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 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 1  |  Issue : 2  |  Page : 55-59

Determinants of multidrug-resistant Acinetobacter sepsis in critically ill patients: A comparative study


1 Department of ICU, Bahrain Defence Force Hospital, Riffa, Kingdom of Bahrain
2 Department of Critical Care Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

Date of Web Publication7-Nov-2017

Correspondence Address:
Khadija Hamed
Department of ICU, Bahrain Defence Force Hospital, Riffa
Kingdom of Bahrain
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/sccj.sccj_15_17

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  Abstract 

Introduction and Background: The incidence of Acinetobacter infections has steadily increased and now has become a major threat with the emergence of its multidrug-resistant strains. Acinetobacter is notorious for their ability to spread among hospitalized patients. This study attempts to identify the intensive care unit (ICU) variables predictive of Acinetobacter sepsis. Methods: In this case–control study, we extracted data from a prospectively collected ICU database on all patients admitted with a diagnosis of sepsis from 2010 to 2015. Data identifying all Acinetobacter isolates were obtained from the section of microbiology database. Patients with Acinetobacter sepsis were compared with control patients. Approval was obtained from the Institutional Research Ethics Committee. Results: Four hundred and thirty-one patients were studied and 43 (9.9%) developed Acinetobacter sepsis. Mean APACHE II score was 26 ± 7.7; median procalcitonin level was 3.9 (interquartile range [IQR] 1.1, 18.4). Mean age was 52.5 ± 21.4 years with median ICU length of stay 6 (IQR 4, 43) days. ICU mortality was 23% (99 patients) with mortality rate of patients with Acinetobacter sepsis at 60.5% (26 patients of 43). Patients who developed Acinetobacter sepsis had a mean SOFA score 14.1 ± 3.7 with 46.5% in septic shock, 9% organ donors, and 7% postsolid organ transplant. The most common site of isolation was the respiratory tract, 34.6%, followed by bloodstream/line sepsis, 30.8%; 32.5% had a single site infected. Median duration on mechanical ventilation was 15.3 (IQR 7, 15.3) days. On univariate regression analysis, multidrug-resistant Acinetobacter sepsis was predicted by vasopressor use, odds ratio (OR) 4.1 (95% confidence interval [CI] 1.6, 9.9, P = 0.002), bloodstream infection, OR 6.3 (95% CI 3.2, 12.4, P < 0.001), single site of initial sepsis, OR 0.4 (95% CI 0.2, 0.9, P = 0.02), APACHE II score, OR 1.05 (95% CI 1.01, 1.1, P = 0.01), malignancy, OR 6 (95% CI 2.2, 15.7, P < 0.001), and appropriate empiric antibiotics, OR 0.04 (95% CI 0.01, 0.15, P < 0.001). On multivariate regression, appropriate empiric antibiotics, OR 0.04 (95% CI 0.01, 0.13, P < 0.001), vasopressor use, OR 3.1 (95% CI 1.07, 9.2, P = 0.03), bloodstream infection, OR 7.5 (95% CI 3.2, 17.4, P < 0.001), and single site of initial sepsis, OR 0.1 (95% CI 0.07, 0.4, P < 0.001) remained significant predictors of Acinetobacter sepsis. Conclusions: Acinetobacter sepsis remains a frequent and hazardous ICU acquisition with a higher risk imposed by continued vasoplegia and septicemia and protective effects from appropriate initial antibiotic coverage and limited sites involved. This study attempts to identify ICU variables predictive of Acinetobacter sepsis.

Keywords: Acinetobacter baumannii, bloodstream infection, intensive care unit, multidrug resistant, risk factors


How to cite this article:
Hamed K, Albadi N, Mahmood WA, Althawadi SI, Al-Hosaini S, Salahuddin N. Determinants of multidrug-resistant Acinetobacter sepsis in critically ill patients: A comparative study. Saudi Crit Care J 2017;1:55-9

How to cite this URL:
Hamed K, Albadi N, Mahmood WA, Althawadi SI, Al-Hosaini S, Salahuddin N. Determinants of multidrug-resistant Acinetobacter sepsis in critically ill patients: A comparative study. Saudi Crit Care J [serial online] 2017 [cited 2017 Nov 18];1:55-9. Available from: http://www.sccj-sa.org/text.asp?2017/1/2/55/217807


  Introduction Top


Acinetobacter baumannii (AB) are aerobic Gram-negative bacilli that can cause health care-associated infections and can survive for prolonged periods in the environment and on the hands of health-care workers. The proportion of health care-associated infections caused by Acinetobacter spp. has increased over the past decade. Furthermore, AB infections have become increasingly difficult to treat because of the emergence of strains resistant to all drugs or all but one commonly prescribed antimicrobial drug. These multidrug-resistant (MDR) strains are sometimes susceptible only to polymyxins (colistin and polymyxin B), a class of antimicrobial drugs that has not been in widespread use for several decades and is more toxic than most currently used antimicrobial drugs.

AB complex, which has a great propensity for epidemic spread, has emerged as a common pathogen of health care-associated infections and poses a growing threat to public health.[1] An even more serious situation is the increasing rate of MDR among AB complex, which usually leads to high treatment failure.[2] Patients with MDR AB complex bacteremia had a significantly lower survival rate than those with non-MDR AB complex bacteremia. Outbreaks caused by MDR Acinetobacter have been reported in hospitals all over the world; more recently, they have become a serious problem in medical facilities; as MDR AB complex bacteremia usually leads to worse outcomes, factors related to MDR acquisition in these bacteria should be identified [Figure 1] and [Figure 2].
Figure 1: Relationship between incidence of MDR Acinetobacter sepsis and number of infected sites. Category 1=Single site of sepsis, Category 2=2 sites of sepsis, Category 3=3 sites of sepsis, Category 4=>3 sites

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Figure 2: Diagnosis by Category

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Outbreaks caused by MDR Acinetobacter have been reported in hospitals all over the world; more recently, they have become a serious problem in medical facilities; as MDR AB complex bacteremia usually leads to worse outcomes, factors related to MDR acquisition in these bacteria should be identified.

According to several similar studies conducted in different regions, the risk factors for MDR acquisition in AB complex bacteremia may include the severity of the host's condition, antimicrobial consumption, and infection control practices.

In addition to more severe health conditions in patients in the intensive care unit (ICU) settings, cross-contamination, to a large extent, is associated with the high drug-resistant rate, which has been demonstrated by previous molecular epidemiology research and numerous outbreaks of MDR isolates in critical centers.

Accordingly, to avoid the transmission of environmental organisms to patients from contaminated hands of medical staffs and equipment, it is of great necessity and importance to reinforce the infection control strategies, especially in the ICU. Meanwhile, we cannot ignore the impact of carbapenem abuse in the acquisition of drug resistance. Consumption of antibiotics has already been shown to be well correlated with increased microbial resistance.

Several previous studies focusing on carbapenem-resistant AB complex have shown that prior exposure to carbapenem increases the risk of acquiring carbapenem-resistant AB complex infection. Therefore, judicious prescribing of carbapenem with strict antibiotic stewardship is critical for controlling MDR AB complex infections.

Awareness of the risk factors would help predict bacteremia in colonized patients and allow administration of appropriate antibiotics before culture results are reported. Delay in appropriate antimicrobial therapy has an adverse influence on the clinical outcome of patients with AB bacteremia.[3],[4],[5]

Data regarding predictors of MDR Acinetobacter sepsis in the Kingdom of Saudi Arabia are limited. Therefore, the aim of this study was to identify ICU care variables predictive of MDR Acinetobacter sepsis in King Faisal Specialist Hospital in Riyadh.


  Methods Top


Study design and setting

This was a case–control study conducted in King Faisal Specialist Hospital and Research Centre in Riyadh, which is an adult tertiary care facility admitting both medical and surgical patients to 49 ICU beds. Data on all patients admitted with diagnosis of sepsis from to 2010 to 2015 were extracted from a prospectively collected ICU database. MDR Acinetobacter isolates from the ICU were identified from the microbiology database.

Information retrieved from medical records included demographics, potential risk factors for developing MDR AB bacteremia, the clinical management, and the potential risk factors for death among the patients contracting AB bacteremia. The following data were recorded: age, sex, diagnosis, referral from another hospital, date of hospital admission, date of ICU admission, days on mechanical ventilation, date of discharge from ICU, APACHE score, SOFA score, source of infection, organism, use of vasopressors, risk factors, reintubation, and the antibiotics that were used.

Definitions

Acinetobacter sepsis was defined on the basis of the isolation of one or more microorganisms from blood cultures 48 h after admission to the ICU with systemic inflammatory response syndrome (SIRS). SIRS was defined as the presence of microbes or their toxins in the blood or two or more of the following conditions: (1) body temperature >38°C or <36°C; (2) leukocytosis (>10,000/mm 3), leukopenia (<4000/mm 3), or >10% bands; (3) heart rate >90 beats/min; or (4) respiratory rate >24 breaths/min.

The microorganism was defined as MDR if it was not susceptible to more than three of the following eight antimicrobial agents: ampicillin/sulbactam, aztreonam, ceftazidime, ciprofloxacin, gentamicin, imipenem, piperacillin, and trimethoprim/sulfamethoxazole.[4]

Antibiotic sensitivity was determined using the disc diffusion method, according to the Clinical and Laboratory Standards Institute guidelines.

Consent and permission

The Institutional Research Ethics Committee of King Faisal Specialist Hospital and Research Centre approved the protocol and gave permission to perform the study. ORA OFFICIAL COMMUNICATION: RAC PROJECT NO. 2161 105.

Statistical analysis

Continuous variables were compared using the Student's t-test or the Mann–Whitney U-test as appropriate. Categorical variables were calculated using a Chi-square test or Fisher's exact test as appropriate.

Univariate analysis was used to identify significant factors for MDR acquisition and mortality, with results presented as odds ratios (ORs) and 95% confidence intervals (95% CI). Independent covariates with P < 0.10 were included in a multivariate logistic regression analysis. All tests of significance were two-sided, and significance was set at P < 0.05. Statistical analyses were performed using SPSS software (version 18.0, SPSS Inc., Chicago, IL, USA).


  Results Top


Four hundred and thirty-one patients were studied and 43 (10%) developed MDR Acinetobacter sepsis. Mean APACHE II score was 26 ± 7.7. Median procalcitonin was 3.9 (interquartile range [IQR] 1.1, 18.4); mean age was 52 ± 21.4 years with median ICU length of stay (LOS) 6 days (IQR 4,43); ICU mortality was 23% (99 patients); patients who developed Acinetobacter had a mortality rate of 60.5% (26 of 43 patients).

Patients who developed multidrug-resistant (MDR) Acinetobacter had a mean SOFA score of 14.1 ± 3.7 with 46.5% in septic shock, 9% organ donor, and 7% postsolid organ transplant. Most common site of isolation was respiratory tract 34.6% followed by bloodstream/line sepsis 30.8%; 32% had single infected site. Median duration on mechanical ventilation was 15.3 (IQR 7, 15.3) days.

MDR Acinetobacter sepsis was predicted by vasopressor use, OR 4.1 (95% CI 1.6,9.9 P = 0.002), bloodstream infection, OR 6.3 (95% CI 3.2, 12.4 P < 0.001), single site of initial sepsis, OR 0.4 (95% CI 0.2, 0.9 P = 0.02), APACHE II score, OR 1.05 (95% CI 1.01,1.1 P + 0.01), malignancy, OR 6 (95% CI 2.2, 15.7 P< 0.001), and appropriate empiric antibiotics, OR 0.04 (95% CI 0.01.0.15 P< 0.001) (refer to [Table 1]).
Table 1: Predictors of MDR Acinetobacter sepsis after multivariate regression analysis

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Appropriate empiric antibiotics, OR 0.04 (95% CI 0.01, 0.13 P < 0.001), vasopressor dependence, OR 3.1 (95% CI 1.07, 9.2 P = 0.03), bloodstream infection, OR 7.5% (95% CI 3.2, 17.4 P < 0.001), and single site of initial sepsis, OR 0.1 (95% CI 0.07, 0.4 P < 0.001), remained significant predictors of MDR Acinetobacter sepsis after multivariate regression analysis.


  Discussion Top


Four hundred and thirty-one patients were included in our study and 43 (10%) developed MDR Acinetobacter sepsis. The results show that MDR Acinetobacter sepsis was predicted by vasopressor use, bloodstream infection, single site of initial sepsis, APACHE II score, malignancy, and appropriate empiric antibiotics. Some of these variables were consistent with the previous studies.

Most of these potential risk factors have been identified by univariate analysis but are not part of a case–control study and thus may simply reflect underlying disease severity or a need for critical care.

Risk factors for MDR AB bacteremia in the ICU have previously been demonstrated with case–control and cohort methodologies, but our sample size was larger. Multivariate analysis identified male gender, APACHE II score, LOS in the ICU, mechanical ventilation, prior infection, antimicrobial therapy, prior colonization, and colonization pressure as independent risk factors for AB bacteremia.[6],[7],[8]

A retrospective, observational study of 200 patients with MDR Acinetobacter was done in a university hospital in South Korea from January 2008 to December 2009 to determine risk factors for MDR Acinetobacter nosocomial bacteremia in patients colonized with MDR Acinetobacter after ICU admission. Our study showed that the presence of infection and respiratory failure at the time of ICU admission, recent central venous catheter insertion, bacteremia caused by other microorganisms after colonization by MDR Acinetobacter, and prior antimicrobial therapy were the independent risk factors for MDR Acinetobacter bacteremia. Moreover, combined factors of maintenance on a mechanical ventilator and maintenance of an endotracheal tube instead of switching to a tracheostomy increased the risk of MDR Acinetobacter bacteremia.[9]

A previous study using the Therapeutic Intervention Scoring System suggested that the high workload in a high-risk unit (surgical ICU) contributed to imipenem-resistant AB acquisition.[10]

Another study done in a tertiary hospital in China which found that increased LOS in ICU, increased Pittsburgh bacteremia score, and prior use of carbapenem were independent risk factors associated with MDR AB complex bacteremia.

Older age, being posttransplantation, higher Pittsburgh bacteremia score, and lower level of albumin were identified as independent risk factors for 30-day mortality in patients with MDR AB complex bacteremia. Pittsburgh score, a grading system consisting of five items (mental status, fever, hypertension, mechanical ventilation, and cardiac arrest), was used to assess the severity of illness, and this has previously been shown to be highly predictive of prognosis of bacteremia caused by Pseudomonas and Enterobacter.[11]

Another hospital-based case–control study was conducted in patients admitted to Siriraj Hospital, Bangkok, Thailand, between January 1, 2005, and December 31, 2005. The study population consisted of 155 cases with MDR AB nosocomial infection and 310 controls without nosocomial infection. The cases were matched with controls by age and ward of admission with a ratio of 1:2.

They found that duration of admission before MDR AB nosocomial infection >1 week, indwelling urinary catheter >1 week, mechanical ventilation >1 week, central venous line >1 week, nasogastric intubation >1 week, prior administration of the 3rd–4th-generation cephalosporins, metronidazole and piperacillin-tazobactam was closely related to MDR AB nosocomial infection.[12]

Another study was conducted in China from January 2010 to June 2011; active screening was performed to define patients with respiratory ICU (RICU)-acquired colonization of MDR AB. Moreover, environment surveillance was carried out and patient data were collected. Logistic regression was applied to identify the risk factors of RICU-acquired colonization of MDR AB. Five risk factors were associated with the colonization of MDR AB through univariate analysis: consciousness disturbance, use of carbapenems, nasal feeding tube, endotracheal intubation, and mechanical ventilation.[13]

It is now speculated that the greater probability of inappropriate empirical antibiotic therapy and the delay in the administration of appropriate antibiotic therapy, rather than the enhanced virulence of this pathogen, has resulted in more severe conditions and worse prognosis for patients with MDR AB complex bacteremia.[14]

Our study should be interpreted with caution given its several limitations. First, our data were collected from a single center which limits the applicability of our results to other geographical areas or institutions. Second, our research focused on investigating the factors associated with the acquisition of MDR among AB complex bacteremia. However, the decision for empiric therapy against MDR AB infection needs to identify the risk factors of both MDR acquisition and AB complex bacteremia. In that situation, a case–control study might be more effective in guiding clinical practice.


  Conclusions Top


MDR Acinetobacter sepsis remains a frequent and hazardous ICU acquisition with higher risks imposed by continuous vasoplegia and septicemia and protective effects from appropriate initial antibiotic coverage and limited sites involvement. This study also suggests that infection or colonization with MDR Acinetobacter is associated with increased mortality.

Emphasis needs to be placed on prevention, strict application of infection control, and appropriate use of antibiotics, all of which might reduce the risk and improve the control of this infection.

Knowledge of the predictors for this serious infection will allow us to be more meticulous and starting empirical antibiotics earlier till the results of the cultures are ready to prevent further harm.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

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Sunenshine RH, Wright MO, Maragakis LL, Harris AD, Song X, Hebden J, et al. Multidrug-resistant Acinetobacter infection mortality rate and length of hospitalization. Emerg Infect Dis 2007;13:97-103.  Back to cited text no. 1
    
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Kwon KT, Oh WS, Song JH, Chang HH, Jung SI, Kim SW, et al. Impact of imipenem resistance on mortality in patients with Acinetobacter bacteraemia. J Antimicrob Chemother 2007;59:525-30.  Back to cited text no. 3
    
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Shih MJ, Lee NY, Lee HC, Chang CM, Wu CJ, Chen PL, et al. Risk factors of multidrug resistance in nosocomial bacteremia due to Acinetobacter baumannii: A case-control study. J Microbiol Immunol Infect 2008;41:118-23.  Back to cited text no. 7
    
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Lee SO, Kim NJ, Choi SH, Hyong Kim T, Chung JW, Woo JH, et al. Risk factors for acquisition of imipenem-resistant Acinetobacter baumannii: A case-control study. Antimicrob Agents Chemother 2004;48:224-8.  Back to cited text no. 9
    
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Zhou J, Qian C, Zhao M, Yu X, Kang Y, Ma X, et al. Epidemiology and outcome of severe sepsis and septic shock in Intensive Care Units in mainland China. PLoS One 2014;9:e107181.  Back to cited text no. 11
    
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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.  Back to cited text no. 12
    
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Wang HL, Sui WJ, Wang JR, Wang M, Huang YF, Gu HT, et al. Risk factors for acquired multidrug-resistant Acinetobacter baumannii colonization in respiratory Intensive Care Unit. Zhonghua Yi Xue Za Zhi 2012;92:960-3.  Back to cited text no. 13
    
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