Drug Resistant Gram Research Articles

Antibacterial and Wound Healing Assessment of Silver Nanoparticles against Multidrug-Resistant Klebsiella variicola

The increase in antimicrobial resistance and the absence of novel antibiotic development cause problems in controlling infections for wound healing. Antibacterial properties of nanomaterials have emerged as a potentially effective approach in the pursuit of superior alternatives, nevertheless, the toxicity associated with higher concentrations has emerged as a significant obstacle. According to this study, green nanoparticle synthesis is demonstrated to be both economical and biocompatible on account of the bioactive compounds present. In the present work, silver nanoparticles prepared by using Pistacia khinjuk gum, then, nanoparticle-based cream was prepared and compared with Fusidin and Vaseline creams via assessment in vitro antibacterial and in vivo wound healing activity on Wistar albino rats infected with multi drug resistant Gram negative bacteria which was newly recorded in Iraq, namely Klebsiella variicola. The findings revealed that the application of nanoparticle cream resulted in more rapid and effective wound healing (11 days), demonstrating a significant synergistic effect in comparison to Fusidin (16 days), Vaseline (20 days), and the untreated control group rats (32 days). The results indicated that green nanoparticles proved to be a significant strategy in the fight against multidrug resistant bacteria, without any toxicity concerns.

Discovery of new antimicrobial thiophene derivatives with activity against drug-resistant Gram negative-bacteria.

Our aim is to identify new small molecules with antimicrobial potential, especially against colistin-resistant (Col-R) Acinetobacter baumannii and Escherichia coli. After initial hits identification by fingerprint similarity, MIC of 24 heterocyclic derivatives for A. baumannii and E. coli reference strains, and bactericidal activity of selected thiophenes against Col-R strains were determined. We analyzed changes in bacterial membrane permeability and the OMPs profile. Additionally, we determined bacterial adherence to host cells and performed molecular docking studies to assess their binding to bacterial targets. The compounds' MICs ranged from 4 to >64mg/L. Thiophene derivatives 4, 5 and 8 exhibited MIC50 values between 16 and 32mg/L for Col-R A. baumannii and 8 and 32mg/L for Col-R E. coli. The time-kill curve assay demonstrated that thiophenes 4 and 8 had bactericidal effects against Col-R A. baumannii and E. coli. Furthermore, treatment with them resulted in increased membrane permeabilization and reduced adherence of these isolates to host cells. Finally, the docking studies showed a stronger binding affinity to CarO1 and Omp33 of A. baumannii and OmpW and OmpC of E. coli. These findings indicate that thiophene derivatives possess antibacterial activity against Col-R A. baumannii and E. coli, suggesting that they may enhance the repertoire of drug treatments against bacteria.

1728. Real world experience with cefiderocol for multi drug resistant gram negative bacterial infection in a tertiary hospital

Abstract Background Increasing rates of antibiotic resistance has emerged as one of the top concerns in health care. New resistance mechanisms such as carbapenemase production present a challenge in treating common infections. Novel antibiotics are being developed to tackle these pathogens, and one of the newest drugs in this arsenal is cefiderocol, a siderophore cephalosporin. Real-world data regarding the clinical use and outcomes of cefiderocol is limited. Methods A single-center, retrospective chart review was completed from July 2020 to March 2022 and included adult patients who received at least one dose of cefiderocol. Patient baseline characteristics were obtained along with other variables related to the primary infection. The primary outcome was clinical failure defined as 30 day mortality following cefiderocol administration. Secondary outcomes were development of resistance to cefiderocol, clearance of bacteremia, adverse drug reactions, and hospital length of stay. Results Cefiderocol was dispensed in 22 unique patient encounters. It was most often used to treat respiratory tract (45.4%, 10/22) and cardiac device infections (40.9%, 9/22). Most infections were polymicrobial, however, the most common organisms isolated were Pseudomonas aeruginosa and Klebsiella pneumoniae. The clinical failure rate was 22.7% (5/22). One patient developed resistance to cefiderocol throughout the hospitalization. Eight patients were treated for bacteremia, and 87.5% (7/8) demonstrated microbiological cure. Minimal side effects were observed in this cohort; two patients developed diarrhea, and one of whom had confirmed C. difficile colitis. The median length of stay was 24 days. Conclusion This cohort of patients demonstrated that cefiderocol can be used in a variety of multidrug resistant infections including bacteremia. Although limited by a small sample size, this study demonstrated a low prevalence of resistance. These results are promising in the ongoing and emerging issue of antibiotic resistance, and larger studies are needed to determine true efficacy and place in therapy for cefiderocol. Disclosures All Authors: No reported disclosures.

Low Dose Ruxolitinib in Indian Haplo-Identical Transplant Patients with Steroid Refractory Acute Graft Versus Host Disease

Background: The number of allogeneic bone marrow transplants done in India is increasing by year. Unlike west, this region had got its own unique complications in the post-transplant period especially multi drug resistant gram negative bacterial sepsis reflecting in a higher transplant related mortality. With increasing number of Haplo-identical transplants, the problem of steroid refractory Graft versus host disease (GVHD) is a major reason for post-transplant morbidity and mortality. As most available immunosuppressive agents worsen cytopenia and in turn sepsis, we need a relatively safer method of managing steroid refractory GVHD in our setting. In this observational study, we used a lower dose of 5mg per day Ruxolitinib for a period of minimum 60 days post-transplant to look into clinical benefit. This dose was chosen considering the recovering platelet count and financial considerations in our resource limited setting. Method: This observational study was conducted from July 2019 to January 2022. A total of 11 steroid refractory GVHD Haploidentical transplant patients were chosen for data analysis that completed the scheduled dosage regimen of Ruxolitinib. Nine out of 11 patients were Acute Myeloid leukemia and two were Acute Lymphoblastic leukemia. The standard conditioning regimen in all was Fludarabine / Busulfan & Cyclophosphamide based conditioning. Additional GVHD medications used were PTCy, Tacrolimus, MMF and steroids with oral budesonide. Tab Ruxolitinib was started around Day +5 post steroids in people who were fitting into steroid refractory acyte GVHD at a fixed dose of 5mg OD for a minimum period of ten weeks. Two cases had one week dose interruption due to cytopenia. Results : At start of Ruxolitinib seven patients had Grade III gut and liver GVHD and rest four had grade II GVHD. Skin was grade II in all patients. When evaluated at Day +58 of Ruxolitinib, all patients were alive and nine of them were on tapering doses of steroids. All continued Tacrolimus at therapeutic doses. No excess bleeding or cytopenia requiring transfusion support happened during this period. As mentioned earlier two cases Ruxolitinib was stopped in view of platelet counts going below 20,000. On evaluation at day +100 post transplant, two patients continued to have grade II Liver, gut and skin GVH and one patient expired on day +48 to sepsis. Rest of eight patients had a Grade I skin, liver and gut GVHD and were able to continue Ruxolitinib further. We started Ruxolitinib taper in cases where steroids were stopped. As case numbers were very low and it's a pilot observation study, we didn't do detailed statistical analysis which may be misleading and give false promises. Conclusion: In our setup, we were finding it a difficulty to use the prescribed 10mg BD Ruxolitinib dose in adults due to fear of worsening cytopenia /sepsis and financial toxicity. We tried to observe the benefit of a lower dose in steroid refractory GVHD post Haplo-identical bone marrow transplant. No pharmaco-genetic assays were done and it's a very small sample size. This observational study revealed a better efficacy and tolerability of this dosing regimen in Indian Haplo-identical patients with a considerable response without compromising blood counts. The results are looking more promising to conduct this study in a bigger scale to benefit our patients from resource limited settings. Reference Zhao Y, Shi J, Luo Y, Gao F, Tan Y, Lai X, Yu J, Wei G, Huang H. Calcineurin Inhibitors Replacement by Ruxolitinib as Graft-versus-Host Disease Prophylaxis for Patients after Allogeneic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2020 May;26(5):e128-e133. doi: 10.1016/j.bbmt.2020.01.012. Epub 2020 Jan 23. PMID: 31982545.

ANTIBIOTICS RESISTANCE PATTERN AMONG GRAM POSITIVE COCCI ISOLATED FROM INTENSIVE CARE UNITS IN A TERTIARY CARE HOSPITAL

Multi drug resistant Gram positive cocci are implicated in life threatening infections, especially in critical care units. In the current study which was conducted from June 2018 to March 2019, the prevalence and antimicrobial resistance among gram positive cocci isolated from intensive care units of a tertiary care hospital has been detected . Various samples like urine, pus, body uids, sputum etc. were processed according to standard procedures. Total 81 gram positive cocci were isolated from 1650 samples. Maximum gram positive cocci were coagulase negative Staphylococcus followed by Staphylococcus aureus and enterococci. Coagulase negative Staphylococcus showed highest resistance to cotrimoxazole, erythromycin, ciprooxacin, and penicillin and maximum sensitivity to gentamicin. Staphylococcus aureus showed maximum resistance to penicillin, tetracycline, co - trimoxazole and ciprooxacin. All the isolates were sensitive to linezolid and vancomicin. Antimicrobial resistance among enterococci varied from 65% to 85%. Formation of antibiogram and strict adherence to hospital antibiotic policy is crucial to prevent spread of resistance among microorganisms.

Colistin A Last Resort Antibiotic

Colistin is an antibiotic of last resort, works as a last line of defense against illness caused by the multiple drug resistant (MDR) gram negative bacteria. Polimixins consist of aqua phobic acyl tail, linear tripeptide part, and heptapeptide ring. Chemical formula of colistin is C52H98N16O13. Colistin is given in two forms, colistin methane sulfonate (CMS) and colistin sulfate.
 Findings: Colistin disturbs or destroys the outer membrane of bacteria, or stops the respiratory enzymes of the inner membrane of bacteria. Colistin also works as an antiendotoxin. Colistin has great bactericidal activity against gram negative rods. Colistin resistance is a serious concern of present time. High rate of the spread of MDR gram negative bacterial infections is leading to high use of colistin for treatment, due to which prevalence of colistin resistance is increasing worldwide. As bacterial outer membrane is the main target of colistin, resistance against it develop by modification of outer membrane LPS. There are several mechanisms of colistin resistance. Intrinsic mechanism involves expression of arnBCADTEF operon and eptB gene. Acquired non-transferable resistance involves pmrAB, PhoPQ, and CrrAB two component systems (TCSs), mgrB gene and ramA. Transferable resistance is more serious concern as it can be spread in population by horizontal gene transfer. Mcr genes are responsible for transferable or plasmid-mediated colistin resistance.
 Conclusion: This review focuses on the chemistry of colistin, mechanism of action, spectrum of action, colistin resistance and different mechanisms behind it.

ChromagarTM Col-Apse for Detection of Colistin Resistance in Clinical Isolates of Multidrug Resistant Gram Negative Bacilli.

To determine the diagnostic accuracy of CHROMagarTM COL-APSE, for detection of colistin resistance in clinical isolates of multi drug resistant (MDR) gram negative bacilli (GNB). Cross-sectional validation study. Department of Microbiology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, Pakistan from February 2019 to August 2019. Total 96 MDR-GNB in clinical isolates were included. Isolates were identified using gram stain, catalase, oxidase, API 20E and API 20NE. After taking approval from Institutional Ethical Review Committee, colistin susceptibility was determined simultaneously by CHROMagarTM COL-APSE (using 1x105 CFU/ml inoculum) and Broth Micro Dilution (BMD) Minimum Inhibitory Concentration (MIC) method as per CLSI. EUCAST guidelines were followed for interpretation of susceptibility profile. Results were validated with gold standard test, i.e. BMD. Out of 96 MDR clinical isolates, the distribution was K. pneumoniae n=63, E. coli n=18, A. baumannii n=11, C. freundii n=3, and E. cloacae n=1. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of CHROMagarTM COL-APSE for detection of colistin resistance, keeping BMD-MIC method as gold standard, was 97.96%, 97.87%, 97.96%, 97.87% and 97.92%, respectively. CHROMagarTM COL-APSE can be used as screening agar by direct streaking of specimen as well as diagnostic for detection of colistin resistance by the use of standardised inoculum. It can be used as a critical time saving method for colistin resistance detection in absence of expertise or manpower required for BMD as well as the cost required for genetic sequencing to detect MCR genes. Key Words: Multi drug resistant (MDR), Gram negative bacilli (GNB), Colistin resistance, CHROMagarTM COL-APSE.

Antimicrobial activity by solvents extracted from Ocimum basilicum herb against multidrug resistant gram negative rods.

ABSTRACT:
 Background: Failure of treatment with antibiotics occurs due to increase in number of Multidrug resistant gram negative bacteria, worldwide. The objective of this study was to find out the antimicrobial activity of crude ethanolic extract and its further three fractions by Ocimum basilicum leaves against multi drug resistant gram negative rods.
 Material and Methods: This descriptive study was conducted in the Department of Microbiology, University of Health Sciences, Lahore from 1st july 2016 to 30th june 2017. Total 80 multidrug resistant gram negative rods were included in this study. Agar dilution method was performed to determine MIC of crude ethanolic extract and different fractions i-e n-hexane, chloroform and ethyl acetate of Ocimum basilicum leaves against multidrug resistant gram negative rods i-e ESBLs and carbapenemase producers. Muti-inoculater was used for inoculation.
 Results: The mean MICs of crude ethanolic extract, n-hexane fraction, chloroform fraction, and ethyl acetate fraction of Ocimum basilicum against ESBLs were 100.0±8.00, 168.13±8.00, 176.88±8.00 41.75±8.00 respectively. Similarly, the mean MICs of crude ethanolic extract, n-hexane fraction, chloroform fraction, and ethyl acetate fraction of Ocimum basilicum against carbapenemase producers were 77.50±8.00, 113.75±8.00, 132.50±8.00 and 29.50±8.00 respectively.
 Conclusions: Ethyl acetate fraction and crude ethanolic extract from leaves of Ocimum basilicum showed good antibacterial effectiveness against ESBLs and carbapenem resistant organisms than other fractions. This finding may also promote the effective use of O. basilicum herb and its components in modern medicine.

Methicillin resistant Staphylococcus aureus - importance of appropriate empirical therapy in serious infections

India has been titled the capital of antimicrobial resistance in the world with the centre for disease dynamics, economics and policy (CDDEP) predicting two million deaths in India by 2050. As per the World Health Organisation’s global priority pathogen list of 2017, methicillin resistant Staphylococcus aureus (MRSA) has been classified as a ‘high priority’ pathogen due to its association with increased mortality rate, rising prevalence of resistance and increased burden on healthcare settings. A recent report by Indian Council of Medical Research signifies the exponential rise in the prevalence of MRSA in India, from 29% in 2009 to 39% in 2018. Serious MRSA infections are commonly associated with poor clinical outcomes coupled with increased hospitalisation stay and cost. Therefore, early identification and appropriate empiric treatment of MRSA plays a crucial role in healthcare settings. However, the constant rise in multi-drug resistance to the currently available anti-MRSA agents as well as their compromised safety profile limits its clinical use to manage severe MRSA infections. This review article explores the implications of severe MRSA infections and inappropriate empirical therapy on the clinical as well as economic outcomes. In addition, it also highlights limitations of the currently available anti-MRSA agents and the need for newer agents to manage multi drug resistant (MDR) gram positive infections.

Early granulocyte infusion in multi drug resistant (MDR) gram negative sepsis: A useful adjunct to the available antibiotics; experience from tertiary cancer care center in South India

Early granulocyte infusion in multi drug resistant (MDR) gram negative sepsis: A useful adjunct to the available antibiotics; experience from tertiary cancer care center in South India

Bacteria from bovine clinical mastitis showed multiple drug resistance.

Mastitis, which often manifests as udder infection in dairy animals, is of great concern as it affects public health and results in heavy economic losses to the dairy industry. A hospital-based cross-sectional study was conducted to determine the cultivable bacterial species associated with bovine clinical mastitis and their resistance patterns towards different antimicrobials. The milk samples from cows suffering from clinical mastitis during monsoon season were investigated. The prevalence of clinical mastitis was significantly high in Holstein-Friesian crossbred cows, followed by in Jersey crossbred, Red Kandhari and Deoni. Significantly high prevalence was observed during 4th to 6th months of lactation. A total of 110 bacterial isolates belonging to 14 different genera were isolated and identified. Aminoglycosides and quinolones were found to be the most effective antibiotics. Vancomycin resistant penicillinase producing Gram positive bacteria were demonstrated. Gram negative bacteria resistant to extended spectrum β lactamases, cephalosporins, tetracyclines, vancomycin and chloramphenicol as well as vancomycin resistant enterococci, multiple drug resistant (MDR) gram negative rods, MDR Pseudomonas and MDR Acinetobacter were found. Widespread resistance of Streptococcus uberis towards cephalosporins was documented. Variable MDR patterns were recorded within a single species. MDR transfer from non-pathogens to emerging foodborne and established mastitis pathogens could be a potential problem to the dairy industry as well as to public health.

Evaluation of extensively drug-resistant gram-negative bacteremia among solid-organ transplant recipients: a multicenter study

The aim of this study is to evaluate the distribution, sources, clinical features, and mortality rates of bacteremia due to evaluation of extensively drug-resistant (XDR) gram negative among solid-organ transplant (SOT) recipients. A retrospective study of SOT recipients with bacteremia due to XDR gram-negative pathogens in 11 centers between 2016 and 2018 was conducted. Patients’ records were evaluated. Of 171 bacteremia that occurred in 164 SOT recipients, 93 (56.7%) were liver, 46 (28%) kidney, 14 (8.5%) heart, and 11 (6.7%) lung recipients. Bacteremia episodes were recorded in the first year in 63.7% of the patients (n = 109), early-onset bacteremia was recorded in 45% (n = 77) of the episodes. In multivariate analysis, catheter-associated bacteremia was an independent risk factor for 7-day mortality (p = 0.037), and early-onset bacteremia was found as an independent risk factor for 30-day mortality (p = 0.017). Difficult-to-treat infections due to XDR bacteria in SOT recipients shadow the success of transplantation. Central venous catheters seem to be the main risk factor. Judicious use of medical devices is of pivotal importance.

Re-thinking treatment strategies for febrile neutropenia in paediatric oncology population: the perspective from a developing country

BackgroundThis study was conducted to evaluate the microbiological profile of bacterial isolates in febrile neutropenia in a pediatric oncology unit, thereby, reviewing the use of restricted antibiotics and need for aggressive medical treatment accordingly.MethodsA prospective observational study was conducted in a paediatric haemat-oncology division of a tertiary care teaching hospital in southern India from September 2014 to August 2016. One hundred and thirty children with febrile neutropenia were enrolled in the study. Blood cultures were performed using automated system. Cultures from other sites were obtained if needed, based on the clinical profile. Standard antibiotic susceptibility testing was done. Statistical analysis was done using SPSS.ResultsOne hundred and thirty children were enrolled for the study. Two hundred and fifty episodes of febrile neutropenia were studied. Three hundred and eighty four cultures were sent and 92 (24%) cultures were positive. There were 48 (52.2%) Gram negative isolates followed by 33 (35.8%) Gram positive isolates, six (6.5%) fungal isolates and five (5.5%) poly-microbial cultures. Lactose fermenting Gram negative bacilli (20 isolates, 31.5%) were the most frequently isolated in the Gram negative group, with Escherichia coli being the most common organism (19 isolates, 20.6%). Amongst the Gram positive coagulase negative staphylococcus was the most common (twenty seven isolates, 29%). Escherichia coli and Non lactose fermenting gram negative bacteria (NFGNB) had only 36, 25% sensitivity to ceftazidime, respectively. Most Gram negative bacilli were found to have better sensitivity to amikacin (mean: 57%). There was a higher prevalence of extended spectrum beta lactamase producing organisms. Pan drug resistance, Extreme drug resistance and Multi drug resistance was found in three, twenty and thirteen Gram negative isolates respectively.Escherichia coli and Klebsiella were often drug resistant. Significantly higher mortality was associated with Gram negative isolates (eight deaths out of the thirteen deaths, 61.5%).ConclusionsOur results show the importance of surveillance, monitoring resistance frequencies and identifying risk factors specific to each region. Given that significant mortality is attributed to drug resistant Gram negative bacilli, early initiation of appropriate antibiotics to cover for drug resistance is required while formulating empirical antibiotic policies for febrile neutropenia in the oncology units in the developing world.

Clinical and Microbiological Profile of Tracheal Aspirates in Chronic Kidney Disease Patients

Introduction: Chronic Kidney Disease (CKD) is a chronic inflammatory state, which inturn suppresses the immune system. CKD patients are hence at more risk for nosocomial infections. Ventilator Associated Pneumonia (VAP) is one of the major nosocomial infections. If not treated early and appropriately, it increases hospital stay and expenses in turn increasing morbidity and mortality. In recent times, due to irrational and rampant use of antibiotics, there is an emergence of multidrug resistant strains of organisms which are difficult to treat. Aim: To study the clinical and microbiological profile of tracheal aspirate samples in CKD patients. Materials and Methods: It was a retrospective cross sectional study conducted in the renal Intensive Care Unit (ICU) of a Tertiary Care Centre, Institute of Nephrourology, Bengaluru over a period of two years from July 2018 to July 2020. Clinical and demographic data of patients who fulfilled the inclusion criteria was recorded. Tracheal aspirates were obtained by convenient sampling technique. The samples were cultured on Blood Agar (BA), chocolate agar, MacConkey agar and Sabouraud’s Dextrose Agar (SDA). Antibiotic sensitivity profiling was done by using Mueller Hinton agar. Statistical analysis was done using Statistical Package For The Social Sciences (SPSS) V23.0 software. Results: Sixty-nine samples were analysed over a period of two years. Males (66.66%) were in majority. Diabetes Mellitus (64%) was the most common associated risk factor. Among the total samples obtained, around 70% showed bacterial growth. Gram negative bacteria (92.4%) were the most commonly isolated microorganism. Among the Gram-negative bacteria, Acinetobacter baumanni (45.3%) was the most common followed by Klebsiella pneumoniae. Majority of the gram negative organisms were sensitive to Polymyxin B, colistin, tigecycline. Acinetobacter and Klebsiella showed resistance to 3rd generation cephalosporins, aminoglycosides and fluoroquinolones. Conclusion: There is emergence of extremely drug resistant gram negative organisms as the cause for VAP. They are dangerous and difficult to treat. They thus increase the hospital expenses by prolonging the hospital stay. Hence, the need of the hour is to formulate an appropriate antibiotic policy based on the population being treated and to follow strict infection control practices in ICU setup.

Isolation and Molecular Characterization of Multi Drug Resistant Gram-Negative Bacteria from Clinical Samples in Tertiary Care Hospital, South India

Background and Aims Emergence of multi drug resistant MDR gram negative bacteria GNB is a serious threat and major challenge encountered by healthcare professionals. This study aimed to evaluate the distribution of antimicrobial resistance patterns in drug resistant GNB isolated at tertiary care hospital.Methods A total of 934 GNB strains were included in this study. Bacterial identification and disk diffusion testing were performed using standard microbiological techniques. Phenotypic detection of ESBL was assessed using double disk synergy test. Multiplex PCR assay was optimized to detect NDM-1 OXA-48 VIM IMP and KPC genes in carbapenem resistant GNB.Results The most common GNB identified were E. coli n46449.7 K. pneumoniae n13714.7 Acinetobacter Sp n13114 P. aeruginosa n11212 and Enterobacter Sp n313.3. Out of 934 isolates 808.6 were resistant to all tested antibiotics including carbapenems fluoroquinolones and aminoglycosides with high rate of resistant among Acinetobacter sp n454.8. On the other hand among 16818 carbapenem resistant isolates NDM-1 was most predominant in E. coli n2313.7 followed by K. pneumoniae n169.5 Acinetobacter Sp. n158.9 and P. aeruginosa n84.8. OXA-48 was most common in Acinetobacter Sp. n4124.4 followed by E. coli n74.2 and K. pneumoniae n63.6. Among 221 23.7 ESBL producing GNB E. coli n16717.9 was most common followed by K. pneumoniae n303.2 and Acinetobacter Sp n91.Conclusions The occurrence of bacterial infections caused by MDR-GNB and carbapenem resistant GNB infections is high. It is important for clinicians to evaluate and focus on the risk factors associated with the acquisition of MDR and carbapenem resistant organisms in hospital environment.

Carriage of multi drug resistant Gram negative bacilli among the intestinal flora of pets in Lebanon

Carriage of multi drug resistant Gram negative bacilli among the intestinal flora of pets in Lebanon

Extensively drug-resistant and multidrug-resistant gram-negative pathogens in the neurocritical intensive care unit.

Abrupt increase of multidrug-resistant, extensively drug-resistant, and pandrug-resistant bacteria may complicate the course, management, and costs of neurocritical patients and is associated with high morbidity and mortality rates. No data exists regarding risk factors for colonization by gram-negative pathogens in neurocritical patients. The aim of the study was to identify risk factors associated with colonization by multidrug-resistant, extensively drug-resistant, and pandrug-resistant gram-negative bacteria in neurocritical patients. We conducted a retrospective cohort study in a neurointensive care unit over a period of 3years. We included adult neurocritical patients admitted for more than 48h. We analyzed several factors including both anamnestic factors and admission diagnosis. Four hundred twenty neurocritical patients were retrospectively enrolled. Seventy-three patients developed colonization by multidrug-resistant and 53 by extensively drug-resistant gram negative pathogens. Logistic regression identified intensive care unit length of stay (LOS) as the strongest predictor for both multidrug-resistant (AUC 0.877; 95% CI 0.841-0.913) and extensively drug-resistant (AUC 0.839 0.787-0.892) gram negative pathogens. In addition, external ventricular drainage and intracerebral pressure monitoring catheter were risk factors for XDR. Survival analysis revealed that MDR bacteria colonization happens earlier (log-rank test p= 0.017). Optimization of healthcare strategies is required in order to reduce patients' length of stay to prevent multi- and extensively-drug gram-negative colonizations. Indeed, an early external ventricular drainage and intracerebral pressure monitoring catheter removal is deemed necessary as soon as clinically appropriate.

Evaluation of Phenotypic and Genotypic Characteristics of Carbapnemases-producing Enterobacteriaceae and Its Prevalence in a Referral Hospital in Tehran City.

Background & Objective:Carbapenem-resistant Enterobacteriaceae is a growing concern worldwide including Iran. The emergence of this pathogen is worrying as carbapenem is one of the 'last-line' antibiotics for treatment of infections caused by multi drug resistant gram- negative bacteria. The main objective of this study was to determine the prevalence of carbapenem-resistant Enterobacteriaceae in a referral hospital in Tehran, Iran.Methods:In this study, all positive isolates of Enterobacteriaceae recorded in blood, urine, and other body fluids were studied during April 2017 to April 2018 in a referral hospital in Tehran. All cases of resistance to carbapenems were first tested by modified Hodge test. All cases with positive or negative test, after gene extraction, were examined genotypically based on the primers designed for the three Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), and OXA-48 genes by conventional PCR method.Results:108 isolates (13.6%) were resistant to all cephalosporins as well as to imipenem and meropenem. In a genotypic study, including 45 isolates, 13 isolates were positive for OXA-48 gene, 11 isolates for OXA-48 and NDM genes, 11 isolates for OXA-48, NDM and KPC genes, 4 isolates for OXA-48 genes and KPC, 3 isolates for NDM, one isolate for KPC. On the other hand, two isolates were negative for all three genes examined.Conclusion: OXA-48 gene was one of the most common genes resistant to carbapenems in Iran. According to studies, the prevalence of antibiotic resistance in Iran is rising dramatically, which reduces the choice of antibiotics to treat severe infections in the future.

Neonatal Sepsis: Treatment of Neonatal Sepsis in Multidrug-Resistant (MDR) Infections: Part 2.

Sepsis is one of the major causes of neonatal deaths in India and worldwide. Pathogens encountered in neonatal sepsis vary worldwide; reports from developing countries more commonly show Gram negative organisms, most common being Acinetobacter spp., Klebsiella spp. and Escherichia coli. Recent studies show that the incidence of antimicrobial resistance, to third generation cephalosporins and carbapenems, has been on a rise. Because of widespread antimicrobial resistance, 'Higher' or 'Reserve' antibiotics are increasingly being used as first/second line antibiotics. In the past decade, there has been a resurgence in the use of colistin as a result of Extended-spectrum β-lactamase (ESBL)- producing Enterobacteriaceae and carbapenem resistant Enterobacteriaceae (CRE), which retain susceptibility only to colistin. The increasing burden of drug resistant Gram negative organisms, particularly Acinetobacter spp., Klebsiella spp., and E. coli might pose a formidable threat in coming years.

Extended Spectrem Beta Lactamases among Multi Drug Resistant Gram Negetive Bacilli Causing Urinry Tract Infection

Extended Spectrum Beta Lactamases (ESBL), the main cause of resistance to broad spectrum β-lactams, among uropathogenic bacteria have increased over time raising a global concern in the therapeutic management of infections caused by these organisms. The study was carried out in Janamaitri Hospital, Kathmandu between December 2012 to May 2013 with an objective to determine the status of ESBL producing Gram negative bacilli isolated from the urine sample, collected from patients suspected of urinary tract infection. Gram negative bacilli isolated were tested for the presence of ESBL by combined disk and antibiotic susceptibility by Kirby Bauer disc diffusion method following Clinical and Laboratory Standard Institute guidelines. Among the total 1105 mid-stream urine samples, 256 Gram negative bacilli were isolated. By screening test using third generation cephalosporins, 156 isolates were screened as ESBL producers and 91 isolates were positive for ESBL test by combined disk method. Among the 91 (35.55%) ESBL producers, 70 (39.32%) Escherichia coli, 16 (44.44%) Klebsiella pneumoniae, and 5 (33.33%) Pseudomonas aeruginosa were found to be ESBL producers. Majority of ESBL producer showed resistance to ampicillin, co-trimoxazole, norfloxacin followed by ofloxacin. imipenem, amikacin and nitrofurantoin seemed to be the agent of choice for urinary tract infections when ESBL producers are susceptible to it. ESBL production found in these Gram negative bacilli with resultant microbial resistance to available cephalosporins and other agents may pose difficulties with the choice of therapeutic options for the treatment of severe infections.
 Keywords: UTI, Extended Spectrum Beta Lactamases, Gram negative bacilli