Search

Purpose: The study aimed to determine whether improvements in intensive care unit (ICU) structural environment affect the incidence of ICU-acquired infections (IAIs), particularly those caused by multidrug-resistant pathogens., Methods: The incidence of IAI and the number of infections caused by organisms during the 6 months immediately before ICU renovation and during the 6 months immediately after ICU renovation were compared. The observational duration was prolonged for an additional 1 year after recruiting the after-renovation data to observe if the found effect of ICU structural renovation is maintained. The relevant data were prospectively gathered., Results: The overall IAI incidence and distribution of infection site showed no difference in both periods. In IAI-causing pathogens, no considerable difference was found between before and after renovation, except for Acinetobacter baumannii. In comparison of the major pathogens' identification rate between the entire hospital and the renovated ICU during the study periods, only A baumannii cases in the renovated ICU significantly decreased. However, the reduction of the IAI cases by A baumannii was not sustained for more than 1 year., Conclusions: These results suggest that structural ICU renovations only may not improve overall IAI incidence, except for transient decrease in IAI by A baumannii., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Acinetobacter baumannii is an important emerging pathogen in health care-acquired infections and is responsible for severe nosocomial and community-acquired pneumonia. Currently available mouse models of A. baumannii pneumonia show poor colonization with little to no extrapulmonary dissemination. Here, we describe a mouse model of A. baumannii pneumonia using a clinical isolate (LAC-4 strain) that reliably reproduces the most relevant features of human pulmonary A. baumannii infection and pathology. Using this model, we have shown that LAC-4 infection induced rapid bacterial replication in the lungs, significant extrapulmonary dissemination, and severe bacteremia by 24 h postintranasal inoculation. Infected mice showed severe bronchopneumonia and dilatation and inflammatory cell infiltration in the perivascular space. More significantly, 100% of C57BL/6 and BALB/c mice succumbed to 10(8) CFU of LAC-4 inoculation within 48 h. When this model was used to assess the efficacy of antimicrobials, all mice treated with imipenem and tigecycline survived a lethal intranasal challenge, with minimal clinical signs and body weight loss. Moreover, intranasal immunization of mice with formalin-fixed LAC-4 protected 40% of mice from a lethal (100× 100% lethal dose) intraperitoneal challenge. Thus, this model offers a reproducible acute course of A. baumannii pneumonia without requiring additional manipulation of host immune status, which will facilitate the development of therapeutic agents and vaccines against A. baumannii pneumonia in humans.

Antimicrobial resistance is a continuing, growing, worldwide iatrogenic complication of modern medical care. Carbapenem resistance among certain pathogens poses a significant challenge. In order to reduce the spread of these nearly untreatable pathogens, preventative efforts should be directed at reducing patient-to-patient transmission and preventing the emergence of resistance among susceptible strains. One theoretical intervention to reduce the emergence of resistance is establishing and strictly adhering to an antimicrobial stewardship program. However, data pertaining to the direct effect of stewardship in curtailing carbapenem resistance among epidemiologically significant organisms are scarce. In this report, we review the potential biases associated with data interpretation in this research field, and we review the data pertaining to the impact of stewardship in curbing carbapenem resistance in three significant groups of pathogens: Pseudomonas aeruginosa, Enterobacteriaceae and Acinetobacter baumannii.

An outbreak in a medical intensive care unit was due to an OXA-23-producing Acinetobacter baumannii strain imported from a repatriate hospitalized in Singapore. This outbreak revealed another multidrug resistant epidemic strain that had been present in the hospital for 2 years. Both outbreaks were controlled after 9 months of an extensive infection control program., (Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.)

Background: Multidrug-resistant organisms (MDRO) are increasing challenges for health care institutions worldwide, and there are many factors associated with their distribution., Objectives: We conducted a national survey of Thai hospitals with 1 or more intensive care units and ≥250 hospital beds to evaluate hospital characteristics and current practices to minimize the endemic burden of multidrug-resistant (MDR) Acinetobacter baumannii (AB) and methicillin-resistant Staphylococcus aureus (MRSA)., Methods: Research nurses collected survey data from participating hospitals between January 1 and April 30, 2011. Data collection focused on hospital characteristics and practices to prevent endemic MDR-AB and MRSA; logistic regression analyses were used to assess associations between hospital characteristics and infection prevention control (IPC) interventions., Results: There was an 80% survey response (N = 204) from 256 eligible hospitals. Endemic MDR-AB and MRSA were reported in 184 (90%) and 100 (40%) hospitals, respectively. The most frequently reported IPC interventions were contact isolation, hand hygiene campaigns, and antimicrobial stewardship; active surveillance, chlorhexidine gluconate bathing, and multifaceted interventions were uncommon. By multivariate analysis, having a physician as the lead infection control professional and participation in a collaborative effort to prevent MDR organisms were associated with multifaceted interventions to reduce MDR-AB, and medical school affiliation and participating in a collaborative effort to prevent MDR organisms were associated with multifaceted interventions to reduce MRSA., Conclusion: Multifaceted interventions to reduce, if not prevent, MDR-AB and MRSA were infrequently reported from Thai hospitals. Our survey findings provide baseline data for IPC interventions for MDR-AB and MRSA. Future efforts that correlate IPC interventions and MDRO trends will help develop evidence-based practices in these resource-limited settings., (Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.)

Methicillin-resistant Staphylococcus aureus (MRSA) and Acinetobacter baumannii are major nosocomial pathogens in burns units. We investigated the impact of an infection control bundle on the incidence of nosocomial MRSA and A. baumannii in our burns unit, comparing a pre-intervention period (December 2006-August 2008) with an intervention period (September 2008-December 2009). The bundle comprised regular hydrogen peroxide vapour (HPV) disinfection of the rooms following discharge of patients colonized or infected by multidrug-resistant bacteria, pre-emptive cohort isolation of newly admitted patients before being proven culture negative, cohorting of colonized or infected patients, installation of two air disinfection systems in the corridors of the unit and improvement of material storage. We also investigated the microbiological efficacy of HPV disinfection by sampling the environment before and after HPV treatments. HPV disinfection eliminated pathogens from the environment and significantly reduced total bacterial surface counts, and total fungal air and surface counts, on both a unit and room scale. The incidence of nosocomial MRSA infection or colonization fell by 89.3% from 7.22 to 0.77 cases/1000 patient days (p<0.0001) and A. baumannii fell by 88.8% from 6.92 to 0.77 cases/1000 patient days (p=0.002) in the intervention period with no further outbreaks of these organisms occurring in this period. The infection control bundle resulted in a significant reduction in the incidence of nosocomial MRSA and A. baumannii in our burns unit and prevented further outbreaks of these organisms., (Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.)

This study describes an epidemic strain of Acinetobacter baumannii (AB) in two long-term care facilities. Assessment was focused on the spreading modalities of AB infection, the risk of acquiring the infection from colonized patients, the multidrug-resistant features, the clinical characteristics of affected patients, and the average length of hospital stay prior to and after AB infection. The effects of AB spreading among the healthcare operators and the environment are also evaluated, along with a description of the clinical course and outcome, and the efficacy of implemented preventive measures. AB is an opportunistic pathogen with increasing relevance in a variety of nosocomial infections.

The emergence of extremely resistant and panresistant Gram-negative bacilli, such as Acinetobacter baumannii, requires consideration of nonantimicrobial therapeutic approaches. The goal of this report was to evaluate the K1 capsular polysaccharide from A. baumannii as a passive immunization target. Its structure was determined by a combination of mass spectrometric and nuclear magnetic resonance (NMR) techniques. Molecular mimics that might raise the concern for autoimmune disease were not identified. Immunization of CD1 mice demonstrated that the K1 capsule is immunogenic. The monoclonal antibody (MAb) 13D6, which is directed against the K1 capsule from A. baumannii, was used to determine the seroprevalence of the K1 capsule in a collection of 100 A. baumannii strains. Thirteen percent of the A. baumannii isolates from this collection were seroreactive to MAb 13D6. Opsonization of K1-positive strains, but not K1-negative strains, with MAb 13D6 significantly increased neutrophil-mediated bactericidal activity in vitro (P < 0.05). Lastly, treatment with MAb 13D6 3 and 24 h after bacterial challenge in a rat soft tissue infection model resulted in a significant decrease in the growth/survival of a K1-positive strain compared to that of a K1-negative strain or to treatment with a vehicle control (P < 0.0001). These data support the proof of principle that the K1 capsule is a potential therapeutic target via passive immunization. Other serotypes require assessment, and pragmatic challenges exist, such as the need to serotype infecting strains and utilize serotype-specific therapy. Nonetheless, this approach may become an important therapeutic option with increasing antimicrobial resistance and a diminishing number of active antimicrobials.

The global emergence of multidrug resistant Acinetobacter baumannii has reduced the number of clinically available antibiotics that retain activity against this pathogen. For this reason, the development of novel prevention and treatment strategies for infections caused by A. baumannii is necessary. Several studies have begun to characterize nonantibiotic approaches that utilize novel mechanisms of action to achieve antibacterial activity. Recent advances in phage therapy, iron chelation therapy, antimicrobial peptides, prophylactic vaccination, photodynamic therapy, and nitric oxide (NO)-based therapies have all been shown to have activity against A. baumannii. However, before these approaches can be used clinically there are still limitations and remaining questions that must be addressed., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Acinetobacter baumannii has become an important cause of human infections, most notably in the hospital setting. In addition, the global dissemination of multidrug resistant strains has complicated effective antibiotic therapy of infections produced by this pathogen, necessitating the development of novel treatment and prevention strategies. Active and passive immunization approaches have begun to be explored in experimental animal models as potential alternative therapies for A. baumannii. In the present review, we discuss the advantages and disadvantages of each therapeutic strategy with respect to A. baumannii infections, and summarize the recent studies that have explored these approaches. The single antigen candidates that have been tested include, the outer membrane protein OmpA, the membrane transporter Ata, the biofilm-associated protein Bap, the K1 capsular polysaccharide and the membrane associated polysaccharide poly-N-acetyl-β -(1-6)-glucosamine. Strategies employing multicomponent antigens include inactivated whole cells, outer membrane complexes and outer membrane vesicles. The strengths and limitations of each approach are discussed and the challenges that remain to be addressed for successful A. baumannii vaccine development are highlighted.

Objective: To determine factors associated with colonization by carbapenem-resistant Pseudomonas aeruginosa and multiresistant Acinetobacter spp., Methods: Surveillance cultures were collected from patients admitted to the intensive care unit at admission, on the third day after admission and weekly until discharge. The outcome was colonization by these pathogens. Two interventions were implemented: education and the introduction of alcohol rubs. Compliance with hand hygiene, colonization pressure, colonization at admission and risk factors for colonization were evaluated., Results: The probability of becoming colonized increased during the study. The incidence density of colonization by carbapenem-resistant P. aeruginosa and multiresistant Acinetobacter spp. and colonization pressure were different between periods, increasing gradually throughout the study. The increase in colonization pressure was due to patients already colonized at admission. The APACHE II score, colonization pressure in the week before the outcome and male gender were independent risk factors for colonization. Every 1% increase in colonization pressure led to a 2% increase in the risk of being colonized., Conclusion: Colonization pressure is a risk factor for carbapenem-resistant P. aeruginosa and multiresistant Acinetobacter spp. colonization. When this pressure reaches critical levels, efforts primarily aimed at hand hygiene may not be sufficient to prevent transmission.

Acinetobacter baumannii is a multidrug-resistant (MDR) nosocomial pathogen for which immunotherapeutic alternatives are needed. We previously identified a surface autotransporter of A. baumannii, Ata, that bound to various extracellular matrix/basal membrane proteins and was required for full virulence, biofilm formation, and the adhesion of A. baumannii to collagen type IV. We show here that Ata binding to collagen type IV was inhibited by antibodies to Ata. In addition, in the presence of complement and polymorphonuclear cells (PMNs), antibodies to Ata were highly opsonic against A. baumannii ATCC 17978 and showed low to moderate killing activity against four heterologous A. baumannii strains, whereas in the absence of PMNs, antibody to Ata efficiently promoted complement-dependent bactericidal killing of all of the tested A. baumannii isolates. Using a pneumonia model of infection in both immunocompetent and immunocompromised mice, we found that, compared to normal rabbit sera, antisera to Ata significantly reduced the levels of A. baumannii ATCC 17978 and two MDR strains in the lungs of infected mice. The ability of Ata to engender anti-adhesive, bactericidal, opsonophagocytic, and protective antibodies validates its potential use as an antigenic target against MDR A. baumannii infections.

Background: Multidrug-resistant Acinetobacter baumannii (MRAB) is a serious nosocomial pathogen characterized by its survival on inanimate surfaces for long periods, making control of outbreaks difficult., Aim: To analyse two hospital outbreaks caused by MRAB, determine their epidemiology, carbapenem-resistance mechanisms and assess the effectiveness of surface disinfection by vaporized hydrogen peroxide (VHP)., Methods: MRAB strains were isolated from patients in two intensive care units (ICUs). Antimicrobial susceptibility testing was performed by E-test. Polymerase chain reaction (PCR) was used to detect the presence of the most common A. baumannii carbapenemases. Epidemiological typing was performed by rep-PCR (DiversiLab) and pulsed-field gel electrophoresis. VHP was used to decontaminate the affected ICUs., Findings: MRAB was isolated from 28 patients between January 2009 and September 2010. All isolates were resistant to ciprofloxacin and gentamicin. Twenty-one were also resistant to carbapenems. Carbapenem resistance was associated primarily with the acquired OXA-23-like enzyme. Genotyping revealed three clones; the predominant clone corresponded to the international clone (IC) 2. Typing of the isolates pointed to a multifocal outbreak without a single source of infection, with horizontal spread of the dominating clone among ICU patients. A combination of rigorous infection control measures including strict isolation, education of staff, hand hygiene and surface decontamination using VHP halted the outbreak., Conclusion: The results of this study confirm the importance of rigorous infection prevention and control measures, combined with VHP decontamination in controlling an outbreak of MRAB., (Copyright © 2012 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Introduction: The hospital environment plays a role in the cross-transmission of multidrug-resistant bacteria. The aim of this study was to evaluate the bacterial contamination of the hospital environment during chronic wound dressing change., Patients and Methods: This study was performed from July 2010 to May 2011. Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii and Enterobacteriaceae were counted in environmental samples (air and surfaces) that were obtained in the rooms of patients with wounds colonized (cases, n=9) or not (controls, n=15) during or not during wound dressing change. Bacterial contamination was compared to that found in the rooms of patients without colonized wounds., Results: The environment was frequently contaminated during wound dressing change (38% of the sampled series were positive). In comparison, the contamination was less frequent in the environment of patients with colonized wounds when the wounds were not being dressed (14.3%) and in controls (3.8%). S. aureus was the most frequent species identified in positive samples., Discussion: These results suggest that previously recommended measures such as hand hygiene after contact with the environment and wearing a mask are justified. Moreover, other measures should be suggested, in particular cleaning the room before and after dressing change of colonized wounds., Level of Evidence: Level III: case control study., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Background: A nosocomial outbreak of Acinetobacter baumannii bloodstream infections (Ab-BSI) was identified in Diyarbakir Children's Hospital's (Diyarbakir, Turkey) 60-bed Neonatal Intensive Care Unit (NICU) in 2006 and 2007., Methods: The investigation and control of the outbreak were based on case-control and epidemiological studies as well as multifaceted interventions. Sixty-four neonates (case patients) with Ab-BSI and 128 neonates (control patients) free of Ab-BSI, who had been hospitalized at the unit during the outbreak period, were included in the study. Case and control patients were compared for possible predisposing factors (e.g., gender, length of NICU stay, antibiotic use, intubation, etc.). An intervention program (cohorting, education, reinforcing hand hygiene, antibiotic restriction, improving processes of patient care, environmental cleaning, and barrier isolation) was implemented to control the outbreak. Surveillance cultures were collected from all possible sources, and the epidemiological investigation was supplemented by a pulsed field gel electrophoresis (PFGE) study., Results: Fifty-three neonates (82.8%) died in the case group and 51 (39.8%) in the control group (P < 0.001). The duration of stay at the NICU [odds ratio (OR) 1.15; 95% confidence interval (CI) 1.07-1.23; P < 0.001] and re-intubation (OR 38.62; CI 12.66-117.87; P < 0.001) were found to be significant risk factors for Ab-BSI. Surveillance cultures showed a heavy contamination in the NICU, and the outbreak ended after a series multifaceted interventions. All A. baumannii isolates, both from the cases and environmental samples, had an identical PFGE fingerprint pattern., Conclusion: The control of Ab-BSI requires a multifaceted intervention program and complex efforts and implementations, especially if the ICU does not implement any suspension of care provision.

Extreme-drug-resistant (XDR) Acinetobacter baumannii is a rapidly emerging pathogen causing infections with unacceptably high mortality rates due to inadequate available treatment. New methods to prevent and treat such infections are a critical unmet medical need. To conduct a rational vaccine discovery program, OmpA was identified as the primary target of humoral immune response after intravenous infection by A. baumannii in mice. OmpA was >99% conserved at the amino acid level across clinical isolates harvested between 1951 and 2009 from cerebrospinal fluid, blood, lung, and wound infections, including carbapenem-resistant isolates, and was ≥89% conserved among other sequenced strains, but had minimal homology to the human proteome. Vaccination of diabetic mice with recombinant OmpA (rOmpA) with aluminum hydroxide adjuvant markedly improved survival and reduced tissue bacterial burden in mice infected intravenously. Vaccination induced high titers of anti-OmpA antibodies, the levels of which correlated with survival in mice. Passive transfer with immune sera recapitulated protection. Immune sera did not enhance complement-mediated killing but did enhance opsonophagocytic killing of A. baumannii. These results define active and passive immunization strategies to prevent and treat highly lethal, XDR A. baumannii infections.

Background: Acinetobacter baumannii is known for its ability to develop resistance to the major groups of antibiotics, form biofilms, and survive for long periods in hospital environments. The prevalence of infections caused by multidrug-resistant A. baumannii is a significant problem for the modern health care system, and application of lytic bacteriophages for controlling this pathogen may become a solution., Methodology/principal Findings: In this study, using atomic force microscopy (AFM) and microbiological assessment we have investigated A. baumannii bacteriophage AP22, which has been recently described. AFM has revealed the morphology of bacteriophage AP22, adsorbed on the surfaces of mica, graphite and host bacterial cells. Besides, morphological changes of bacteriophage AP22-infected A. baumannii cells were characterized at different stages of the lytic cycle, from phage adsorption to the cell lysis. The phage latent period, estimated from AFM was in good agreement with that obtained by microbiological methods (40 min). Bacteriophage AP22, whose head diameter is 62±1 nm and tail length is 88±9 nm, was shown to disperse A. baumannii aggregates and adsorb to the bacterial surface right from the first minute of their mutual incubation at 37°C., Conclusions/significance: High rate of bacteriophage AP22 specific adsorption and its ability to disperse bacterial aggregates make this phage very promising for biomedical antimicrobial applications. Complementing microbiological results with AFM data, we demonstrate an effective approach, which allows not only comparing independently obtained characteristics of the lytic cycle but also visualizing the infection process.

Acinetobacter baumannii, a major nosocomial pathogen, has remarkable capacity to acquire antimicrobial resistance attributable to its biofilm formation ability. Biofilm associated protein (Bap), a specific cell surface protein, is directly involved in biofilm formation by A. baumannii and plays a major role in bacterial infectious processes. In the present study we cloned, expressed and purified a 371 amino acid subunit of Bap. Mice were immunized using recombinant Bap subunit. They were then challenged with A. baumannii to evaluate the immunogenicity and protectivity of Bap subunit. Humoral immune response to Bap was determined by ELISA. Injection of Bap subunit resulted in high antibody titers. Decrease in bacterial cell counts of the immunized mice was evident 18 h after challenge. Reaction of antibodies against Bap with several strains suggests that not only immunodominant regions of Bap in A. baumannii strains are conserved but also have the same epitope presenting pattern in different strains. Immunodominant region of Bap possesses target sites for a protective humoral immune response to A. baumannii. This seems to be a conserved region erecting efficacy of Bap as an appropriate vaccine candidate., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Multidrug-resistant Acinetobacter baumannii (MDRAB) is difficult to treat and eradicate. Several reports describe isolation and environmental cleaning strategies that controlled hospital MDRAB outbreaks. Such interventions were insufficient to interrupt MDRAB transmission in 2 intensive care unit-based outbreaks in our hospital. We describe strategies that were associated with termination of MDRAB outbreaks at the National Institutes of Health Clinical Center., Methods: In response to MDRAB outbreaks in 2007 and 2009, we implemented multiple interventions, including stakeholder meetings, enhanced isolation precautions, active microbial surveillance, cohorting, and extensive environmental cleaning. We conducted a case-control study to analyze risk factors for acquiring MDRAB. In each outbreak, infection control adherence monitors were placed in MDRAB cohort areas to observe and correct staff infection control behavior., Results: Between May 2007 and December 2009, 63 patients acquired nosocomial MDRAB; 57 (90%) acquired 1 or more of 4 outbreak strains. Of 347 environmental cultures, only 2 grew outbreak strains of MDRAB from areas other than MDRAB patient rooms. Adherence monitors recorded 1,330 isolation room entries in 2007, of which 8% required interventions. In 2009, around-the-clock monitors recorded 4,892 staff observations, including 127 (2.6%) instances of nonadherence with precautions, requiring 68 interventions (1.4%). Physicians were responsible for more violations than other staff (58% of hand hygiene violations and 37% of violations relating to gown and glove use). Each outbreak terminated in temporal association with initiation of adherence monitoring., Conclusions: Although labor intensive, adherence monitoring may be useful as part of a multifaceted strategy to limit nosocomial transmission of MDRAB.

Objective: To determine whether restricting the use of ceftriaxone and ciprofloxacin could significantly reduce colonization and infection with resistant Gram-negative bacilli (r-GNB)., Methods: A two-phase prospective study (before/after design) was conducted in an intensive care unit in two time periods (2004-2006). During phase 1, there was no antibiotic restriction. During phase 2, use of ceftriaxone or ciprofloxacin was restricted., Results: Atotal of 200 patients were prospectively evaluated. In phase 2, the use of ceftriaxone was reduced by 93.6% (P = 0.0001) and that of ciprofloxacin by 65.1% (P = 0.041), accompanied by a 113.8% increase in use of ampicillin-sulbactam (P = 0.002).During phase 1, 48 GNB were isolated [37 r-GNB (77.1%) and 11 non-r-GNB (22.9%)], compared with a total of 64 during phase 2 [27 r-GNB (42.2%) and 37 non-r-GNB (57.8%)](P = 0.0002). Acinetobacter spp. was isolated 13 times during phase 1 and 3 times in phase 2 (P = 0.0018). The susceptibility of Pseudomonas aeruginosa to ciprofloxacin increased from 40.0% in phase 1 to 100.0% in phase 2 (P = 0.0108)., Conclusions: Restriction of ceftriaxone and ciprofloxacin reduced colonization by Acinetobacter spp. and improved the susceptibility profile of P. aeruginosa.

The frequent development of acquired antibiotics resistance in bacteria represents a challenge for Public Health in terms of healthcare associated infections control. Apart from the appropriate use of drugs, in particular the choice of proper antimicrobial therapy, increasing interest is, therefore, given to the non-pharmacological prevention of these infections. Acinetobacter (A.) baumannii is a micoorganism that commonly causes infections for patients hospitalized in critical hospital wards (intensive care units, burn centers, surgery, neonatology, etc) potentially severe and difficult to treat, because A. baumannii is resistant to many or sometimes all, available antibiotics (PDR - pan drug resistant). The aim of the present paper was to review the available measures for preventing and controlling the contamination and the spread of these types of bacterial infections in health care scenarios, with particular attention to two methods that stand out for efficiency and safety: hand hygiene and environmental disinfection.

Acinetobacter baumannii has emerged as a major cause of both community-associated and nosocomial infections worldwide. A. baumannii rapidly develops resistance to multiple antibiotics; as a result, infections by this pathogen have become increasingly difficult to treat. In this study, we evaluated the effect of 3',5'-cyclic diguanylic acid (c-di-GMP), a bacterial second messenger and immunomodulator, in the host defense against A. baumannii infection in a mouse model of intranasal infection. Our results showed that 50 μg of c-di-GMP administered 18 h prior to infection provided the best protection against intranasal infection with A. baumannii. Mechanistically, administration of c-di-GMP induced the production of chemokines KC, MCP-1, MIP-1α, MIP-2 and RANTES, and enhanced neutrophil recruitment in the lung. Moreover, depletion of neutrophils abolished the protective role of c-di-GMP. Taken together, our data suggest that c-di-GMP confers resistance against intranasal A. baumannii infection in mice through a neutrophil-dependent mechanism and that c-di-GMP should be further explored as an immunomodulator for the treatment of A. baumannii infection., (Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.)

Acinetobacter baumannii produces different types of infections including pneumonia, meningitis, and bloodstream infections. The optimal treatment of these infections has been complicated by the global emergence of multidrug resistant strains, requiring the development of novel approaches for treatment and prevention. Outer membrane vesicles are outpouchings of the bacterial outer membrane that are secreted from numerous pathogenic Gram-negative bacteria. In the present study, we describe the isolation of outer membrane vesicles from A. baumannii and their use as a vaccine in a mouse model of disseminated sepsis. Immunization produced a robust antibody response against multiple bacterial antigens which consisted of antigen-specific IgG and IgM. In addition, both IgG1 and IgG2c subtypes were produced by immunization. Immunized mice had lower tissue bacterial loads and lower serum levels of the pro-inflammatory cytokines IL-6 and IL-1β post-infection compared to control mice. Importantly, vaccination protected mice from challenge with the ATCC 19606 strain and provided protection against two clinical isolates, including a pan-resistant strain. These results indicate that vaccination with outer membrane vesicles may be a viable strategy for preventing A. baumannii infection., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

This article is an executive summary of the Association for Professionals in Infection Control and Epidemiology's guide to the elimination of multidrug-resistant Acinetobacter baumannii transmission in health care settings. Infection preventionists are encouraged to obtain the original, full-length elimination guide for more thorough coverage., (Copyright © 2011 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.)

Extensively drug-resistant Acinetobacter baumannii (XDRAb) emerges as an important pathogen of health care-associated infections and outbreaks worldwide. During January and February 2006, there was a hospital-wide outbreak of XDRAb at a medical center in Taiwan. Without limiting the usage of carbapenems or the closure of any ward, this outbreak was effectively controlled. We investigated the molecular epidemiology and reported the infection control experiences. XDRAb is defined as A baumannii that is resistant to multiple antibiotics but susceptible to tigecycline and polymyxin B. During the outbreak, the clinical and environmental XDRAb isolates were collected and studied by antimicrobial susceptibility testing, pulsed-field gel electrophoresis, and polymerase chain reaction for Verona integron-encoded metallo-beta-lactamases, imipenemases, and oxacillinases (OXA). Our measures to control the outbreak included private room isolation of patients until there were three successive negative cultures, reinforcement of contact precautions, daily environmental cleansing with room-dedicated cleaning tools and sodium hypochlorite, and careful auditing of adherence. During the outbreak, 32 clinical XDRAb isolates came from 13 patients who were hospitalized in four intensive care units and three wards. Most (7 of 13, 53.8%) cases were associated with a surgical intensive care unit. The results from pulsed-field gel electrophoresis study indicated that all isolates were of one genotype. All 32 isolates harbored ISAba1-bla(OxA-51-like) and bla(OxA-72) genes. After this outbreak till August 2010, further incidences of XDRAb were sporadic cases of XDRAb with different clones and did not reach the level of outbreak. To our knowledge, this is the first reported hospital-wide outbreak caused by OXA-72 carbapenemase-producing A baumannii in the Asia-Pacific region, with successful and sustained control. Although the source or vehicle of the outbreak was not identified, our results suggest that a hospital-wide outbreak can be successfully managed with strict infection control measures, and that the limitation of the use of carbapenems and closure of wards may not be necessary., (Copyright © 2011 Elsevier Taiwan LLC. All rights reserved.)

Acinetobacter baumannii infection is responsible for a wide range of infections, including pneumonia, bacteraemia, meningitis, wound infections, and urinary tract infections. During June 2010, two patients on an intensive care unit in an acute hospital in the UK had multi-resistant A. baumannii identified in samples obtained from a variety of specimens. A further case was identified 31 days following confirmation of the first outbreak. The investigation and management of this outbreak included the introduction of enhanced infection prevention and control precautions; the establishment of an Outbreak Control Team; epidemiological investigations; and the decontamination of equipment and the environment. Isolate typing by the Health Protection Agency Centre for Infections laboratory confirmed the three cases had identical A. baumannii strains: European clone II lineage encoded with an OXA-51-type carbapenemase. This suggests that there was a patient-to-patient spread of multi-resistant A. baumannii.

Introduction: Control of Acinetobacter baumannii is a challenge., Methods: A survey was conducted on the control measures introduced against A baumannii in 30 Spanish hospitals., Results: We found significant differences in the application of contact precautions, active surveillance, hygiene of colonised patients, environmental cleaning, and educational activities. Hospitals with a written control program for A. baumannii had a lower incidence of colonisation/infection due to this organism., Conclusion: A multidisciplinary consensus document for the control of A. baumannii is needed in Spain., (Copyright © 2010 Elsevier España, S.L. All rights reserved.)

Objective: To investigate the mode of transmission of and assess control measures for an outbreak of carbapenem-resistant (multidrug-resistant) Acinetobacter baumannii infection involving 6 premature infants., Design: An outbreak investigation based on medical record review was performed for each neonate during the outbreak (from November 2008 through January 2009) in conjunction with an infection control investigation., Setting: A 36-bed, level 3 neonatal intensive care unit in a university-affiliated teaching hospital in Detroit, Michigan., Interventions: Specimens were obtained for surveillance cultures from all infants in the unit. In addition, geographic cohorting of affected infants and their nursing staff, contact isolation, re-emphasis of adherence to infection control practices, environmental cleaning, and use of educational modules were implemented to control the outbreak., Results: Six infants (age, 10-197 days) with multidrug-resistant A. baumannii infection were identified. All 6 infants were premature (gestational age, 23-30 weeks) and had extremely low birth weights (birth weight, 1000 g or less). Conditions included conjunctivitis (2 infants), pneumonia (4 infants), and bacteremia (1 infant). One infant died of causes not attributed to infection with the organism; the remaining 5 infants were discharged home. All surveillance cultures of unaffected infants yielded negative results., Conclusions: The spread of multidrug-resistant A. baumannii infection was suspected to be due to staff members who spread the pathogen through close contact with infants. Clinical staff recognition of the importance of multidrug-resistant A. baumannii recovery from neonatal intensive care unit patients, geographic cohorting of infected patients, enhanced infection control practices, and staff education resulted in control of the spread of the organism.

Acinetobacter baumannii causes pneumonias, bacteremias, and skin and soft tissue infections, primarily in the hospitalized setting. The incidence of infections caused by A. baumannii has increased dramatically over the last 30 years, while at the same time the treatment of these infections has been complicated by the emergence of antibiotic-resistant strains. Despite these trends, no vaccines or antibody-based therapies have been developed for the prevention of A. baumannii infection. In this study, an outer membrane complex vaccine consisting of multiple surface antigens from the bacterial membrane of A. baumannii was developed and tested in a murine sepsis model. Immunization elicited humoral and cellular responses that were able to reduce postinfection bacterial loads, reduce postinfection proinflammatory cytokine levels in serum, and protect mice from infection with human clinical isolates of A. baumannii. A single administration of the vaccine was able to elicit protective immunity in as few as 6 days postimmunization. In addition, vaccine antiserum was used successfully to therapeutically rescue naïve mice with established infection. These results indicate that prophylactic vaccination and antibody-based therapies based on an outer membrane complex vaccine may be viable approaches to preventing the morbidity and mortality caused by this pathogen.

The treatment of infections caused by Acinetobacter baumannii has become increasingly complicated due to the emergence of highly resistant strains. In the present study we demonstrate that immunization with an inactivated whole cell vaccine elicits a robust antibody response that provides protection against challenge with multiple A. baumannii strains in a murine model of disseminated sepsis. In addition, we show that passive immunization with serum raised against inactivated cells protects mice from subsequent infection. These results demonstrate that active and passive immunization using an inactivated whole cell vaccine may be an effective approach for preventing infection by A. baumannii., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Objectives: To describe vaporized hydrogen peroxide (VHP) as an adjuvant in the control of multidrug-resistant (MDR) Acinetobacter baumannii infection in a long-term acute care hospital (LTACH) and to describe the risk factors for acquisition of MDR A. baumannii infection in the LTACH population., Design: Outbreak investigation, case-control study, and before-after intervention trial., Setting: A 54-bed LTACH affiliated with a tertiary care center in northeastern Ohio., Methods: Investigation of outbreak with clinical and environmental cultures, antimicrobial susceptibility testing, polymerase chain reaction assay of repetitive chromosomal elements to type strains, and case-control study; and intervention consisting of comprehensive infection control measures and VHP environmental decontamination., Results: Thirteen patients infected or colonized with MDR A. baumannii were identified from January 2008 through June 2008. By susceptibility testing, 10 (77%) of the 13 isolates were carbapenem-resistant. MDR A. baumannii was found in wound samples, blood, sputum, and urine. Wounds were identified as a risk factor for MDR A. baumannii colonization. Ventilator-associated pneumonia was the most common clinical syndrome caused by the pathogen, and the associated mortality was 14% (2 of the 13 case patients died). MDR A. baumannii was found in 8 of 93 environmental samples, including patient rooms and a wound care cart; environmental and clinical cultures were genetically related. Environmental cultures were negative immediately after VHP decontamination and both 24 hours and 1 week after VHP decontamination. Nosocomial acquisition of the pathogen in the LTACH ceased after VHP intervention. When patients colonized with MDR A. baumannii reoccupied rooms, environmental contamination recurred., Conclusion: Environmental decontamination using VHP combined with comprehensive infection control measures interrupted nosocomial transmission of MDR A. baumannii in an LTACH. The application of this novel approach to halt the transmission of MDR A. baumannii warrants further investigation.

Acinetobacter baumannii has been increasingly reported as a significant causative organism of various nosocomial infections. Here we describe an outbreak of carbapenem-resistant A. baumannii (CRAB) in the ICUs of a Korean university hospital, along with a successful outbreak control program. From October 2007 through July 2008, CRAB was isolated from 57 ICU patients. Nineteen patients were diagnosed as being truly infected with CRAB, four of whom were presumed to have died due to CRAB infection, producing a case-fatality rate of 21.1%. In surveillance of the environment and the healthcare workers (HCWs), CRAB was isolated from 24 (17.9%) of 135 environmental samples and seven (10.9%) of 65 HCWs. The pulsed field gel electrophoresis patterns showed that the isolates from patients, HCWs, and the environment were genetically related. Control of the outbreak was achieved by enforcing contact precautions, reducing environmental contamination through massive cleaning, and use of a closed-suctioning system. By August 2008 there were no new cases of CRAB in the ICUs. This study shows that the extensive spread of CRAB can happen through HCWs and the environmental contamination, and that proper strategies including strict contact precautions, massive environmental decontamination, and a closed-suctioning system can be effective for controlling CRAB outbreaks.

In the midst of an outbreak, carbapenem-resistant Acinetobacter baumannii was grown from samples of multiple environmental sites in an intensive care unit. A commercial oxidizing disinfectant (potassium peroxomonosulphate 50%, sodium alkyl benzene sulphonate 15%, and sulphamic acid 5%) was introduced throughout the intensive care unit, and its use coincided with cessation of the outbreak.

Concerns about drug-resistant infectious organisms are increasing in rehabilitation facilities. Resulting isolation protocols can potentially challenge the patients' access to medical care, psychological adaptation, mobility, and environmental interaction and therefore hinder the rehabilitation process. We report a systematic, retrospective case review of an active-duty Army sergeant who sustained a C5 American Spinal Cord Injury Association Impairment Scale A spinal cord injury while serving in Operation Iraqi Freedom. The patient's acute rehabilitation was complicated by an Acinetobacter calcoaceticus-baumannii complex infection, in the blood and urine, contracted while in Iraq. Isolation protocols were designed to enable regular hands-on contact for proprioceptive neuromuscular facilitation, transfers, wheelchair fitting, mobility training, and environmental control. After 1 mo of comprehensive acute interdisciplinary rehabilitation, delivered in a single room on the spinal cord injury unit, the patient acquired functional skills comparable with other complete C5 tetraplegics in our unit. If a patient with spinal cord injury must be placed in isolation, it is still feasible to conduct a comprehensive interdisciplinary rehabilitation program while strictly adhering to contact isolation protocols.

Background: The Aga Khan University Hospital is a tertiary care centre in Karachi, Pakistan, where tigecycline has not been used previously. We report findings of a pre-use in vitro study to evaluate sensitivity of nosocomial Acinetobacter spp. Tigecycline minimum inhibitory concentration (MIC) was correlated with that of other tetracyclines to assess their predictive potential., Methods: Acinetobacter spp. were collected from hospitalized inpatients admitted to Aga Khan University Hospital from April to November 2007. Tigecycline, tetracycline, doxycycline, and minocycline MICs were determined by E-test., Results: One hundred isolates of Acinetobacter spp. were tested. Ninety-eight percent of Acinetobacter spp. were carbapenem-resistant. Tigecycline MIC(50) and MIC(90) were 1.5 and 2.0 microg/ml, respectively. Unavailability of standard breakpoints hindered categorization of these values. Minocycline was highly active, with MIC(90) of 2.0 microg/ml., Conclusions: Tigecycline breakpoints for Acinetobacter spp. should be established to prevent injudicious use of this antibiotic based on misleading in vitro results. The therapeutic potential of minocycline needs more in-depth study., (Copyright 2010 S. Karger AG, Basel.)

Background: Acinetobacter baumannii (Ab) is emerging as a multidrug-resistant (MDR) nosocomial pathogen of considerable clinical importance. Data on the efficacy of infection control measures in endemic situations are lacking. Here, we investigated the impact of a long-term multifaceted "bundle" approach in controlling endemic MDR Ab in a 950-bed tertiary care center., Methods: Ongoing staff education, promotion of hand hygiene, strict Contact and Isolation Precautions, environmental cleaning, and targeted active surveillance in high-risk areas during periods of likely transmission and contamination were initiated in this program. To assess the efficacy of our interventions, we recorded (before and after the intervention) the epidemiologic and clinical features of MDR Ab infections and determined the clonal relationship among MDR Ab bloodstream isolates by pulsed-field gel electrophoresis., Results: Before the "bundle" was instituted, the rate of colonization/infection was 0.82 cases per 100 admissions (1994-1995). Colonization/infection rates showed a sustained decrease after implementation of the control program in 1995 to 0.46 in 1996-1997 and to 0.21 in 1998-2003 (P < .001). Coincident with the institution of this program, the rate of bacteremia because of MDR Ab decreased 6-fold during the 8-year observation period. A notable change in the clonal distribution of the MDR Ab isolates was also demonstrated., Conclusion: The implementation of a comprehensive and multifaceted infection control program ("bundle") in a tertiary care center effectively controlled the spread and clinical impact of MDR Ab.

A prolonged outbreak of carbapenem-resistant Acinetobacter baumannii in a German university medical centre in 2006 was investigated; the investigation included a descriptive epidemiological analysis, a case-control study, environmental sampling, molecular typing of A. baumannii isolates using PFGE and repetitive-sequence-based PCR (rep-PCR) typing, and detection of OXA-type carbapenemases by multiplex PCR. Thirty-two patients acquired the outbreak strain in five intensive care units (ICUs) and two regular wards at a tertiary care hospital within 10 months. The outbreak strain was resistant to penicillins, cephalosporins, ciprofloxacin, gentamicin, tobramycin, imipenem and meropenem, and carried the bla(OXA-23)-like gene. Based on PFGE and rep-PCR typing, it was shown to be related to the pan-European A. baumannii clone II. The most likely mode of transmission was cross-transmission from colonized or infected patients via the hands of health-care workers, with the severity of disease and intensity of care (therapeutic intervention scoring system 28 score >median) being independently associated with acquisition of the outbreak strain (odds ratio 6.67, 95 % confidence interval 1.55-36.56). Control of the outbreak was achieved by enforcement of standard precautions, education of personnel, screening of ICU patients for carbapenem-resistant A. baumannii and cohorting of patients. This is believed to be the first report of an outbreak of A. baumannii carrying the carbapenemase OXA-23 in Germany.

Acinetobacter baumannii colonization and infection, frequent in Intensive Care Unit (ICU) patients, is commonly associated with high morbimortality. Several outbreaks due to multidrug-resistant (MDR) A. baumanii have been reported but few of them in Brazil. This study aimed to identify risk factors associated with colonization and infection by MDR and carbapenem-resistant A. baumannii strains isolated from patients admitted to the adult ICU at HC/UFMG. A case-control study was performed from January 2007 to June 2008. Cases were defined as patients colonized or infected by MDR/carbapenem-resistant A. baumannii, and controls were patients without MDR/carbapenem-resistant A. baumannii isolation, in a 1:2 proportion. For statistical analysis, due to changes in infection control guidelines, infection criteria and the notification process, this study was divided into two periods. During the first period analyzed, from January to December 2007, colonization or infection by MDR/carbapenem-resistant A. baumannii was associated with prior infection, invasive device utilization, prior carbapenem use and clinical severity. In the multivariate analysis, prior infection and mechanical ventilation proved to be statistically significant risk factors. Carbapenem use showed a tendency towards a statistical association. During the second study period, from January to June 2008, variables with a significant association with MDR/carbapenem-resistant A. baumannii colonization/infection were catheter utilization, carbapenem and third-generation cephalosporin use, hepatic transplantation, and clinical severity. In the multivariate analysis, only CVC use showed a statistical difference. Carbapenem and third-generation cephalosporin use displayed a tendency to be risk factors. Risk factors must be focused on infection control and prevention measures considering A. baumanni dissemination.