Multidrug-resistant Gram-negative Bacilli Research Articles

In vitro activity of fosfomycin against multidrug-resistant urinary and nonurinary gram-negative isolates

Background:The era of multidrug-resistant (MDR) Gram-negative bacilli (GNB) has renewed interest in fosfomycin.Aim:The present study evaluated the in vitro activity of fosfomycin against MDR urinary and nonurinary GNB isolates.Materials and Methods:Fosfomycin susceptibility was carried out by agar dilution for a total of 279 (142 from urine and 137 from other samples) MDR-GNB. Disk diffusion was done for urinary isolates only.Results:Urinary tract isolates had a high degree of susceptibility to fosfomycin (overall susceptibility, 90.8%), whereas only 42.9% of nonurinary isolates retained susceptibility to the drug. Percentage susceptibility rates for urinary and nonurinary isolates of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter spp. were 99%, 91.3%, 66%, 0% and 62%, 44.4%, 32%, 11%, respectively.Conclusion:Fosfomycin showed excellent in vitro activity for uropathogens. Large-scale evaluation of fosfomycin against MDR systemic isolates is required to evaluate its therapeutic efficacy.

Resistant Gram-Negative Bacilli (Red Plague) from ICU in Sohag University Hospital

Background: Gram-negative bacteria; such as Escherichia, Klebsiella, Enterobacter, proteus, Pseudomonas and Acinetobacter, are common human pathogens. Now, it is difficult to treat these infections by most of the available antibiotics due to emergence of multidrug resistant Gram-negative bacilli or Red Plague. Objectives: This work aims to identify the rate of resistant gram negative bacteria in Sohag University hospital. Methodology: The present study was done in Sohag University Hospital, a tertiary care teaching hospital in Upper Egypt, more than 1000 bed capacity. Clinical specimens from the ICU patients were collected aseptically and transferred immediately to the microbiology laboratory for culture and sensitivity during the period from September 2016 to March 2017. Identification and antimicrobial sensitivity of the isolated Gram-negative bacilli were done by Vitek 2 automated system. Susceptibility was confirmed using the disc diffusion (modified Kirby Bauer) method using antimicrobial susceptibility testing discs supplied by (Oxoid, UK). The results were interpreted according to CLSI guidelines. Results: Out of 226 isolates from the different clinical specimens; 118 (52.2%) isolates were Gram-negative bacilli. Escherichia coli was the most common isolated among these Gram-negative bacilli (53 out of 118 isolates, 44.9%) and was the most common cause of urinary tract infection in ICU, 84% (42 isolates out of 50 urine samples). Klebsiella pneumoniae was the commonest cause of pneumonia in ICU (28 out of 34 respiratory isolates, 82.3%). Pseudomonas spp.; (17 isolates, 14.4%; Pseudomonas aeruginosa 15 isolates and Pseudomonas stutzeri 2 isolates) also isolated. Acinetobacter baumonni complex (6 isolates, 5.1%), Serratia liquefaciens (2 isolates, 1.7%) and Stenotrophomonas maltophilia (2 isolates, 1.7%) were the least common in ICU. Nearly all the MDR Gram-negative bacilli isolated in this study were sensitive to Tigecycline. Conclusion: This study highlights high rates of multidrug resistant gram negative bacilli. Almost all the isolates were sensitive to Tigecycline. Therefore; antibiotic stewardship, rigorous adherence to infection control guidelines, prevention of antibiotic misuse and continuous surveillance system should be followed to decrease emergence of new resistant strains. ohag University, Upper Egypt

Risk factors and outcomes for multidrug-resistant Gram-negative bacilli bacteremia.

The incidence of multidrug-resistant (MDR) organisms is increasing along with mortality. Identifying risk factors for the development of MDR Gram-negative bacilli (GNB) bacteremia could greatly impact patient care and management. Data from the electronic health record of patients with GNB over 13-month period were collected at a single university medical center. Baseline demographic data, risk factor, microbiological data, recurrence of bacteremia, and mortality were recorded. A total of 177 patients were included in the analysis. MDR GNB occurred in 46 patients (26%). The mortality rate in the MDR group was 34.8% compared to 13.7% in non-MDR group (p = 0.002). In multivariate analysis, diabetes mellitus [DM; odds ratio (OR): 2.8, 95% confidence interval (CI): 1-4.88], previous antibiotic use (OR: 2.93, 95% CI: 1.25-6.87), and urinary catheter as a source of infection (OR 5.96, 95% CI: 1.78-19.94) were significant risk factors for the development of MDR GNB. In addition, end-stage liver disease (OR: 3.64, 95% CI: 1.07-12.3), solid organ malignancy (OR: 3.64, 95% CI: 1.25-10.56), intra-abdominal source of infection (OR: 3.66, 95% CI: 1.14-11.73), inappropriate empiric antibiotics (OR 7.59, 95% CI: 1.68-34.34) and urinary catheter as a source of infection (OR 5.68, 95% CI: 1.37-23.5) were significant factors for mortality in patients with MDR GNB. Our study provides important information about the risk factors for the development of MDR GNB bacteremia and helps prognosticate patient with MDR GNB.

Polymyxin Resistance in Gram-negative Pathogens.

The polymyxins are one of the last line antimicrobial classes to retain activity against multidrug-resistant Gram-negative bacilli. However, with the increased use of polymyxins in recent years, reports of resistance have also been increasing. We aimed to describe the mechanisms and occurrence of polymyxin resistance in Gram-negative organisms and propose strategies to overcome resistance. The most common mechanism of acquired resistance to the polymyxins is via modification of the bacterial outer membrane lipopolysaccharide. Global epidemiological surveillance studies have reported the occurrence of polymyxin resistance to be most common in Enterobacteriaceae, specifically Enterobacter species and Acinetobacter baumannii. Prevalence of polymyxin-resistant Gram-negative organisms varies significantly by geographical location. Emergence of polymyxin resistance is of great concern, given the limited number of agents available to treat infections caused by multidrug-resistant Gram-negative organisms. Strategies to mitigate the development of polymyxin resistance include dose optimization and using polymyxin agents in combination with other highly active antimicrobial agents.

Phenotypic and genotypic detection of carbapenemase enzymes producing gram-negative bacilli isolated from patients in Khartoum State

Background: Carbapenems are used as antibiotics of last resort for treating infections due to multidrug-resistant Gram-negative bacilli, but emergence of Carbapenem resistant Gram-negative bacilli have been reported due to the production of Carbapenemase enzymes that significantly limits treatment options for life-threatening infections.Objective: This study aimed to detect Carbapenem resistant Gram-negative bacilli from patients attended to different hospitals in Khartoum state and to detect Carbapenemase enzymes production by phenotypic and genotypic methods.Methods: A hospital based cross sectional study was conducted in Khartoum state in the period from February to August 2016. Hundred and forty nine Gram-negative bacilli bacteria were isolated from different clinical specimens. Blood agar, Chromogenic agar media, MacConkey agar, XLD mediaandstandard biochemical tests were used for isolation and identification of Gram-negative bacilli from different samples. Standard antimicrobial susceptibility testing to Carbapenem antibiotic was performed for all isolates, then detection of Carbapenemase enzymes production for the resistant isolates was performed usingModified Hodge Test and PCR.Results: Hundred and forty nine Gram-negative bacilli were isolated from 147 different clinical specimens. The most predominant Gram-negative bacilli isolates was E.coli(54.4%), followed byKlebsiellaspecies (29.5%). More than fifty percent of the isolates were Carbapenem resistant. Fifty six percent of the resistant isolates were positive by Modified Hodge Test. By using PCR, 17.3% of resistant organisms were harbored blaOXA48gene, and 6.7% harbored blaIMPgene.E.coliwas the most bacteria that harbored the blaoxa48followed byKlebsiellaspecies. blaIMPgene was harbored only byE.coli.Conclusion: The percentage of resistance to Carbapenems due to production of Carbapenemase enzymes is very high in Sudan.BlaOXA48gene is more predominant than blaIMPin this study.

Similarities and differences between doxycycline and minocycline: clinical and antimicrobial stewardship considerations.

Doxycycline and, to a lesser extent, minocycline, have been used for decades to treat various serious systemic infections, but many physicians remain unfamiliar with their spectrum, interpretation of susceptibility results, pharmacokinetic/pharmacodynamic (PK/PD) properties, optimal dosing regimens, and their activity against MRSA, VRE, and multidrug-resistant (MDR) Gram-negative bacilli, e.g., Acinetobacter sp. This article reviews the optimal use of doxycycline and minocycline to treat a variety of infections and when minocycline is preferred instead of doxycycline.

The management of infections with multidrug-resistant gram-negative bacilli in lower respiratory tract

The management of infections with multidrug-resistant gram-negative bacilli in lower respiratory tract

Management of multidrug resistant Gram-negative bacilli infections in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations.

Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate's phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection.

Pharmacodynamic Evaluation of Fosfomycin against Escherichia coli and Klebsiella spp. from Urinary Tract Infections and the Influence of pH on Fosfomycin Activities.

Fosfomycin is widely used for the treatment of uncomplicated urinary tract infection (UTI), and it has recently been recommended that fosfomycin be used to treat infections caused by multidrug-resistant (MDR) Gram-negative bacilli. Whether urine acidification can improve bacterial susceptibility to fosfomycin oral dosing regimens has not been analyzed. The MIC of fosfomycin for 245 Gram-negative bacterial isolates, consisting of 158 Escherichia coli isolates and 87 Klebsiella isolates which were collected from patients with urinary tract infections, were determined at pH 6.0 and 7.0 using the agar dilution method. Monte Carlo simulation of the urinary fosfomycin area under the concentration-time curve (AUC) after a single oral dose of 3,000 mg fosfomycin and the MIC distribution were used to determine the probability of target attainment (PTA). Fosfomycin was effective against E. coli (MIC90 ≤ 16 μg/ml) but not against Klebsiella spp. (MIC90 > 512 μg/ml). Acidification of the environment increased the susceptibility of 71% of the bacterial isolates and resulted in a statistically significant decrease in bacterial survival. The use of a regimen consisting of a single oral dose of fosfomycin against an E. coli isolate with an MIC of ≤64 mg/liter was able to achieve a PTA of ≥90% for a target pharmacodynamic index (AUC/MIC) of 23 in urine; PTA was not achieved when the MIC was higher than 64 mg/liter. The cumulative fractions of the bacterial responses (CFR) were 99% and 55% against E. coli and Klebsiella spp., respectively, based on simulated drug exposure in urine with an acidic pH of 6.0. A decrease of the pH from 7.0 to 6.0 improved the PTA and CFR of the target pharmacodynamic index in both E. coli and Klebsiella isolates.

Susceptibility Testing for the Polymyxins: Two Steps Back, Three Steps Forward?

Optimizing and standardizing susceptibility testing for the polymyxins have become pressing issues, given the rise in multidrug-resistant Gram-negative bacilli. Recently, both the CLSI and EUCAST have recommended broth microdilution (BMD) (without polysorbate) as the reference method for polymyxin susceptibility testing. In this issue, K. L. Chew et al. (J Clin Microbiol 55:2609-2616, 2017, https://doi.org/10.1128/JCM.00268-17) compare the performances of three commercial BMD panels and the Etest to the reference, BMD, for polymyxin B and colistin, using 76 Enterobacteriaceae isolates (21 of which were mcr-1 positive). Although none of the commercial BMD panels strictly met FDA performance standards in this evaluation, possibly because of the small number isolates tested, the Sensititre panel achieved >90% categorical agreement for both polymyxin compounds. These results also reaffirm CLSI and EUCAST guidance that gradient diffusion testing, which had unacceptable error rates, should be abandoned. In a simulated analysis with lowered breakpoints (susceptible, ≤1 mg/liter; intermediate, 2 mg/liter; resistant, ≥4 mg/liter), error rates and agreement were improved across the various methods and the rate of detection of mcr-1-positive isolates improved. These observations, taken together with recent pharmacokinetic data on optimizing target attainment for the polymyxins, suggest that more-stringent (lower) breakpoints may be reasonable, although such an approach may be limited by the inherent reliability of current testing methodologies and a lack of robust clinical correlative data, which are sorely needed.

Changing trends in the aetiology, treatment and outcomes of bloodstream infection occurring in the first year after solid organ transplantation: a single-centre prospective cohort study.

To analyse trends in the aetiology, treatment and outcomes of bloodstream infection (BSI) within the first year post-transplant over the last 10-year period, we prospectively recorded all episodes of BSI occurring in solid organ transplant (SOT) recipients during the first year post-transplant from 2007 to 2016. Trends of factors were analysed by 2-year periods. Of 475 consecutive episodes of BSI, 218 occurred within a year of SOT in 178 SOT recipients. Gram-positive BSI decreased over time (40.5-2.2%). In contrast, there was a steady increase in Gram-negative bacilli (GNB) BSI (54.1-93.3%; P<0.001), mainly due to Pseudomonas aeruginosa (2.4-20.4%) and Klebsiella pneumoniae (7.1-26.5%). Multidrug-resistant (MDR) GNB (4.8-38.8%; P<0.001) rose dramatically, especially due to extended-spectrum β-lactamase (ESBL) production (7.1-34.7%). There was a sharp rise in the use of carbapenems, both as empirical (11.9-55.3%; P<0.001) and as targeted antibiotic treatment (11.9-46.9%; P<0.001). In conclusion, today, GNB are the leading causative agents of BSI in SOT recipients within the first year after SOT. In addition, MDR GNB have emerged mainly due to ESBL-producing strains. In spite of these changes, length of hospital stay, days of treatment and mortality have remained stable over time.

Alarming emergence, molecular characterization, and outcome of blaNDM-1 in patients infected with multidrug-resistant Gram-negative bacilli in a tertiary care hospital.

INTRODUCTION:This study was conducted to assess the prevalence of metallo-beta-lactamases (MBLs) in general and blaNDM-1 in particular. It also aimed at evaluating clinical characteristics and outcome in patients infected with MBLs.MATERIALS AND METHODS:A total of 116 carbapenem-resistant Gram-negative bacilli (CRGNB) were evaluated in the study. These CRGNB were tested for MBL production both phenotypically for MBLs and genotypically for blaNDM-1 gene by polymerase chain reaction (PCR). Representative stains of NDM-1 isolates were further sequenced by Triyat Scientific Co., (Nagpur, India).RESULTS:Among 116 CRGNB Citrobacter species 28 (24.13%) was the most common pathogen. Phenotypically, MHT, imipenem-EDTA (IPM-EDTA) double-disk synergy test and IPM-EDTA combined disk synergy test (CDST) detected MBL production in 105 (90.51%), 96 (81.03%), and 87 (75%) CRGNB, respectively. However, blaNDM-1 genes were detected in 66 (56.89%) isolates. The prevalence of blaNDM-1 gene was highest among Escherichia coli 26 (100%). Considering PCR as gold standard, it was observed that IMP-EDTA CDST was most specific (78.38%) while MHT was most sensitive (97.47%). Results of blaNDM-1 gene by PCR were further confirmed by sequencing (Triyat genomics, Nagpur). All the 11 representative strains were confirmed to be an NDM-1 gene. The presence of MBLs in our group of patients (non-Intensive Care Unit patients) is a cause for concern. However, on tracing their outcome, it was interesting to note that while the duration of stay lengthened in a large number of patients 112 (96.5%), mortality was relatively low 5 (4.31%).CONCLUSION:The results of this study provide insight into the prevalence of MBLs, including blaNDM-1, in a tertiary care hospital. Antibiotic stewardship implemented in all seriousness may to a great extent stave off the impending pan-drug resistance. The surprising outcome of our patients suggests either that the bacteria trade off virulence for drug resistance or the relatively robust immune response of non ICU patients fights back.

Never Let a Crisis Go to Waste: Recruiting the Next Generation of Infectious Diseases Physicians.

Sometimes infectious diseases can seem to be the least interesting subspecialty of internal medicine. We don’t offer lifesaving or pain-relieving procedures. We offer the same advice over and over again hoping someday it might stick: wash your hands; stop prescribing antibiotics when there is no evidence of infection; and take your flu shot—it really won’t give you the flu. We give advice that some consider expendable. Shouldn’t all physicians be able to prescribe antibiotics with a little help from an online textbook or computer app? On top of all that, we apparently aren’t very stylish. One of my female colleagues recently told me she can pick out all of the male infectious disease physicians at scientific meetings by the standard uniform of ill-fitting khakis and button-down shirts.But a new crisis is always lurking to remind us that infectious diseases can be one of the most interesting and challenging areas of medicine. Emerging infections—often exotic and frightening—grab the attention of everyone from frontline personnel to the news media: Legionnaires’ disease; HIV; West Nile virus; SARS; MERS; chikungunya; Ebola virus; Zika virus; and Mycobacterium chimaera to name just a few. Without warning, common pathogens create havoc when they acquire new resistance mechanisms or virulence factors: multidrug-resistant gram-negative bacilli; Staphylococcus aureus; and Clostridium difficile. Standard procedures such as transrectal biopsy of the prostate and endoscopic retrograde cholangiopancreatography suddenly become risky due to increasing antimicrobial resistance or inadequate methods for device reprocessing.

Multidrug-Resistant Enterobacteriaceae in Lebanese Hospital Wastewater: Implication in the One Health Concept.

Extended-spectrum beta-lactamases (ESBL) and carbapenemase-producing organisms pose severe problems for hospitalized patients. In the absence of efficient sanitation and sewage disposal, the risks for transmission of hospital organisms into the community are high. Our objectives were to study the occurrence and mechanisms of resistance of multidrug-resistant gram-negative bacilli in two Lebanese hospital sewage treatment plants. Wastewater samples were collected, filtered, and cultivated on MacConckey+cefotaxime agars. ESBL, AmpC, metallo-β-lactamases (MBL), and Klebsiella pneumoniae Carbapenemases (KPC) production were phenotypically detected using plain Mueller Hinton agar plates, and plates impregnated with 5 mM EDTA, 10 mg/mL phenyl boronic acid, and 250 μg/mL cloxacillin (embedded). Temocillin discs were used for the presumptive detection of OXAs. ESBL, carbapenemase, outer membrane protein F (OMPF), and outer membrane protein C (OMPC) genes were detected using polymerase chain reaction. Pulsed-field gel electrophoresis (PFGE) was performed to study the clonality of Enterobacter cloacae isolates. In total, 32 and 38 Enterobacteriaceae were detected from Hospital 1 and Hospital 2, respectively. All Escherichia coli and Klebsiella spp. isolates were ESBL producers. AmpC reached 25% and 28.9% of all isolates. Only one Enterobacter cloacae isolate from one hospital showed full resistance to carbapenems. Molecular tests, however, detected NDM-1 in two strains of Enterobacter cloacae. PFGE results showed 80% similarity between these two strains. The isolation of NDM-1-producing Enterobacter cloacae from hospital wastewater occurred almost a year before the first case of carbapenem-resistant Enterobacter spp. was detected from a patient sample in the laboratory hospital. Understanding the local epidemiology of resistance in hospitals should include areas of potential resistance, such as wastewater and hospital environment.

A cold hard menace: A contaminated ice machine as a potential source for transmission of carbapenem-resistant Acinetobacter baumannii

During an investigation of potential sources of transmission of multidrug-resistant gram-negative bacilli on a spinal cord injury unit, we recovered genetically related carbapenem-resistant Acinetobacter baumannii isolates from the stool of 3 patients, the hands of a nurse, and an ice machine water outlet spout and drain. Our findings suggest that contaminated ice machines could serve as a potential reservoir for dissemination of multidrug-resistant gram-negative bacilli.

In Vitro Activity of Ceftolozane-Tazobactam against Multidrug-Resistant Nonfermenting Gram-Negative Bacilli Isolated from Patients with Cystic Fibrosis.

Ceftolozane-tazobactam was tested against 58 multidrug-resistant nonfermenting Gram-negative bacilli (35 Pseudomonas aeruginosa, 11 Achromobacter xylosoxydans, and 12 Stenotrophomonas maltophilia isolates) isolated from cystic fibrosis patients and was compared to ceftolozane alone, ceftazidime, meropenem, and piperacillin-tazobactam. Ceftolozane-tazobactam was the most active agent against P. aeruginosa but was inactive against A. xylosoxydans and S. maltophilia In time-kill experiments, ceftolozane-tazobactam had complete bactericidal activity against 2/6 clinical isolates (33%).

Nitrofurantoin safety and effectiveness in treating acute uncomplicated cystitis (AUC) in hospitalized adults with renal insufficiency: antibiotic stewardship implications.

Nitrofurantoin remains a key oral antibiotic stewardship program (ASP) option in the treatment of acute uncomplicated cystitis (AUC) due to multi-drug resistant (MDR) Gram negative bacilli (GNB). However, there have been concerns regarding decreased nitrofurantoin efficacy with renal insufficiency. In our experience over the past three decades, nitrofurantoin has been safe and effective in treating AUC in hospitalized adults with renal insufficiency. Accordingly, we retrospectively reviewed our recent experience treating AUC in hospitalized adults with decreased renal function (CrCl < 60 ml/min) with nitrofurantoin. Excluded were complicated urinary tract infections. Urinary isolated susceptibility testing was done by micro broth dilution (MBD). Treatment duration was 5-7 days. Cure was defined as eradication of the uropathogen and failure was defined as minimal/no decrease in urine colony counts. Of 26 evaluable patients with renal insufficiency (CrCl < 60 ml/min), nitrofurantoin eradicated the uropathogen in 18/26 (69%) of patients, and failed in 8/26 (31%). Of the eight failures, five were due to intrinsically resistant uropathogens, e.g., Proteus sp., and one failure was related to an alkaline urine. Of the treatment failures, only two were due to renal insufficiency, i.e., CrCl < 30 ml/min. Since there are few oral antibiotics available to treat AUC due to MDR GNB uropathogens, these results have important ASP implications. Currently, nitfurantoin is not recommended if CrCl < 60 ml/min. In our experience, used appropriately against susceptible uropathogens, nitrofurantoin was highly effective in nearly all patients with CrCl = 30-60 ml/min., and only failed in two patients due to renal insufficiency (CrCl < 30 ml/ml).

Risk factors for acute kidney injury in patients treated with polymyxin B experience from 139 cases at a tertiary university hospital in Colombia

The rise of infections caused by multidrug-resistant Gram negative bacilli (MDR-GNB), added to paucity of newer therapy, have led to increase polymyxin B use, despite adverse renal toxicity profile. To determine the incidence and risk factors associated to acute kidney injury (AKI) and polymyxin B use, in patients with infections caused by MDR-GNB. A retrospective cohort, with a nested case-control study of adults who received polymyxin B for more than 48 hours at a tertiary university hospital in Colombia (2011-2015) was performed. AKI was defined by AKIN criteria. Of 139 patients included in our study, 102 were male with median age of 49 years (IQR:28-64). Sixty-one patients (44%) developed AKI. Independent risk factors for development of AKI included: total polymyxin B daily dose (OR = 2.19, 95% CI, 1.04-4.64); length of stay at ICU (OR = 1.03, 95% CI, 1.00-1.06); nosocomial infection (OR = 6.43, 95% CI, 2.12, -19.47); and vasopressor use (OR = 5.38, 95% CI, 2.40-12.07). Mortality was higher among AKI-patients (58.6%) compared with non-AKI patients (25.6%) (p = 0.001). In this study, the rate of AKI associated to polymyxin B use was greater than reported in studies from last decade, and associated with increased mortality. AKI associated to polymyxin B use is likely multifactorial and aggravated by the critically ill state of patients suffering nosocomial infections caused by mdr-gnb.

Use of Colistin in a Neonatal Intensive Care Unit: A Cohort Study of 65 Patients.

BackgroundThe emergence of infections related to multidrug-resistant Gram-negative bacilli (MDR-GNB) reintroduced the use of colistin, an antibiotic that was previously abandoned due to adverse effects. However, because of its limited use in neonatal intensive care units, there is very little data about the effectiveness and safety of colistin in children and newborns. In this study, which will be the largest case study in the literature, we aimed to evaluate the effectiveness and safety of colistin in full-term and preterm newborns.Material/MethodsThe study included patients admitted into 2 level 3 neonatal intensive care units between January 2013 and June 2015. The medical records of patients diagnosed with sepsis, meningitis, pneumonia, and urinary tract infection based on the diagnostic culture results and treated with colistin were analyzed retrospectively. The patients whose infections were not verified were excluded from the study.ResultsThe study included 65 patients (18 term, 47 preterm). The most frequently isolated pathogens were Klebsiella pneumoniae and Acinetobacter baumannii followed by Pseudomonas aeruginosa and Enterobacter cloacae. Mean colistin treatment time was 15±3.5 days. All patients treated with colistin were being treated with at least 1 other antibiotic. While a complete clinical response was achieved in 51 (72.3%) patients, 14 (21.5%) patients died during treatment. Four (7.7%) patients died during as a result of another infection. Three patients developed renal toxicity, another 3 patients had seizures, and apnea was observed in 3 patients.ConclusionsColistin was found to be effective and safe for treatment of MDR-GNB infections in preterms and infants with very low birth weight. Given the severity of the infection, the adverse effects of colistin were at acceptable levels.

Colistin- and carbapenem-resistant Klebsiella oxytoca harboring blaVIM-2 and an insertion in the mgrB gene isolated from blood culture

A carbapenemase-producing colistin-resistant Klebsiella oxytoca isolate was recovered from a blood culture of a female patient without previous report of risk factors to obtain multidrug-resistant Gram-negative bacilli. A combination of biochemical and molecular methods was used to identify the resistance mechanism of this isolate. Carbapenemase production was mediated by Verona integron-encoded metallo-β-lactamase (VIM)-2. Colistin resistance was not due to plasmid- borne mcr-1 gene, but we found an integration of IS5-like sequence in the mgrB gene of K. oxytoca. This gene is known to be an important regulator of the PhoPQ two-component system, and the disruption of this gene is most likely the cause of lipid A modification resulting in colistin resistance of our isolate. To the best of our knowledge this constitutes the first report of a carbapenemase-producing K. oxytoca with colistin resistance, a case that demonstrates the limited treatment options for infections with multidrug-resistant organisms.