Multiresistant Enterobacter Research Articles

Role of the Environment in Transmission of Multiresistant Enterobacter cloacae in a Hematology-Oncology Department

Background: The patient environment is increasingly considered a major source of transmission of nosocomial bacteria to patients. In May 2019, a cluster of 3 patients with multiresistant Enterobacter cloacae was discovered in the hematology-oncology department of the Maastricht University Medical Center (built in 1991). The strains had an identical antibiogram: ESBL-positive, ciprofloxacin R, cotrimoxazole R, meropenem S, and colistin S. One neutropenic patient had a positive blood culture for this strain, resistant to the empiric treatment with piperacillin-tazobactam, but the patient recovered after switching the antibiotic regimen to meropenem. All strains were determined to be identical by amplified-fragment length polymorphism and whole-genome multi-locus sequencing typing (genotype A). New cases occurred, despite the introduction of contact isolation of positive and contact patients. Therefore, weekly point-prevalence screening was introduced, in which more newly colonized patients were identified in the subsequent weeks. Attention to hand hygiene was enforced, and the hypothesis of contamination from “wet” environmental locations was tested by performing cultures of sinks and shower drains. In June and July, 47 of 241 environmental cultures (19.5%) were positive for E. cloacae with an identical antibiogram, among which some were typed as genotype A. To diminish the environmental contamination, all siphons of sinks were replaced, and disinfection of sinks and shower drains was intensified using chlorine and soda on a daily basis. Replacement of shower drains was not possible. After this intervention, the incidence of newly colonized patients declined gradually. A change in the regimen of selective gut decontamination in hematology patients was considered as an alternative intervention, but with the decrease in new patient cases, this was not implemented. A final round of environmental cultures at the end of August revealed 8 positive cultures, of which 5 were positive for genotype A. In retrospect, this finding could be explained by the fact that the cleaning team did not follow the intensified instructions for disinfection. From week 29, genotype A E. cloacae was no longer cultured in weekly patient screenings. Based on this observation, it is important that in (re)building plans for hospitals, a master plan for the prevention of nosocomial transmission from environment to patients is incorporated.Funding: NoneDisclosures: None

Identification of a multi-resistant Enterobacter cloacae strain from diseased crayfish (Procambarus clarkii)

Diseases of crayfish in May often result in severe economic losses to crayfish farming in Qianjiang, China. Several bacterial pathogens have been identified that responsible to the diseases. In our present study, a virulent strain named L21 was separated from diseased crayfish. The strain was identified as Enterobacter cloacae (E. cloacae) by phenotypical and molecular identification. Then the susceptibility of the strain was examined by K-B method, and the minimum inhibitory concentrations were acquired by broth micro-dilution method. Moreover, carbapenemase and mcr-1 genes were detected. The results showed that L21 strain was multi-resistant strain carrying carbapenemase genes and mcr-1 gene. L21 strain showed susceptibility to cefotaxime, enrofloxacin and tetracycline among all the tested antibiotics. These results demonstrated that E. cloacae was a novel pathogen to farmed crayfish in China.

Severe tricuspid valve destruction due to untreated endocarditis

A 23 years old previously healthy man, admitted for tricuspid infective endocarditis complicated with severe tricuspid regurgitation and multiple septic pulmonary embolism. (A and B). Blood cultures grew multiresistant Enterobacter cloacae. He was treated with imipenem 3g per day with amikacin 900 mg per day for 22 days. Given the uncontrolled infection and the worsening of the tricuspid regurgitation, surgery was indicated but was not performed due to a lack of means.

Dissemination of multiresistant Enterobacter cloacae isolates producing OXA-48 and CTX-M-15 in a Spanish hospital

Twenty-one multiresistant Enterobacter cloacae isolates producing OXA-48 (n=10), CTX-M-15 (n=7) or both (n=4) β-lactamases were detected in a Spanish hospital during a 1-year period (June 2013 to June 2014). The isolates were also resistant to non-β-lactam antimicrobials, further complicating the therapeutic options. Genotyping of the isolates identified two major clones (ST74 and ST66) that caused prolonged outbreaks in different buildings of the hospital as well as some sporadic isolates (ST78, ST45 and ST295). Isolates belonging to clone 1 (n=7) were carbapenem-resistant and carried the blaOXA-48 gene on a conjugative IncL/M plasmid of ca. 65kb. Clone 2 isolates (n=11) were resistant to cefepime and harboured the blaCTX-M-15 gene on an ca. 150-kb, non-conjugative plasmid of the IncF group, co-harbouring the qnrB and aac(6′)-Ib-cr genes encoding quinolone resistance. Four clone 2 isolates were also resistant to carbapenems owing to the co-production of OXA-48. Most of the isolates were recovered from critically ill patients and were admitted to intensive care units; a single patient was transferred from another Spanish hospital. Intrahospital and interhospital dissemination of multiresistant E. cloacae isolates is of major clinical concern as it could lead to endemic nosocomial situations.

Treatment of chronic septic osteoarthritis of the antebrachiocarpal joint with a synovial‐cutaneous fistula utilising arthroscopic lavage combined with ultrasonic assisted wound therapy and vacuum assisted closure with a novel wound lavage system

SummaryThis case report describes the successful management of a chronic multidrug resistant infection of the antebrachiocarpal joint with a synovial‐cutaneous fistula 7 weeks after initial trauma in a 14‐year‐old Icelandic stallion. Resolution of the multiresistant Enterobacter cloacae (extended‐spectrum β‐lactamase) infection from the joint and complete closure of the fistula was achieved by arthroscopic lavage under general anaesthesia repeated on 3 occasions, surgical debridement, ultrasound assisted wound therapy and vacuum assisted closure. Lavage of the wound with the vacuum assisted closure in place was facilitated via the novel VeraFlo instillation system consisting of specially designed therapeutic regulated accurate care pad tubing. The combination of these therapies resulted in resolution of the septic arthritis and fistula. Six weeks after admission the horse was discharged from the hospital with a completely healed wound and was not lame at a walk.

Role of IncHI2 plasmids harbouring blaVIM-1, blaCTX-M-9, aac(6′)-Ib and qnrA genes in the spread of multiresistant Enterobacter cloacae and Klebsiella pneumoniae strains in different units at Hospital Vall d’Hebron, Barcelona, Spain

Seven Enterobacter cloacae isolates and seven Klebsiella pneumoniae isolates harbouring a phenotype compatible with the production of a metallo-β-lactamase were recovered between 2009 and 2011 in three Intensive Care Units of Hospital Vall d’Hebron (Barcelona, Spain). The presence of blaVIM, blaIMP, blaNDM, blaCTX-M, aac(6′)-Ib, qnrA, qnrB and qnrS genes was screened by polymerase chain reaction (PCR) and sequencing. Clonal relatedness of the isolates was assessed by pulsed-field gel electrophoresis (PFGE) and, in the case of K. pneumoniae isolates, by multilocus sequence typing (MLST). PCR-based replicon typing, Southern hybridisation, plasmid double-locus sequence typing and MOB relaxase classification methods were used to identify and characterise the plasmids carrying the resistance genes. Transferability of the identified plasmids was tested by conjugation assays. All 14 isolates were found to carry blaVIM-1, blaCTX-M-9 (except one isolate), aac(6′)-Ib and qnrA genes. Clonality assessment demonstrated that E. cloacae isolates were distributed in three clonal clusters, whereas all of the K. pneumoniae isolates belonged to one unique clone, identified as sequence type ST252. All studied isolates harboured a large conjugative IncHI2 MOBH11 plasmid carrying all of the detected resistance genes. Plasmid DNA analysis showed that all of them belonged to the ST1 IncHI2 plasmid cluster and shared the same relaxase partial sequence. In conclusion, the present study describes the dissemination within a hospital of multiresistant E. cloacae and K. pneumoniae isolates producing VIM-1. A complex clonal epidemiology of the E. cloacae isolates was observed and plasmid DNA analysis strongly supports horizontal exchanges of the same IncHI2 plasmid between different strains and species.

Outbreak of a novel Enterobacter sp. carrying blaCTX-M-15 in a neonatal unit of a tertiary care hospital in Tanzania

Enterobacter hormaechei and Cronobacter sakazakii are amongst the most important causes of outbreaks of neonatal sepsis associated with powdered milk. In this study, we report for the first time an outbreak of a novel Enterobacter sp. harbouring bla CTX-M-15 in a neonatal unit in Tanzania. Seventeen Gram-negative enteric isolates from neonatal blood cultures were studied. Antibiotic susceptibility was assessed by disc diffusion testing, and the presence of the bla CTX-M-15 gene was established by polymerase chain reaction (PCR) and sequencing. Isolates were typed by pulsed-field gel electrophoresis (PFGE). Identification by biochemical profiling was followed by nucleotide sequencing of 16S ribosomal DNA (rDNA), rpoB and hsp60 alleles. Environmental sampling was done and control measures were established. Isolates were initially misidentified based on their fermentation characteristics and agglutination as Salmonella enterica serotype Paratyphi. All isolates were resistant to multiple antibiotics, except for ciprofloxacin and carbapenems, and were found to harbour bla CTX-M-15 on a 291-kb narrow-range plasmid. PFGE analysis indicated the clonal outbreak of a single strain, infecting 17 neonates with a case fatality rate of 35%. The same strain was isolated from a milk bucket. Phylogenetic analysis using 16S rDNA, rpoB and hsp60 sequences permitted no definitive identification, clustering the strains in the Enterobacter cloacae complex with similarities of 92–98.8%. The data describe an outbreak of a novel bla CTX-M-15-positive, multiresistant Enterobacter strain in an African neonatal unit that can easily be misidentified taxonomically. These data highlight the need for constant surveillance of bacteria harbouring extended-spectrum β-lactamases as well as improvements in hygiene measures in developing countries.

Enterobacter Bacteremia: Clinical Features, Risk Factors for Multiresistance and Mortality in a Chinese University Hospital

This study was performed to characterize the clinical features and to identify the risk factors for multiresistance and mortality in patients with Enterobacter bacteremia. A number of 126 patients with Enterobacter bacteremia in 1995-2004 at the Medical university-affiliated Hospital of Anhui, China were retrospectively analyzed. Of the 126 cases of bacteremia, 81 (64.3%) patients were identified as nosocomial infection. The overall multiresistance rate was 45.2% (57/126). Multiresistance was associated with nosocomial infection, recent invasive procedure, previous third-generation cephalosporins therapy, prolonged perioperative prophylaxis, the species of Enterobacter (E. cloacae) and polymicrobial bacteremia in univariate analysis. In multivariate analysis, previous third-generation cephalosporins therapy (OR = 13.6, p = 0.007) and prolonged perioperative prophylaxis (OR = 6.4, p = 0.029) were the strong, independent risk factors for the multiresistance. The crude 30-day mortality rate was 39.7% (50/126). Mortality directly attributed to Enterobacter spp. was 32.5% (41/126), which was significantly associated with multiresistance, nosocomial infection, recent invasive procedure, and inadequately empirical therapy in univariate analysis. Multivariate analysis revealed that only nosocomial infection (OR = 3.292, p = 0.049) was independently associated with mortality. The survival curve showed that the inappropriate initial therapy group had a lower probability of survival than the appropriate therapy group in infection-related mortality (Log Rank, p = 0.0142). Enterobacter is becoming increasingly important nosocomial pathogens. Nosocomial infection is a clinical risk factor tightly associated with multiresistance and worse outcome. More judicious use of third-generation cephalosporins may decrease the incidence of nosocomial multiresistant Enterobacter spp. in China.

Multiresistant Enterobacter cloacae outbreak in an intensive care unit associated with therapeutic beds

We report a multiresistant Enterobacter cloacae outbreak in an intensive care unit, associated with mattresses and with antibacterial-treated and vapour-permeable polyurethane synthetic mattress covers of therapeutic beds.

Urinary tract infections caused by endemic multi-resistant Enterobacter cloacae in a dialysis and transplantation unit

In the period 1994–1998, 42 multi-resistant Enterobacter cloacae isolates responsible for urinary tract infections (UTIs) were obtained from children hospitalized in our dialysis and transplantation unit. E. cloacae isolates obtained between 1994 and 1996 were susceptible to aminoglycosides, carbapenems and fluoroquinolones, whereasE. cloacae isolates obtained between 1997 and 1998 were susceptible to carbapenems and fluoroquinolones, only. All isolates were characterized by use of the polymerase chain reaction-based random amplification of polymorphic DNA and pulsed-field gel electrophoresis. It was found that the majority of multiresistant E. cloacae isolates obtained during 1997–1998, and all isolates obtained during 1994–1996, belonged to predominant clones A or B. These strains were responsible for gastrointestinal tract colonization and UTI of renal transplant recipients for several years, and persisted as endemic E. cloacae strains in the dialysis and transplantation unit from 1994 to 1998.

Reduction in colonization and nosocomial infection by multiresistant bacteria in a neonatal unit after institution of educational measures and restriction in the use of cephalosporins

Introduction: Previous administration of third-generation cephalosporins predisposes to colonization and infections by multiresistant Enterobacter sp. The emergence of multiresistant bacteria infections in a neonatal unit during 1995, especially Enterobacter cloacae , stimulated this study. Objective: To evaluate the efficacy of measures to control colonization and nosocomial infection by multiresistant bacteria in a neonatal unit. Setting: A tertiary care university hospital. Patients and Methods: This study was conducted from October 1995 through December 1999 in 4 phases: a cross-sectional study, a longitudinal study with intervention measures, monthly cross-sectional studies, and determination of nosocomial infections caused by multiresistant bacteria (oxacillin-resistant Staphylococcus aureus and gram-negative bacteria resistant to either aminoglycosides or third-generation cephalosporins). Specimens for surveillance culture were obtained through umbilical and rectal swabs, and tracheal aspirates from intubated babies. The intervention measures were as follows: (1) appropriated training of the whole health care team, emphasizing measures to reduce cross-colonization, and the importance of rational usage of antibiotics and (2) suppression of usage of third-generation cephalosporins. Risk factors were analyzed through univariate and multivariate logistic regression. Results: In the first phase, 32% (10/31) of the patients were colonized by multiresistant bacteria (29% by multiresistant E cloacae ). In the second phase, 342 patients were evaluated; 33% of them were colonized by E cloacae, and a multiresistant strain was isolated in 10.8% (37/342) of the babies. A logistic regression model indicated parenteral nutrition and antibiotic usage as risk factors for colonization by multiresistant E cloacae. In the third phase, for 6 months, only 2 patients were colonized by multiresistant E cloacae. In the fourth phase, the analysis of bacterial resistance profile indicated a reduction of nosocomial infections due to multiresistant bacteria from 18 cases in 1995 to 2 cases per year until 1999. Conclusion: These results have shown that the measures adopted were effective. (Am J Infect Control 2001;29:133-8)

Role of infection control measures in limiting morbidity associated with multi-resistant organisms in critically ill patients

A retrospective comparative study was performed to determine the impact of infection control measures (ICMs) on colonization and infections due to methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae (producing transferable extended-spectrum β-lactamase, KPESBL), and multi-resistant Enterobacter aerogenes (MREA) in intensive care unit patients. Infection Control Measures included surveillance cultures, isolation procedures and mupirocin for MRSA nasal carriage. The numbers of patients infected and/or colonized by MRSA, KPESBL or MREA were compared during two consecutive one-year periods (Period 1 before ICMs, and Period 2 after ICMs). The antibiotic consumption during the two periods was analysed. In Period 1 and Period 2, respectively, the rate of patients infected or colonized by at least one of the three organisms was 15% and 6.8% (P=0.001); by MRSA 7.7% and 2.6% (P=0.004); by KPESBL 1.7% and 0% (P=0.25); and by MREA 5.6% and 4.3% (P=0.47). During Period 2, there was a clear-cut decrease in the percentage of patients infected by MRSA (P=0.018), a non-significant decrease in those infected by KPESBL (P=0.06), and no decrease in patients infected by MREA (P=0.22). When calculated per 1000 patient-days, for Period 1 and Period 2, respectively, the rate of patients infected or colonized by at least one of the three organisms was 11.9 and 8.8; for MRSA it was 4 and 2.2; for KPESBL it was 1 and 0; and for MREA it was 4 and 4. Antibiotic cost was £98.7 in Period 1 and £62.7 in Period 2. ICMs contributed to the control of infections and colonizations due to MRSA and KPESBL but not those due to MREA.

Investigation of an outbreak of multiresistant Enterobacter aerogenes infection in an intensive care unit

In February 1996 we have experienced an outbreak with a multiresistant E aerogenes strain in a 12-bed intensive care unit (ICU) separated in two rooms. Over a 3-day period, four patients were found to be colonized at multiple sites (endotracheal aspirate, urine) by E aerogenes. The medical and nursing charts were reviewed in order to define the sequence of events which led to colonization in these patients. It was found that one patient probably acted as the index-case since he was retrospectively found to be already colonized with E aerogenes in another ward before his admission to the ICU. The three other patients were housed in boxes immediately adjacent to the one of the index case but no strict isolation precautions were taken for these patients since the index case had not been reported as being colonized with a multiresistant organism. All four patients had previously received broad-spectrum antibiotics and three of them were intubated and mechanically ventilated. Colonization ultimately progressed to infection in three of the four patients [one pneumonia, two urinary tract infections (UTI)]. Three patients were treated with cefepime as single drug therapy (2 × 1–2 g iv/day); two of them died (one due to underlying disease, the other because of uncontrolled infection) whereas one was cured clinically. Bacteriological failure was observed in two patients and eradication failure was associated with the development of resistance to cefepime during treatment in one of them. All E aerogenes strains isolated in the four patients had the same identification characteristics and displayed a similar in vitro antimicrobial resistance profile (the strains were sensitive only to gentamicin, amikacin, imepenem and to cefepime). Molecular epidemiological typing studies using random amplification of polymorphic DNA (RAPD) with two different 10-mer oligonucleotide primers yielded indistinguishable patterns for the four outbreak strains while these were clearly different from five non-outbreak associated strains which were included as controls. Nosocomial outbreaks due to multiresistant E aerogenes is an emerging concern in ICU. Infections caused by this organism are often not detected at an early stage and are both difficult to control and to treat. In the present case, antibiotic treatment with cefepime did not prove very effective for controlling the outbreak which terminated only following the reinforcement of handwashing and isolation contact precautions. RAPD fingerprinting proved useful in this outbreak for discriminating the outbreak strains from epidemiologically unrelated strains. Further clinical trials are needed to optimize the therapy of multiresistant E aerogenes infection.

Cycling of antibiotics: an approach to circumvent resistance in specialized units of the hospital

Cycling of antibiotics: an approach to circumvent resistance in specialized units of the hospital

Enterobacter Bacteremia: Clinical Features and Emergence of Antibiotic Resistance during Therapy

To study the effect of previously administered antibiotics on the antibiotic susceptibility profile of Enterobacter, the factors affecting mortality, and the emergence of antibiotic resistance during therapy for Enterobacter bacteremia. Prospective, observational study of consecutive patients with Enterobacter bacteremia. Three university tertiary care centers, one major university-affiliated hospital, and two university-affiliated Veterans Affairs medical centers. A total of 129 adult patients were studied. The two main end points were emergence of resistance during antibiotic therapy and death. Previous administration of third-generation cephalosporins was more likely to be associated with multiresistant Enterobacter isolates in an initial, positive blood culture (22 of 32, 69%) than was administration of antibiotics that did not include a third-generation cephalosporin (14 of 71, 20%; P less than 0.001). Isolation of multiresistant Enterobacter sp. in the initial blood culture was associated with a higher mortality rate (12 of 37, 32%) than was isolation of a more sensitive Enterobacter sp. (14 of 92, 15%; P = 0.03). Emergence of resistance to third-generation cephalosporin therapy (6 of 31, 19%) occurred more often than did emergence of resistance to aminoglycoside (1 of 89, 0.01%; P = 0.001) or other beta-lactam (0 of 50; P = 0.002) therapy. More judicious use of third-generation cephalosporins may decrease the incidence of nosocomial multiresistant Enterobacter spp., which in turn may result in a lower mortality for Enterobacter bacteremia. When Enterobacter organisms are isolated from blood, it may be prudent to avoid third-generation cephalosporin therapy regardless of in-vitro susceptibility.

Ciprofloxacin in neonatal Enterobacter cloacae septicaemia.

Multiresistant Enterobacter cloacae infection in six premature infants was eradicated with intravenous ciprofloxacin (10 mg/kg/day). Bacterial resistance did not develop. Adequate plasma ciprofloxacin concentrations were achieved in all treated patients. No clinical evidence of side effects was observed.