Pharmacokinetic and pharmacodynamic profiling of four antimicrobials against Acinetobacter baumannii infection.

BACKGROUND: The aim of this study was to evaluate common antimicrobial regimens used in eradicating Acinetobacter baumannii in Shenyang, China. METHODS: Monte Carlo simulation was conducted to estimate the probability target attainment (PTA) and cumulative fraction of response (CFR) for imipenem, cefoperazone/sulbactam (2:1), tigecycline and colistin methanesulfonate. RESULTS: For the results of PTAs, imipenem following administration of 0.5 g q6 h, 1 g q8 h, and 1 g q6 h for both 0.5 h and 2 h infusion achieved＞90% PTAs when MIC was 8 µg/ml; cefoperazone/ sulbactam (2:1) following administration of 4.5 g q6 h and 6 g q6 h achieved＞90% PTAs when MIC was 64µg/ml; tigecycline following administration of 50 mg q12 h and 100 mg q12 h achieved＞90% PTAs when MIC was 1 µg/ml; colistin methanesulfonate with high dosages (3MU q8 h) could provide high PTA (95.13%) in patients with CLCr＜60 ml/min when MIC was 2 µg/ml. As for CFR values of four antibiotics, imipenem achieved the lowest CFR values. For cefoperazone/sulbactam (2:1) and tigecycline, with simulated regimens improvement, the CFR values were both increased, and there were obviously increasing CFR values against Acinetobacter baumannii. For colistin methanesulfonate, the most aggressive dosage of 3MU q8 h could provide satisfactory CFR values (≥86.94%) against Acinetobacter baumannii in patients at various CLCr. CONCLUSION: This study suggested that measurement of MICs, individualized therapy and therapeutic drug-level monitoring should be considered together to achieve the optimal drug exposure. That will provide the best chance of achieving the highest probability of a successful clinical or microbiological response, and avoiding the induced resistance.

Successful Use of Colistin Monotherapy as Outpatient Parenteral Antibiotic Therapy for XDR Acinetobacter Hepatic Abscesses.

Acinetobacter baumannii is naturally resistant to several classes of antibiotics and readily develops further resistance mechanisms under antibiotic pressure. For patients infected with extremely drug-resistant organisms, effective antibiotic treatments are intravenous and often require inpatient hospitalization for monitoring and dose adjustment. A 31-year-old active duty service member, stationed in Southeast Asia, sustained thermal burns from an electrical arc injury to over 40% of his total body surface area. His hospital course was complicated by multiple extensively drug resistant (XDR) A. baumanii infections including bacteremia and hepatic abscesses. To facilitate discharge to his family, his hepatic abscesses were treated successfully as an outpatient with several weeks of parenteral colistin monotherapy. With regular renal function testing, his dosages were held and/or adjusted to compensate for acute kidney injuries, and he was successfully cleared of his infection. Up to 50% of A. baumannii isolates in American hospitals, including major DOD facilities, are carbapenem resistant. As a result, historically last-line therapies, such as polymyxins, are increasingly used as treatment. New dosing guidance is emphasized to minimize renal toxicities. This case demonstrates the ability to administer parenteral colistin as an outpatient under close supervision.

Acinetobacter Pneumonia: Improving Outcomes With Early Identification and Appropriate Therapy.

In an era of increasing antimicrobial resistance, Acinetobacter distinguishes itself as one of the most resistant Gram-negative bacteria responsible for significant morbidity and mortality. New solutions are needed to combat the detrimental effects of increasing rates of antimicrobial resistance. Using empiric broad-spectrum antibiotics in patients deemed at risk for infections caused by multidrug-resistant pathogens may protect against attributable mortality, but this temporary solution furthers the risk of antimicrobial resistance. In this article we will review relevant strategies to aid with early identification and appropriate treatment of Acinetobacter pneumonia while preserving antibiotic susceptibility.

Severe infections caused by multidrug-resistant non-fermentative bacilli in southern Poland.

BACKGROUND: The impact of multidrug-resistant organisms (MDROs), including non-fermentative bacilli (NFBs), is rising and underestimated, especially in intensive care units (ICUs). The growing prevalence of multidrug resistance (MDR) and extensive drug resistance (XDR) is challenging for clinicians, as the treatment options are limited. OBJECTIVES: The purpose of this study was to analyze the extent of the epidemiological problem of multidrugresistant, extensively drug-resistant and pandrug-resistant (PDR) non-fermentative bacilli isolated from pneumonia and bloodstream infections (BSIs) in patients hospitalized in southern Poland. MATERIAL AND METHODS: This study included 253 NFBs belonging to Acinetobacter sp. (ACI), Pseudomonas sp. (PAR), and Stenotrophomonas sp. (STM). The microorganisms were identified, and susceptibility testing was performed using a semi-automatic system. The different patterns of resistance were defined as MDR, XDR, or PDR strains. Epidemiological typing of A. baumannii from ICUs was performed by repetitive polymerase chain reaction (rep-PCR). RESULTS: More than half of the strains (57.7%) were isolated within ICUs. ACI-strains came significantly more often from ICU wards. The highest prevalence of ACI and PAR was found in pneumonia, whereas STM dominated in BSIs. ACIs were more frequently resistant than other pathogens to all studied antibiotics except colistin (n = 76; 58.9%), and they belonged to the XDR category. DiversiLab demonstrated the presence of 2 dominant clones in the ACI group, both classified as European Clone 2 (EUII). CONCLUSIONS: Our results indicate serious potential therapeutic problems related to high antibiotic resistance of ACI isolates. The stratification of drug resistance (MDR/XDR/PDR) may become an important tool for the assessment of public health epidemiology and microbiological hazards at the local, national, and international level. It allows clear presentation of the issues concerning the epidemiology of highly resistant bacilli, and the exchange of information between medical staff and local representatives of public health for the implementation of effective measures to reduce drug resistance.

Microbiological Characteristics and Clinical Outcomes of Acinetobacter spp. Endophthalmitis with the First Reported Case of Acinetobacter haemolyticus Endophthalmitis.

AIM: To present the microbiological details and clinical outcomes of Acinetobacter spp. endophthalmitis with the first reported case of A. haemolyticus. METHODS: A retrospective study of microbiologically proven Acinetobacter spp. endophthalmitis was carried out from 2010 to 2015. The data collected included age, type of endophthalmitis, best-corrected visual acuity (BCVA), species involved, and antibiotic susceptibility pattern. The primary outcomes measured were anatomical outcomes in terms of globe integrity and functional outcome as BCVA at last follow-up. RESULTS: Eleven patients out of 3004 patients who underwent surgery for endophthalmitis were due to Acinetobacter spp. Seven cases (63.6%) were both smear and culture positive; there were two cases (18%) each of A. haemolyticus and A. baumanii. Four cases (36%) were only culture positive with negative smear. Three cases (27.2%) were polymicrobial. Ten cases (91%) were susceptible to amikacin and nine (82%) to ciprofloxacin. Six (54.5%) were resistant to ceftazidime. Mean logMAR BCVA improved to 1.8 (20/1330) from an initial 2.5 (20/6839). Pthisis bulbi was seen in two cases (18%). CONCLUSIONS: Even though the outcomes of Acinetobacter spp. endophthalmitis are modest to poor, outcomes following intervention are relatively good for A. haemolyticus. These cases have good susceptibility to amikacin, but are often resistant to ceftazidime.

Antibiotic strategies and clinical outcomes in critically ill patients with pneumonia caused by carbapenem-resistant Acinetobacter baumannii.

OBJECTIVES: This study aimed to investigate antibiotic prescribing patterns and effectiveness of different anti-carbapenem-resistant Acinetobacter baumannii (CRAB) strategies for CRAB pneumonia. METHODS: We conducted a multicentre, retrospective study in three hospitals. During 2010-2015, adult ICU patients with CRAB pneumonia treated with at least one antimicrobial agent covering the CRAB isolate in vitro for more than 2 days were included. We used multivariate logistic regression to analyse the associations of anti-CRAB strategies with ICU mortality and other clinical outcomes. RESULTS: Among 238 patients with CRAB pneumonia, tigecycline monotherapy (84, 35.3%) was the most common antibiotic strategy, followed by tigecycline with colistin (43, 18.1%), colistin monotherapy (34, 14.3%), colistin combination without tigecycline (33, 13.9%), tigecycline combination without colistin (32, 13.4%), and sulbactam-based therapy without tigecycline and colistin (12, 5.0%). In multivariate analysis, tigecycline-based therapy was associated with higher ICU mortality than non-tigecycline therapy (adjusted OR 2.30, 95% CI 1.19-4.46). There was no difference between colistin-based therapy and non-colistin therapy. Compared with tigecycline monotherapy, colistin monotherapy was associated with lower ICU mortality (aOR 0.30, 95% CI 0.10-0.88). Treatment failure analyses showed similar trends. Tigecycline-based therapy was associated with higher treatment failure rate than non-tigecycline therapy (aOR 2.51, 95% CI 1.39-4.54), whereas colistin-based therapy was associated with lower treatment failure rate than non-colistin-based therapy (aOR 0.48, 95% CI 0.27-0.86). CONCLUSIONS: Tigecycline was commonly prescribed for CRAB pneumonia. However, tigecycline-based therapy was associated with higher ICU mortality and treatment failure. Our study suggests that colistin monotherapy may be a better antibiotic strategy for CRAB pneumonia.

OXA-type Carbapenemases and Susceptibility of Colistin and Tigecycline Among Carbapenem-Resistant Acinetobacter Baumannii Isolates from Patients with Bacteremia in Turkey.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) has emerged as one of the most troublesome pathogens in healthcare settings worldwide. The present study was conducted to analyze the genes encoding resistance to carbapenems and to determine in vitro activity of colistin and tigecycline against CRAB isolates from blood culture of hospitalized patients at Istanbul University Cerrahpasa Medical School hospital. METHODS: Between January 2012 and June 2014, a total of 72 CRAB isolates were isolated by conventional methods from blood cultures of patients with bacteremia who were hospitalized in intensive care units and in various departments of the hospital. The isolates were confirmed using a Phoenix automated system. Antibiotic susceptibilities were determined by disk diffusion method and Etest. Molecular detection of resistance genes were screened by multiplex real time polymerase chain reaction (qPCR) and PCR parameters. RESULTS: CRAB isolates were highly resistant to tetracycline (86.1%), trimethoprim/sulfamethoxazole (84.7%), ceftazidime (83.3%), cefepime (81.9%), ciprofloxacin (81.9%), amikacin (75.0%), piperacillin/tazobactam (75.0%), cefotaxime (72.2%), and gentamicin (69.4%). Tigecycline and colistin resistance were not detected. MIC50 and MIC90 of tigecycline (MIC ranges 0.016-1 µg/mL) and colistin (MIC ranges 0.125-1.5 µg/mL) were found to be 0.5 µg/mL and 1 µg/mL, respectively. All isolates were positive for OXA-51 that shows molecular identification of A. baumannii. Fifty-one (70.8%) and 2 (2.8%) of these isolates were positive for OXA-23 and OXA-58 genes, re- spectively. CONCLUSIONS: This study indicated the most of the CRAB isolates in our hospital carry the OXA-23 gene. Colistin and tigecycline resistance were not detected. However, significant effort must be done to prevent the spread of OXA-23-producing CRAB-isolates and continuous monitoring of drug resistance is necessary in clinical settings.

Successful Eradication of Multidrug Resistant Acinetobacter in the Helsinki Burn Centre.

Multidrug-resistant (MDR) Acinetobacter is an important pathogen implicated in nosocomial infections in healthcare environments. Virulence factors, resistance mechanisms, and limited therapeutic options make this pathogen a major problem currently facing burn intensive care units (ICUs) worldwide. The purpose of this study was to assess the effect of infection control measures taken in Helsinki Burn Centre in 2001 on MDR Acinetobacter prevalence in ICU burn patients. Data were retrospectively collected from patient files from 1998 to 2012. ICU burn patients were defined as those with either over 30% of total body surface area burnt or requiring mechanical ventilation. Inclusion criteria consisted of patients who tested positive for Acinetobacter sp. in routine bacterial cultures or cultures taken because of a clinically suspected infection. Infection control interventions performed in 2001 consisted of various shower room renovations and changes in hospital hygiene and burn treatment regimes. Between 1998 and 2012, 75 patients were diagnosed with Acinetobacter sp. colonization. Following the infection control interventions the incidence of Acinetobacter sp. radically declined. Between 1998 and 2001, there were 31 cases of MDR Acinetobacter colonizations diagnosed, but from 2002 to 2012 no MDR strains were found. Changes to hospital hygiene and wound treatment protocols as well as structural changes to the hospital environment can have a major impact on preventing and treating Acinetobacter outbreaks in burn centers.

Integrating rapid diagnostics and antimicrobial stewardship improves outcomes in patients with antibiotic-resistant Gram-negative bacteremia.

BACKGROUND: An intervention for Gram-negative bloodstream infections that integrated mass spectrometry technology for rapid diagnosis with antimicrobial stewardship oversight significantly improved patient outcomes and reduced hospital costs. As antibiotic resistance rates continue to grow at an alarming speed, the current study was undertaken to assess the impact of this intervention in a challenging patient population with bloodstream infections caused by antibiotic-resistant Gram-negative bacteria. METHODS: A total of 153 patients with antibiotic-resistant Gram-negative bacteremia hospitalized prior to the study intervention were compared to 112 patients treated post-implementation. Outcomes assessed included time to optimal antibiotic therapy, time to active treatment when inactive, hospital and intensive care unit length of stay, all-cause 30-day mortality, and total hospital expenditures. RESULTS: Integrating rapid diagnostics with antimicrobial stewardship improved time to optimal antibiotic therapy (80.9 h in the pre-intervention period versus 23.2 h in the intervention period, P < 0.001) and effective antibiotic therapy (89.7 h versus 32 h, P < 0.001). Patients in the pre-intervention period had increased duration of hospitalization compared to those in the intervention period (23.3 days versus 15.3 days, P = 0.0001) and longer intensive care unit length of stay (16 days versus 10.7 days, P = 0.008). Mortality among patients during the intervention period was lower (21% versus 8.9%, P = 0.01) and our study intervention remained a significant predictor of survival (OR, 0.3; 95% confidence interval [CI], 0.12-0.79) after multivariate logistic regression. Mean hospital costs for each inpatient survivor were reduced $26,298 in the intervention cohort resulting in an estimated annual cost savings of $2.4 million (P = 0.002). CONCLUSIONS: Integration of rapid identification and susceptibility techniques with antimicrobial stewardship resulted in significant improvements in clinical and financial outcomes for patients with bloodstream infections caused by antibiotic-resistant Gram-negatives. The intervention decreased hospital and intensive care unit length of stay, total hospital costs, and reduced all-cause 30-day mortality.

Successful treatment of skin and soft tissue infection due to carbapenem-resistant Acinetobacter baumannii by ampicillin-sulbactam and meropenem combination therapy.

In recent years, carbapenem-resistant Acinetobacter baumannii infections have been responsible for outbreaks in medical facilities. A 35-year-old Japanese woman developed a skin and soft tissue infection due to carbapenem-resistant A. baumannii. The isolate was resistant to antibiotics other than ampicillin-sulbactam and colistin, suggesting drug resistance due to carbapenemase production by OXA-23. We selected a combination therapy consisting of intravenous ampicillin-sulbactam and meropenem. No changes were observed in aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, or serum creatinine during therapy, and carbapenem-resistant A. baumannii was not detected in wound exudates 3 days after therapy initiation. In our patient's case, combination therapy with ampicillin-sulbactam and meropenem was successful. Thus, combination therapy with ampicillin-sulbactam and meropenem is effective against skin and soft tissue infection due to carbapenem-resistant A. baumannii. Combination therapy with intravenous ampicillin-sulbactam and meropenem may be an option for skin and soft tissue infections due to carbapenem-resistant A. baumannii.

Antimicrobial susceptibility pattern in nosocomial infections caused by Acinetobacter species in Asir Region, Saudi Arabia.

This study aimed at evaluating the sensitivity of antibiotics towards nosocomial infections caused by Acinetobacter species. The study took place during the period Dec. 2011- Dec. 2012 at Assir Central Hospital in collaboration with the department of microbiology, college of medicine, King Khalid University, Abha. A prospective study involving 150 patients presented with nosocomial infections due to Acinetobacter species detected by bacteriological tests; direct microscopy, culture in blood agar media, fermentation test in MacConkey media and MIC (minimum inhibitory concentration) for antibiotics sensitivity using Muller Hinton media and Chemical test using API 20. A 150 nosocomial infections in this study showed gram-negative coccobacilli, non motile, glucose-negative fermentor and oxidase negative. All isolates showed 100% sensitivity to: Imipramine, Meropenem, Colistin. From the rest of tested antibiotics the higher resistant ones were; Nitrofurantoin 87% and Cefoxitin 85%. The least resistant antibiotics; Imipenem 3% and Ticarcillin 7%. While variable resistance in the rest of tested antimicrobials. A 47 patients (31.3%) have used antibiotics prior to this study. The high rate of usage occurred in elder patients. The frequency of Acinetobacter calcoaceticus baumannii complex multi-drugs resistance ABCMDR is rising including almost all commonly used antibiotics. Only few antibiotics exert 100% sensitivity towards these bacteria.

[Acinetobacter baumannii: a rare cause of deep neck infection]. / Acinetobacter baumannii: Derin boyun enfeksiyonunun nadir bir nedeni.

Deep neck infections, which are originated from upper respiratory tract, are bacterial infections involving deep structures of the neck. Unless diagnosed and managed appropriately, these infections may progress rapidly, leading to severe morbidity and mortality. Although, Acinetobacter baumannii plays a significant role in several nosocomial infections, ear nose throat physicians are usually unfamiliar with this bacteria and it is rarely isolated in deep neck infections. In this article, we present a serious case of deep neck infection in which Acinetobacter baumannii was cultured from the abscess. The patient was treated successfully with antibiotic and surgical drainage.

Colistimethate sodium therapy for multidrug-resistant isolates in pediatric patients.

AIM: The aim of the present study was to assess the efficacy and safety of colistimethate sodium therapy in multidrug-resistant nosocomial infections caused by Pseudomonas aeruginosa or Acinetobacter baumannii in neonates and children. METHODS: Pediatric patients hospitalized at the Uludag University Hospital who had nosocomial infections caused by multidrug-resistant P. aeruginosa or A. baumannii, were enrolled in the study. Colistimethate sodium at a dosage of 50-75 x 10(3) U/kg per day was given i.v. divided into three doses. RESULTS: Fifteen patients received 17 courses of colistimethate sodium for the following infections: ventilator-associated pneumonia (n= 14), catheter-related sepsis (n= 1) and skin and soft-tissue infection (n= 2). The mean age of patients was 53.2 + 74.7 months (range, 8 days-15 years) and 60% were male. Mortality was 26.6%. CONCLUSION: Colistimethate sodium appears to be safe and effective for the treatment of severe infections caused by multidrug-resistant P. aeruginosa or A. baumannii in pediatric patients.

Endemic nosocomial Acinetobacter calcoaceticus bacteremia. Clinical significance, treatment, and prognosis.

The medical records of 27 patients with blood cultures positive for Acinetobacter calcoaceticus over a recent five-year period (0.7% of all positive blood cultures) were reviewed retrospectively to determine the epidemiologic and clinical significance of these isolates. Eighteen isolates represented true bacteremias, 16 of which were hospital acquired. Patients most frequently were located in an intensive care unit or on a surgical ward. A seasonal July-to-September peak incidence was noted. The most common site of primary infection was the respiratory tract. Aminoglycosides, alone or in combination with a second agent, were used to treat all but one infection. Bacteriologic cure was achieved in 15 cases (88%); six patients had polymicrobial sepsis that carried a higher mortality than pure A calcoaceticus bacteremia (50% vs 0%). Acinetobacter, a low-virulence opportunistic pathogen, may be an infrequent but potentially serious endemic agent of nosocomial bacteremia in some institutions. The prognosis of bacteremia, when appropriately treated, appears to be good.