Methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and vancomycin-resistant enterococci (VRE) are important hospital pathogens in Canada and worldwide.
To genotypically and phenotypically characterize the isolates of MRSA, VRE and ESBL-producing E coli collected from patients in Canadian intensive care units (ICUs) in 2005 and 2006.
Between September 1, 2005, and June 30, 2006, 19 medical centres participating in the Canadian National Intensive Care Unit (CAN-ICU) study collected 4133 unique patient isolates associated with infections in ICUs. Isolates of MRSA underwent mecA polymerase chain reaction (PCR) and Panton-Valentine leukocidin analysis; they were typed using pulsed-field gel electrophoresis. All isolates of E coli with ceftriaxone minimum inhibitory concentrations greater than or equal to 1 μg/mL were tested for the presence of an ESBL using the Clinical Laboratory Standards Institute double-disk diffusion method. Subsequently, PCR and sequence analysis were used to identify blaSHV, blaTEM and blaCTX-M. Isolates of VRE were tested for the presence of vanA and vanB genes by PCR.
Of the 4133 ICU isolates collected, MRSA accounted for 4.7% (193 of 4133) of all isolates. MRSA represented 21.9% (193 of 880) of all S aureus collected during the study; 90.7% were health care-associated MRSA strains and 9.3% were community-associated MRSA strains. Resistance rates for the isolates of MRSA were 91.8% to levofloxacin, 89.9% to clarithromycin, 76.1% to clindamycin and 11.7% to trimethoprim-sulfamethoxazole; no isolates were resistant to vancomycin, linezolid, tigecycline or daptomycin. ESBL-producing E coli accounted for 0.4% (18 of 4133) of all isolates and 3.7% (18 of 493) of E coli isolates. All 18 ESBL-producing E coli were PCR-positive for CTX-M, with blaCTX-M-15 occurring in 72% (13 of 18) of isolates. All ESBL-producing E coli displayed a multidrug-resistant phenotype (resistant to third-generation cephalosporins and one or more other classes of antimicrobials), with 77.8% of isolates resistant to ciprofloxacin, 55.6% resistant to trimethoprim-sulfamethoxazole, 27.8% resistant to gentamicin and 26.3% resistant to doxycycline; all isolates were susceptible to ertapenem, meropenem and tigecycline. VRE accounted for 0.4% (17 of 4133) of all isolates and 6.7% (17 of 255) of enterococci isolates; 88.2% of VRE had the vanA genotype. Isolated VRE that were tested were uniformly susceptible to linezolid, tigecycline and daptomycin.
MRSA isolated in Canadian ICUs in 2005 and 2006 was predominately health care-associated (90.7%), ESBL-producing E coli were all CTX-M producers (72% blaCTX-M-15) and VRE primarily harboured a vanA genotype (88.2%). MRSA, ESBL-producing E coli and VRE were frequently multidrug resistant.
CAN-ICU; ESBL E coli; Intensive care; MRSA; Resistance; VRE
Resistance to third generation cephalosporins due to acquisition and expression of extended spectrum β-lactamase (ESBL) enzymes among Gram-negative bacteria is on the increase. Presence of ESBL producing organisms has been reported to significantly affect the course and outcome of an infection. Therefore infections due to ESBL isolates continue to pose a challenge to infection management worldwide. The aim of this study was to determine the existence and to describe phenotypic and genotypic characteristics of ESBLs in an Intensive Care Unit (ICU) setting in Tanzania.
Between October 2002 and April 2003, clinical information and samples were collected from patients suspected to have nosocomial infections in an Intensive Care Unit of a tertiary hospital in Tanzania. The isolates were identified, tested for antimicrobial susceptibility and analysed for presence of ESBL genes.
Thirty-nine Gram-negative bacteria were isolated from clinical samples of 39 patients. These isolates included 13 Escherichia coli, 12 Enterobacter spp, 5 Pseudomonas spp, 4 Proteus spp, 2 Klebsiella. pneumoniae, 2 Citrobacter freundii and 1 Chryseomonas luteola. Eleven (28.2%) of these isolates were ESBL producing. The ESBL genes characterised were SHV-12, SHV-28 and CTX-M-15. The ESBL producing isolates were more resistant to gentamicin and ciprofloxacin than non-ESBL producing isolates.
This study shows the presence of ESBL genes among Gram-negative bacteria in the ICU setting in Tanzania. There is a need to institute strict hospital infection control policy and a regular surveillance of resistance to antimicrobial agents.
After renovation of the adult intensive care unit (ICU) with installation of ten single rooms, an enhanced infection control program was conducted to control the spread of methicillin-resistant Staphylococcus aureus (MRSA) in our hospital.
Since the ICU renovation, all patients colonized or infected with MRSA were nursed in single rooms with contact precautions. The incidence of MRSA infection in the ICU was monitored during 3 different phases: the baseline period (phase 1); after ICU renovation (phase 2) and after implementation of a hand hygiene campaign with alcohol-based hand rub (phase 3). Patients infected with extended spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella species were chosen as controls because they were managed in open cubicles with standard precautions.
Without a major change in bed occupancy rate, nursing workforce, or the protocol of environmental cleansing throughout the study period, a stepwise reduction in ICU onset nonbacteraemic MRSA infection was observed: from 3.54 (phase 1) to 2.26 (phase 2, p = 0.042) and 1.02 (phase 3, p = 0.006) per 1000-patient-days. ICU onset bacteraemic MRSA infection was significantly reduced from 1.94 (phase 1) to 0.9 (phase 2, p = 0.005) and 0.28 (phase 3, p = 0.021) per 1000-patient-days. Infection due to ESBL-producing organisms did not show a corresponding reduction. The usage density of broad-spectrum antibiotics and fluoroquinolones increased from phase 1 to 3. However a significant trend improvement of ICU onset MRSA infection by segmented regression analysis can only be demonstrated when comparison was made before and after the severe acute respiratory syndrome (SARS) epidemic. This suggests that the deaths of fellow healthcare workers from an occupational acquired infection had an overwhelming effect on their compliance with infection control measures.
Provision of single room isolation facilities and promotion of hand hygiene practice are important. However compliance with infection control measures relies largely on a personal commitment, which may increase when personal safety is threatened.
Newer β-lactamases such as extended-spectrum β-lactamases (ESBLs), transferable AmpC β-lactamases, and carbapenemases are associated with laboratory testing problems of false susceptibility that can lead to inappropriate therapy for infected patients. Because there appears to be a lack of awareness of these enzymes, a study was conducted during 2001 to 2002 in which 6,421 consecutive, nonduplicate clinical isolates of aerobically growing gram-negative bacilli from patients at 42 intensive care unit (ICU) and 21 non-ICU sites across the United States were tested on-site for antibiotic susceptibility. From these isolates, 746 screen-positive isolates (11.6%) were referred to a research facility and investigated to determine the prevalence of ESBLs in all gram-negative isolates, transferable AmpC β-lactamases in Klebsiella pneumoniae, and carbapenemases in Enterobacteriaceae. The investigations involved phenotypic tests, isoelectric focusing, β-lactamase inhibitor studies, spectrophotometric assays, induction assays, and molecular analyses. ESBLs were detected only in Enterobacteriaceae (4.9% of all Enterobacteriaceae) and were found in species other than those currently recommended for ESBL testing by the CLSI (formerly NCCLS). These isolates occurred at 74% of the ICU sites and 43% of the non-ICU sites. Transferable AmpC β-lactamases were detected in 3.3% of K. pneumoniae isolates and at 16 of the 63 sites (25%) with no difference between ICU and non-ICU sites. Three sites submitted isolates that produced class A carbapenemases. No class B or D carbapenemases were detected. In conclusion, organisms producing ESBLs and transferable AmpC β-lactamases were widespread. Clinical laboratories must be able to detect important β-lactamases to ensure optimal patient care and infection control.
The global increase in multidrug resistance of Acinetobacter spp. has created widespread problems in the treatment of patients in intensive care units (ICUs) of hospitals. To assess the sensitivity of Acinetobacter isolates to antibiotics routinely used in ICUs, we investigated antibiotic resistance patterns and extended-spectrum β-lactamase (ESBL) production among Acinetobacter spp. isolated from the ICU of a university hospital in Kerman, Iran.
Fifteen isolates of Acinetobacter spp. were recovered from one hundred clinical specimens collected from the ICU of Afzalipoor Hospital in Kerman, Iran, from October 2010 to June 2011. Preliminary antibiotic sensitivity testing was carried out using the disk-diffusion breakpoint assay, and MICs of different antibiotics were determined using the E-test. ESBL production was detected by a double-disk synergy test and confirmed by a phenotypic confirmatory test. Substrate hydrolysis in the presence and absence of the following inhibitors was carried out using the rapid fixed-time method: para-chloromercuribenzoate (p-CMB), clavulanic acid, sulbactam, and NaCl.
Overall, 73.3% of the isolates were resistant to imipenem (MIC range 240-128 µg/mL) and 66% to ciprofloxacin (MIC range 240-64 ± 0.08 µg/mL). All of the isolates were fully resistant (MIC 240 µg/mL) to piperacillin, while 93.3%, 53.3%, and 93.3% were resistant to piperacillin + tazobactam (MIC 240 µg/mL), amikacin (MIC range 128-16 µg/mL), and cefepime (MIC range 240-60 µg/mL), respectively. The isolates were also resistant to chloramphenicol and tetracycline: MICs of these two agents were ≥ 240 µg/mL. The test for ESBL production was positive for only three isolates (nos. 1, 10, and 15). The rate of substrate hydrolysis was highest in the presence of p-CMB (80.2 ± 0.02) and lowest in the presence of NaCl (2.1 ± 0.01) (P ≤ 0.05).
Many isolates of Acinetobacter spp. are resistant to almost all antibiotics routinely used in the ICU of our hospital, including imipenem, ciprofloxacin, and piperacillin + tazobactam. Three isolates were ESBL producers. The other isolates exhibited high resistance to β-lactams, but they did not produce any ESBL enzymes.
Acinetobacter spp; antibiotic resistance; MIC; extended-spectrum β-lactamase
Recent clinical studies performed in a large number of patients showed that colistin "forgotten" for several decades revived for the management of infections due to multidrug-resistant (MDR) Gram-negative bacteria (GNB) and had acceptable effectiveness and considerably less toxicity than that reported in older publications. Colistin is a rapidly bactericidal antimicrobial agent that possesses a significant postantibiotic effect against MDR Gram-negative pathogens, such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. The optimal colistin dosing regimen against MDR GNB is still unknown in the intensive care unit (ICU) setting. A better understanding of the pharmacokinetic-pharmacodynamic relationship of colistin is urgently needed to determine the optimal dosing regimen. Although pharmacokinetic and pharmacodynamic data in ICU patients are scarce, recent evidence shows that the pharmacokinetics/pharmacodynamics of colistimethate sodium and colistin in critically ill patients differ from those previously found in other groups, such as cystic fibrosis patients. The AUC:MIC ratio has been found to be the parameter best associated with colistin efficacy. To maximize the AUC:MIC ratio, higher doses of colistimethate sodium and alterations in the dosing intervals may be warranted in the ICU setting. In addition, the development of colistin resistance has been linked to inadequate colistin dosing. This enforces the importance of colistin dose optimization in critically ill patients. Although higher colistin doses seem to be beneficial, the lack of colistin pharmacokinetic-pharmacodynamic data results in difficulty for the optimization of daily colistin dose. In conclusion, although colistin seems to be a very reliable alternative for the management of life-threatening nosocomial infections due to MDR GNB, it should be emphasized that there is a lack of guidelines regarding the ideal management of these infections and the appropriate colistin doses in critically ill patients with and without multiple organ failure.
The emergence of KPC-producing K. pneumoniae has now become a global concern. KPC beta-lactamases are plasmid-borne and, like extended spectrum beta lactamases (ESBLs), can accumulate and transfer resistance determinants to other classes of antibiotics. Therefore, infection control guidelines on early identification and control of the spread of organisms carrying these resistant determinants are needed.
Klebsiella pneumoniae carbapenemase (KPC) was detected in two isolates of carbapenem-resistant K. pneumoniae obtained from patients at an Italian teaching hospital. The first strain was isolated from a culture drawn from a central venous device (CVC) in a patient with Crohn's disease who was admitted to a gastroenterology ward. The second was isolated from a urine sample collected from an indwelling urinary catheter in an intensive care unit (ICU) patient with a subdural haematoma. The patients had not travelled abroad. Both isolates were resistant to all β-lactams and were susceptible to imipenem and meropenem but resistant to ertapenem. Isolates also showed resistance to other classes of non-β-lactam antibiotics, such as quinolones, aminoglycosides (with the exception for amikacin), trimethoprim-sulfamethoxazole (TMP-SMX) and nitrofurantoin. They were determined to contain the plasmid encoding the carbapenemase gene bla-KPC and were also positive in the Hodge test.
This is the second report of KPC-producing isolates in Italy, but the first concerning KPC type 2 gene, and it may have important implications for controlling the transmission of microorganisms resistant to antibiotics.
Background: An alarming rise in the rates of the antibiotic resistance has now become a serious and an increasingly common public health concern, with severe implications, especially in the intensive care units. A variety of β-lactamases which include ESBLs, AmpC β-lactamases and metallo-βlactamases, have emerged as the most worrisome mechanism of resistance among the gram negative bacteria, which pose a therapeutic challenge to the health care settings.
Materials and Methods: The present study was aimed at knowing the prevalence of various β-lactamases in the gram negative isolates which were obtained from ICU patients. A total 273 gram negative isolates from 913 clinical samples which were received over a period of one year were processed for their identification and their antimicrobial susceptibility pattern was determined. They were then screened for the β-lactamase production.
Results: Among the 273 isolates, the β-lactamase production was observed in 193 strains. 96 (35.16%) strains were ESBL producers, followed by 30 (10.98%) metallo β- lactamase (MBL) producers and 15(5.4%) AmpC producers. The major ESBL and AmpC producer was Escherichia coli, while Klebsiella pneumonia was the predominant MBL producer. The co production of the ESBL/MBL/ AmpC β- lactamases was observed in 52 (19.04%) strains and it was more common in Escherichia coli. A multidrug resistance to the fluoroquinolones and the aminoglycosides was also observed in the β- lactamase producing organisms.
Conclusion: The high prevalence of the β- lactamases in the ICU isolates emphasizes the need for a continuous surveillance in the ICUs to detect the resistant strains, strict guidelines for the antibiotic therapy and the implementation of infection control measures to reduce the increasing burden of antibiotic resistance.
Extended spectrum β-lactamases (ESBLs); AmpC β-lactamases; Metallo-β-lactamases (MBLs); Antibiotic resistance; Intensive care units (ICUs)
Enterobacter cloacae has been associated with several outbreaks, usually involving strains that overproduce chromosomal β-lactamase or, uncommonly, strains expressing extended-spectrum β-lactamases (ESBL). Only sporadic cases of ESBL-producing E. cloacae have been identified in our hospital in recent years. We describe the epidemiology and clinical and microbiological characteristics of an outbreak caused by ESBL-producing E. cloacae in a cardiothoracic intensive care unit (CT-ICU). Prospective surveillance of patients with infection or colonization by ESBL-producing E. cloacae among patients admitted to the CT-ICU was performed during the outbreak. Production of ESBL was determined by decreased susceptibility to expanded-spectrum cephalosporins and a positive double-disk test result. Clone relatedness was determined by pulsed-field gel electrophoresis (PFGE). From July to September 2005, seven patients in the CT-ICU with ESBL-producing E. cloacae were identified (four males; median age, 73 years; range, 45 to 76 years); six patients had cardiac surgery. Four patients developed infections; three had primary bacteremia, one had ventilator-associated pneumonia, and one had tracheobronchitis. ESBL-producing E. cloacae showed resistance to quinolones and aminoglycosides. PFGE revealed two patterns. Five isolates belonged to clone A; two carried a single ESBL (pI 8.2 and a positive PCR result for the SHV type), and three carried two ESBLs (pIs 8.1 and 8.2 and positive PCR results for the SHV and CTX-M-9 types). Isolates belonging to clone B carried a single ESBL (pI 5.4 and a positive PCR result for the TEM type). Review of antibiotic consumption showed increased use of cefepime and quinolones during June and July 2005. The outbreak was stopped by the implementation of barrier measures and cephalosporin restriction. ESBL production could be increasingly common in nosocomial pathogens other than Escherichia coli or Klebsiella pneumoniae.
The increasing problem of infections due to multidrug-resistant Gram-negative bacteria has led to re-use of polymyxins in several countries. However, there are already clinical isolates of Gram-negative bacteria that are resistant to all available antibiotics, including polymyxins.
We present a case series of patients with infections due to pathogens resistant to all antimicrobial agents tested, including polymyxins. An isolate was defined as pandrug-resistant (PDR) if it exhibited resistance to all 7 anti-pseudomonal antimicrobial agents, i.e. antipseudomonal penicillins, cephalosporins, carbapenems, monobactams, quinolones, aminoglycosides, and polymyxins.
Clinical cure of the infection due to pandrug-resistant (PDR) Gram-negative bacteria, namely Pseudomonas aeruginosa or Klebsiella pneumoniae was observed in 4 out of 6 patients with combination of colistin and beta lactam antibiotics.
Colistin, in combination with beta lactam antibiotics, may be a useful agent for the management of pandrug-resistant Gram-negative bacterial infections. The re-use of polymyxins, an old class of antibiotics, should be done with caution in an attempt to delay the rate of development of pandrug-resistant Gram-negative bacterial infections.
Tigecycline, a glycylcycline related to the tetracycline class of antibiotics, represents a new option for the treatment of complicated intra-abdominal and complicated skin and skin structure infections. It displays favorable activity in vitro against the most common causative Gram-positive, Gram-negative and anaerobic pathogens. In addition, tigecycline demonstrates activity against drug-resistant pathogens such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and organisms (such as Escherichia coli and Klebsiella pneumoniae) producing extended-spectrum beta-lactamases. Tigecycline lacks activity in vitro against Pseudomonas and Proteus spp. In randomized clinical trials, tigecycline administered intravenously twice daily has demonstrated efficacy similar to comparators for a variety of complicated skin and skin structure and complicated intra-abdominal infections. The potential for significant drug interactions with tigecycline appears to be minimal. Dosing adjustment is needed for patients with severe hepatic impairment. The predominant side effect associated with its use to date has been gastrointestinal intolerance (nausea and vomiting).
tigecycline; intra-abdominal infections; complicated skin and skin structure infections
Infections caused by multidrug-resistant (MDR) Acinetobacter baumannii are a challenging problem worldwide. Here, the molecular epidemiology and the genetic basis of antibiotic resistance in 111 MDR A. baumannii strains isolated from June 2005 to March 2009 from infected patients in 10 intensive care units (ICUs) in central Italy were investigated.
Epidemiological typing was performed by random amplification of polymorphic DNA, PCR-based sequence grouping and macrorestriction analysis. MICs of antibiotics were determined by the broth microdilution method. Genes for OXA carbapenemases, metallo-β-lactamases and the CarO porin were searched for by PCR.
Molecular genotyping identified one predominant A. baumannii lineage, related to the international clonal lineage II, accounting for 95.6% of isolates. Isolates referable to this lineage were recovered from all ICUs surveyed and were resistant to nearly all classes of antimicrobials, with the exception of tigecycline and colistin. A high percentage (60.5%) of A. baumannii isolates showed elevated resistance to imipenem (MICs ≥ 128 mg/L), concomitant with resistance to meropenem. Carbapenem resistance was associated with the presence of either blaOXA-58-like (22.8%) or blaOXA-23-like (71.1%) carbapenemase genes. Molecular typing showed that the epidemic lineage encoding OXA-23 emerged in 2007 and displaced a genetically related clone encoding OXA-58 that had been responsible for previous ICU outbreaks in the same region.
Emergence of the OXA-23 epidemic lineage could result from selective advantage conferred by the blaOXA-23-like determinant, which provides increased resistance to carbapenems.
genotyping; intensive care units; OXA-23
Ventilator-associated pneumonia (VAP) is an important intensive care unit (ICU) infection in mechanically ventilated patients. VAP occurs approximately in 9-27% of all intubated patients. Due to the increasing incidence of multidrug-resistant organisms in ICUs, early and correct diagnosis of VAP is an urgent challenge for an optimal antibiotic treatment.
AIM OF THE STUDY:
The aim of the study was to assess the incidence of VAP caused by multidrug-resistant organisms in the multidisciplinary intensive care unit (MICU) of our tertiary care 1,400-bedded hospital.
MATERIALS AND METHODS:
This prospective study was done in the period from December 2005 to August 2006, enrolling patients undergoing mechanical ventilation (MV) for >48 h. Endotracheal aspirates (ETA) were collected from patients with suspected VAP, and quantitative cultures were performed on all samples. VAP was diagnosed by the growth of pathogenic organism ≥105 cfu/ml.
Incidence of VAP was found to be 45.4% among the mechanically ventilated patients, out of which 47.7% had early-onset (<5 days MV) VAP and 52.3% had late-onset (>5 days MV) VAP. Multiresistant bacteria, mainly Acinetobacter spp. (47.9%) and Pseudomonas aeruginosa (27%), were the most commonly isolated pathogens in both types of VAP. Most of the isolates of Escherichia coli (80%) and Klebsiella pneumoniae (100%) produced extended-spectrum beta lactamases (ESBLs). As many as 30.43% isolates of Acinetobacter spp. showed production of AmpC beta lactamases among all types of isolates. Metallo-beta lactamases (MBLs) were produced by 50% of Pseudomonas aeruginosa and 21.74% of Acinetobacter spp.
High incidence (45.4%) of VAP and the potential multidrug-resistant organisms are the real threat in our MICU. This study highlighted high incidence of VAP in our setup, emphasizing injudicious use of antimicrobial therapy. Combined approaches of rotational antibiotic therapy and education programs might be beneficial to fight against these MDR pathogens and will also help to decrease the incidence of VAP.
Multidrug-resistant organisms; nosocomial pneumonia; ventilator-associated pneumonia
An outbreak due to extended-spectrum β-lactamase-producing Klebsiella pneumoniae (ESBL-KP) was detected from May 1993 to June 1995. A total of 145 patients, particularly patients in intensive care units (ICUs) (107 patients [72%]), were colonized or infected. Infection developed in 92 (63%) patients, and primary bacteremia caused by ESBL-KP was the most frequent infection (40 of 92 patients [43%]). A single clone of ESBL-KP was identified by pulsed-field gel electrophoresis analysis throughout the whole period, and no molecular epidemiological relationship could be found between the epidemic strain and non-ESBL-KP isolates. To determine risk factors for ESBL-KP infection weekly rectal swabs were obtained in three serial incidence surveys (470 patients); the probabilities of carriage of ESBL-KP in the digestive tract were 33% (October and November 1993), 40% (May and June 1994), and 0% (October and November 1995) at 10 days of ICU admission. A logistic regression model identified prior carriage of ESBL-KP in the digestive tract (odds ratio, 3.4; 95% confidence interval 1.1 to 10.4) as an independent variable associated with ESBL-KP infection. A statistically significant correlation was observed between the restricted use of oxyimino-β-lactams (189 defined daily doses [DDD]/1,000 patient-days to 24 DDD/1,000 patient-days) and the trends of ESBL-KP infection (r = 0.7; P = 0.03).
Resistance to third generation cephalosporins by acquisition and expression of extended spectrum beta lactamase (ESBL) enzymes among gram-negative bacilli is on a rise. The presence of ESBL producing organisms significantly affects the course and outcome of an infection and poses a challenge to infection management worldwide.
Materials and Methods:
In the period from June 2007 to 2008, we collected 1489 samples from patients suspected of nosocomial infection. The isolates were identified based on colony morphology and biochemical reaction. Gram negative bacilli resistant to third generation cephalosporins were tested for ESBL by double disc synergy test (DDST- a screening test)and then phenotypic confirmatory test. Antimicrobial susceptibility testing was done by modified Kirby Bauer disc diffusion method.
From the sample of 238 gram-negative bacilli, we isolated Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Citrobacter freundii, Proteus mirabilis, Morganella morganii and Enterobacter cloacae. Following both methods, 34% isolates were ESBL-positive. The ESBL producing isolates were significantly resistant (p < 0.01) to ampicillin, piperacillin, piperacillin/tazobactam, trimethoprim/sulfamethoxazole, tetracycline, ciprofloxacin and gentamicin as compared to non-ESBL producers. Multidrug resistance was significantly (p < 0.01) higher (69.14%) in ESBL positive isolates than non-ESBL isolates (21.66%).
High prevalence of ESBL in our hospital cannot be ignored. ESBL producers can be detected by DDST and phenotypic confirmatory test with equal efficacy. The sensitivity of screening test improved with the use of more than one antibiotic and addition of one or two antibiotics would not increase cost and labor. We recommend DDST using multiple antibiotics in all microbiology units as a routine screening test.
ESBL; Gram negative bacilli; Nosocomial
There is a lack of consensus regarding the definition of risk factors for healthcare-associated infection (HCAI). The purpose of this study was to identify additional risk factors for HCAI, which are not included in the current definition of HCAI, associated with infection by multidrug-resistant (MDR) pathogens, in all hospitalized infected patients from the community.
This 1-year prospective cohort study included all patients with infection admitted to a large, tertiary care, university hospital. Risk factors not included in the HCAI definition, and independently associated with MDR pathogen infection, namely MDR Gram-negative (MDR-GN) and ESKAPE microorganisms (vancomycin-resistant Enterococcus faecium, methicillin-resistant Staphylococcus aureus, extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species, carbapenem-hydrolyzing Klebsiella pneumonia and MDR Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species), were identified by logistic regression among patients admitted from the community (either with community-acquired or HCAI).
There were 1035 patients with infection, 718 from the community. Of these, 439 (61%) had microbiologic documentation; 123 were MDR (28%). Among MDR: 104 (85%) had MDR-GN and 41 (33%) had an ESKAPE infection. Independent risk factors associated with MDR and MDR-GN infection were: age (adjusted odds ratio (OR) = 1.7 and 1.5, p = 0.001 and p = 0.009, respectively), and hospitalization in the previous year (between 4 and 12 months previously) (adjusted OR = 2.0 and 1,7, p = 0.008 and p = 0.048, respectively). Infection by pathogens from the ESKAPE group was independently associated with previous antibiotic therapy (adjusted OR = 7.2, p < 0.001) and a Karnofsky index <70 (adjusted OR = 3.7, p = 0.003). Patients with infection by MDR, MDR-GN and pathogens from the ESKAPE group had significantly higher rates of inadequate antibiotic therapy than those without (46% vs 7%, 44% vs 10%, 61% vs 15%, respectively, p < 0.001).
This study suggests that the inclusion of additional risk factors in the current definition of HCAI for MDR pathogen infection, namely age >60 years, Karnofsky index <70, hospitalization in the previous year, and previous antibiotic therapy, may be clinically beneficial for early diagnosis, which may decrease the rate of inadequate antibiotic therapy among these patients.
Healthcare-associated infections; Multidrug resistant pathogens infection; Multidrug resistant gram negatives infection; ESKAPE microorganisms’ infection; Independent risk factors; Inadequate antibiotic therapy
Background and Objectives
Patients at intensive-care-unit (ICU) are at risk of acquiring nosocomial infections which contributes to higher rates. Approximately 25% of all hospital infections and 90% of outbreaks occur in ICUs. Multi- resistant gram-negative rods are important pathogens in ICUs, causing high rate of mortality. The purpose of this study was to investigate the antimicrobial resistance patterns among common Gram-negative bacilli isolated from patients with nosocomial infection at Army Hospitals.
Materials and Methods
A total of 187 isolates of Gram-negative bacilli were isolated from 904 patients at ICUs of three Army hospitals in Iran during May 2007 to May 2008. All isolates were examined for antimicrobial resistance using disc diffusion method.
The most frequent pathogens were E. coli (32.08%) followed by K. pneumoniae (31%), P. aeruginosa (12.8%) and Acinetobacter spp. (9.1%). High rate of resistance to third generation cephalosporines was observed among isolates of E. coli and K. pneumoniae. Production of extended spectrum beta lactamases (ESBLs) was found in 46.6% of isolates of both organisms, but in 38% of all Gram negative bacteria.
The prevalence of ESBL producing strains at three Army Hospitals is considerable (38%). However, resistance to imipenem has emerged in these hospitals. Furthermore, studies are required to clarify the situation with multi-drug resistant organisms including the Gram positive bacteria at Army hospitals.
Gram-negative; ICU; Antimicrobial resistance; Antibiotic
Klebsiella pneumoniae is an opportunistic gram-negative pathogen involved in outbreaks of nosocomial infections in intensive care units. Strains are resistant to multiple antibiotics, and 15 to 30% of them are also resistant to the broad-spectrum cephalosporins by the production of R plasmid-encoded extended-spectrum beta-lactamases. Because the gastrointestinal tracts of patients have been shown to be the reservoir for nosocomial strains of K. pneumoniae, we looked for a correlation between antibiotic resistance and adhesion of K. pneumoniae strains to intestinal cells. We investigated adhesion to the human intestinal epithelial Caco-2 cell line of 61 clinical K. pneumoniae strains isolated in hospitals in Clermont-Ferrand, France. None of the strains tested expressed the previously described adhesive factors CF29K and KPF-28. Adhesive properties were found for 42.6% of the strains tested (26 strains). Just 7.7% (2 strains) of the 26 strains producing only the chromosomally encoded SHV-1 beta-lactamase adhered to the Caco-2 cell line, whereas 68.5% (24 strains) of the 35 strains producing a plasmid-encoded beta-lactamase were adherent. All the adherent strains, and even the two strains producing only the SHV-1 enzyme, harbored at least one self-transmissible R plasmid. At variance for CAZ-1/TEM-5 or CAZ-5/SHV-4 beta-lactamase-producing K. pneumoniae strains, curing and mating experiments demonstrated that the self-transmissible R plasmids encoding the TEM-1, CTX-1/TEM-3, CAZ-2/TEM-8, CAZ-6/TEM-24, or CAZ-7/TEM-16 beta-lactamase were not involved in the adhesion of K. pneumoniae strains to intestinal epithelial cells. Nevertheless, there was an association of multiple antibiotic resistance, including resistance to extended-spectrum cephalosporins, and adhesive properties in K. pneumoniae clinical isolates.
Antibiotic exposure exerts strong selective pressure and is an important modifiable risk factor for antibiotic resistance. We aimed to identify the role of various antibiotics as risk factors for the isolation of extended-spectrum-β-lactamase (ESBL)-producing Klebsiella spp. in hospitalized patients at a tertiary-care hospital. A parallel multivariable model was created to compare two groups of cases with either nosocomially acquired ESBL- or non-ESBL-producing Klebsiella spp. to a common control group of hospitalized patients (a case-case-control design). Seventy-eight ESBL cases, 358 non-ESBL cases, and 444 controls were analyzed. Significant factors associated with the isolation of Klebsiella spp. were an age of >65 years, transfer from a health care facility, an intensive care unit (ICU) stay, and the presence of a comorbid malignancy or lung, hepatic, or renal disease. A propensity score was generated from the above, and our ability to discriminate between Klebsiella cases and controls (area under the receiver-operating-characteristic [ROC] curve, 0.78) was good. The ESBL phenotype was tightly linked with fluoroquinolone resistance (95% versus 18%, P < 0.001). Factors associated with isolation of ESBL Klebsiella spp. in a multivariable analysis, adjusting for the propensity score, included exposure to β-lactam-β-lactamase inhibitor combinations (odds ratio [OR], 10.17; 95% confidence interval [CI], 1.19 to 86.92) and to fluoroquinolones (OR, 2.86; 95% CI, 1.37 to 5.97). Exposure to broad-spectrum cephalosporins was statistically associated with ESBL Klebsiella spp. only among the subgroup of patients not treated with fluoroquinolones. In our institution, where the ESBL-producing-Klebsiella phenotype is coselected with fluoroquinolone resistance, fluoroquinolone and β-lactam-β-lactamase inhibitor combinations, rather than cephalosporins, are the main risk factors for ESBL isolates. Formulary interventions to limit the spread of ESBL-producing isolates should be tailored to each setting.
Coexisting conditions and previous antimicrobial drug exposure predict colonization.
Extended-spectrum β-lactamase (ESBL)–producing bacteria are emerging pathogens. To analyze risk factors for colonization with ESBL-producing bacteria at intensive care unit (ICU) admission, we conducted a prospective study of a 3.5-year cohort of patients admitted to medical and surgical ICUs at the University of Maryland Medical Center. Over the study period, admission cultures were obtained from 5,209 patients. Of these, 117 were colonized with ESBL-producing Escherichia coli and Klebsiella spp., and 29 (25%) had a subsequent ESBL-positive clinical culture. Multivariable analysis showed the following to be statistically associated with ESBL colonization at admission: piperacillin-tazobactam (odds ratio [OR] 2.05, 95% confidence interval [CI] 1.36–3.10), vancomycin (OR 2.11, 95% CI 1.34–3.31), age >60 years (OR 1.79, 95% CI 1.24–2.60), and chronic disease score (OR 1.15; 95% CI 1.04–1.27). Coexisting conditions and previous antimicrobial drug exposure are thus predictive of colonization, and a large percentage of these patients have subsequent positive clinical cultures for ESBL-producing bacteria.
Drug-resistance microbial; risk factors; intensive care units; beta lactamases; Escherichia coli; Klebsiella; research
Infections caused by antimicrobial-resistant bacteria are associated with substantial morbidity and mortality. Residents of long-term care facilities (LTCF) are among the main reservoirs of antimicrobial-resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Multidrug-resistant gram-negative organisms (MDRGN) are emerging as important pathogens among LTCF residents. Data on the clinical epidemiology of MDRGN, especially in comparison to VRE and MRSA, are limited.
All clinical cultures collected from residents of a 750-bed LTCF for a period of 2 years were analyzed for the presence of MDRGN, VRE, and MRSA. Multidrug resistance among gram-negative bacteria was defined as resistance to three or more antimicrobials or antimicrobial groups including extended-spectrum penicillins (ampicillin/sulbactam or piperacillin/tazobactam), cephalosporins (cefazolin or ceftriaxone), gentamicin, ciprofloxacin, and trimethoprim-sulfamethoxazole (TMP/SMX).
A total of 1,661 clinical cultures were included in the analysis. MDRGN were recovered from 180 (10.8%) cultures, MRSA from 104 (6.3%), and VRE from 11 (0.6%). MDRGN were isolated more frequently than MRSA or VRE throughout the study period. The prevalence of MDRGN increased significantly from 7% in 2003 to 13% in 2005 (p = .001). More than 80% of MDRGN isolates were resistant to ciprofloxacin, TMP/SMX, and ampicillin/sulbactam. Resistance to three, four, and five or more antimicrobials were identified among 122 (67.8%), 47 (26.1%), and 11 (6.1%) MDRGN isolates, respectively.
Rates of MDRGN exceeded those of MRSA and VRE and increased throughout the study period. Resistance to multiple, commonly prescribed antimicrobials among MDRGN raises concerns about therapeutic options available to treat MDRGN infections among LTCF residents.
Antimicrobial resistance; Long-term care; Multidrug-resistant gram negative; Geriatrics
Extended-spectrum beta-lactamase (ESBL) producing bacteria have been increasingly reported as causal agents of nosocomial infection worldwide. Resistance patterns vary internationally, and even locally, from one institution to the other. We investigated the clinical isolates positive for ESBL-producing bacteria in our institution, a tertiary care hospital in Madrid (Spain), during a 2-year period (2007–2008).
Clinical and microbiological data were retrospectively reviewed. Two hundred and nineteen patients were included in the study.
Advanced age, diabetes, use of catheters, previous hospitalization and previous antibiotic treatment were some of the risk factors found among patients. Escherichia coli was the most frequent isolate, and urinary tract the most common site of isolation. Internal Medicine, Intensive Care Unit (ICU) and General Surgery presented the highest number of isolates. There were no outbreaks during the study period. Antibiotic patterns showed high resistance rates to quinolones in all isolates. There was 100% sensitivity to carbapenems.
Carbapenems continue to be the treatment of choice for ESBL-producing bacteria. Infection control measures are of great importance to avoid the spread of these nosocomial infections.
extended spectrum beta-lactamases; ESBL; Enterobacteriaceae; institutional epidemiology; nosocomial infection; antimicrobial resistance
Newborn infants cared for in neonatal intensive care units may develop nosocomial infections. Cefepime, a “fourth-generation” cephalosporin (i.e., with activity against virtually all of the chromosomal-beta-lactamase-producing and many extended-spectrum-beta-lactamase-producing organisms), provides excellent activity against many gram-negative pathogens resistant to expanded-spectrum cephalosporins currently used to treat neonatal infections. The purpose of this study was to determine the pharmacokinetics of cefepime in this population to optimize dosing and minimize potential adverse events. Premature and term infants <4 months of age hospitalized in two neonatal intensive care units were studied. Limited pharmacokinetic (PK) sampling occurred following a dose of cefepime at 50 mg/kg of body weight infused over 30 min. Population pharmacokinetic parameters were determined using the program NONMEM. Fifty-five infants were enrolled. Their average (± standard deviation) gestational age at birth was 30.5 ± 5.3 weeks, and their average postnatal age at PK evaluation was 14.5 ± 14.7 days. In the final PK model, cefepime clearance (CL) was strongly associated with serum creatinine (SCr) (CL [ml/min/kg] = 0.26 + 0.59/SCr). The volume of distribution for infants with a postconceptional age of <30 weeks was larger than that for infants with a postconceptional age of >30 weeks (0.51 versus 0.39 liter/kg, respectively). The Bayesian analysis-predicted cefepime trough concentration at a dose of 50 mg/kg every 12 h for infants ≤14 days of age was 29.9 ± 16.6 μg/ml. Cefepime, dosed at 30 mg/kg/dose every 12 h for infants less than 14 days of age, regardless of gestational age, should provide antibiotic exposure equivalent to or greater than 50 mg/kg every 8 h in older infants and children.
Bloodstream infection (BSI) is the most frequent infection in critically ill patients. As BSI’s among patients in intensive care units (ICU’s) are usually secondary to intravascular catheters, they can be caused by both Gram-positive and Gram-negative microorganisms as well as fungi. Infection with multidrug-resistant (MDR) organisms is becoming more common, making the choice of empirical antimicrobial therapy challenging. The objective of this study is to evaluate the spectrum of microorganisms causing BSI’s in a Medical-Surgical Intensive Care Unit (MSICU) and their antimicrobial resistance patterns.
A prospective observational study among all adult patients with clinical signs of sepsis was conducted in a MSICU of an inner-city hospital in New York City between May 1, 2010 and May 30, 2011.
A total of 722 adult patients with clinical signs of systemic inflammatory response syndrome (SIRS) and/or sepsis were admitted to the MSICU between May 1, 2010 and May 30, 2011. From those patients, 91 (12.6%) had one or more positive blood culture. A 122 isolates were identified: 72 (59%) were Gram-positive bacteria, 38 (31.1%) were Gram-negative organisms, and 12 (9.8%) were fungi. Thirteen (34.2%) Gram-negative organisms and 14 (19.4%) Gram-positive bacteria were classified as MDR.
Antimicrobial resistance, particularly among Gram-negative organisms, continues to increase at a rapid rate, especially in the ICU’s. Coordinated infection control interventions and antimicrobial stewardship policies are warranted in order to slow the emergence of resistance.
Bloodstream infection (BSI); Multidrug-resistant (MDR); Extended-spectrum β-lactamase (ESBL); Carbapenem-resistant Enterobacteriaceae (CRE); Intensive care units (ICU’s)
The burden of infection with antibiotic-resistant gram-positive cocci, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE), continues to increase, leading to substantial morbidity and high mortality rates, particularly in intensive care units (ICUs). Creative interventions may be required to reverse or stabilize this trend.
The efficacy of empiric cycling of antibiotics active against gram-positive organisms was tested in a before–after intervention in a single surgical ICU. Four years of baseline data were compared with two years of data compiled after the implementation of a strategy where the empiric antibiotic of choice for the treatment of gram-positive infections (linezolid or vancomycin) was changed every three months. Whatever the initial choice of drug, if possible, the antibiotic was de-escalated after final culture results were obtained. The rates of all gram-positive infections were analyzed, with a particular focus on MRSA and VRE. Concurrently, similar outcomes were followed for patients treated on the same services but outside the ICU, where cycling was not practiced.
During the four years prior to cycling, 543 infections with gram-positive organisms were acquired in the ICU (45.3/1,000 patient-days), including 105 caused by MRSA (8.8/1,000 patient days) and 21 by VRE (1.8/1,000 patient-days). In the two years after implementation of cycling, 169 gram-positive infections were documented (28.1/1,000 patient-days; p < 0.0001 vs. non-cycling period), including 11 caused by MRSA (1.8/1,000 patient-days; p < 0.0001 vs. non-cycling period). The percentage of S. aureus infections caused by MRSA declined from 67% to 36%. The rate of infection with VRE was unchanged. Outside the ICU, the yearly numbers of infections with both MRSA and VRE increased over time.
Quarterly cycling of linezolid and vancomycin in the ICU is a promising method to reduce infections with MRSA.