Multidrug-resistant Acinetobacter Infections Research Articles

Combination antibiotic treatment versus monotherapy for multidrug-resistant, extensively drug-resistant, and pandrug-resistant Acinetobacter infections: a systematic review

Controversy surrounds combination treatment or monotherapy against multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) Acinetobacter infections in clinical practice. We searched the PubMed and Scopus databases for studies reporting on the clinical outcomes of patients infected with MDR, XDR, and PDR Acinetobacter spp. with regard to the administered intravenous antibiotic treatment. Twelve studies reporting on 1,040 patients suffering from 1,044 infectious episodes of MDR Acinetobacter spp. were included. The overall mortality between studies varied from 28.6 to 70%; from 25 to 100% in the monotherapy arm and from 27 to 57.1% in the combination arm. Combination treatment was superior to monotherapy in three studies, where carbapenem with ampicillin/sulbactam (mortality 30.8%, p = 0.012), carbapenem with colistin (mortality 23%, p = 0.009), and combinations of colistin with rifampicin, sulbactam with aminoglycosides, tigecycline with colistin and rifampicin, and tigecycline with rifampicin and amikacin (mortality 27%, p < 0.05) were used against MDR Acinetobacter spp. resistant at least to carbapenems. The benefit was not validated in the remaining studies. Clinical success varied from 42.4 to 76.9% and microbiological eradication varied from 32.7 to 67.3%. Adverse events referred mainly to polymixins nephrotoxicity that varied from 19 to 50%. The emergence of resistance was noted with tigecycline regimens in off-label uses in three studies. The available data preclude a firm recommendation with regard to combination treatment or monotherapy. For the time being, combination treatment may be preferred for severely ill patients. We urge for randomized controlled trials examining the optimal treatment of infections due to MDR, XDR, and PDR Acinetobacter spp.

Comparison of multidrug-resistant Acinetobacter and non-Acinetobacter infections in terms of outcome in critically ill patients

Acinetobacter infections have increased and gained attention because of the organism's prolonged environmental survival and propensity to develop antimicrobial drug resistance [1],[2]. We performed a retrospective, matched cohort investigation at a tertiary care hospital in a tier II city hospital of India to examine morbidity and mortality outcome of patients with multidrug-resistant (MDR) Acinetobacter (AB) infection compared with patients with MDR non- Acinetobacter (non-AB) infections.

Mortality audit of neonatal sepsis secondary to Acinetobacter

Background:Multidrug resistant Acinetobacter infection has emerged as an important pathogen in neonatal sepsis in the recent years causing morbidity as well as mortality.Materials and Methods:A retrospective analysis was performed over a one and a half year period of all neonates admitted with sepsis in our neonatal intensive care unit (NICU), who developed Acinetobacter infection and to identify mortality-associated risk factors in these neonates.Results:Incidence of neonatal septicaemia due to Acinetobacter species was 9.18%. All were cases of early onset sepsis. Predominant species isolated was Acinetobacter baumanii (67.5%). The major symptoms were lethargy and poor feeding. The major signs were tachypnoea, rib retraction, and respiratory distress. The major fetal risk factors were low birth weight and prematurity. Overall, 53.75% were multidrug resistant (MDR) Acinetobacter. Resistance to more than two drugs (MDR) was statistically significant in A. baumanii as compared with nonbaumanii. Overall mortality due to Acinetobacter neonatal sepsis was 20%. Septicemia due to A. baumanii was associated with higher mortality than those due to nonbaumanii isolates. Lethargy, tachypnoea, rib retraction, tachycardia, respiratory distress, and mechanical ventilation were significant predictors of mortality.Conclusion:Multidrug resistant Acinetobacter infection is fatal, particularly in premature and low birth weight neonates. Therefore, an effective infection control policy and rational antibiotic use are mandatory in neonatal intensive care areas of each hospital in order to control Acinetobacter infection and improve outcome.

Nosocomial Meningitis Caused by Acinetobacter baumannii : Risk Factors and Their Impact on Patient Outcomes and Treatments

To increase our understanding of the clinical characteristics of nosocomial meningitis caused by Acinetobacter baumannii and provide a basis for improving its treatment. A retrospective analysis was undertaken of 35 cases of A. baumannii meningitis to identify risk factors and their impact on patient outcomes (treatment effectiveness and survival rates). Most patients were from a neurosurgery ward and had multidrug-resistant Acinetobacter infections. Brain neoplasms were the most frequent underlying disease. In total, 97.1% of patients had undergone surgical procedures within the previous month, mostly craniotomies with shunts. For treatment, intravenous carbapenems alone or combined with other antibiotics were used in 28 patients (80.0%), and were effective in 13 of these patients (46.4%). In addition to intravenous antibiotics, intrathecal therapy (gentamicin) or removal of all neurosurgical hardware was used in 18 patients (51.4%). In view of the lack of effective therapeutic options for the treatment of A. baumannii meningitis at the present time, there is a need for new therapies, well-controlled clinical trials of existing antimicrobial regimens and a greater emphasis on preventing nosocomial transmission of multidrug-resistant Acinetobacter strains.

Multidrug-resistant acinetobacter infection and their susceptibility patterns in a tertiary care hospital

Background:Antibiotic-resistant Acinetobacter nosocomial infection is a leading problem. It acts as an opportunistic pathogen to cause a wide spectrum of infection including nosocomial pneumonia, meningitis, endocarditis, skin and soft tissue infections, urinary tract infection, conjunctivitis, burn wound infection and bacteremia. Multidrug-resistant Acinetobacter infection creates a great problem in hospital setting.Materials and Methods:The clinical specimens obtained from ICU and different surgical and medical wards were investigated using standard microbiological techniques to know the distribution of and their resistant profile. Antimicrobial resistance was studied using the modified Kirby Bauer disk diffusion technique following the CLSI protocol.Results:Major infections found in different medical wards, surgical wards and ICU were due to Acinetobacter baumannii (74.02%), A. lowfii (14.2%), A. haemolyticus (7.79%), A. junii (3.8%) among Acinetobacter spices. Acinetobacter showed increased resistant against majority of commercially available drugs imipenem (5.2%), meropenem (9.75%), piperacillin-tazobactum (18.2%), netilmicin (16.24%), amikacin (14.29%), ceftazidime (74.1%), gentamicin (70.13%), ofloxacin (42.21%).Conclusion:A. baumannii was found to be associated with UTI, RTI, septicemia, bacteremia, and meningitis and wound infection. A. baumannii displayed higher resistance to more number of antibiotics than other nosocomial pathogens from ICU.

Combat-related L3 fracture treated with L2–L4 posterior spinal fusion complicated by multidrug-resistant acinetobacter infection

Combat-related L3 fracture treated with L2–L4 posterior spinal fusion complicated by multidrug-resistant acinetobacter infection

Factors Associated with Multidrug-Resistant Acinetobacter Transmission: An Integrative Review of the Literature

Multidrug-resistant (MDR) Acinetobacter infections are occurring at alarming rates in traumatic war injuries. Causative factors have not been specifically identified. We used an integrative review of the literature guided by the Identifying, Organizing, and Synthesizing strategy to identify factors related to MDR Acinetobacter transmission. We identified five major themes of commonality relating to transmission—wound types, risk factors, contributing factors, modes of transmission, and prevention strategies—and we identified studies that should be replicated in military populations. We identified sources of transmission (ie, environment to wound, health care worker to wound) and interventions to reduce or eliminate health care-associated or surgical site MDR Acinetobacter infections (ie, using strict infection control guidelines, appropriate use of antibiotics, notification of infected patients).

Can Pharmacokinetic and Pharmacodynamic Principles Be Applied to the Treatment of Multidrug-Resistant Acinetobacter?

To discuss treatment options that can be used for treatment of Acinetobac/erinfections. A MEDLINE search (1966-November 2010) was conducted to identify English-language literature on pharmacotherapy of Acinetobacter and the bibliographies of pertinent articles. Programs and abstracts from infectious diseases meetings were also searched. Search terms included Acinetobacter, multidrug resistance, pharmacokinetics, pharmacodynamics, Monte Carlo simulation, nosocomial pneumonia, carbapenems, polymyxins, sulbactam, aminoglycosides, tetracyclines, tigecycline, rifampin, and fluoroquinolones. All articles were critically evaluated and all pertinent information was included in this review. Multidrug resistant (MDR) Acinetobacter, defined as resistance to 3 or more antimicrobial classes, has increased over the past decade. The incidence of carbapenem-resistant Acinetobacter is also increasing, leading to an increased use of dose optimization techniques and/or alternative antimicrobials, which is driven by local susceptibility patterns. However, Acinetobacter infections that are resistant to all commercially available antibiotics have been reported. General principles are available to guide dose optimization of aminoglycosides, β-lactams, fluoroquinolones, and tigecycline for infections due to gram-negative pathogens. Unfortunately, data specific to patients with Acinetobacter infections are limited. Recent pharmacokinetic-pharmacodynamic information has shed light on colistin dosing. The dilemma with colistin is its concentration-dependent killing, which makes once-daily dosing seem like an attractive option, but its short postantibiotic effect limits a clinician's ability to extend the dosing interval. Localized delivery of antimicrobials is also an attractive option due to the ability to increase drug concentration at the infection site while minimizing systemic adverse events, but more data are needed regarding this approach. Increased reliance on dosage optimization, combination therapy, and localized delivery of antimicrobials are methods to pursue positive clinical outcomes in MDR Acinetobacter infections since novel antimicrobials will not be available for several years. Well-designed clinical trials with MDR Acinetobacter are needed to define the best treatment options for these patients.

In vitro activity of aminoglycosides, lactam- lactamases inhibitor combinations and tetracyclines against multi-drug resistant Acinetobacter baumannii, isolated from a tertiary care hospital

Acinetobacter baumannii has emerged as a significant nosocomial pathogen, particularly in intensive care units. Isolates of A. baumannii resistant to major groups of antibiotics have been identified. These multi-drug resistant (MDR) organisms are limiting the treatment options. The study was performed to determine the in vitro activity of aminoglycosides, β lactam- β lactamase inhibitor combinations and tetracyclines against MDR A. baumannii, isolated from a tertiary care hospital. The study was carried out from January, 2009 - August, 2009, at the Department of Microbiology, Army Medical College/National University of Sciences and Technology, Rawalpindi, Pakistan looking after an 1100 bedded tertiary care hospital. Routine clinical specimens were received from various wards. A. baumannii was identified by using standard microbiological procedures. Antimicrobial susceptibility test (gentamicin, amikacin, tobramycin, ampicillin-sulbactam, piperacillin-tazobactam, cefoperazone-sulbactam, tetracycline, doxycycline, minocycline, tigecycline,) was performed according to CLSI guidelines using Kirby-Bauer disc diffusion technique. Resistance to carbapenems, fluoroquinolones and the beta-lactams were observed in significant proportion of fifty isolates. Among the aminoglycosides, the isolates were more susceptible to tobramycin than gentamicin and amikacin. Cefoperazone-sulbactam was superior to piperacillin-tazobactam and ampicillin-sulbactam in activity against MDR A. baumannii. Both tigecycline and minocycline were the active agents against most isolates. Multidrug resistantAcinetobacter infections are posing an increasing threat to our population. Minocycline, tobramycin and cefoperazone-sulbactam provide an effective option against infections caused by resistant A. baumannii. Key words: Aminoglycosides, β-lactam/ β-lactamase inhibitor combinations, multi-drug resistant Acinetobacter, tetracyclines.

Pan-resistant Acinetobacter Infection in Neonates in Karachi, Pakistan.

Pan-resistant Acinetobacter infection has emerged as an important nosocomial pathogen in our inpatient neonates over the past few years. We performed a retrospective chart review during a five-year period (July 2003 - June 2008) of all neonates hospitalized in our neonatal intensive care unit (NICU) who developed Acinetobacter infection to identify mortality-associated risk factors in Acinetobacter neonatal infection. During the five-year study period, 122 cultures from 78 neonates grew Acinetobacter. Source sites of positive culture were in the following descending order: blood (n = 57), trachea (n = 55), tissue/wound/body fluids (n = 4), eye (n = 4), urine (n = 1), and cerebrospinal fluid (n = 1). Twenty-four (31%) patients had Acinetobacter isolated from more than one site. At the time of admission the mean age was 2.08 +/- 4 days and mean weight was 1.77 +/- 0.88 kg; 75% were premature. Pan-resistance (87/122; sensitive only to Polymyxin) was present in 71% of Acinetobacter isolates. Crude mortality rate of this cohort was 47%, while 70% of patients died within four days after positive Acinetobacter culture. We identified weight of less than 1 kg on admission (p 0.06, adjusted Odds Ratio (AOR) 1.53), gestational age 28 weeks or less (p 0.011, AOR 2.88), poor perfusion (p 0.007, AOR 2.4), thrombocytopenia (p 0.01; AOR 1.6) and metabolic acidosis (p 0.01; AOR 1.67) as predictors associated with poor outcome. Pan-resistant Acinetobacter infection is exceedingly fatal in newborns, particularly in premature and very low-birth weight neonates. Rational antibiotic use and vigilant infection control in NICUs are key to controlling multi-drug resistant Acinetobacter infection and improving clinical outcome.

P150 Acinetobacter bacteremia and multi-drug resistant Acinetobacter infection at a Canadian tertiary-care hospital

P150 Acinetobacter bacteremia and multi-drug resistant Acinetobacter infection at a Canadian tertiary-care hospital

Factors influencing survival in patients with multi-drug-resistant Acinetobacter bacteraemia

Objectives The incidence of multi-drug-resistant (MDR) Acinetobacter strains is increasing and therapeutic options are limited. However, controversy exists regarding the mortality attributable to antimicrobial resistance. The aim of this study was to analyse the clinical features and outcomes of patients with MDR Acinetobacter calcoaceticus–Acinetobacter baumannii complex (Acb complex) bacteraemia and determine the factors influencing survival by using 14-day mortality as the main outcome measure. Methods An observational study was conducted at a tertiary care hospital in Turkey from February 2007 to March 2008. Only one bacteraemic episode from one patient was included in the study. Results A total of 100 clinically significant Acb complex bacteraemic episodes were detected. The overall mortality was 63% in 14 days. According to univariate analysis, diabetes mellitus, haematological malignancy, unknown source of bacteraemia, septic shock, resistance to carbapenems, and inappropriate empirical therapy were associated with mortality amongst patients with Acb complex bacteraemia. Multivariate analysis showed that diabetes mellitus (RR, 1.68; 95% CI, 1.22–1.76), carbapenem resistance (RR, 1.63; 95% CI, 1.19–1.89), and septic shock (RR, 1.65; 95% CI, 1.23–1.85) were independent risk factors for 14-day mortality. Conclusion Although severe underlying diseases play an important role in the clinical outcome of patients with Acb complex bacteraemia, carbapenem resistance and inappropriate therapy are of great concern. Special attention should be paid to infection control practices in the hospitals where MDR Acinetobacter infections are endemic, and well-controlled prospective clinical trials are needed to determine the optimal antimicrobial therapy in critically ill patients suspected of having MDR Acinetobacter bacteraemia.

Nephrotoxicity associated with the use of intravenous colistin

We retrospectively assessed the renal toxicity associated with the use of intravenous colistin. Fifty-four patients with multidrug-resistant Acinetobacter infections were included. At the end of therapy 6/54 patients (11%) suffered renal impairment. Renal impairment associated with the use of colistin is less frequent than initially reported.

Drug Treatment for Multidrug-Resistant Acinetobacter Baumannii Infections

Acinetobacter baumannii has emerged in the last decades as a major cause of healthcare-associated infections and nosocomial outbreaks. Multidrug-resistant (MDR) A. baumannii is a rapidly emerging pathogen in healthcare settings, where it causes infections that include bacteremia, pneumonia, meningitis, and urinary tract and wound infections. Antimicrobial resistance poses great limits for therapeutic options in infected patients, especially if the isolates are resistant to the carbapenems. Other therapeutic options include sulbactam, aminoglycosides, polymixyns and tigecycline. The discovery of new therapies coupled with the development of controlled clinical trial antibiotic testing combinations and the prevention of transmission of MDR Acinetobacter infection are essential to face this important hospital problem.

Antimicrobial Resistance:Acinetobacter baumannii:Epidemiology, Antimicrobial Resistance, and Treatment Options

Multidrug-resistant Acinetobacter baumannii is recognized to be among the most difficult antimicrobial-resistant gram-negative bacilli to control and treat. Increasing antimicrobial resistance among Acinetobacter isolates has been documented, although definitions of multidrug resistance vary in the literature. A. baumannii survives for prolonged periods under a wide range of environmental conditions. The organism causes outbreaks of infection and health care-associated infections, including bacteremia, pneumonia, meningitis, urinary tract infection, and wound infection. Antimicrobial resistance greatly limits the therapeutic options for patients who are infected with this organism, especially if isolates are resistant to the carbapenem class of antimicrobial agents. Because therapeutic options are limited for multidrug-resistant Acinetobacter infection, the development or discovery of new therapies, well-controlled clinical trials of existing antimicrobial regimens and combinations, and greater emphasis on the prevention of health care-associated transmission of multidrug-resistant Acinetobacter infection are essential.

Tigecycline for the treatment of multidrug-resistant (including carbapenem-resistant) Acinetobacter infections: a review of the scientific evidence

New antibacterial agents are required for the treatment of infections caused by multidrug-resistant (MDR) Acinetobacter spp. Whether tigecycline constitutes an effective treatment option or not, is not well established. We sought to evaluate the available evidence regarding the microbiological activity and clinical effectiveness of tigecycline for MDR (including the subset of carbapenem-resistant) Acinetobacter spp. We searched PubMed for relevant articles and extracted/evaluated the available evidence. We identified 22 microbiological studies reporting data for 2384 Acinetobacter spp. (1906 Acinetobacter baumannii). Susceptibility of at least 90% of the Acinetobacter isolates to tigecycline (with an MIC breakpoint of susceptibility < or =2 mg/L) was noted in 9/18 studies reporting data on MDR Acinetobacter and in 7/15 studies reporting specific data on carbapenem-resistant Acinetobacter. In an additional study reporting data for both resistance categories, adequate susceptibility of Acinetobacter spp. was observed by one (broth microdilution) of the methods employed. The effectiveness of tigecycline for MDR Acinetobacter infections was evaluated in eight identified clinical studies, reporting retrospective data regarding 42 severely ill patients, among whom 31 had respiratory tract infection (in 4 cases with secondary bacteraemia) and 4 had bacteraemia. Tigecycline therapy (in combination with other antibiotics in 28 patients) was effective in 32/42 cases. In three cases, resistance to tigecycline developed during treatment. Tigecycline showed considerable, though not consistent, antimicrobial activity against MDR (including carbapenem-resistant) Acinetobacter spp. However, data to support its clinical use, particularly for ventilator-associated pneumonia or bacteraemia, caused by these pathogens, are still limited.

Multidrug-ResistantAcinetobacter baumannii

To the Editor: In the January 2007 issue of Emerging Infectious Diseases, Sunenshine et al. (1) described their finding of an independent association between patients with multidrug-resistant (MDR) Acinetobacter infection and increased hospital and intensive care unit (ICU) length of stay compared with that for patients with antimicrobial drug–susceptible Acinetobacter infection. The authors did not, however, find a statistically significant difference in mortality rates between the 2 groups of patients.

Multidrug-resistantAcinetobacterInfection Mortality Rate and Length of Hospitalization

Acinetobacter infections have increased and gained attention because of the organism’s prolonged environmental survival and propensity to develop antimicrobial drug resistance. The effect of multidrug-resistant (MDR) Acinetobacter infection on clinical outcomes has not been reported. A retrospective, matched cohort investigation was performed at 2 Baltimore hospitals to examine outcomes of patients with MDR Acinetobacter infection compared with patients with susceptible Acinetobacter infections and patients without Acinetobacter infections. Multivariable analysis controlling for severity of illness and underlying disease identified an independent association between patients with MDR Acinetobacter infection (n = 96) and increased hospital and intensive care unit length of stay compared with 91 patients with susceptible Acinetobacter infection (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.2–5.2 and OR 2.1, 95% CI 1.0–4.3] respectively) and 89 uninfected patients (OR 2.5, 95% CI 1.2–5.4 and OR 4.2, 95% CI 1.5–11.6] respectively). Increased hospitalization associated with MDR Acinetobacter infection emphasizes the need for infection control strategies to prevent cross-transmission in healthcare settings.

Hypercalcaemia resulting from the use of tigecycline in the treatment of multidrug-resistant Acinetobacter in patients with multiorgan failure

Tigecycline (Wyeth) is a new glycylcycline antimicrobial that has been used in the treatment of deep-seated multidrug-resistant Acinetobacter (MDRA) infections. Unexpected changes in routine hematology or serum chemistry have not been reported.

In Vitro Activities of Polymyxin B, Imipenem, and Rifampin against Multidrug-Resistant Acinetobacter baumannii

In a previous issue of this journal, Yoon et al. reported the activities of polymyxin B, imipenem, and rifampin in double and triple combinations against multidrug-resistant strains of Acinetobacter baumannii (7). These organisms have emerged as important nosocomial pathogens responsible for outbreaks of pneumonia, bacteremia, and sepsis among critically ill patients throughout the world (2, 3). As treatment options are limited, studies demonstrating enhanced activity with combinations of one or more agents are welcomed as they may be useful in selecting and guiding therapy. Yoon et al. have used standard checkerboard microtiter plate and time-kill assays against eight isolates of A. baumannii and conclude that bactericidal synergy can be obtained using polymyxin B in combination with imipenem or rifampin and using all three agents combined. In drawing their conclusions, Yoon et al. have defined synergy in checkerboard assays as a fractional inhibitory concentration index (FICI) of <1.0. We are concerned that this interpretation of the FICI overemphasizes the significance of their findings. It is widely accepted that variability in MIC determinations means the true value may lie within a three-dilution range (6). When testing two antibiotics, this effect is cumulative, and the errors are subsequently incorporated in the FICI score. In view of this, the editorial policies of many journals, including Antimicrobial Agents and Chemotherapy (1) and the Journal of Antimicrobial Chemotherapy (5), require FICI data of <0.5 to be defined as synergy. We feel the inclusion of a third antibiotic is not sufficient reason to merit the use of different criteria for interpreting FICI data. In fact, these scores will carry even greater inbuilt error and should therefore be interpreted at least as conservatively as FICI data derived from testing with two antibiotics. If the results of Yoon et al. are reinterpreted using these criteria, then only three of their double combinations and two of their triple combinations are in fact synergistic, with the remainder having only additive, if any, effect. Some authors have suggested more stringent criteria, with a FICI of ≤0.25 obtained in at least five replicate experiments (6). If these criteria are used, then none of the combinations tested by Yoon et al. are synergistic. Combinations of imipenem, rifampin, and colistin have been found to be effective in animal models (4), and these combinations may yet prove to be the most effective means of treating multidrug-resistant Acinetobacter infections. However, until there is a well-designed clinical trial of the safety and efficacy of these regimens, clinicians should remain cautious in extrapolating the existing in vitro and animal data to humans.