Pathogens In Intensive Care Unit Research Articles

Antibiotic-Mediated Selection of Quorum-Sensing-Negative Staphylococcus aureus

ABSTRACTStaphylococcus aureus is a human commensal that at times turns into a serious bacterial pathogen causing life-threatening infections. For the delicate control of virulence, S. aureus employs the agr quorum-sensing system that, via the intracellular effector molecule RNAIII, regulates virulence gene expression. We demonstrate that the presence of the agr locus imposes a fitness cost on S. aureus that is mediated by the expression of RNAIII. Further, we show that exposure to sublethal levels of the antibiotics ciprofloxacin, mupirocin, and rifampin, each targeting separate cellular functions, markedly increases the agr-mediated fitness cost by inducing the expression of RNAIII. Thus, the extensive use of antibiotics in hospitals may explain why agr-negative variants are frequently isolated from hospital-acquired S. aureus infections but rarely found among community-acquired S. aureus strains. Importantly, agr deficiency correlates with increased duration of and mortality due to bacteremia during antibiotic treatment and with a higher frequency of glycopeptide resistance than in agr-carrying strains. Our results provide an explanation for the frequent isolation of agr-defective strains from hospital-acquired S. aureus infections and suggest that the adaptability of S. aureus to antibiotics involves the agr locus.

CXA-201 Effective against Common ICU Pathogens, Including MDR Gram-Negative Pathogens and Pseudomonas aeruginosa

Using a pharmacokinetic/pharmacodynamic (PK/PD) target algorithm, the in vitro potency of CXA-201 (CXA101/tazobactam), a novel cephalosporin and b-lactamase inhibitor combination that is being developed to treat serious bacterial infections, was reported to be lower in isolates from the intensive care unit (ICU) compared with non-ICU isolates.

Changes in antimicrobial susceptibility and major clones of Acinetobacter calcoaceticus–baumannii complex isolates from a single hospital in Korea over 7 years

Acinetobacter species have emerged as opportunistic nosocomial pathogens in intensive care units. Epidemic spread and outbreaks of multidrug-resistant or carbapenem-resistant Acinetobacter baumannii infections have been described worldwide. Species distribution, antimicrobial resistance and genotypes were investigated for Acinetobacter species isolates collected from a single institution in Korea over 7 years. Two hundred and eighty-seven Acinetobacter species isolates were collected from patients with bloodstream infections in one Korean hospital from 2003 to 2010. Most of them belonged to the Acinetobacter calcoaceticus-baumannii complex (94.4 %). The most frequently isolated species was A. baumannii (44.2 %), followed by Acinetobacter nosocomialis (formerly Acinetobacter genomic species 13TU) (34.1 %). The proportion of A. baumannii increased significantly from 2008 to 2010 (40.4 to 50.0 %). From 2008, imipenem and meropenem resistance rates increased significantly compared with 2003-2007 (12.9 % and 20.5 %, respectively, to 41.4 % and 41.5 %, respectively). An increased carbapenem resistance rate between the two periods was identified more clearly amongst A. baumannii isolates. Polymyxin-resistant A. baumannii isolates emerged in 2008-2010, despite the availability of few isolates. The increase of carbapenem resistance in A. baumannii might be due to the substitution of main clones. Although ST92 and ST69 were the most prevalent clones amongst A. baumannii in 2003-2007 (47.8 % and 15.9 %, respectively), ST75 and ST138 had increased in 2008-2010 (39.7 % and 25.9 %, respectively). Although ST92 showed moderate resistance to carbapenems, most ST75 and ST138 isolates were resistant to carbapenems. All ST75 and ST138 isolates, but only one ST92 isolate, contained the bla(OXA-23-like) gene. Increased carbapenem resistance in Acinetobacter species and A. baumannii isolates might be due to the expansion of specific carbapenem-resistant clones.

Intravenous Colistin Administration in Neonates

Nosocomial infection due to multidrug-resistant Gram-negative pathogens in intensive care units is a challenge for clinicians and microbiologists, and has led to resurgence of parenteral colistin use in the last decade. Safety and efficacy data regarding intravenous colistin (colistimethate) use in neonates is sparse. We present our experience of efficacy and safety of colistimethate in the treatment of sepsis in critically sick term and preterm neonates. The records of the neonates who received colistimethate in a neonatal intensive care unit of a tertiary care center from January 2009 to December 2009 were reviewed. Eighteen critically sick neonates (10 term and 8 preterm) received 21 courses of colistimethate (dose ranging from 50,000 to 75,000 IU/kg/d) for treatment of pneumonia, blood stream infections, meningitis, and empyema thoracis. The isolated pathogens in decreasing order of frequency were Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonos aeruginosa, and Enterobacter. Mean duration of colistimethate was 13.1 days/course (range: 5-21 days). At least one other antibiotic was coadministered in all courses. A favorable clinical outcome occurred in 16 of 21 (76%) courses, 5 patients died due to severe sepsis with multiple organ dysfunction. Microbiologic clearance was documented in 17 courses. Increase in serum creatinine by > 0.5 mg/dL above baseline in 2 babies was associated with the presence of multiple organ dysfunction syndrome in both and coadministration of netilmicin in one. Colistimethate intravenous administration appears to be safe and efficacious for multidrug-resistant Gram-negative infections in neonates, including preterm and extremely low birth weight neonates.

Prevalence of antimicrobial resistance among gram-negative isolates in an adult intensive care unit at a tertiary care center in Saudi Arabia

BACKGROUND AND OBJECTIVES:Patients in the ICU have encountered an increasing emergence and spread of antibiotic-resistant pathogens. We examined patterns of antimicrobial susceptibility in gram-negative isolates to commonly used drugs in an adult ICU at a tertiary care hospital in Riyadh, Saudi Arabia.METHODS:A retrospective study was carried out of gram-negative isolates from the adult ICU of King Fahad National Guard Hospital (KFNGH) between 2004 and 2009. Organisms were identified and tested by an automated identification and susceptibility system, and the antibiotic susceptibility testing was confirmed by the disk diffusion method.RESULTS:The most frequently isolated organism was Acinetobacter baumannii, followed by Pseudomonas aeruginosa, Escherichia coli, Klebsiella pnemoniae, Stenotrophomonas maltophilia, and Enterobacter. Antibiotic susceptibility patterns significantly declined in many organisms, especially A baumannii, E coli, S marcescens, and Enterobacter. A baumannii susceptibility was significantly decreased to imipenem (55% to 10%), meropenem (33% to 10%), ciprofloxacin (22% to 10%), and amikacin (12% to 6%). E coli susceptibility was markedly decreased (from 75% to 50% or less) to cefuroxime, ceftazidime, cefotaxime, and cefepime. S marcescens susceptibility was markedly decreased to cefotaxime (100% to 32%), ceftazidime (100% to 35%), and cefepime (100% to 66%). Enterobacter susceptibility was markedly decreased to ceftazidime (34% to 5%), cefotaxime (34% to 6%), and pipracillin-tazobactam (51% to 35%). Respiratory samples were the most frequently indicative of multidrug-resistant pathogens (63%), followed by urinary samples (57%).CONCLUSION:Antimicrobial resistance is an emerging problem in the KFNGH ICU, justifying new more stringent antibiotic prescription guidelines. Continuous monitoring of antimicrobial susceptibility and strict adherence to infection prevention guidelines are essential to eliminate major outbreaks in the future.

Molecular epidemiology of Pseudomonas aeruginosa in intensive care units over a 10-year period (1998-2007)

Pseudomonas aeruginosa is one of the leading nosocomial pathogens in intensive care units (ICUs). The source of this microorganism can be either endogenous or exogenous. The proportion of cases as a result of transmission is still debated, and its elucidation is important for implementing appropriate control measures. To understand the relative importance of exogenous vs. endogenous sources of P. aeruginosa, molecular typing was performed on all available P. aeruginosa isolated from ICU clinical and environmental specimens in 1998, 2000, 2003, 2004 and 2007. Patient samples were classified according to their P. aeruginosa genotypes into three categories: (A) identical to isolate from faucet; (B) identical to at least one other patient sample and not found in faucet; and (C) unique genotype. Cases in categories A and B were considered as possibly exogenous, and cases in category C as possibly endogenous. A mean of 34 cases per 1000 admissions per year were found to be colonized or infected by P. aeruginosa. Higher levels of faucet contamination were correlated with a higher number of cases in category A. The number of cases in category B varied from 1.9 to 20 cases per 1000 admissions. This number exceeded 10/1000 admissions on three occasions and was correlated with an outbreak on one occasion. The number of cases considered as endogenous (category C) was stable and independent of the number of cases in categories A and B. The present study shows that repeated molecular typing can help identify variations in the epidemiology of P. aeruginosa in ICU patients and guide infection control measures.

Can fungal biomarkers be used to improve antifungal therapy in the intensive care unit?

Invasive fungal infections have an increasing incidence worldwide, and patients in intensive care settings are particularly vulnerable to them. Candidemia is the third most common bloodstream pathogen in intensive care units (ICUs) in the United States, and a number of reports have recently been published regarding the increasing incidence of invasive aspergillosis in ICUs throughout the world. Because research has shown that early antifungal therapy is associated with better outcomes, clinicians are starting to explore new diagnostic fungal markers, which are more sensitive and faster than the traditional diagnostic standards of culture and histopathology.

Extreme Drug Resistance inAcinetobacter baumanniiInfections in Intensive Care Units, South Korea

Extreme Drug Resistance in<i>Acinetobacter baumannii</i>Infections in Intensive Care Units, South Korea

Antimicrobial-resistant pathogens in intensive care units in Canada: results of the Canadian National Intensive Care Unit (CAN-ICU) study, 2005-2006.

Between 1 September 2005 and 30 June 2006, 19 medical centers collected 4,180 isolates recovered from clinical specimens from patients in intensive care units (ICUs) in Canada. The 4,180 isolates were collected from 2,292 respiratory specimens (54.8%), 738 blood specimens (17.7%), 581 wound/tissue specimens (13.9%), and 569 urinary specimens (13.6%). The 10 most common organisms isolated from 79.5% of all clinical specimens were methicillin-susceptible Staphylococcus aureus (MSSA) (16.4%), Escherichia coli (12.8%), Pseudomonas aeruginosa (10.0%), Haemophilus influenzae (7.9%), coagulase-negative staphylococci/Staphylococcus epidermidis (6.5%), Enterococcus spp. (6.1%), Streptococcus pneumoniae (5.8%), Klebsiella pneumoniae (5.8%), methicillin-resistant Staphylococcus aureus (MRSA) (4.7%), and Enterobacter cloacae (3.9%). MRSA made up 22.3% (197/884) of all S. aureus isolates (90.9% of MRSA were health care-associated MRSA, and 9.1% were community-associated MRSA), while vancomycin-resistant enterococci (VRE) made up 6.7% (11/255) of all enterococcal isolates (88.2% of VRE had the vanA genotype). Extended-spectrum beta-lactamase (ESBL)-producing E. coli and K. pneumoniae occurred in 3.5% (19/536) and 1.8% (4/224) of isolates, respectively. All 19 ESBL-producing E. coli isolates were PCR positive for CTX-M, with bla CTX-M-15 occurring in 74% (14/19) of isolates. For MRSA, no resistance against daptomycin, linezolid, tigecycline, and vancomycin was observed, while the resistance rates to other agents were as follows: clarithromycin, 89.9%; clindamycin, 76.1%; fluoroquinolones, 90.1 to 91.8%; and trimethoprim-sulfamethoxazole, 11.7%. For E. coli, no resistance to amikacin, meropenem, and tigecycline was observed, while resistance rates to other agents were as follows: cefazolin, 20.1%; cefepime, 0.7%; ceftriaxone, 3.7%; gentamicin, 3.0%; fluoroquinolones, 21.1%; piperacillin-tazobactam, 1.9%; and trimethoprim-sulfamethoxazole, 24.8%. Resistance rates for P. aeruginosa were as follows: amikacin, 2.6%; cefepime, 10.2%; gentamicin, 15.2%; fluoroquinolones, 23.8 to 25.5%; meropenem, 13.6%; and piperacillin-tazobactam, 9.3%. A multidrug-resistant (MDR) phenotype (resistance to three or more of the following drugs: cefepime, piperacillin-tazobactam, meropenem, amikacin or gentamicin, and ciprofloxacin) occurred frequently in P. aeruginosa (12.6%) but uncommonly in E. coli (0.2%), E. cloacae (0.6%), or K. pneumoniae (0%). In conclusion, S. aureus (MSSA and MRSA), E. coli, P. aeruginosa, H. influenzae, Enterococcus spp., S. pneumoniae, and K. pneumoniae are the most common isolates recovered from clinical specimens in Canadian ICUs. A MDR phenotype is common for P. aeruginosa isolates in Canadian ICUs.

Antibiotic synergy profiles of multidrug-resistantPseudomonas aeruginosain a nosocomial environment

Pseudomonas aeruginosa is one of the most common nosocomial pathogens in intensive care units (ICUs), with an increased prevalence of multidrug resistance in nosocomial infections. This study aimed to determine antibiotic synergy profles of multidrug-resistant P. aeruginosa originating from ICU patients in a teaching hospital in Pretoria, South Africa. Susceptibility studies and in vitro synergy testing were performed, utilising agar dilution and Etest methodology, respectively. Susceptibility studies revealed 94% of isolates exhibiting resistance to more than three anti-pseudomonal agents tested. Results from antibiotic synergy studies suggested that cefepime (p‹0.0001) or meropenem (p‹0.0001) in combination with amikacin are possible treatment options available in this specifc setting.

Molecular Epidemiology of Pseudomonas aeruginosa in the Intensive Care Units - A Review

Pseudomonas aeruginosa is one of the leading nosocomial pathogens in intensive care units (ICU). This opportunist pathogen is commonly recovered from moist environments, and is also found colonizing 2.6 to 24% of hospitalized patients. We reviewed the recent literature that used highly discriminatory typing methods to precisely identify the reservoirs and modes of transmission of this microorganism in the ICU setting. In most ICUs, the endogenous flora was suspected to be the main source of infection compared to exogenous sources (other patients, the contaminated environment such as sinks or taps). However, the percentage of endogenous versus exogenous sources might vary considerably from one setting to another. Reasons for this include the compliance of health care workers to infection control measures, the contamination of the environment, and probably also the biology of the pathogen (intrinsic fitness factors). As P. aerugi-nosa is ubiquitous in the environment and colonizes up to 15% of hospitalized patients, eradication of the reservoir is difficult, if not impossible. Therefore, efforts should primarily focus on reinforcement of infection control measures to limit its transmission.

Impact of an antibiotic restriction policy on the antibiotic resistance patterns of Gram-negative microorganisms in an Intensive Care Unit in Greece

The purpose of this study was to investigate the influence of an antibiotic policy programme based on restriction of the empirical use of fluoroquinolones and ceftazidime on the susceptibilities of Gram-negative microorganisms in a general Intensive Care Unit (ICU). The epidemiology of infections caused by the predominant ICU pathogens, i.e. Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae, and their resistance patterns as well as antibiotic consumption were recorded for a 6-month period. An antibiotic restriction policy including ceftazidime and quinolones was applied. After an 18-month period of protocol application, the same parameters were recorded for another 6-month period. Consumption of restricted and overall antibiotics was reduced by 92.5% and 55.4%, respectively. Susceptibilities to ciprofloxacin of the three predominant infection-causing Gram-negative bacilli were significantly increased. Ceftazidime showed an increase in susceptibility only for P. aeruginosa. Similar rates of infectious episodes were recorded in the two periods and no differences were observed either in overall mortality or in ICU ecology as expressed by the type of microorganisms implicated in colonisation and/or infection. The reported data suggest that an antibiotic restriction policy can significantly reduce antimicrobial consumption and antimicrobial resistance rates, although the latter effect can be also influenced by the prevalent resistance mechanisms and the prevalence of imported resistance.

Increasing Fungal Infections in the Intensive Care Unit

Yeasts and molds now rank among the most common pathogens in intensive care units. Whereas the incidence of Candida infections peaked in the late 1970s, aspergillosis is still increasing. Review of the pertinent English-language literature. Most factors promoting an invasive fungal infection are difficult to avoid because they are connected directly to treatment of the underlying disease. Antifungal treatment is often commenced on an empiric basis, whereas it might be preferable to adopt a strategy based on a diagnostic procedure able to demonstrate or exclude fungal disease. Polyenes have been the drugs of choice, but voriconazole is the new standard for aspergillosis. For invasive candidiasis, fluconazole is a more convenient option, with the new echinocandins or voriconazole as alternatives. The incidence of invasive fungal infection is increasing, but so too are the choices of agents for therapy. For reasons of efficacy and safety, therapy with an echinocandin or azole antifungal agent is supplanting the use of polyenes.

Correlation between the genetic diversity of nosocomial pathogens and their survival time in intensive care units

Bacteria differ in their ability to survive in the hospital environment outside the human host. Species remaining viable and infectious have a higher chance of being transmitted, giving them a fitness advantage in hospitals. This differential fitness could be expected to alter the genetic population structure of bacterial populations in hospitals, and should be reflected by the relative abundance of several successful clones. The objective of this study was to test for a potential correlation between tenacity, i.e. environmental survival, and clonal abundance determined by the genetic diversity in different bacterial species from prospectively collected isolates of intensive care patients. A literature review was performed to identify mean environmental survival times for the most important pathogens in intensive care units (ICUs): Staphylococcus aureus, enterococci, Acetinobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp., Escherichia coli, Klebsiella pneumoniae and Stenotrophomonas maltophilia. To determine the genetic diversity of the natural population of these species in ICUs, a prospective 18-month study was conducted in five units with median nosocomial infection rates. All clinical isolates were collected, and highly discriminatory DNA fingerprinting techniques were used to identify specific clones. A diversity index for each species was calculated as the number of distinguishable genotypes in the population divided by size. The correlation between survival times and the diversity indices for the individual pathogens was investigated using non-parametric methods. Although 21 studies were identified in the literature, only two were relevant. They showed median survival times between 1.5 days (P. aeruginosa) and 60.0 days (Enterococcus faecium). During the prospective ICU study, 1264 pathogens were investigated and simple diversity indices between 49.1 (Enterococcus faecalis) and 89.8 (E. coli) were found. A correlation between survival times and the diversity indices for the individual pathogens was found (correlation coefficient 0.821, P=0.024). Environmental survival may be an important factor contributing to the ecological fitness of some nosocomial pathogens in ICUs. Infection control measures should consider this finding.

Multicenter surveillance of antimicrobial resistance of major bacterial pathogens in intensive care units in 2000 in Taiwan.

A susceptibility surveillance study of 1,274 bacterial isolates recovered from various clinical specimens from patients in intensive care units (ICUs) of five major teaching hospitals was carried out from March, 2000, to June, 2000, in Taiwan. This study demonstrated a high rate (66%) of oxacillin resistance in Staphylococcus aureus (ORSA), a high rate of nonsusceptibility to penicillin (intermediate, 50% and highly resistant, 8%), and high rates of cefotaxime nonsusceptibility for S. pneumoniae (intermediate, 29% and resistant, 4%), Enterobacter cloacae (57%), Serratia marcescens (34%), and Citrobacter freundii (60%). High rate of ceftazidime nonsusceptibility for Pseudomonas aeruginosa (22%), and high rates of imipenem nonsusceptibility for P. aeruginosa (15%) and Acinetobacter baumannii (22%) were also found. The percentage (11.9%) of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli was greater than that (11.3%) for Klebsiella pneumoniae. Rates of quinupristin-dalfopristin nonsusceptibility for S. pneumoniae (42%), Enterococcus faecium (71%), and ORSA (39%) were high, but no vancomycin-resistant enterococci were found in this study. The resistance rates of some pathogen varied by institution or type of ICUs. Surveillance for antimicrobial resistance among bacterial pathogens in hospitals, particularly in ICU settings with a preexisting higher resistance burden, is mandatory in establishing and/or modifying guidelines for empirical treatment of severe infections in ICU patients caused by these antimicrobial-resistant pathogens.

Impact of antibiotic resistance on clinical outcomes and the cost of care.

Antibiotic-resistant organisms are common in intensive care unit infection and can be either Gram-positive or Gram-negative. A number of studies have evaluated whether these organisms can lead to excess morbidity, mortality, or cost. In general, the studies are confounded by a number of methodologic issues, including the selection of an appropriate control population. Cases and controls must be appropriately matched for the presence of infection, the presence of infection with similar organisms (but ones that are either antibiotic-sensitive or -resistant), and severity of illness. In addition, studies must account for the therapies given to patients who are infected with resistant organisms because resistance is an important risk factor for inadequate empirical therapy, and such therapy is itself a potent determinant of a number of adverse outcomes, including mortality. To date, the data with methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococcus are inconsistent with regard to the effect on mortality rates, although infection with both organisms can lead to excess length of stay and increased cost of care. When studies have been adequately controlled and powered, infection with vancomycin-resistant enterococcus has had more of an effect on the mortality rate than infection with antibiotic-sensitive enterococci. Infection with resistant Gram-negatives also has adverse impact on outcome, with excess mortality being seen in patient groups infected with Acinetobacter and Pseudomonas aeruginosa. If we are to minimize the effect of resistance on medical outcomes and cost, it will be necessary to have a current knowledge of each intensive care unit's pathogens and susceptibility patterns, so that empirical therapy will have a good likelihood of being effective. In addition, new therapeutic agents may improve on the efficacy of older agents and could reduce cost if they allow for some patients to leave the hospital and to finish therapy with an oral formulation of a highly bioavailable agent.

A control programme for MRSA (methicillin-resistant Staphylococcus aureus) containment in a paediatric intensive care unit: evaluation and impact on infections caused by other micro-organisms

Methicillin-resistant Staphylococcus aureus (MRSA) is increasingly reported as a hospital-acquired pathogen in intensive care units (ICUs). The inconsistent application of hygiene measures by healthcare workers accounts largely for the epidemic dissemination of such resistant strains. The efficacy of a control programme to prevent spread of MRSA was assessed in our paediatric ICU (PICU) from April 1992 to December 1995. Patients initially had weekly MRSA cultures taken from samples of anterior nares and perineum, but from January 1994, cultures were also obtained upon admission. Immediately after notification, all MRSA carriers were isolated. Education of hospital staff was an essential component of our programme. Nosocomial infection rates were recorded retrospectively in 1992 and 1993, and prospectively in 1994 and 1995. Incidence rates between ‘pre-programme’ and ‘programme’ periods were compared. The rate of MRSA infection decreased from 5·9-0·8/1000 Patient-Days (PD), ( P < 10 −1). MRSA carriage also decreased from 34-2% ( P < 10 −9 ) and the ratio of MRSA to all S. aureus fell from 71-11% ( P < 10 −4 ). The decrease in the global incidence of infection from 20·1–13·9/1000 PD ( P = 0·002) was due only to the decrease in MRSA infection. However, between 1994 and 1995, there was a significant increase in the number of transplant patients despite a constant patient/nurse ratio. The nosocomial infection rates caused by other micro-organisms decreased among the transplant patients from 64·8–33·2/ 1000 transplanted PD ( P = 0·009) between 1994 and 1995. At the same time, we observed a slight increase of infections in non-transplanted patients, which may have been due to the effect of increased overall workload on those patients who were supposed to have fewer nosocomial risk factors. We conclude that implementation of infection control measures directed towards limiting person-to-person spread was effective in controlling high MRSA infection rates in a PICU, but it is important to allow enough time for staff to carry out hygiene practices thoroughly.

Impact of Acinetobacter spp. in intensive care units in Great Britain and Ireland

Acinetobacter spp. are of increasing importance as hospital pathogens in intensive care units (ICUs) but it is unclear what clinical impact these bacteria have in Great Britain and Ireland. A survey was carried out by questionnaire on the impact of Acinetobacter in ICUs and the laboratory methods used to identify and type isolates. There were 70 respondents, of whom 25 reported that Acinetobacter had not been recovered from ICU patients within the previous 12 months. The remaining 45 respondents reported that the respiratory tract was the most common site from which these bacteria were isolated, but they were currently endemic in one ICU only. There were considerable differences in methods used to identify Gram-negative bacilli recovered from ICU patients, which may partly explain differences in the reported prevalence of isolates between centres, and 12 laboratories attempted to type isolates by a range of techniques. The availability and use of agreed antibiotic policies specific for ICUs may be particularly important in prevention and control where infection with Acinetobacter is prevalent.