Epidemiology of sepsis in intensive care units in Turkey: a multicenter, point-prevalence study.

BACKGROUND: The prevalence and mortality of sepsis are largely unknown in Turkey, a country with high antibiotic resistance. A national, multicenter, point-prevalence study was conducted to determine the prevalence, causative microorganisms, and outcome of sepsis in intensive care units (ICUs) in Turkey. METHODS: A total of 132 ICUs from 94 hospitals participated. All patients (aged > 18 years) present at the participating ICUs or admitted for any duration within a 24-h period (08:00 on January 27, 2016 to 08:00 on January 28, 2016) were included. The presence of systemic inflammatory response syndrome (SIRS), severe sepsis, and septic shock were assessed and documented based on the consensus criteria of the American College of Chest Physicians and Society of Critical Care Medicine (SEPSIS-I) in infected patients. Patients with septic shock were also assessed using the SEPSIS-III definitions. Data regarding demographics, illness severity, comorbidities, microbiology, therapies, length of stay, and outcomes (dead/alive during 30 days) were recorded. RESULTS: Of the 1499 patients included in the analysis, 237 (15.8%) had infection without SIRS, 163 (10.8%) had infection with SIRS, 260 (17.3%) had severe sepsis without shock, and 203 (13.5%) had septic shock. The mortality rates were higher in patients with severe sepsis (55.7%) and septic shock (70.4%) than those with infection alone (24.8%) and infection + SIRS (31.2%) (p < 0.001). According to SEPSIS-III, 104 (6.9%) patients had septic shock (mortality rate, 75.9%). The respiratory system (71.6%) was the most common site of infection, and Acinetobacter spp. (33.7%) were the most common isolated pathogen. Approximately, 74.9%, 39.1%, and 26.5% of Acinetobacter, Klebsiella, and Pseudomonas spp. isolates, respectively, were carbapenem-resistant, which was not associated with a higher mortality risk. Age, acute physiology and chronic health evaluation II score at ICU admission, sequential organ failure assessment score on study day, solid organ malignancy, presence of severe sepsis or shock, Candida spp. infection, renal replacement treatment, and a nurse-to-patient ratio of 1:4 (compared with a nurse-to-patient ratio of 1:2) were independent predictors of mortality in infected patients. CONCLUSIONS: A high prevalence of sepsis and an unacceptably high mortality rate were observed in Turkish ICUs. Although the prevalence of carbapenem resistance was high in Turkish ICUs, it was not associated with a higher risk for mortality. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT03249246 . Date: August 15, 2017. Retrospectively registered.

Costs and Mortality Associated With Multidrug-Resistant Healthcare-Associated Acinetobacter Infections.

BACKGROUND Our objective was to estimate the per-infection and cumulative mortality and cost burden of multidrug-resistant (MDR) Acinetobacter healthcare-associated infections (HAIs) in the United States using data from published studies. METHODS We identified studies that estimated the excess cost, length of stay (LOS), or mortality attributable to MDR Acinetobacter HAIs. We generated estimates of the cost per HAI using 3 methods: (1) overall cost estimates, (2) multiplying LOS estimates by a cost per inpatient-day ($4,350) from the payer perspective, and (3) multiplying LOS estimates by a cost per inpatient-day from the hospital ($2,030) perspective. We deflated our estimates for time-dependent bias using an adjustment factor derived from studies that estimated attributable LOS using both time-fixed methods and either multistate models (70.4% decrease) or matching patients with and without HAIs using the timing of infection (47.4% decrease). Finally, we used the incidence rate of MDR Acinetobacter HAIs to generate cumulative incidence, cost, and mortality associated with these infections. RESULTS Our estimates of the cost per infection were $129,917 (method 1), $72,025 (method 2), and $33,510 (method 3). The pooled relative risk of mortality was 4.51 (95% CI, 1.10-32.65), which yielded a mortality rate of 10.6% (95% CI, 2.5%-29.4%). With an incidence rate of 0.141 (95% CI, 0.136-0.161) per 1,000 patient-days at risk, we estimated an annual cumulative incidence of 12,524 (95% CI, 11,509-13,625) in the United States. CONCLUSION The estimates presented here are relevant to understanding the expenditures and lives that could be saved by preventing MDR Acinetobacter HAIs. Infect Control Hosp Epidemiol 2016;1-7.

Clinical importance and cost of bacteremia caused by nosocomial multi drug resistant acinetobacter baumannii.

BACKGROUND: A. baumannii is an important nosocomial pathogen associated with high mortality, morbidity and medical cost. AIM: The aim of this study was to investigate risk factors for MDR A. baumannii bacteremia and also evaluate cost of hospitalization of these patients. METHODS: Study was conducted in Ankara Atatürk Training and Research Hospital. Patients who were hospitalized in ICU and diagnosed for nosocomial blood stream infection (BSI) between January 2007 and December 2010 were checked retrospectively. Patients with nosocomial BSI caused by multidrug resistant A. baumannii were compared with the patients who had BSI caused by other Gram-negative microorganisms in terms of risk factors, mortality and medical costs. FINDINGS: In multivariate analysis previous use of carbapenem, quinolone and metronidazole, and SAPS II score were found as independent risk factors. In case group; immunosupression, SAPS II score, and hospital stay until infection were independently associated with mortality in multivariate analysis. CONCLUSION: Our results suggest that the occurrence of MDR A.baumannii bacteremia was related with the usage of the wide spectrum antibiotics, and mortality rates were increased in patients that high SAPS II scores, long term hospitalization. Infection control procedures and limited antibiotic usage are very important for prevent nosocomial infections.

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.

Impact of carbapenem resistance on clinical and economic outcomes among patients with Acinetobacter baumannii infection in Colombia.

Acinetobacter baumannii is a major cause of healthcare-associated infection, often affecting critically ill patients. The purpose of the study was to examine the associations of carbapenem resistance with mortality, length of hospital stay and hospital costs among patients infected with A. baumannii in intensive-care units (ICUs) in Colombia. A prospective, multicentre cohort study was conducted among 165 patients with A. baumannii infection admitted to ICUs between April 2006 and April 2010. Patients with carbapenem-resistant A. baumannii had higher risk of 30-day mortality than patients with carbapenem-susceptible A. baumannii in the univariate analysis (unadjusted hazard ratio = 2.12; 95% CI 1.14-3.95; p 0.018). However, carbapenem resistance was not significantly associated with risk of mortality (adjusted hazard ratio = 1.45; 95% CI 0.74-2.87; p 0.28) after adjusting for APACHE II score and other confounding factors. We did not find a significant difference in length of stay in ICU after the onset of infection between the two groups in the multivariate analysis (adjusted mean = 13.1 days versus 10.5 days; p 0.14). The average total cost of hospitalization among patients with carbapenem-resistant A. baumannii was significantly higher than that among patients with carbapenem-susceptible A. baumannii in the multivariate analysis (adjusted cost; US$ 11 359 versus US$ 7049; p <0.001). Carbapenem resistance was not significantly associated with mortality, though we are unable to rule out an increased risk due to the limited sample size. Carbapenem resistance was associated with an additional cost of hospitalization.

Prediction of patient outcome from Acinetobacter baumannii bacteremia with Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores.

OBJECTIVE: Acinetobacter baumannii is an important nosocomial pathogen associated with a high mortality rate. However, no objective and quantitative severity scores are available for the severity stratification. We aimed to assess the effectiveness of SOFA and APACHE II scores calculated at the onset of bacteremia in predicting the mortality of patients with A. baumannii bacteraemia. PATIENTS AND METHODS: A total of 110 patients with A. baumannii bacteremia were included in this retrospective study during the 40-month study period. Information including clinical and laboratory data was collected. RESULTS: Multivariate analysis showed that both SOFA and APACHE II scores were independent outcome predictors after adjustment for other parameters. Goodness-of-fit was good for SOFA and APACHE II, and both models displayed excellent AUROCs (SOFA: 0.83 ± 0.06, APACHE II: 0.82 ± 0.08 in predicting 14-day mortality; SOFA: 0.85 ± 0.04, APACHE II: 0.81 ± 0.04 in predicting in-hospital mortality). There was no significant difference in the predictions of the two scoring systems, and the scores were highly correlated (r(2)=0.724, p <0.001). We found that SOFA >8, APACHE II >29 and SOFA >7, APACHE II >23 are associated with significantly higher 14-day and in-hospital mortality rates, respectively. CONCLUSION: SOFA and APACHE II scores assessed at the onset of bacteremia are reliable risk stratifying tools in predicting 14-day and in-hospital mortality in A. baumannii bacteremia. For ease of calculation, the use of SOFA rather than APACHE II score to predict mortality of A. baumannii bacteremia might have clinical application.

Epidemiology and impact of imipenem resistance in Acinetobacter baumannii.

BACKGROUND: Acinetobacter baumannii is an emerging gram-negative pathogen that can cause healthcare-acquired infections among patients. Treatment is complicated for cases of healthcare-acquired infection with A. baumannii resistant to imipenem. OBJECTIVE: To elucidate the risk factors for imipenem-resistant A. baumannii (IRAB) infection or colonization and to identify the effect of resistance on clinical and economic outcomes. METHODS: We analyzed data from 2 medical centers of the University of Pennsylvania. Longitudinal trends in the prevalence of IRAB clinical isolates were characterized during the period from 1989 through 2004. For A. baumannii isolates obtained from 2001 through 2006, a case-control study was conducted to investigate the association between prior carbapenem use and IRAB infection or colonization, and a cohort study was performed to identify the effect of IRAB infection or colonization on mortality, length of stay after culture, and hospital cost after culture. RESULTS: From 1989 through 2004, the annual prevalence of IRAB isolates ranged from 0% to 21%. During the period from 2001 through 2006, there were 386 unique patients with A. baumannii isolates, and 89 (23.1%) had IRAB isolates. Prior carbapenem use was independently associated with IRAB infection or colonization (adjusted odds ratio, 3.04 [95% confidence interval, 1.07-8.65]). There was a borderline significant association between IRAB infection or colonization and mortality, although this association was limited to isolates recovered from blood samples (adjusted odds ratio, 5.30 [95% confidence interval, 0.81-34.59]). Compared with patients with imipenem-susceptible A. baumannii infection or colonization, patients with IRAB infection or colonization had a longer hospital stay after culture (median, 21 vs 16 days; P = .07) and greater hospital charges after culture (mean, $334,516 vs $276,059; P = .03). After controlling for patient location in an intensive care unit, transfer from another facility, and length of hospital stay before culture, there was no longer an independent association between IRAB infection or colonization and higher cost after culture and length of stay after positive culture result. CONCLUSIONS: Many A. baumannii isolates exhibit imipenem resistance, which is strongly associated with prior use of carbapenems. Given the high mortality rate associated with A. baumannii infection or colonization, interventions to curb further emergence of cases of IRAB infection and strategies to optimize therapy are needed.

Multidrug-resistant Acinetobacter meningitis in neurosurgical patients with intraventricular catheters: assessment of different treatments.

BACKGROUND: The treatment of multidrug-resistant Acinetobacter baumannii meningitis is a serious therapeutic problem due to the limited penetration of antibiotics into the CSF. We describe the clinical features and the outcome of a group of patients with nosocomial neurosurgical meningitis treated with different therapeutic options. METHODS: All patients with nosocomial post-surgical meningitis due to A. baumannii diagnosed between 1990 and 2004 were retrospectively reviewed. RESULTS: During the period of study, 51 cases of this nosocomial infection were identified. Twenty-seven patients were treated with intravenous (iv) monotherapy: carbapenems (21 cases), ampicillin/sulbactam (4 cases) and other antibiotics (2 cases). Four patients were treated with iv combination therapy. Nineteen patients were treated with iv and intrathecal regimens: colistin by both routes (8 cases), carbapenems plus iv and intrathecal (4 cases) or only intrathecal (5 cases) aminoglycosides, and others (2 cases). Seventeen patients died due to the infection. One patient died without treatment. The mean (SD) duration of therapy was 17.4 (8.3) days (range 3-44). Although no patients treated with colistin died, we did not observe statistically significant differences in the mortality among the groups with different treatments. CONCLUSIONS: Nosocomial Acinetobacter meningitis has a high mortality. Combined therapy with iv and intrathecal colistin is a useful and safe option in the treatment of nosocomial Acinetobacter meningitis.

Clinical and economic impact of multidrug resistance in nosocomial Acinetobacter baumannii bacteremia.

OBJECTIVE: To investigate the impact of antimicrobial resistance on clinical and economic outcomes among hospitalized patients with multidrug-resistant (MDR) Acinetobacter baumannii bacteremia. DESIGN: A retrospective, matched-cohort study. SETTING: A tertiary care university teaching hospital. METHODS: A matched case-control (1 : 1) study was conducted to compare the differences in clinical and economic outcomes of patients with MDR A. baumannii bacteremia and patients with non-MDR A. baumannii bacteremia. Case patients were matched to control patients on the basis of sex, age, severity of underlying and acute illness, and length of hospital stay before onset of bacteremia. RESULTS: Forty-six (95.8%) of 48 cases with MDR A. baumannii bacteremia were eligible for the study and matched with appropriate controls. The sepsis-related mortality rate was 34.8% among cases and 13.0% among controls, for an attributable mortality rate of 21.8% (adjusted odds ratio, 4.1 [95% confidence interval, 1.1-15.7]; P=.036). After the onset of bacteremia, cases and controls had a significantly different length of hospital stay (54.2 vs 34.1 days; P=.006), hospitalization cost (US$9,349 vs US$4,865; P=.001), and antibiotic therapy cost (US$2,257 vs US$1,610; P=.014). Thus, bacteremia due to MDR A. baumannii resulted in 13.4 days of additional hospitalization and US$3,758 of additional costs, compared with bacteremia due to non-MDR A. baumannii. CONCLUSIONS: Patients with MDR A. baumannii bacteremia had a higher mortality rate and incurred greater medical costs than patients with non-MDR A. baumannii bacteremia.

Evaluation of Acinetobacter baumannii infection and colonization, and antimicrobial treatment patterns in an urban teaching hospital.

In 1990 there was a sudden increase in the incidence of colonization and infection due to Acinetobacter baumannii (AB) in our intensive care units (ICUs). The isolates were multiply resistant to beta-lactam and aminoglycoside antibiotics, but remained susceptible to imipenem, amikacin, and ampicillin-sulbactam. We examined the frequency of infection and colonization with AB and the effects of increased imipenem and amikacin therapy on Pseudomonas aeruginosa. We also used disease-matched controls to determine the clinical and financial impacts of treating colonization. All patients with at least one AB isolate from January-December 1992 were identified retrospectively and classified as infected or colonized based on published Centers for Disease Control criteria; the control group was selected from a computerized medical records data base matching primary diagnostic codes (102 patients both groups). The 102 patients yielded 140 isolates, 124 resistant AB and 16 sensitive AB. Thirty three patients were infected, 69 colonized. Mortality correlated with APACHE II scores. Patients acquired the organism approximately 2 weeks after admission; they had a mean ICU stay of 27.35 days, compared with 5.53 days for controls. Patients with positive AB cultures required significantly more use of ventilators than those with negative AB cultures. They also had significantly longer hospital stay, more bed transfers, greater duration and number of antibiotics, and higher hospital and pharmacy charges. Unnecessary treatment for colonization with either imipenem or amikacin resulted in a substantial decrease of P. aeruginosa susceptibility to each agent. The financial impact of treating colonization was significant and is a potential area for cost avoidance. Our results emphasize the need to extubate and move patients to non-ICU beds as soon as possible to decrease the risk of nosocomial infection. It also highlights the need to avoid treating colonization, thus avoiding unnecessary antibiotic therapy.