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Acinetobacter baumannii bloodstream infection while receiving tigecycline: a cautionary report.

OBJECTIVES: Tigecycline has shown in vitro activity against Acinetobacter baumannii. Yet, published clinical experience with tigecycline use outside clinical trials is lacking. We describe, for the first time, bloodstream infection caused by tigecycline-non-susceptible A. baumannii occurring in patients receiving tigecycline for other indications. The possible mechanisms of resistance and pharmacokinetic limitations of the drug are addressed. METHODS: The clinical records of involved patients were systematically reviewed. Tigecycline susceptibility testing was initially performed using the Etest method and confirmed by agar dilution. Involved isolates underwent PFGE and exposure to phenyl-arginine-beta-naphthylamide (PAbetaN), an efflux pump inhibitor. RESULTS: Two patients developed A. baumannii bloodstream infection while receiving tigecycline. Tigecycline was administered for other indications for 9 and 16 days, respectively, before the onset of A. baumannii infection. Patient 1 died of overwhelming A. baumannii infection and Patient 2 recovered after a change in antibiotic therapy. The MICs of tigecycline were 4 and 16 mg/L, respectively. Both isolates had a multidrug-resistant phenotype and were genotypically unrelated. After exposure to PAbetaN, the MICs reduced to 1 and 4 mg/L, respectively. CONCLUSIONS: To our knowledge, this is the first clinical description of bloodstream infection caused by tigecycline-non-susceptible A. baumannii. Such resistance appears to be at least partly attributable to an efflux pump mechanism. Given the reported low serum tigecycline levels, we urge caution when using this drug for treatment of A. baumannii bloodstream infection.

Acinetobacter baumannii↗

Mechanisms of cefiderocol resistance in carbapenem-resistant Acinetobacter baumannii: a Swiss 2023-2025 collection.

OBJECTIVES: The numbers of infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) are increasing globally and present a significant burden on healthcare systems. This study describes the CRAB isolates received at the Swiss National Reference Centre for Emerging Antibiotic Resistance (NARA) over a 3-year period, from January 2022 to December 2025, and aimed to characterize the prevalence and mechanisms of FDC resistance. METHODS: Two-hundred and thirty-four non-duplicate CRAB isolates were submitted to NARA over the study period from hospitals and laboratories across Switzerland. Susceptibility testing was performed by disk diffusion and broth microdilution, according to EUCAST methodology. Whole-genome sequencing was performed on 11 isolates. ADC alleles were cloned into vector pVRL1 and transformed into Escherichia coli Top10. RESULTS: All isolates exhibited resistance to the carbapenems, and most were resistant to cephalosporins. Most isolates harboured an acquired class D carbapenemase, most frequently OXA-23 (181/234; 77.4%). One quarter of isolates were resistant to cefiderocol (FDC), exhibiting MICs ranging from 4->32 mg/L. Whole genome sequencing analyses, performed on 11 FDC-resistant isolates, identified that FDC resistance was due a combination of mechanisms including NDM and PER-production, mutations within the iron transporters, piuA and pirA, and the overexpression of ADC variants. CONCLUSIONS: This study showed that OXA-23 was the dominant mechanism of carbapenem-resistance in CRAB in Switzerland. Almost one quarter of CRAB isolates were resistant to "last resort" antimicrobial, FDC. The mechanisms of FDC resistance identified in this study emphasise that resistance to this antimicrobial is often complex and multifactorial, requiring high-resolution methods, including WGS, to identify.

Acinetobacter baumannii↗

Clinical and bacteriological features of relapsing shunt-associated meningitis due to Acinetobacter baumannii.

A case is reported of a patient who developed Acinetobacter baumannii meningitis ten days after a ventriculoperitoneal shunt had been placed for control of elevated intracranial pressure. Intravenous antimicrobial therapy was instituted with imipenem and tobramycin after shunt removal and insertion of a ventriculostomy tube. Following the placement of a ventriculoatrial shunt, clinical and microbiological relapse occurred that was eventually cured after complete removal of the ventricular drainage system and a second course of systemic antibiotics. Relapse was confirmed by modern molecular typing techniques including plasmid DNA fingerprinting and analysis of total genomic DNA by pulsed-field gel electrophoresis.

Acinetobacter↗

[Antimicrobial susceptibility of phenotypically extended spectrum beta-lactamase producing Pseudomonas aeruginosa and Acinetobacter baumannii isolates].

The aim of this study was to investigate the antimicrobial susceptibilities of Pseudomonas aeruginosa and Acinetobacter baumannii strains that were identified as producers of extended spectrum beta-lactamases (ESBL) phenotypically. Fifty three P. aeruginosa and 53 A. baumannii strains that were isolated from patients with hospital infections followed-up by Infectious Diseases Unit of Hacettepe University Adult Hospital in 2002-2004, were included in the study. The susceptibilities of the isolates to ceftazidime, cefotaxime, cefepime, tobramycin, ciprofloxacin, piperacillin-tazobactam, imipenem and meropenem were determined by Etest (AB Biodisk, Solna, Sweden) method. The susceptibility rates of A. baumannii isolates against tobramycin and carbapenem group were 54.7% and 49.1%, respectively; whereas for the rest of the antimicrobial agents tested, these rates were lower than 25 percent. The susceptibility rates of P. aeruginosa isolates against ciprofloxacin, carbapenem group, piperacillin-tazobactam and tobramycin differed between 35-38 percent. Of the P. aeruginosa isolates, 37.5%, and of the A. baumannii isolates 37.7% were resistant against imipenem/meropenem, piperacillin-tazobactam, ciprofloxacin and tobramycin simultaneously. As a result, phenotypically ESBL producing P. aeruginosa and A. baumannii isolates were found highly resistant not only against the third and fourth generation cephalosporins, but also to the antibiotics currently used in the therapy including carbapenemes.

Acinetobacter baumannii↗

Integron-mediated antibiotic multiresistance in Acinetobacter baumannii clinical isolates from Spain.

OBJECTIVE: To determine whether non-epidemiologically related, antibiotic-resistant isolates of Acinetobacter baumannii from different geographical origins possess common type 1 integrons. METHODS: The epidemiologic relationships between seven A. baumannii strains recovered from different Spanish hospitals were established by pulsed-field gel electrophoresis, the presence of integrons being determined by PCR and DNA sequencing. RESULTS: Integron analysis showed the presence of four different integrons, containing six different known genes (aacC1, aacA4, aadA1, aadB, oxa21 and oxa37) plus an ORF. It was found that the same integron was present in different unrelated strains and that related strains could have different integrons. CONCLUSION: These results show the potential risk of integron dissemination among different strains of A. baumannii.

Acinetobacter Infections↗

The diversity of definitions of multidrug-resistant (MDR) and pandrug-resistant (PDR) Acinetobacter baumannii and Pseudomonas aeruginosa.

Different definitions of the terms multidrug-resistant (MDR) and pandrug-resistant (PDR) Acinetobacter baumannii and Pseudomonas aeruginosa have been used in the biomedical literature. The authors searched for relevant studies indexed in the PubMed database (01/2000-09/2005) to systematically examine the various definitions of MDR and PDR for these bacteria. Initially 107 retrieved relevant studies were reviewed. Ninety-two studies were further analysed, 50 of which focused on A. baumannii and 42 on P. aeruginosa. A considerable diversity of definitions of the terms MDR and PDR A. baumannii and P. aeruginosa was found. Of note, the term PDR was inappropriately used in all five studies that used it. The review reveals that various definitions have been used for the terms MDR and PDR A. baumannii and P. aeruginosa, a fact that causes confusion to researchers and clinicians. The authors believe that at least a widely accepted definition for PDR A. baumannii and P. aeruginosa should be uniformly used worldwide.

Acinetobacter baumannii↗

Comparison of outbreak and nonoutbreak Acinetobacter baumannii strains by genotypic and phenotypic methods.

Thirty-one Acinetobacter baumannii strains, comprising 14 strains from 14 outbreaks in different northwestern European cities and 17 sporadic strains, were compared by investigating various properties of the strains including biotype, antibiogram, cell envelope protein electrophoretic profile, ribotype pattern, and the band pattern generated by a novel genomic fingerprinting method, named AFLP, which is based on the selective amplification of restriction fragments. Results showed that 12 strains from unrelated outbreaks were linked together in two clusters according to their similarities by these typing methods, whereas sporadic strains were more heterogeneous. Outbreak strains appeared to be markedly more resistant to antibiotics than nonoutbreak strains. The uniformity of typing characters in two sets of outbreak strains suggests that strains in each cluster have a common clonal origin.

Acinetobacter↗

Comparison of a repetitive extragenic palindromic sequence-based PCR method and clinical and microbiological methods for determining strain sources in cases of nosocomial Acinetobacter baumannii bacteremia.

Using a repetitive extragenic palindromic PCR (REP-PCR), we genotypically characterized strains causing nosocomial Acinetobacter baumannii infections and analyzed the source of bacteremia in 67 patients from an institution in which infections by this bacterium were endemic. Six different genotypes were found, including 21, 27, 3, 9, 3, and 4 strains. The probable source of bacteremia, according to clinical and/or microbiological criteria, was known in 42 patients (63%): respiratory tract (n = 19), surgical sites (n = 12), intravascular catheters (n = 5), burns (n = 3), and urinary tract (n = 3). The definite source of bacteremia, according to REP-PCR, could be established in 30 (71%) out of the 42 patients with strains from blood and other sites; in these cases clinical and microbiological criteria for the source of bacteremia were thus confirmed. In the remaining 12 patients (29%) the probable source was refuted by the REP-PCR method. The definite sources of bacteremia according to genotype were as follows: respiratory tract in 13 patients (31%), surgical sites in 8 (19%), intravascular catheters in 4 (9%), burns in 3 (7%), and urinary tract in 2 (5%). A comparison of strains from blood cultures and other sites with regard to their REP-PCR and antimicrobial resistance profiles was also made. Taking the REP-PCR as the "gold standard," the positive predictive value of antibiotype was 77% and the negative predictive value was 42%. In summary, the utility of the diagnosis of the source of nosocomial A. baumannii bacteremia using clinical and/or microbiological criteria, including antibiotyping, is limited, as demonstrated by REP-PCR.

Acinetobacter Infections↗

Integron-associated imipenem resistance in Acinetobacter baumannii isolated from a regional hospital in Taiwan.

We investigated the genetic properties of imipenem-resistant Acinetobacter baumannii collected from a regional hospital in Taiwan. Pulsed-field gel electrophoresis demonstrated that the isolates were genetically diverse. Polymerase chain reaction, DNA sequencing, and DNA-DNA hybridisation showed that the bla(IMP-1) gene resided as a cassette in a plasmid-borne class 1 integron in two isolates. The majority of the resistant isolates were plasmid-less and carried no bla(IMP), bla(VIM) or bla(CFI) genes, indicating that other uncharacterised metallo-beta-lactamases or mechanisms other than enzyme production are involved in carbapenem resistance in this group of A. baumannii. We conclude that multidrug resistance of A. baumannii was a combined effect of lateral gene transfer and clonal spread of multiple resistant clones. Strict measures should be implemented to control the further spread of resistance.

Acinetobacter baumannii↗

Colistin efficacy in an experimental model of Acinetobacter baumannii endocarditis.

The in-vivo activity of colistin was evaluated in an experimental rabbit model of Acinetobacter baumannii endocarditis with a strain susceptible to colistin and intermediate to imipenem. Compared to a control group, colistin was effective (p < 0.05) in bacterial clearance from blood and in the sterilisation of blood cultures, but was not effective in clearing A. baumannii from vegetations. Thus, although colistin may be effective in treating bacteraemia caused by susceptible strains of A. baumannii, it may not be a suitable treatment for endocarditis, perhaps because of poor penetration into vegetations and a low C(max)/MIC ratio in tissue.

Acinetobacter Infections↗

Cephalosporinase over-expression resulting from insertion of ISAba1 in Acinetobacter baumannii.

ISAba1-like sequences were identified immediately upstream of the bla(ampC) gene in ceftazidime-resistant Acinetobacter baumannii isolates, but were absent in ceftazidime-susceptible A. baumannii isolates. AmpC over-expression resulted from insertion of ISAba1-like sequences upstream of bla(ampC). ISAba1 provided strong promoter sequences, and it was demonstrated that the change in the ribosome binding site sequence resulting from insertion of ISAba1 did not influence expression of the bla(ampC) gene. Sequence analysis revealed that AmpC sequences of A. baumannii isolates were almost identical and that ISAba1 elements had a high percentage of identity.

Acinetobacter baumannii↗

[Acinetobacter baumannii bacteremia: clinical and prognostic features].

OBJECTIVE: The incidence, clinical features, and prognosis of bacteremia due to Acinetobacter baumannii were investigated. METHODS: Prospective study of all episodes of A. baumanii bacteremia detected during the period of January 1995 to December 1998. A. baumannii was identified using recent standard methods. RESULTS: A total of 133 episodes of bacteremia due to A. baumannii were studied, all of them nosocomial-acquired. The incidence-density diminished from 2.02 episodes per 10,000 patient-days to 0.40 episodes per 10,000 patient-days after the implementation of a control program. Most of the patients (70%) were, or had been, in the ICU when bacteremia occurred. Some 80% of patients had a chronic illness and 62% had a Hilf's severity score > 4. Among the strains identified, 74% were multidrug-resistant and 28% were imipenem-resistant. Attributable mortality was 25.6%. Multivariate analysis showed that inappropriate antibiotic treatment, septic shock, and high Hilf's severity score were associated with poorer prognosis. CONCLUSION: A. baumannii bacteremia mainly affects severely ill patients who have undergone several invasive procedures, and who may have relevant associated morbidity and mortality. Among other variables, inappropriate antibiotic treatment was a risk factor for increased mortalilty.

Acinetobacter Infections↗

Environmental contamination by multidrug-resistant Acinetobacter baumannii in an intensive care unit.

Contamination in an intensive care unit caused by multidrug-resistant Acinetobacter baumannii complex (MRAB)-colonized patients was evaluated using environmental and patient cultures. MRAB occurred in 21% of patients' cultures, 2.1% of 513 areas surrounding MRAB-patients, and one of 372 common areas. No transmission to other patients occurred. Barrier precautions and ethanol disinfection may prevent dissemination.

Acinetobacter Infections↗

Acinetobacter baumannii ventilator-associated pneumonia: epidemiological and clinical findings.

OBJECTIVE: To investigate prognostic factors and predictors of Acinetobacter baumannii isolation in ventilator-associated pneumonia (VAP). We specifically analyzed these issues for imipenem-resistant episodes. DESIGN AND SETTING: All episodes of VAP are prospectively included in a database. Information about risk factors was retrieved retrospectively. PATIENTS: Eighty-one patients exhibiting microbiologically documented VAP: 41 by A. baumannii (26 by imipenem-resistant) and 40 by other pathogens. MEASUREMENTS AND RESULTS: The following variables were noted: underlying diseases, severity of illness, duration of mechanical ventilation and of hospitalization before VAP, prior episode of sepsis, previous antibiotic, corticosteroid use, type of nutrition, renal replacement therapy, reintubation, transportation out of the ICU, micro-organisms involved in VAP, concomitant bacteremia, clinical presentation, Sequential Organ Failure Assessment (SOFA) scale on the day of diagnosis, and adequacy of empirical antibiotic therapy. Prior antibiotic use was found to be associated with development of VAP by A. baumannii (OR 14). Prior imipenem exposure was associated with the isolation of imipenem-resistant strains (OR 4). SOFA score on the day of diagnosis was the only predictor of in-hospital mortality (OR 1.22); adequacy of empirical antibiotic therapy was a protective factor (OR 0.067). CONCLUSIONS: Our results confirm that prior exposure to antimicrobials is an independent predictor for the development of A. baumannii VAP, the prognosis of which is similar to that of infections caused by other pathogens. This study highlights the importance of initial antibiotic choice in VAP or whatever cause.

Acinetobacter Infections↗

Clinical features and epidemiology of Acinetobacter baumannii colonization and infection in Spanish hospitals.

OBJECTIVE: To investigate the clinical features and the epidemiology of Acinetobacter baumannii in Spanish hospitals. DESIGN: Prospective multicenter cohort study. SETTING: Twenty-seven general hospitals and one paraplegic center in Spain. METHODS: All cases of A. baumannii colonization or infection detected by clinical samples during November 2000 were included. Isolates were identified using phenotypic and genotypic methods. The molecular relatedness of the isolates was assessed by pulsed-field gel electrophoresis. RESULTS: Twenty-five (89%) of the hospitals had 221 cases (pooled rate in general hospitals, 0.39 case per 1,000 patient-days; range, 0 to 1.17). The rate was highest in intensive care units (ICUs). Only 3 cases were pediatric. The mean age of the patients in the general hospitals was 63 years; 69% had a chronic underlying disease and 80% had previously received antimicrobial treatment. Fifty-three percent of the patients had an infection (respiratory tract, 51%; surgical site, 16%; and urinary tract, 11%). Crude mortality was higher in infected than in colonized patients (27% vs 10%; relative risk, 1.56; 95% confidence interval, 1.2 to 2.0; P = .003). Molecular analysis disclosed 79 different clones. In most hospitals, a predominant epidemic clone coexisted with other sporadic clones. Imipenem resistance was present in 39% of the hospitals. CONCLUSIONS: A. baumannii was present in most participating Spanish hospitals (particularly in ICUs) with different rates among them. The organisms mainly affected predisposed patients; half of them were only colonized. Epidemic and sporadic clones coexisted in many centers.

Acinetobacter Infections↗

Assessment of Acinetobacter baumannii susceptibility to antiseptics and disinfectants.

Disinfection and antisepsis are of primary importance in controlling outbreaks of Acinetobacter baumannii, a nosocomial pathogen that frequently shows multiple antibiotic resistance. In this study we assessed the susceptibility of nine A. baumannii strains isolated during a sustained intensive care unit outbreak, to several antiseptics and disinfectants based on European Standards. While the tested strains showed diverse antibiotic resistance patterns, they were equally sensitive to the biocides assessed in vitro. We observed neither evidence of development of resistance to biocides over time, nor a correlation between resistance to antibiotics and a decreased susceptibility to antiseptics or disinfectants.

Acinetobacter Infections↗

Risk-factors for the acquisition of imipenem-resistant Acinetobacter baumannii in Spain: a nationwide study.

Potential risk-factors for the acquisition of imipenem-resistant Acinetobacter baumannii were investigated in a cohort study in 25 Spanish hospitals. The clonal relationship among isolates was determined by pulsed-field gel electrophoresis (PFGE). In total, A. baumannii was isolated from 203 patients, with imipenem-resistant (MIC(90) 128 mg/L) isolates being obtained from 88 patients (43%), and imipenem-susceptible isolates from 115 patients (57%). A wide clonal distribution was observed among the imipenem-resistant isolates, but spread of the same clone among centres was not demonstrated. The results indicated that imipenem-resistant A. baumannii is a widely distributed nosocomial pathogen in Spain and reaches an alarming frequency in some centres. Independent risk-factors for the acquisition of imipenem-resistant A. baumannii were a hospital size of >500 beds (multivariate OR, 6.5; 95% CI, 1.8--23), previous antimicrobial treatment (multivariate OR, 4.3; 95% CI, 1.6--11), a urinary catheter (multivariate OR, 2.7; 95% CI, 1.1--6.7) and surgery (multivariate OR, 2; 95% CI, 1.07--3.8).

Acinetobacter Infections↗

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↗