP bacteremia in burn patients. A retrospective observational study was conducted between 2014 and 2017 in Hangang Sacred Heart Hospital located in Seoul, South Korea. Among the burn patients admitted to the burn intensive care unit with CR-GNP bacteremia due to wound infections, colistin monotherapy or colistin-based combination therapy were investigated. We determined both eradication rate within seven days as well as mortality rate within 30 days. A total of 84 burn patients with CR-GNP bacteremia were analyzed—32 were treated with colistin monotherapy and 52 with colistin-based combination therapy. We found that eradication rate within 7 days and 30-day mortality rate were not significantly different between the two groups (71.9% versus 75.0%, P = 0.752 and 31.2% versus 38.5%, P = 0.503). In the Cox regression analysis, Charlson’s comorbidity index, renal replacement therapy before colistin use, and duration of antibiotics were associated with 30-day mortality (HR, 1.23; 95% CI, 1.02–1.49; P = 0.030, HR, 2.28; 95% CI, 1.05–4.94; P = 0.037 and HR, 0.94; 95% CI, 0.89–0.99, P = 0.042, respectively). Colistin-based combination therapy did not show significant differences with regard to microbiologic and clinical outcomes compared with colistin monotherapy.

Implementation of Preventive Actions to Control Carbapenem-Resistant Enterobacteriaceae and MDR Gram Negatives at a Neurological Hospital

Objectives: Objective: The aim of this study is to describe the epidemiological surveillance of Carbapenem-Resistant Enterobacteriaceae (CRE) effected at the Neurological Hospital Carlo Besta, Milano, Italy. The primary causes in our division of multidrug-resistant (MDRs) infections in 2016 were K. pneumoniae and A. baumannii; the preventive actions have ensured the reduction of their incidence in 2017 and allowed us to discover the microbiological sentinel events (SE) and start appropriate precautionary behavior and isolation. Methods: The setting is inpatient care with MDR infections and the aim of the procedure is to formalize the management mode, reporting and transmission of SE, collected at the end of study period for previous years from January 1st, 2015 to December 31st, 2017. Results: It should be noted that of a total of 5772 hospitalizations detected in 2016 there was an increase in rate of A. baumannii compared to the rate found in 2015 for 5679 hospitalizations and in 2017 for 5682 hospitalizations; the same trend was observed for K. pneumoniae. For as regards P. aeruginosa carbapenemase producing or MDR, the rates were lower in 2016 and in 2017. Conclusions: The main goals that we achieved in the three years considered are the decreased incidence of healthcare-associated infections (HAIs) and the decreased incidence of multidrug-resistant (MDR) microorganisms. These actions were of course associated with the control of antibiotic pressure and a careful stewardship. The strict surveillance of HAIs is fundamental to control the growing reservoir within hospital communities. J Microbiol Infect Dis 2020; 10(1):1-9.