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PubMed2006

In vitro activities of non-traditional antimicrobials alone or in combination against multidrug-resistant strains of Pseudomonas aeruginosa and Acinetobacter baumannii isolated from intensive care units.

The aim of this study was to assess the in vitro activity of a number of non-traditional antibiotics (colistin, azithromycin, doxycycline and rifampicin) against multidrug-resistant (MDR) strains of Pseudomonas aeruginosa and Acinetobacter baumannii isolated from Intensive Care Units (ICUs). We also used the checkerboard method to determine whether combinations of colistin with another non-traditional antibiotic or meropenem act synergistically against these strains. Thirty-five P. aeruginosa and 25 A. baumannii strains that were found to be MDR were included the study. Isolates were collected from the specimens of patients in ICUs from 2001 to 2003. All isolates were identified by standard methods and stored at -20 degrees C until use. Antibiotic powders of azithromycin, doxycycline, rifampicin, meropenem and colistin were obtained from their manufacturers. Minimum inhibitory concentrations (MICs) were determined by the agar dilution method on Mueller-Hinton agar. Five strains of A. baumannii and five strains of P. aeruginosa, all of which had different MIC values for colistin, were selected for the synergy study using the checkerboard titration method. The susceptibility results for doxycycline and meropenem were interpreted according to National Committee for Clinical Laboratory Standards guidelines. The susceptibility breakpoints for colistin and rifampicin were established as 4 mg/L and 2 mg/L, respectively, based on previous studies. Pseudomonas aeruginosa ATCC 27853 and Escherichia coli ATCC 25922 were used as control strains. Testing against the P. aeruginosa strains revealed high MIC50 values for all the drugs except colistin. Doxycycline and colistin were both effective against the A. baumannii strains, with high susceptibility rates of 92% and 100%, respectively. Azithromycin had a high MIC50 value against these strains, whilst rifampicin had a moderate effect (susceptibility rate 64%). The combination of colistin and rifampicin was fully synergistic against four A. baumannii and two P. aeruginosa strains. Combinations of colistin with meropenem and of colistin with azithromycin each showed synergistic activity against three A. baumannii isolates, whilst the same combinations resulted in generally additive or indifferent effects against P. aeruginosa strains. The colistin and doxycycline combination was generally partially synergistic or additive against all the isolates. MDR strains of P. aeruginosa and A. baumannii, which cause nosocomial infections with an increasing ratio in recent years, have limited treatment options. According to our in vitro study results, non-traditional antibiotics such as doxycycline and colistin can be an alternative for the treatment of infections caused by these strains. Combinations of colistin with non-traditional antibiotics or meropenem could be promising alternatives for the treatment of infections due to MDR strains of A. baumannii and P. aeruginosa.

Acinetobacter Infections↗
PubMed2006

Molecular investigation of an outbreak of multidrug-resistant Acinetobacter baumannii, with characterisation of class 1 integrons.

We investigated a multidrug-resistant Acinetobacter baumannii outbreak in the Intensive Care Unit (ICU) of a tertiary care hospital in Greece over a 3-month period. Molecular typing of the outbreak isolates from 31 patients revealed that two distinct genotypes were involved. Nine isolates, belonging to both genotypes, were resistant to carbapenems. Samples from the ICU environment and from the hands of personnel were collected to identify possible contamination. Class 1 integrons of 3.1, 2.5 and 2.2 kb were amplified from the clinical and environmental isolates. The 3.1 kb integron carrying five gene cassettes was found for the first time in A. baumannii. The outbreak ceased after implementation of hygienic measures in the ICU, including complete cleaning and disinfection.

Acinetobacter Infections↗
PubMed2007

Colistin offers prolonged survival in experimental infection by multidrug-resistant Acinetobacter baumannii: the significance of co-administration of rifampicin.

The effect of colistin on bacterial eradication and survival was tested in experimental infection by multidrug-resistant Acinetobacter baumannii. The thigh infection model was applied in 86 neutropenic Wistar rats. Six rats were used for the induction of neutropenia and for the selection of the dose regimen of colistin; the remainder was equally divided into four groups: A, controls; B, rifampicin; C, colistin; and D, both agents. Therapy was administered 5 h after bacterial challenge; 5mg/kg of rifampicin was administered intravenously and 3mg/kg of colistin intramuscularly. Survival was recorded in 10 animals of each group. The remaining 10 rats per group were killed 4h after therapy; blood and tissue samples were sampled. Median survival of animals of groups A, B, C and D was 2.00, 2.50, 4.00 and 4.00 days, respectively (P=0.0048 between A and C and P=0.0012 between A and D. Mortality rates after 6 days of follow-up were 100, 100, 100 and 70%, respectively (P=0.018 between groups). Statistically significant decreases of bacteria were found in blood, liver, lung and spleen of group B compared with A; in lung of group C compared with A; and in blood and liver of group D compared with A. Colistin was effective in prolonging survival in an experimental thigh infection by multidrug-resistant A. baumannii in neutropenic rats. Its activity was enhanced after co-administration with rifampicin. These results mandate the application of colistin in the event of infections by multidrug-resistant pathogens and the need for its co-administration with rifampicin.

Acinetobacter Infections↗
PubMed2006

Fatal multidrug-resistant Acinetobacter baumannii sepsis in a patient with travel history and recent onset of systemic lupus erythematosus: a case report.

Severe infections are a common cause of death in patients suffering from systemic lupus erythematosus (SLE). We here report on a fatal multidrug-resistant Acinetobacter baumannii sepsis in a patient with newly diagnosed SLE, who had to be treated with immunosuppressants due to lupus nephritis. Detailed analysis of the patient's history revealed that colonisation probably had occurred during a recent hospitalisation of the patient in the Mediterranean region. E-test analysis indicated that resistance to carbapenems was mediated by a plasmid-encoded metallo-beta-lactamase. We conclude that travel history including previously visited health care facilities always should be carefully considered for decisions on anti-infective therapy, as travel activities increasingly facilitate spread of antimicrobial resistances.

Acinetobacter Infections↗
PubMed2004

Investigation of an outbreak of multidrug-resistant Acinetobacter baumannii in trauma intensive care unit.

Between January and June 2002, an outbreak of multidrug-resistant Acinetobacter baumannii occurred in a trauma intensive care unit (TICU) at the Hamad Medical Corporation, Qatar. The outbreak involved 21 patients whose infection/colonization was hospital acquired. All the strains were resistant to all tested antibiotics except amikacin. An A. baumannii strain with a similar antibiogram was isolated from the environment, equipment and hands of healthcare workers (HCWs). The technique of open suctioning probably resulted in aerosilization and contamination of the immediate patient environment. This allowed the hands of HCWs to be contaminated with the outbreak strain, with subsequent transmission to other patients and their environment. Lack of proper hand hygiene between patients and equipment contact facilitated this transmission. A review of hand hygiene practices, extensive environmental cleaning, a closed suctioning system, education and review of other infection-control practices, contributed to the termination of the outbreak.

Acinetobacter Infections↗
PubMed2004

Role of environmental cleaning in controlling an outbreak of Acinetobacter baumannii on a neurosurgical intensive care unit.

An outbreak of Acinetobacter baumannii colonization and infection occurred in 19 patients over a 14-month period during 1998-1999 on a neurosurgical intensive care unit. During efforts to control the outbreak a significant correlation was observed between the number of environmental isolates of A. baumannii obtained during each monthly screening and the number of patients with A. baumannii colonization/infection in the same calendar month (P < 0.004). Use of 1000 ppm hypochlorite solution and the introduction of new cleaning protocols reduced the number of environmental isolates. Failure to maintain low levels of environmental contamination with A. baumannii resulted in increases in patient colonization. This study showed that high standards of cleaning play an integral role in controlling outbreaks of A. baumannii in the intensive care unit setting.

Acinetobacter Infections↗
PubMed2004

Outbreak of nosocomial meningitis caused by Acinetobacter baumannii in neurosurgical patients.

An outbreak of nosocomial meningitis caused by Acinetobacter baumannii, which developed postoperatively in seven neurosurgical patients is described. The clinical isolates of A. baumannii were typed by biochemical profiles and antibiogram patterns, and by random amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) and amplified fragment length polymorphism (AFLP) fingerprinting. The implicated strain was multi-drug resistant, however, susceptibility to imipenem and netilmicin was detected. An extensive search for the environmental source of the epidemic strain was carried out. Two of several isolates from hospital environment, corresponded to the A. baumannii outbreak strain, one being cultured from the suctioning equipment used in the care of these patients. The introduction of multiresistant epidemic A. baumannii into a neurosurgical unit is a severe risk factor for patients undergoing neurosurgical procedures. Genotypic typing methods are important for definitive identification of these strains in patients and their environment.

Acinetobacter Infections↗
PubMed2004

Metallo-beta-lactamase expressing multi-resistant Acinetobacter baumannii transmitted in the operation area.

Outbreaks of Acinetobacter baumannii demonstrating multiple antibiotic resistance, including meropenem resistance, have been described as severe therapeutic problems. Here we describe a monoclonal outbreak of infection and colonization with multidrug-resistant A. baumannii over a two-month period. Resistance to meropenem was mediated by expression of a metallo-beta-lactamase enzyme. Four of 14 patients showed clinical signs of infection and two died. Contamination of the environment, water, or instruments were excluded as causes of the outbreak. All patients, except one, underwent surgery in a specific operation theatre where surgery of contamination class IV (infected, dirty) was performed. Although individual surgeon error was eliminated, analyses of the patients' histories suggested that bacterial transmission had occurred during surgery. Five patients showed signs of A. baumannii infection and two of these patients suffered from large abdominal wounds infected with a high density of A. baumannii requiring repeated revisions. Presumably, these revisions favoured the transmission of A. baumannii, which is remarkably resistant to various environmental stresses including soaps, disinfectants and dry conditions. No case of meropenem-resistant A. baumannii had been observed in the hospital before the outbreak. Interestingly, the resistant bacteria appear to have been imported by a patient returning from West Africa. This indicates that, similar to MRSA, multiresistant A. baumannii may be introduced by patients from foreign hospitals. The outbreak was stopped in the following months by reinforcing standard procedures and by taking all necessary precautions such as patient isolation, and finally only one new case was detected.

Acinetobacter Infections↗
PubMed2004

A prevalent, multiresistant clone of Acinetobacter baumannii in Southeast England.

A multiresistant clone of Acinetobacter baumannii was identified in 24 hospitals in the UK, predominantly in the London area, over a period of three years. Isolates were characterized by distinctive ApaI macrorestriction profiles, as resolved by pulsed-field gel electrophoresis (PFGE), which all clustered within 80% similarity using a 1% band position tolerance setting. The first isolates identified were received by the reference laboratories in April 2000, and by June 2003, a total of 375 isolates with similar PFGE profiles from 310 patients from 24 hospitals had been received. The isolates originated mainly from sputum and wound specimens, with the majority from patients in intensive care units. Amplified fragment length polymorphism analysis of a subset of isolates showed that they clustered closely, supporting the PFGE results. All the isolates tested were highly resistant to ampicillin, piperacillin, piperacillin/tazobactam, ceftazidime, cefotaxime, gentamicin and ciprofloxacin, and most isolates were carbapenem resistant. Amikacin sensitivity varied from susceptible [minimum inhibitory concentration (MIC) 256 mg/L).

Acinetobacter Infections↗
PubMed2005

Investigation of a nosocomial outbreak of extended-spectrum beta-lactamase VEB-1-producing isolates of Acinetobacter baumannii in a hospital setting.

A nosocomial outbreak of epidemiologically related VEB-1 extended-spectrum beta-lactamase-producing isolates of Acinetobacter baumannii occurred in 33 patients in an intensive care unit. A case-control study identified previous treatment with third-generation cephalosporins as the only risk factor for A. baumannii acquisition. Rationale for antibiotic use should be strengthened.

Acinetobacter Infections↗
PubMed2005

Control of an outbreak of multi-drug-resistant Acinetobacter baumannii in an intensive care unit and a surgical ward.

We describe an outbreak of multi-drug-resistant Acinetobacter baumannii (MRAB) that occurred in an intensive care unit (ICU) and a surgical ward from December 2003 to March 2004. Mapping patient movements on a timeline indicated that the outbreak was confined to these two areas. Investigation by the hospital's infection prevention service found that a possible source of spread was improper cleaning methods used on respiratory equipment. Pulsed-field gel electrophoresis analysis of available isolates indicated the presence of two distinct strains. One strain was seen in patients from the ICU and the other strain was seen in the surgical ward patients. Cleaning and environmental decontamination as well as staff education were implemented to halt further immediate spread. The deficiencies identified during the investigation were also resolved. The final outcome was the successful termination of this outbreak.

Acinetobacter Infections↗
PubMed2005

Investigation of a nosocomial outbreak of Acinetobacter baumannii producing PER-1 extended-spectrum beta-lactamase in an intensive care unit.

We investigated an outbreak of Acinetobacter baumannii in an adult intensive care unit of Kosin University Gospel Hospital in Busan, Republic of Korea. The outbreak involved 10 cases of infection by A. baumannii producing PER-1 extended-spectrum beta-lactamase over a seven-month period, and was caused by a single pulsed-field gel electrophoresis clone. The epidemic isolates were characterized by slight synergy between clavulanic acid and cefepime. Isoelectric focusing of crude bacterial extracts detected two nitrocefin-positive bands with pI values of 8.0 and 5.3. Polymerase chain reaction amplification and characterization of the amplicons by restriction analysis and direct sequencing indicated that the epidemic isolates carried a bla(PER-1) determinant. The epidemic isolates were characterized by a multidrug-resistant phenotype that remained unchanged over the outbreak, including penicillins, beta-lactam/beta-lactamase inhibitor, extended-spectrum cephalosporins and monobactams. Isolation of infected patients and appropriate carbapenem therapy were successful in ending the outbreak. Our report indicates that the bla(PER-1) resistance determinant may become an emerging therapeutic problem.

Acinetobacter Infections↗
PubMed2005

Acinetobacter baumannii: emergence and spread in Israeli hospitals 1997-2002.

The incidence of multi-drug-resistant Acinetobacter baumannii bloodstream infections (BSIs) increased two- to four-fold in three Israeli hospitals between 1997 and 2002, accounting for 3.5-18% of all hospital-acquired BSIs. This was associated with increasing carbapenem resistance reaching 35-54%, and by a dramatic increase in carbapenem consumption. In-hospital fatality rates ranged between 47% and 58% and were significantly higher than those seen with other nosocomial Gram-negative pathogens. A. baumannii was not restricted to intensive care units, but had spread to all hospital wards. Multi-drug-resistant A. baumannii has the potential to reach endemicity in hospitals and warrants more vigorous and innovative efforts to limit its spread.

Acinetobacter Infections↗
PubMed2006

Risk factors for the isolation of multi-drug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa: a systematic review of the literature.

An understanding of the epidemiology of multi-drug-resistant (MDR) Acinetobacter baumannii and Pseudomonas aeruginosa infections is necessary in order to develop strategies to curtail their spread. For this purpose, the evidence linking the isolation of MDR A. baumannii and P. aeruginosa with specific risk factors was evaluated. PubMed was searched for the 20-year period from September 1985 to September 2005, and eligible studies were considered to be those that: (1) linked the isolation of A. baumannii and P. aeruginosa with specific risk factors; (2) described the characteristics of the affected patients in detail; and (3) provided data on the antibiotic resistance profile of the isolated micro-organisms. Fifty-five studies were found referring to A. baumannii (28 with case-control methodology and 27 outbreak investigations without case-control methodology), and 42 studies were found referring to P. aeruginosa (25 with case-control methodology and 17 outbreak investigations without case-control methodology). Although heterogeneous study designs and investigated risk factors limited this analysis, it was concluded that acquisition and spread of these micro-organisms appear to be related to a large number of variables. Among the most important were deficiencies in the implementation of infection control guidelines and the use of broad-spectrum antibiotics. Use of carbapenems and third-generation cephalosporins appear to be related to the development of an MDR phenotype by A. baumannii, while carbapenems and fluoroquinolones are implicated in MDR P. aeruginosa. The diversity of risk factors associated with the development of MDR A. baumannii and P. aeruginosa suggests that a separate outbreak investigation should be performed in each hospital setting. The development of innovative control strategies is needed in order to limit the spread of these pathogens.

Acinetobacter Infections↗
PubMed2006

The significance of Acinetobacter baumannii bacteraemia compared with Klebsiella pneumoniae bacteraemia: risk factors and outcomes.

Risk factors and outcomes for patients with nosocomial Acinetobacter baumannii bacteraemia were compared with those for patients with nosocomial Klebsiella pneumoniae bacteraemia in a single centre in Israel between 2000 and 2003. Data were collected retrospectively through patient chart review. In total, 112 patients with A. baumannii bacteraemia and 90 patients with K. pneumoniae bacteraemia were identified. A. baumannii was significantly associated with poorer performance status, mechanical ventilation, presence of devices, prior treatment with carbapenems, pneumonia as the source of infection and inappropriate empirical antibiotic treatment. All-cause 30-day mortality was higher for A. baumannii bacteraemia compared with K. pneumoniae bacteraemia (61.6% vs 38.9%, P=0.001). Variables significantly associated with mortality at the univariate level (P<0.1) were entered into a multi-variable logistic regression model for mortality. A. baumannii remained significantly associated with mortality when adjusted for all other risk factors (odds ratio 3.61, 95% confidence interval 1.55-8.39). This result did not change when the analysis was repeated for subgroups of less severely ill patients, i.e. those who were not ventilated and those who did not present with septic shock. These results support the view that nosocomial bacteraemia due to A. baumannii is associated with increased mortality.

Acinetobacter Infections↗
PubMed2005

Amikacin and colistin for treatment of Acinetobacter baumannii meningitis.

We report a case of a 52-year-old man with post-surgical meningitis due to a multi-drug resistant Acinetobacter baumannii. Despite therapy with intravenous amikacin and imipenem the meningitis progressed. Upon institution of combination therapy with amikacin by the intravenous and intrathecal (IT) routes, and intravenous colistin the patient experienced successful clinical and microbiological outcomes.

Acinetobacter Infections↗
PubMed2006

Colistin and rifampicin in the treatment of nosocomial infections from multiresistant Acinetobacter baumannii.

INTRODUCTION: The increased incidence of nosocomial infections by multi-drug resistant Acinetobacter baumannii creates demand on the application of some combinations of older antimicrobials on that species. We conducted the present observational study to evaluate the efficacy of intravenous and aerosolized colistin combined with rifampicin in the treatment of critically patients with nosocomial infections caused by multiresistant A. baumannii. PATIENTS AND METHODS: Critically ill patients with nosocomial infections caused by A. baumannii resistant to all antibiotics except colistin in a medical intensive care unit. Diagnosis of infection was based on clinical data and isolation of bacteria. The bacterial susceptibilities to colistin were tested. Clinical response to colistin+rifampicin was evaluated. RESULTS: Twenty-six patients (43.58+/-18.29 years, Acute Physiology and Chronic Health Evaluation II Score (APACHE II): 6.35+/-2.99), of whom 16 cases of nosocomial pneumonia treated by aerosolized colistin (1x10(6) IU three times/day) associated with intravenous rifampicin (10 mg/kg every 12h), nine cases of bacteraemia treated by intravenous colistin (2x10(6)IU three times/day) associated with intravenous rifampicin (10 mg/kg every 12h) in which three cases associated with ventilator associated pneumonia and one case of nosocomial meningitis treated by intrathecal use of colistin associated with intravenous rifampicin. The clinical evolution was favourable for all ill patients. Concerning side effects, we have noticed a moderate hepatic cytolysis in three patients. CONCLUSION: This is the first clinical report of colistin combined with rifampicin for treatment of A. baumannii infection. Despite the lack of a control group and the limited number of patients, the results seem to be encouraging.

Acinetobacter Infections↗
PubMed2025

New Delhi metallo-&#x3b2;-lactamase-producing Acinetobacter baumannii in the USA from October, 2013, to March, 2022: a retrospective molecular epidemiological analysis.

BACKGROUND: Most US carbapenem-resistant Acinetobacter baumannii (CRAB) isolates harbour carbapenem-hydrolysing class D &#x3b2;-lactamases. Other carbapenemases, such as New Delhi metallo-&#x3b2;-lactamase (NDM), are uncommon but emerging. We describe the epidemiology of NDM-producing CRAB reported to the US Centers for Disease Control and Prevention (CDC). METHODS: We defined cases as A baumannii with blaNDM confirmed by molecular testing and isolated from any specimen source from a patient in the USA between Oct 1, 2013, and March 31, 2022, and passively reported to the CDC from regional, state, local public health, and CDC laboratories. Epidemiologically linked cases had epidemiological linkage (eg, overlapping health-care facility stay) with one or more other cases. We assessed case relatedness through analysis of whole-genome sequence data using traditional multilocus sequence typing (MLST; Oxford scheme [sequence typeOX]) and core genome MLST. To understand the potential origins of NDM-CRAB in the USA, we compared sequences of cases to US CRAB without NDM and to NDM-CRAB from non-US locations. FINDINGS: We identified 327 NDM-CRAB cases from 264 patients in 21 US states. Among patients with available epidemiological information, 192 (90%) of 214 had epidemiological linkage to at least one additional case and 13 (7%) of 193 were hospitalised outside the USA 12 months or less before index specimen collection. Five regionally distinct sequence type clusters were identified among the 264 case patients; three (sequence type OX218, sequence type OX281, and sequence type OX1697) were closely related to international NDM-CRAB isolates. INTERPRETATION: We identified regionally distinct NDM-CRAB strains, suggesting localised transmission in the USA. Some NDM-CRAB strains in the USA are closely related to strains identified outside the USA, suggesting that spread followed importation. FUNDING: None.

Acinetobacter baumannii↗