|Year : 2015 | Volume
| Issue : 4 | Page : 256-262
|Impact of empirical antimicrobial therapy on the outcome of critically ill patients with Acinetobacter bacteremia
Hasan M Al-Dorzi1, Abdulaziz M Asiri1, Abdullah Shimemri1, Hani M Tamim2, Sameera M Al Johani3, Tarek Al Dabbagh1, Yaseen M Arabi1
1 Department of Intensive Care, King Abdulaziz Medical City, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
2 Department of Epidemiology and Biostatistics, King Abdulaziz Medical City, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
3 Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
|Date of Submission||23-Oct-2014|
|Date of Acceptance||08-May-2015|
|Date of Web Publication||9-Oct-2015|
Hasan M Al-Dorzi
Department of Intensive Care, King Abdulaziz Medical City, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, PO Box 22490, Mail Code 1425, Riyadh 11426
| Abstract|| |
Rationale: Empirical antimicrobial therapy (EAT) for Acinetobacter infections may not be appropriate as it tends to be multidrug-resistant. This study evaluated the relationship between appropriate EAT and the outcomes of Intensive Care Unit (ICU) patients with Acinetobacter bacteremia.
Methods: This is a retrospective study of patients admitted to a medical-surgical ICU (2005-2010) and developed Acinetobacter bacteremia during the stay. Patients were categorized according to EAT appropriateness, defined as administration of at least one antimicrobial agent to which the Acinetobacter was susceptible before susceptibility results were known. The relation between EAT appropriateness and outcomes was evaluated.
Results: Sixty patients developed Acinetobacter bacteremia in the 6-year period (age = 50 ± 19 years; 62% males; Acute Physiology and Chronic Health Evaluation II score = 28 ± 9; 98.3% with central lines; 67% in shock and 59% mechanically ventilated) on average on day 23 of ICU and day 38 of hospital stay. All isolates were resistant to at least three of the tested antimicrobials. Appropriate EAT was administered to 60% of patients, mostly as intravenous colistin. Appropriate EAT was associated with lower ICU mortality risk (odds ratio: 0.15; 95% confidence interval: 0.03-0.96) on multivariate analysis.
Conclusions: In this 6-year cohort, Acinetobacter bacteremia was related to multidrug-resistant strains. Appropriate EAT was associated with decreased ICU mortality risk.
Keywords: Acinetobacter , critical illness, treatment outcome
|How to cite this article:|
Al-Dorzi HM, Asiri AM, Shimemri A, Tamim HM, Al Johani SM, Dabbagh TA, Arabi YM. Impact of empirical antimicrobial therapy on the outcome of critically ill patients with Acinetobacter bacteremia. Ann Thorac Med 2015;10:256-62
|How to cite this URL:|
Al-Dorzi HM, Asiri AM, Shimemri A, Tamim HM, Al Johani SM, Dabbagh TA, Arabi YM. Impact of empirical antimicrobial therapy on the outcome of critically ill patients with Acinetobacter bacteremia. Ann Thorac Med [serial online] 2015 [cited 2020 Feb 25];10:256-62. Available from: http://www.thoracicmedicine.org/text.asp?2015/10/4/256/164302
Acinetobacter species is a strictly aerobic, Gram-negative coccobacillus that may cause pulmonary, bloodstream, urinary and surgical wound infections.  It is notorious as a nosocomial pathogen  and is capable of acquiring resistance against almost all currently available antibiotics through a variety of mechanisms such as acquisition of mobile genetic elements (integrons, plasmids, and transposons) and natural transformation.  In addition, Acinetobacter displays antibiotic resistance through efflux pumps, porin deficiency, and expression of antimicrobial degrading enzymes.  Typically, the multi-drug resistant (MDR) Acinetobacter shows characteristic patterns of resistance to multiple antimicrobials including aminoglycosides, antipseudomonal penicillins, carbapenems, cephalosporins, and quinolones.  This intrinsic antimicrobial resistance along with a resistance to desiccation  is responsible for outbreaks of Acinetobacter infections in clinical settings and makes this pathogen a high burden on healthcare. ,,
There is considerable dichotomy regarding the impact of Acinetobacter nosocomial infection on patient prognosis and length of stay in the Intensive Care Unit (ICU). Several groups have reported that Acinetobacter infections are associated with a higher mortality rate ,,,, while some investigators suggest that morbidity and mortality due to Acinetobacter are dependent on many variables and not due to the infection itself. , Since infections with MDR Acinetobacter strains are increasing, it can be expected that empirical treatment, which is commenced before susceptibility results are known, may be inappropriate. The main aim of this study was to describe the characteristics of critically ill patients who developed Acinetobacter bacteremia during ICU stay, study empirical antimicrobial use, and evaluate the relationship between appropriate empirical therapy and outcomes.
| Methods|| |
This was a retrospective study of all adult patients (age ≥18 years) who were admitted to the ICU of King Abdulaziz Medical City between January 1, 2005 and December 31, 2010 and developed Acinetobacter bacteremia while in the ICU. The hospital was a 900-bed tertiary-care referral center in Riyadh, Saudi Arabia and was accredited by Joint Commission International. The ICU was a 21-bed medical-surgical unit staffed by board-certified staff 24 h a day, 7 days per week  and admitted about 900 patients per year. In addition, the ICU service covered an 8-bed burn unit on a consultation basis usually for mechanical ventilation care and shock management. Clinical rounds were multidisciplinary and led by intensivists, some of whom were also infectious disease specialists, and included a clinical pharmacist. Decisions on antimicrobial therapy were usually made during these rounds. In our hospital, colistin was available as Colomycin (Dumex-Alpharma A/S, Copenhagen, Denmark). The hospital had an active infection control and prevention program with the ICU implementing ventilator-associated pneumonia and central line-associated bloodstream infection bundles.  The study was approved by the Institutional Review Board of the hospital.
Patients with nosocomial bloodstream infection  due to Acinetobacter were identified from the Microbiology Laboratory database as those who had at least one blood culture growing Acinetobacter species 48 h after hospital admission. Patients with the same blood culture growing >1 organism were excluded from the study to avoid confounding effect. Acinetobacter was identified to the species level using an automated system (MicroScan Walkaway, Simens ® ) that also provided antimicrobial susceptibility testing results according to the guidelines of the Clinical and Laboratory Standards Institute. The antimicrobial activity of colistin was provided as susceptible or resistant, based on minimal inhibitory concentration cut-off of ≤2 μg/mL and ≥4 μg/mL, respectively.
The antimicrobial susceptibility patterns of Acinetobacter species were recorded. The cultured Acinetobacter was considered to be MDR if the organism was resistant to three or more classes of the tested antimicrobial agents.  Specifically, the susceptibility of Acinetobacter to cephalosporins, antipseudomonal penicillins, carbapenems, quinolones, aminoglycosides, and colistin was recorded. Then, the medical records of ICU patients who developed Acinetobacter bacteremia were reviewed to evaluate the appropriateness of empirical antimicrobial therapy (EAT). Appropriate empirical antibiotic therapy was defined as the empirical administration of at least one antimicrobial agent to which the Acinetobacter strain was susceptible before susceptibility test results were known,  otherwise the therapy was considered inappropriate. Other recorded variables included age, gender, admission Acute Physiology and Chronic Health Evaluation II (APACHE II) score,  ICU admission category (medical, surgical, burn and trauma), reason for ICU admission, presence of shock, central lines and mechanical ventilation, and the main laboratory test results on the day of bacteremia, institution of a new do-not-resuscitate order during ICU stay, ICU and hospital length of stay and ICU and hospital mortality.
Data were analyzed using SAS software (version 9·0, SAS Institute, Cary, NC, USA). Continuous data were presented as medians with the first and third quartiles or as means with standard deviations, whereas categorical variables were summarized as numbers and percentages. Chi-square or Fisher's exact test was used to evaluate differences in categorical variables between groups. Similarly, the Student's t-test was used to assess differences in continuous variables. Multiple logistic regression analysis was used to evaluate factors associated with appropriate antimicrobial therapy. The studied factors were 2008-2010 versus 2005-2007 admission period, age, gender, APACHE II score, medical versus nonmedical admission, chronic illnesses, shock state, mechanical ventilation, central line, white blood cell and platelet counts, lactate, creatinine, and the international normalized ratio (INR). In addition, multivariate analysis was used to study whether appropriate empirical therapy predicted mortality. The clinically-relevant variables entered in the model were age, gender, APACHE II score, medical versus nonmedical admission, chronic illnesses, presence of shock, mechanical ventilation, creatinine, lactate, and INR. Results were presented as odds ratios (ORs) with 95% confidence interval (CI).
| Results|| |
A total of 60 patients developed Acinetobacter bacteremia during the ICU stay in the study period. [Table 1] describes the general patient profile. These patients had an average age of 50.4 ± 19.3 years, were predominantly males (56.7%) and admitted mostly for medical reasons and had high severity of illness (APACHE II score = 27.6 ± 8.6). Twelve (20%) patients had burns involving >40% of total body surface area and seven (11.7%) patients had solid organ transplant. Acinetobacter bacteremia occurred at variable frequency during the 6 years of the study period. There were 3 episodes in 2005, 11 in 2006, 16 in 2007 and 2008, 5 in 2009 and 9 in 2010. On average, Acinetobacter bacteremia occurred on the 23 rd day of ICU admission (Q1-Q3 = 6 th and 17 th day), which corresponded to the 38 th day of hospital admission (Q1-Q3 = 12 th and 34 th day). [Figure 1] describes the distribution of Acinetobacter bacteremia from ICU and hospital admission. Eleven (18.3%) patients had ≥2 blood cultures growing Acinetobacter.
|Figure 1: Distribution of Acinetobacter bacteremia from Intensive Care Unit and hospital admission|
Click here to view
|Table 1: Characteristics of the 60 patients who developed Acinetobacter bacteremia during stay in the ICU|
Click here to view
The characteristics of patients who received appropriate empirical therapy were largely not different from those who did not as shown in [Table 1]. At the time of bacteremia, 59.3% were mechanically ventilated, 98.3% had central venous catheters, and 66.7% of patients had a shock with elevated lactate (7.0 ± 6.5 mmol/L). In addition, they had high creatinine (140 ± 101 μmol/L) with 13 patients requiring renal replacement therapy. Three patients were on total parenteral nutrition. Fourteen patients had Acinetobacter cultured from a different source within the 14 days before bacteremia (7 from the respiratory tract, 1 from a wound, 3 from central line tips, none from the urine and 4 from other sites).
Forty percent of cultured Acinetobacter species were identified as baumannii. [Figure 2] describes the results for the antimicrobial susceptibilities of the cultured Acinetobacter. All cultured Acinetobacter were found to be resistant to at least 3 of the antimicrobials tested making them MDR. There were 44 Acinetobacter isolates that were resistant to five classes of antimicrobials. Only one (1.7%) isolate was resistant to colistin.
|Figure 2: Antimicrobial susceptibility of the isolated Acinetobacter species from the blood of 60 critically ill patients|
Click here to view
Despite being MDR, EAT for Acinetobacter bacteremia was appropriate in 36 (60.0%) patients and comprised of intravenous colistin in all except for 3 patients. In 6 patients, colistin was started a median of 7 days before the blood culture was taken. The mean daily colistin dose was 158 ± 32 mg (Q1-Q3 = 145 and 160 mg; Colomycin ® with each 160 mg equivalent to 2 million units). For patients requiring renal replacement therapy, it was 180 ± 47 mg. In other patients, the daily dose was 166 ± 26 mg for those with serum creatinine <121 μmol/L, the median of the cohort, and 148 ± 27 for those with creatinine ≥121 μmol/L. Colistin was combined with carbapenem in 27 patients and with antipseudomonal penicillin in 6 patients. For patients on inappropriate therapy (n = 24, 40% of patients), 17 were on carbapenems, 12 on quinolones, 6 on antipseudomonal penicillins, and 3 on aminoglycosides with 16 patients being on combination therapy. Factors associated with appropriate antimicrobial therapy were female gender (OR: 6.57; 95% CI: 1.48-29.21), admission in 2008-2010 versus the 2005-2007 period (OR: 5.36; 95% CI: 1.38-20.77), mechanical ventilation (OR: 4.19; 95% CI: 1.01-17.33) and age (OR: 0.96 per 1-year increment: 95% CI: 0.92-0.99).
Compared with nonsurvivors, ICU survivors had a lower APACHE II score (23.0 ± 10.0 vs. 29.8 ± 7.2, P = 0.006) at the time of admission. Survivors also had lower rates of medical admissions (40.0% vs. 67.5%, P = 0.04), and fewer had been either in shock (47.4% vs. 77.5%, P = 0.02) or on mechanical ventilation (32.3% vs. 74.4%, P = 0.003) at the time of bacteremia. The outcomes of patients are described in [Table 2] according to the appropriateness of empirical therapy. The ICU and hospital mortality rates were lower in the appropriate therapy group, but the difference was not statistically significant. However, appropriate empirical therapy was associated with lower ICU mortality risk (OR: 0.15; 95% CI: 0.03-0.96) on multivariate analysis. The other variables associated with ICU mortality were mechanical ventilation (OR: 8.99; 95% CI: 1.75-46.13) and serum lactate on the day of Acinetobacter bacteremia (OR: 1.21 per 1 mmol increment: 95% CI: 1.01-1.45).
|Table 2: The outcomes for the cohort patients who were received the appropriate empirical antimicrobial therapy versus inappropriate therapy|
Click here to view
| Discussion|| |
This retrospective cohort study of 60 adult critically ill patients who developed Acinetobacter bacteremia during ICU stay from January 2005 to December 2010 found a high prevalence of antimicrobial resistance among cultured Acinetobacter strains and showed that appropriate empirical antibiotic therapy was given only to 60% of patients and associated with reduced ICU mortality risk.
Acinetobacter bacteremia is mainly a nosocomial infection, mostly acquired in the ICU.  In our study, the overall occurrence of Acinetobacter bacteremia in our patient population was rare as only 60 cases were identified within a 6-year period in our ICU, which admitted approximately 900 patients annually. This relatively rare incidence has been seen in other studies. A prospective study in a Dutch university hospital between 1999 and 2006 found that the incidence of Acinetobacter isolates from all cultured specimens to be around 1.7-3.7 per 10,000 patient-days.  Another study evaluated nosocomial bloodstream infections from 1995 to 1998 at 49 US hospitals and found that infections caused by Acinetobacter species accounted for only 1.5% of all infections and were more likely to occur in ICUs. 
Risk factors for nosocomial Acinetobacter bacteremia are generally thought to be those of opportunistic infections.  A cohort study in a 40-bed medical and surgical ICU identified immunosuppressed state, respiratory failure at ICU admission, previous antimicrobial therapy, previous sepsis in the ICU, and the invasive procedures index as independent risk factors for Acinetobacter bacteremia.  Another study additionally found that burn infections preceded Acinetobacter bacteremia.  In burn patients, total body surface area burn of >50% was significantly associated with the development of Acinetobacter bacteremia.  In our study, Acinetobacter bacteremia occurred in patients several days after hospital and ICU admission, suggesting that prolonged stay and probably extended antimicrobial exposure were significant risk factors. Moreover, most patients had central venous catheters (98%) and required mechanical ventilation (61%) at the time of bacteremia and there was a high prevalence of burn and solid organ transplant patients in our cohort suggesting that these factors and conditions might also be important.
Importantly, all Acinetobacter cultures in this study were found to be MDR. The vast majority (90%) of cultured strains were resistant to carbapenems. This high rate of MDR strains has also been reported in other studies. ,,,, The susceptibility patterns of A. baumannii strains seem to be different according to study dates and geographical locations. A US study from 1995 to 1998 found that A. baumannii isolates were 100% susceptible to imipenem, 92% to tobramycin and 90% to amikacin.  More recently, a study from the UK showed increasing resistance to carbapenems from 0% in 1998 to 55% in 2006.  In Saudi Arabia, Acinetobacter isolates from a tertiary-care ICU had decreasing susceptibility patterns from 2004 to 2009.  For instance, the susceptibility to imipenem decreased from 55% to 10% (P < 0.001) and to meropenem from 33% to 10% (P < 0.001).  In our study, we found limited resistance (1.7% of isolates) to colistin. Nevertheless, resistance in A. baumannii to colistin is an emerging problem. ,, Regional colistin resistance ranged between 1.8% and 12%. ,
It can be logically expected that the presence of high rates of resistance to multiple antimicrobials would lead to high rates of inappropriate EAT. In a Turkish study, the initial antimicrobial treatment was appropriate in only 19.7% of patients with imipenem-resistant A. baumannii bacteremia.  In a study from Taiwan, inappropriate EAT for Acinetobacter junii bacteremia occurred in 53.5%.  However, in our study, appropriate therapy was colistin-based, correctly administered in 60% of patients and more common in the 2008-2010 admission period than the preceding 3 years suggesting that the ability of the treating intensivists to predict and treat MDR pathogens as the cause of ICU-acquired septic shock improved with time. Prior cultures from other sites growing Acinetobacter might be another reason for the administration of appropriate empirical therapy.
In our study, Acinetobacter bacteremia was associated with high morbidity and mortality. A retrospective matched cohort study of 45 ICU patients with A. baumannii bacteremia and 90 matched controls found that A. baumannii bacteremia was associated with 5 additional days of ICU stay, longer duration of mechanical ventilation than controls,  but not with mortality (hazard ratio: 0.96; 95% CI: 0.67-1.38).  The attributable mortality was estimated at 7.8%.  A systematic review of 6 matched case-control studies which examined the attributable mortality from infection with or acquisition of A. baumannii found that the attributable ICU mortality ranged from 10% to 43% and hospital mortality from 7.8% to 23%.  The relationship between the appropriateness of empirical therapy and outcomes of Acinetobacter infections showed mixed results. Zaragoza et al. failed to attribute inappropriate empirical therapy to increased patient mortality in Acinetobacter related nosocomial infections.  Falagas et al. also found no significant difference in the mortality of patients who had appropriate or inappropriate treatment.  In contrast, Erbay et al. found that mortality was statistically greater for patients receiving inappropriate initial antimicrobial treatment within 48 h compared with appropriate initial treatment (65.0% vs. 39.5%; P = 0.011).  Similarly, Choi et al. found that inappropriate antimicrobial therapy within 72 h was associated with higher mortality compared to appropriate therapy (40% vs. 8%; P = 0.007) with OR = 6.6 (95% CI: 1.7-26.0).  A recent systematic review on the relation between antimicrobial resistance and the mortality associated with Acinetobacter infections showed that inappropriate antimicrobial therapy was associated with adjusted OR of mortality that ranged between 1.39 and 8.05.  We found that appropriate empirical therapy was associated with decreased ICU mortality risk. In general, appropriate antimicrobial therapy has been shown to improve the outcomes of patients with severe sepsis or septic shock. , The absence of association between appropriate empirical therapy and decreased mortality in some studies can be due to the ineffectiveness of drugs such as intravenous colistin against MDR Acinetobacter,  which could be due to levels below the minimal inhibitory concentration at the recommended doses.  The timing of appropriate antimicrobial therapy might also be very important.  Of note, Erbay et al. used a 48 h interval for establishing the appropriateness of treatment  while Falagas et al.  used a 72 h interval. Our study suggests that the reported poor outcomes of Acinetobacter bacteremia may be related in part to the inappropriate empiric antimicrobial therapy, the delay in administering the appropriate regimen and the inadequate dosing. We used a pragmatic long window, until susceptibility results were available, for defining appropriate empirical therapy. However, evidence suggests that each hour delay in the administration of appropriate antimicrobials adds substantially to the mortality of septic patients.  The Surviving Sepsis Campaign recommends the administration of antibiotics within 1 h for patients with severe sepsis and septic shock.  This is probably true for Acinetobacter sepsis as well. In addition, there is considerable debate about including colistin in the empiric antimicrobial regimen because of concerns about inducing resistance. However, this concern must be weighed against the benefit of early and appropriate institution of antimicrobial therapy. Administering the correct dose of colistin is also important. There are two forms of colistin, colistin base and its produrg colistimethate sodium (also known as sodium colistin methanesulphonate, colistin methanesulfonate, and colistin sulfomethate), with different dosing recommendations.  Colistin base has a potency of 30,000 IU/mg, whereas colistimethate sodium has a potency of 12,500 IU/mg.  This may confuse physicians and lead to inappropriate dosing.  Actually, optimal colistin dose for the treatment of MDR Gram-negative bacterial infections in the ICU is still unknown as its pharmacokinetic and pharmacodynamic data are scarce in this setting.  Loading and higher maintenance doses, increased administration frequency or its use as part of combination therapy may be needed to increase colistin effectiveness. , A study in critically ill patients demonstrated that colistimethate sodium monotherapy was unable to achieve adequate plasma concentrations of colistin base.  Further studies are needed to examine the most effective colistin compound, dosing frequency, whether the dose selection should be based on the minimal inhibitory concentrations and the clinical utility of serum colistin levels in guiding dosing. Obviously, there is a growing need for other antimicrobials for the treatment of MDR Acinetobacter infections. Tigecycline and minocycline may be good candidates.  However, data on their effectiveness are lacking, and tigecycline resistance is emerging and has reached 43% in Saudi Arabia. 
This study should be interpreted in the light of its strengths and limitations. The limitations of this study include its retrospective nature and the small number of the patients. Further, it analyzed data from critically ill patients from one center, so the results may not be generalizable. The mortality rate was high for both appropriate and inappropriate antimicrobial therapy groups, which makes the interpretation of results difficult.
| Conclusion|| |
All episodes of Acinetobacter bacteremia occurring in this 6-year cohort were related to MDR strains and had a poor prognosis. Appropriate EAT was administered in 60% of patients and associated with decreased ICU mortality risk. The study highlights the seriousness of Acinetobacter bacteremia and suggests that the poor outcomes of patients with Acinetobacter bacteremia may have been related, at least in part, to inappropriate and delayed antimicrobial therapy as well as inadequate dosing.
| References|| |
Bergogne-Bérézin E, Towner KJ. Acinetobacter
spp. as nosocomial pathogens: Microbiological, clinical, and epidemiological features. Clin Microbiol Rev 1996;9:148-65.
Gaynes R, Edwards JR, National Nosocomial Infections Surveillance System. Overview of nosocomial infections caused by Gram-negative bacilli
. Clin Infect Dis 2005;41:848-54.
Fournier PE, Richet H. The epidemiology and control of Acinetobacter baumannii
in health care facilities. Clin Infect Dis 2006;42:692-9.
Van Looveren M, Goossens H, ARPAC Steering Group. Antimicrobial resistance of Acinetobacter
spp. in Europe. Clin Microbiol Infect 2004;10:684-704.
Gootz TD, Marra A. Acinetobacter baumannii
: An emerging multidrug-resistant threat. Expert Rev Anti Infect Ther 2008;6:309-25.
Jawad A, Heritage J, Snelling AM, Gascoyne-Binzi DM, Hawkey PM. Influence of relative humidity and suspending menstrua on survival of Acinetobacter
spp. on dry surfaces. J Clin Microbiol 1996;34:2881-7.
Hsueh PR, Teng LJ, Chen CY, Chen WH, Yu CJ, Ho SW, et al.
Pandrug-resistant Acinetobacter baumannii
causing nosocomial infections in a university hospital, Taiwan. Emerg Infect Dis 2002;8:827-32.
Villegas MV, Hartstein AI. Acinetobacter
outbreaks, 1977-2000. Infect Control Hosp Epidemiol 2003;24:284-95.
Centers for Disease Control and Prevention (CDC). Acinetobacter baumannii
infections among patients at military medical facilities treating injured U.S. service members, 2002-2004. MMWR Morb Mortal Wkly Rep 2004;53:1063-6.
Sunenshine RH, Wright MO, Maragakis LL, Harris AD, Song X, Hebden J, et al.
infection mortality rate and length of hospitalization. Emerg Infect Dis 2007;13:97-103.
Erbay A, Idil A, Gözel MG, Mumcuoglu I, Balaban N. Impact of early appropriate antimicrobial therapy on survival in Acinetobacter baumannii
bloodstream infections. Int J Antimicrob Agents 2009;34:575-9.
Lee NY, Lee HC, Ko NY, Chang CM, Shih HI, Wu CJ, et al.
Clinical and economic impact of multidrug resistance in nosocomial Acinetobacter baumannii
bacteremia. Infect Control Hosp Epidemiol 2007;28:713-9.
Zaragoza R, Artero A, Camarena JJ, Sancho S, González R, Nogueira JM. The influence of inadequate empirical antimicrobial treatment on patients with bloodstream infections in an Intensive Care Unit. Clin Microbiol Infect 2003;9:412-8.
Falagas ME, Rafailidis PI. Attributable mortality of Acinetobacter baumannii
: No longer a controversial issue. Crit Care 2007;11:134.
Daniels TL, Deppen S, Arbogast PG, Griffin MR, Schaffner W, Talbot TR. Mortality rates associated with multidrug-resistant Acinetobacter baumannii
infection in surgical Intensive Care Units. Infect Control Hosp Epidemiol 2008;29:1080-3.
Trottier V, Namias N, Pust DG, Nuwayhid Z, Manning R, Marttos AC Jr, et al.
Outcomes of Acinetobacter baumannii
infection in critically ill surgical patients. Surg Infect (Larchmt) 2007;8:437-43.
Arabi Y, Alshimemeri A, Taher S. Weekend and weeknight admissions have the same outcome of weekday admissions to an Intensive Care Unit with onsite intensivist coverage. Crit Care Med 2006;34:605-11.
Al-Dorzi HM, El-Saed A, Rishu AH, Balkhy HH, Memish ZA, Arabi YM. The results of a 6-year epidemiologic surveillance for ventilator-associated pneumonia at a tertiary care Intensive Care Unit in Saudi Arabia. Am J Infect Control 2012;40:794-9.
Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control 2008;36:309-32.
Falagas ME, Karageorgopoulos DE. Pandrug resistance (PDR), extensive drug resistance (XDR), and multidrug resistance (MDR) among Gram-negative bacilli
: Need for international harmonization in terminology. Clin Infect Dis 2008;46:1121-2.
Kollef MH, Sherman G, Ward S, Fraser VJ. Inadequate antimicrobial treatment of infections: A risk factor for hospital mortality among critically ill patients. Chest 1999;115:462-74.
Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: A severity of disease classification system. Crit Care Med 1985;13:818-29.
Wareham DW, Bean DC, Khanna P, Hennessy EM, Krahe D, Ely A, et al.
Bloodstream infection due to Acinetobacter
spp: Epidemiology, risk factors and impact of multi-drug resistance. Eur J Clin Microbiol Infect Dis 2008;27:607-12.
van den Broek PJ, van der Reijden TJ, van Strijen E, Helmig-Schurter AV, Bernards AT, Dijkshoorn L. Endemic and epidemic Acinetobacter
species in a university hospital: An 8-year survey. J Clin Microbiol 2009;47:3593-9.
Wisplinghoff H, Edmond MB, Pfaller MA, Jones RN, Wenzel RP, Seifert H. Nosocomial bloodstream infections caused by Acinetobacter
species in United States hospitals: Clinical features, molecular epidemiology, and antimicrobial susceptibility. Clin Infect Dis 2000;31:690-7.
Joly-Guillou ML. Clinical impact and pathogenicity of Acinetobacter
. Clin Microbiol Infect 2005;11:868-73.
García-Garmendia JL, Ortiz-Leyba C, Garnacho-Montero J, Jiménez-Jiménez FJ, Pérez-Paredes C, Barrero-Almodóvar AE, et al.
Risk factors for Acinetobacter baumannii
nosocomial bacteremia in critically ill patients: A cohort study. Clin Infect Dis 2001;33:939-46.
Tilley PA, Roberts FJ. Bacteremia with Acinetobacter
species: Risk factors and prognosis in different clinical settings. Clin Infect Dis 1994;18:896-900.
Wisplinghoff H, Perbix W, Seifert H. Risk factors for nosocomial bloodstream infections due to Acinetobacter baumannii
: A case-control study of adult burn patients. Clin Infect Dis 1999;28:59-66.
Al-Sweih NA, Al-Hubail MA, Rotimi VO. Emergence of tigecycline and colistin resistance in Acinetobacter
species isolated from patients in Kuwait hospitals. J Chemother 2011;23:13-6.
Chang KC, Lin MF, Lin NT, Wu WJ, Kuo HY, Lin TY, et al.
Clonal spread of multidrug-resistant Acinetobacter baumannii
in eastern Taiwan. J Microbiol Immunol Infect 2012;45:37-42.
Al Johani SM, Akhter J, Balkhy H, El-Saed A, Younan M, Memish Z. Prevalence of antimicrobial resistance among Gram-negative isolates in an adult Intensive Care Unit at a tertiary care center in Saudi Arabia. Ann Saudi Med 2010;30:364-9.
Baadani AM, Thawadi SI, El-Khizzi NA, Omrani AS. Prevalence of colistin and tigecycline resistance in Acinetobacter baumannii
clinical isolates from 2 hospitals in Riyadh Region over a 2-year period. Saudi Med J 2013;34:248-53.
Tsai HY, Cheng A, Liu CY, Huang YT, Lee YC, Liao CH, et al.
Bacteremia caused by Acinetobacter
junii at a medical center in Taiwan, 2000-2010. Eur J Clin Microbiol Infect Dis 2012;31:2737-43.
Blot S, Vandewoude K, Colardyn F. Nosocomial bacteremia involving Acinetobacter baumannii
in critically ill patients: A matched cohort study. Intensive Care Med 2003;29:471-5.
Falagas ME, Bliziotis IA, Siempos II. Attributable mortality of Acinetobacter baumannii
infections in critically ill patients: A systematic review of matched cohort and case-control studies. Crit Care 2006;10:R48.
Falagas ME, Kasiakou SK, Rafailidis PI, Zouglakis G, Morfou P. Comparison of mortality of patients with Acinetobacter baumannii
bacteraemia receiving appropriate and inappropriate empirical therapy. J Antimicrob Chemother 2006;57:1251-4.
Choi JY, Park YS, Kim CO, Park YS, Yoon HJ, Shin SY, et al.
Mortality risk factors of Acinetobacter baumannii
bacteraemia. Intern Med J 2005;35:599-603.
Lemos EV, de la Hoz FP, Einarson TR, McGhan WF, Quevedo E, Castañeda C, et al.
Carbapenem resistance and mortality in patients with Acinetobacter baumannii
infection: Systematic review and meta-analysis. Clin Microbiol Infect 2014;20:416-23.
Kumar A, Ellis P, Arabi Y, Roberts D, Light B, Parrillo JE, et al.
Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest 2009;136:1237-48.
Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, et al.
Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006;34:1589-96.
Metan G, Sariguzel F, Sumerkan B. Factors influencing survival in patients with multi-drug-resistant Acinetobacter
bacteraemia. Eur J Intern Med 2009;20:540-4.
Li J, Nation RL, Turnidge JD, Milne RW, Coulthard K, Rayner CR, et al.
Colistin: The re-emerging antibiotic for multidrug-resistant Gram-negative bacterial infections. Lancet Infect Dis 2006;6:589-601.
Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, et al.
Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008;36:296-327.
Michalopoulos A, Falagas ME. Colistin and polymyxin B in critical care. Crit Care Clin 2008;24:377-91, x.
Michalopoulos AS, Falagas ME. Colistin: Recent data on pharmacodynamics properties and clinical efficacy in critically ill patients. Ann Intensive Care 2011;1:30.
Garonzik SM, Li J, Thamlikitkul V, Paterson DL, Shoham S, Jacob J, et al.
Population pharmacokinetics of colistin methanesulfonate and formed colistin in critically ill patients from a multicenter study provide dosing suggestions for various categories of patients. Antimicrob Agents Chemother 2011;55:3284-94.
Pogue JM, Neelakanta A, Mynatt RP, Sharma S, Lephart P, Kaye KS. Carbapenem-resistance in Gram-negative bacilli
and intravenous minocycline: An antimicrobial stewardship approach at the Detroit Medical Center. Clin Infect Dis 2014;59 Suppl 6:S388-93.
Saeed NK, Kambal AM, El-Khizzi NA. Antimicrobial-resistant bacteria in a general Intensive Care Unit in Saudi Arabia. Saudi Med J 2010;31:1341-9.
[Figure 1], [Figure 2]
[Table 1], [Table 2]
| Article Access Statistics|
| Viewed||2346 |
| Printed||52 |
| Emailed||0 |
| PDF Downloaded||288 |
| Comments ||[Add] |