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  Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 38  |  Issue : 1  |  Page : 24-31
 

Mortality from acinetobacter infections as compared to other infections among critically ill patients in South India: A prospective cohort study


1 Department of Medicine, Christian Medical College, Vellore, Tamil Nadu, India
2 Hospital Infection Control Committee, Christian Medical College, Vellore, Tamil Nadu, India
3 Department of Clinical Microbiology, Christian Medical College, Vellore, Tamil Nadu, India
4 Department of Medicine, Division of Critical Care, Christian Medical College, Vellore, Tamil Nadu, India
5 Microbiology, Christian Medical College, Vellore, Tamil Nadu, India

Date of Submission26-Dec-2019
Date of Decision18-Feb-2020
Date of Acceptance30-Apr-2020
Date of Web Publication25-Jul-2020

Correspondence Address:
Dr. Ajoy Oommen John
Department of Medicine, Christian Medical College, Vellore - 632 004, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmm.IJMM_19_492

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 ~ Abstract 


Background: Acinetobacter baumannii has become a common pathogen causing hospital-acquired infections (HAIs). Although acquiring any nosocomial infection is associated with increased mortality, we do not know if the acquisition of Acinetobacter infection confers a worse prognosis as compared to non-Acinetobacter-related HAI. The aim of the current study is to compare the clinical outcomes of ventilator-associated pneumonia (VAP) and central line associated blood stream infections (CLABSIs) caused by A. baumannii with those caused by other bacterial pathogens. Materials and Methods: This prospective cohort study was conducted among critically ill adults admitted to a tertiary care hospital in South India from January 2013 to June 2014. We enrolled patients who developed new-onset fever ≥48 h after admission and fulfilled pre-specified criteria for VAP or CLABSI. The patients were followed up until the primary outcomes of death or hospital discharge. Results: During the study period, 4047 patients were admitted in the intensive care units, among which 129 eligible HAI events were analysed. Of these, 95 (73.6%) were VAP, 34 (26.4%) were CLABSI, 78 (60.4%) were A. baumannii-related HAI (AR-HAI) and 51 (39.6%) were non-A. baumannii-related HAI (NAR-HAI). Mortality among AR-HAI was 57.6% compared to 39.2% in NAR-HAI (P = 0.04) which on multivariate analysis did not achieve statistical significance, although the trend persisted (odds ratio [OR] = 4.2, 95% confidence interval [CI]: 0.95–18.4, P = 0.06). The acquisition of VAP due to A. baumannii was associated with poor ventilator outcomes even after adjusting for confounders (adjusted OR = 3.5, 95% CI: 1.07–11.6, P = 0.04). Conclusion: In our cohort of critically ill adults with VAP and CLABSI, AR-HAI was associated with poor ventilator outcomes and a trend towards higher mortality. These findings add to the evidence suggesting that A. baumannii is a dangerous pathogen, perhaps even more so than others.


Keywords: Acinetobacter baumannii, central line-associated blood stream infections, hospital-acquired infection, ventilator-associated pneumonia


How to cite this article:
John AO, Paul H, Vijayakumar S, Anandan S, Sudarsan T, Abraham OC, Balaji V. Mortality from acinetobacter infections as compared to other infections among critically ill patients in South India: A prospective cohort study. Indian J Med Microbiol 2020;38:24-31

How to cite this URL:
John AO, Paul H, Vijayakumar S, Anandan S, Sudarsan T, Abraham OC, Balaji V. Mortality from acinetobacter infections as compared to other infections among critically ill patients in South India: A prospective cohort study. Indian J Med Microbiol [serial online] 2020 [cited 2020 Aug 11];38:24-31. Available from: http://www.ijmm.org/text.asp?2020/38/1/24/290680





 ~ Introduction Top


Hospital-acquired infection (HAI) is associated with substantial increase in direct healthcare associated costs and mortality.[1]Acinetobacter baumannii are becoming an increasingly common cause of HAI, especially in the intensive care units (ICUs). A 2008 report from the National Healthcare Safety Network found that A. baumannii accounted for 8.4% of the ventilator-associated pneumonias (VAPs) and 2.2% of all catheter-related blood stream infections (BSIs).[2] Studies have also demonstrated an increasing incidence of Carbapenem-resistant strains of A. baumannii, estimating to almost 50% increase in the incidence of drug-resistant isolates[3],[4] with increased mortality and length of hospital stay.[5] However, a debate exists regarding the attributable mortality from Acinetobacter infection which stems from the difficulty in determining whether the cause of death was due to the underlying illness or due to the super-added infection. As a pathogen, it usually targets mucous membranes, and its ability to form biofilms over invasive devices makes the critically ill patient an easy target.[6] However, differentiation of infection from colonisation adds further complications to the debate of attributable mortality.

The mortality from VAPs has been estimated between 13% and 30%[7],[8] with a similar mortality rate from nosocomial BSIs.[9] Therefore, we know that the acquisition of any of the above nosocomial infections is associated with an increase in mortality. However, it is not known if the acquisition of Acinetobacter-related infection confers a worse prognosis as compared to the acquisition of a non-Acinetobacter-related HAI.

In this study, we aim to compare the clinical outcomes among critically ill patients with HAI-related VAP and central line-associated BSIs (CLABSIs) caused by A. baumannii, with HAI caused by other bacterial pathogens.


 ~ Materials and Methods Top


Study setting

This prospective cohort study was undertaken in a 2500-bed, university-affiliated, private teaching hospital in semi-urban India. The hospital is serviced by patients from all over India. Most patients admitted in the critical care units, medical ICU (MICU), medical high-dependency unit (MHDU) and surgical ICU (SICU) arrived through the accident and emergency department, although the SICU also had post-operative patients admitted for stabilisation before shifting to the wards.

Inclusion criteria

This study included consecutive adult patients above the age of 18 years admitted in the MICU, MHDU and SICU for a consecutive 18 months who fulfilled the pre-defined classification criteria for VAP and CLABSI.

Exclusion criteria

Infections with coagulase-negative Staphylococci and patients for whom subsequent evaluation demonstrated an alternate aetiological focus other than the lung or the central venous catheter were excluded from the study.

Study participants

Any patient who developed fever, 48 h after admission to the ICU, was evaluated by the principal investigator to determine whether the fever was due to VAP or CLABSI. The patients' clinical progress and investigations were followed up to determine if they fulfilled the pre-defined criteria for diagnosis of VAP or CLABSI. During this entire process, all investigations and clinical management plans were made by the treating physicians, with no involvement from the study team. If a patient fulfilled the criteria of VAP or CLABSI, then they were classified as study participants and were recruited after obtaining informed consent from the family members. The patient's demographics, clinical details, disease severity on admission and blood investigations were entered into the clinical research form.

Bacterial isolates

The study participants whose clinical isolates grew Acinetobacter baumannii calcoaceticus complex (Acb complex) were classified as Acinetobacter-related HAI (ARHAI). The study participants whose clinical isolates grew other non-Acinetobacter organisms such as Klebsiella, E. coli, Pseudomonas, S. aureus and Proteus were classified as non-Acinetobacter-related HAI (NARHAI). The accurate identification of Acb complex at the species level as A. baumannii was confirmed using MALDI-TOF. If the culture grew more than one organism of which one was A. baumannii, the patient was still classified as belonging to the ARHAI group. The patients were followed up until death or discharge from the hospital.

During the course of hospital stay, if the patient developed another episode of fever and fulfilled criteria for VAP or CLABSI, then the details were entered as a separate event and followed up accordingly. Hence, a single patient could have more than one HAI event during the course of hospital stay.

Central line-associated blood stream infection case definition

CLABSI was defined according to the National Healthcare Safety Network criteria, as follows:[10] (i) recognised pathogen, identified from one or more blood culture specimens and (ii) organism(s) identified in blood is not related to infection at any other site and (iii) an eligible central line is present on the day of the positive blood culture or the day before.

An eligible central line was defined as one that had been in place for two or more consecutive calendar days.

Ventilator-associated pneumonia case definition

If the patient is clinically suspected to have VAP, then the Clinical Pulmonary Infection Score (CPIS) was calculated. A score more than 6 is considered highly suggestive of VAP. Appropriate tracheal aspirate and blood cultures were taken as per the normal protocol in the ICU. The patient was reassessed again at 72 h and a repeat CPIS score was calculated. The results of the ET aspirate were also followed up by this time. A patient is classified as having VAP if day 1 and day 3 CPIS is >6 and the ET aspirate culture is positive or day 1 CPIS <6 and day 3 CPIS >6 and the ET aspirate culture is positive. Bacterial growth of >105 colony-forming unit/ml is considered positive for ET aspirate cultures.

Outcome assessment

Primary outcome

The primary outcome was in-hospital mortality. For the purpose of this study, patients who were discharged against medical advice were included as 'death'.

Secondary outcome

We compared the duration of ICU stay and duration of hospital stay among patients with NARHAI with those of ARHAI.

Factors affecting duration of mechanical ventilation

We assessed factors affecting duration of mechanical ventilation among our patients who were mechanically ventilated. The duration of mechanical ventilation was expressed in terms of ventilator-free days (VFDs). This was defined as number of days between successful weaning from mechanical ventilation and day 28 after initiation of mechanical ventilation (VFD = 28 − number of days on the ventilator). If the patient required mechanical ventilation beyond 28 days or if the patient died during the course of hospital stay, the number of VFD was taken as 0. Successful weaning was defined as a continuous period of 48 h or more off mechanical ventilation.

Antimicrobial susceptibility testing

Antimicrobial susceptibility testing (AST) was performed for all the study isolates for different class of antimicrobials such as cephalosporins, β-lactam-β-lactamase inhibitors, carbapenems, fluoroquiolones, aminoglycosides, tetracycline, trimethoprim-sulfamethoxazole and colistin. The breakpoints were interpreted as per CLSI guidelines.

Statistical methods

A prior study published from our ICU showed VAP-related mortality rates to be 52.7%.[11] We calculated that a total of 93 patients in each arm would yield a power of 80% at an alpha error of 5% to detect a 20% difference in mortality between the two groups. We calculated t-test, Chi-square test and ANOVA as appropriate for all analyses. Odds ratio (OR) and confidence intervals (CI) were calculated, and a 'P' < 0.05 was considered statistically significant. Data was entered using Epi Data version 3.1 (Lauritsen JM and Bruus M. EpiData (version 3.1). A comprehensive tool for validated entry and documentation of data. The EpiData Association, Odense Denmark, 2004.) and the data was analysed using SPSS version 21 (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp.).

Ethical approval

The study was approved by the institutional review board and ethics committee (IRB min no. 8159/13).


 ~ Results Top


Study participants

During the study period, a total of 4047 patients were admitted in the ICUs (MICU/MHDU/SICU), out of which 129 patients fulfilled the case definitions for VAP or CLABSI as defined earlier.

Patient demographics

Among these 129 patients, 78 (60.5%) had ARHAI and the remaining 51 (39.5%) had NARHAI. At baseline, the patients in this cohort were found to have a mean age of 40 years, with a mild male predominance (57.7% and 67.9% in ARHAI and NARHAI, respectively). The two groups were found to have comparable median APACHE III scores at presentation (70 and 66, respectively, in ARHAI and NARHAI) and comparable median Charlson comorbidity index (1 and 0 in ARHAI and NARHAI, respectively). The baseline characteristics of the patients are described in [Table 1].
Table 1: Patient characteristics at baseline

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Of 78 patients with ARHAI, 68 (87.2%) had VAP, while only 24 (45.3%) among the 53 patients with NARHAI had VAP. Most of the VAP (71.5%) were caused by ARHAI [Figure 1]. The most common non-Acinetobacter organisms were Klebsiella and Pseudomonas. The distribution of NARHAI is shown in [Figure 2].
Figure 1: Proportion of ventilator-associated pneumonia and central line-associated blood stream infection due to Acinetobacter-related hospital-acquired infection and non-Acinetobacter-related hospital-acquired infection (central line-associated blood stream infection n = 34, ventilator-associated pneumonia n = 95)

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Figure 2: Distribution of non-Acinetobacter organisms

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Primary outcome

Of the 78 patients with ARHAI, 45 died (57.6%), while only 20 of 51 patients (39.2%) with NARHAI died (P = 0.04). Multivariate analysis was done after adjusting for confounders such as severity of illness (using APACHE scores), underlying disease condition (using the syndromic diagnosis at admission), age and duration of ICU stay. This analysis showed a trend towards higher mortality among those with ARHAI compared to those with NARHAI although this difference did not achieve statistical significance (OR = 4.2, 95% CI: 0.95–18.4, P = 0.06) [Table 2].
Table 2: Antibiotic susceptibility profile of Acinetobacter species

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Secondary outcome

The median duration of ICU stay among patients with ARHAI and NARHAI was 18 and 17 days, respectively, with no statistically significant difference (P = 0.2) between them. The median duration of hospital stay was 26 and 27 days among ARHAI and NARHAI, respectively, without any statistically significant difference (P = 0.94).

Mortality between ventilator-associated pneumonia and central line-associated blood stream infection

We performed a subgroup analysis among the patients who developed VAP (95 patients) and CLABSI (34 patients), to determine if there were any differences in mortality. We found no significant differences in mortality even after adjusting for potential confounders.

Factors affecting duration of mechanical ventilation

We also performed an analysis to evaluate the factors which affected the ventilator-related outcomes. We categorised the patient's ventilator outcomes as 'poor outcome' if they died during hospital stay, or remained ventilator dependent on day 28 of mechanical ventilation (VFD = 0). 'Good outcome' was defined as those patients who survived and had <28 days of mechanical ventilation. This analysis was only performed among the subgroup of patients who developed VAP. The patients who had poor ventilator outcomes were older and had higher median APACHE III scores.

Acinetobacter-related hospital-acquired infection versus non-Acinetobacter-related hospital-acquired infection

We found that the patients admitted with diseases requiring surgical intervention, following which they developed the HAI, as well as those with neoplastic processes, had a significantly worse ventilator outcome when compared to those with infections and poisoning or drug overdose (P ≤ 0.001). A larger proportion of patients who had a poor ventilator outcome after VAP had ARHAI (78%). This difference in ventilator outcomes based on the type of organism causing the VAP (ARHAI vs. NARHAI) showed a trend to significance on univariate analysis.

After adjusting for possible confounders using a multivariable regression model, we found that ARHAI, higher APACHE III scores at admission and admission with a surgical or neoplastic process were significant predictive factors for poor ventilator outcomes [Table 3].
Table 3: Primary outcome: Death during hospital stay

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Antimicrobial susceptibility profile

Among the isolates of A. baumannii identified in this study, 145 were tested for carbapenem susceptibility. Of which, 143 (98.6%) were carbapenem resistant, while only two (1.3%) were carbapenem susceptible. A subset of 75 isolates were tested for colistin susceptibility and one isolate (1.3%) was found to be resistant, while the remaining 74 (98.6%) were found to be susceptible. The proportion of A. baumannii isolates who were resistant to BL/BLI, fluoroquinolones and aminoglycosides was 97%, 85.9% and 96%, respectively. Therefore one A. baumannii isolate was pan-drug resistant, while the remaining were either multidrug resistant or extremely drug resistant according to prior published definitions.[12] The antimicrobial susceptibility profile of A. baumannii is shown in [Table 4].
Table 4: Secondary outcomes: Factors affecting ventilator outcomes among those who developed a ventilator-associated pneumonia (95 patients)

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 ~ Discussion Top


In this study, among the adults admitted in the MICU and SICU, patients who developed ARHAI and those who developed NARHAI had similar demographic characteristics, Charlson comorbidity scores and APACHE III scores at the time of admission. The time taken to acquire the HAI as well as the duration of time, the device had been in situ prior to acquisition of the HAI was also similar between both thegroups. The patients with ARHAI differed from those with NARHAI in that significantly more of them had been admitted with infections (48.7% vs. 15.1%). It was also noted that most of the patients who developed VAP were AR-HAI, with the converse being true for those with CLABSI.

On univariate analysis, we found a statistically significant increase in crude in-hospital mortality among those with ARHAI. After adjustment for confounding variables using binary logistic regression analysis, we found that there was only a trend towards increase in mortality. We also found that patients with VAP caused by A. baumannii had significantly prolonged duration of mechanical ventilation and death during mechanical ventilation when compared to those with non-Acinetobacter-related VAP. There has been a long-standing belief that Acinetobacter infections do not result in higher mortality.[13]

Infections from A. baumannii primarily occur among critically ill patients, and a debate has existed regarding the attributable mortality from these infections. A retrospective matched cohort study concluded that pneumonia caused by A. baumannii was not associated with any significant difference in mortality or length of stay.[14] A similar study by Blot et al. also concluded that there was no significant increase in mortality due to A. baumannii bacteraemia, albeit with more hemodynamic instability, longer duration of ICU stay and longer ventilation dependence.[15]

The argument for A. baumannii being a less potent pathogen than other organisms is finding less support from published literature. The SCOPE National surveillance programme on nosocomial BSIs in United States hospitals found similar crude mortality rates with A. baumannii-related BSI compared to BSI caused by other organisms.[16] A comparison of mortality rates among patients with A. baumannii bacteraemia with those of Klebsiella bacteraemia found an increased mortality of 22.7% among the Acinetobacter group even after adjusting for potential confounders.[17] A large single-centre retrospective matched cohort study which compared 52 cases of nosocomial bacteraemia with matched controls found an excess mortality with Acinetobacter bacteraemia, even after adjusting for disease severity and risk-exposure time.[18] Finally, a systematic review of published case–control and cohort studies found attributable in-hospital mortality rates that ranged from 7.8% to 23% among patients with Acinetobacter-related infections.[19] However, there was significant heterogeneity among the studies in the review.

Although the current study findings did not show increase in mortality among patients with Acinetobacter-related infections, it may be construed as an argument against its pathogenicity; we believe it is equally important to note the crude difference in mortality between ARHAI and NARHAI (57.6% vs. 39.2%). The additional 18% mortality in our cohort of patients with ARHAI suggests that the acquisition of an Acinetobacter-related infection in ICU is at least as bad, if not worse than being infected with any of the other 'proven' pathogens. This finding is in concurrence with other studies. Furthermore, we believe that the difference in mortality may have become more evident with a larger sample size. The results of these studies show that A. baumannii is a significant pathogen as any of the other Gram-negative organisms encountered in the ICU.

The current study findings of poor ventilator outcomes among A. baumannii-related VAP patients are not surprising given our evolving understanding of the ability of A. baumannii to form biofilms over the surface of endotracheal tubes. This is believed to be the cause for the high levels of colonisation seen in the lower respiratory tract.[20]

Kollef et al. found that the occurrence of late-onset VAP due to a certain 'high-risk' pathogen (Pseudomonas sp., Acinetobacter sp. and Xanthomonas maltophila) was an independent risk factor for mortality (adjusted OR = 5.4, 95% CI: 2.8–10.3; P = 0.009).[21] A retrospective study by Yang et al. from Taiwan compared 14-day mortality among patients with A. baumannii-related VAP and bacteraemic Acinetobacter- related non-ventilated hospital-acquired pneumonia. This study showed surprising result that adjusted mortality was lower among ventilated patients with Acinetobacter-related infection (OR = 0.021, 95% CI: 0.075–0.538, P = 0.001). The authors attributed this difference to better airway management and more intensive monitoring and treatment among those on ventilator.[22] Another retrospective study among mechanically ventilated patients in Malaysia compared patients with respiratory isolates positive for A. baumannii versus those with negative cultures. No significant increase in mortality was found, but there was a significantly longer duration of hospital stay among those with A. baumannii positive cultures.

In this study, majority (96%) of the A. baumannii isolates fulfilled the definition of multidrug resistance.[12] Debate has also existed with regard to whether the acquisition of multidrug resistance confers increasing pathogenicity to the organism,[23] thus accounting for the increased mortality seen among patients in ICUs. However, a recent study in Thailand found no statistically significant difference in mortality rates between imipenem-resistant and imipenem-susceptible isolates on multivariate analysis.[24],[25]

Trend analysis of antibiotic susceptibility rates of A. baumannii based on unpublished data from the same hospital showed significant changes over the past 6 years (2014–2019). The most important trends were decreased susceptibility rates to commonly used antibiotics as well as increasing resistance rates to last resort antibiotics [Supplementary Figure 1] and [Supplementary Figure 1].



Among the BSIs, susceptibility to ceftazidime, cefepime, piperacillin/tazobactam, amikacin, gentamicin, tetracycline and co-trimoxazole has declined. Cefoperazone/sulbactam retained 40% susceptibility over the years, and the reason behind could be due to sulbactam's intrinsic activity against A. baumannii. Decreased susceptibility to carbapenems was observed, and it could be due to rise in the use of meropenem as empiric therapy along with colistin by the clinicians. Among aminoglycosides, netilmicin and tobramycin showed 40% to 45% susceptibility. Minocycline retained 60% susceptibility over the years, whereas tigecycline's susceptibility declined. Though more than 90% susceptibility rates were observed for colistin, gradual increase in resistance is emerging [Supplementary [Figure 1]. The overall susceptibility rate of 25% to 30% was reported for all class of antibiotics except for colistin which showed 92% susceptibility rate against respiratory infections [Supplementary [Figure 2].

Based on thein vitro susceptibility profile from various studies, minocycline, tigecycline, sulbactam and colistin are the most commonly used agents in combination for treating Acinetobacter infections. Minocycline can be considered as an alternative choice, and global studies such as TEST/ATLAS revealed 80% susceptibility against A. baumannii.[26] Despite various studies reporting higher susceptibility rates to tigecycline, the FDA does not recommend tigecycline for treating hospital-acquired VAP, while treatment of bacteraemia with tigecycline is controversial due to its low serum concentration levels.[27] Sulbactam has intrinsic antibacterial activity against A. baumannii due to its selective affinity for the penicillin-binding proteins.[28] However, studies report approximately 50% susceptibility for sulbactam.

Though colistin-based combinations can be considered for treating A. baumannii infections such as BSI and VAP, several controversies have been reported. Due to limited clinical efficacy, colistin is not recommended for the treatment of BSI and VAP. Despite excellent bactericidal activity, low level of colistin was achieved in the epithelial lining fluid (ELF) and with higher doses of nebulised colistin, the concentration can be attained among VAP patients.[29],[30] Based on the PK/PD data, clinical outcome and MIC distribution, CLSI 2020 excluded the susceptible breakpoint for colistin (Humphires, 2019).[31] EUCAST agrees with CLSI that non-polymyxin agents should be preferred over colistin, and this would be effectively helpful in considering colistin as a treatment option in selected cases.[32]

Recently, various novel agents such as cefiderocol and eravacycline were approved and showed goodin vitro activity. However, further clinical trials are warranted to understand the efficacy against BSI and VAP.[33] None of the newly available combinations such as ceftazidime-avibactam, aztreonam-avibactam, imipenem-relebactam and meropenem-vaborbactam have clinical activity against A. baumannii infections except for the β-lactam-β-lactamase enhancer, cefepime-zidebactam.[34],[35]In vivo studies on cefepime-zidebactam revealed pronounced bacterial killing and show potential clinical utility in the treatment of infections caused by A. baumannii.[36],[37]

The strengths of this study are (a) the patients were prospectively recruited, (b) each patient was assessed by the same clinician (the principal investigator) to ascertain if they fulfilled the pre-defined definitions for VAP and CLABSI and (c) the criteria for diagnosis of VAP were modified to make it strict – instead of using a single CPIS score, the trend of the score over 48 h because the onset of symptoms with the culture results was considered. We believe that this enhanced the diagnostic confidence prior to study entry.

The limitations of this study are (a) we were unable to achieve the calculated sample size to identify the difference in the primary outcome, (b) we recruited both medical and SICU patients. Both these populations of patients were very different, in that the MICU patients entered the hospital/ICU with a very high APACHE III score as compared to SICU patients, who usually entered the hospital well (with low APACHE III scores at the time of admission), but subsequently entered the ICU after surgical complications and (c) the inherent flaws of the CPIS score in the diagnosis of VAP would still remain despite our best efforts to circumvent them. The new CDC guidelines for diagnosis of VAP were published while this study was close to completion, and hence no changes in the protocol were made (CDC VAP definition, 2020).


 ~ Conclusion Top


Based on the findings of the current study, In our cohort of critically ill adult patients with VAP and CLABSI, acquiring an Acinetobacter baumanii related HAI resulted in significantly poorer ventilator outcomes and a trend towards higher mortality. Such findings add to the evidence suggesting that A. baumannii is a dangerous pathogen and an argument can be made for early aggressive treatment of mechanically ventilated patients with respiratory isolates positive for A. baumannii.

Financial support and sponsorship

This work was supported by funding from the Fluid Research Grant of Christian Medical College, Vellore.

Conflicts of interest

There are no conflicts of interest.



 
 ~ References Top

1.
Klevens RM, Edwards JR, Richards CL, Horan TC, Gaynes RP, Pollock DA, et al. Estimating health care-associated infections and deaths in US hospitals, 2002. Public Health Rep 2007;122:160.  Back to cited text no. 1
    
2.
Hidron AI, Edwards JR, Patel J, Horan TC, Sievert DM, Pollock DA, et al. NHSN annual update: Antimicrobial-resistant pathogens associated with healthcare-associated infections: Annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006-2007. Infect Control Hosp Epidemiol 2008;29:996-1011.  Back to cited text no. 2
    
3.
Dizbay M, Tunccan OG, Sezer BE, Hizel K. Nosocomial imipenem-resistant Acinetobacter baumannii infections: Epidemiology and risk factors. Scand J Infect Dis 2010;42:741-6.  Back to cited text no. 3
    
4.
Su CH, Wang JT, Hsiung CA, Chien LJ, Chi CL, Yu HT, et al. Increase of carbapenem-resistant Acinetobacter baumannii infection in acute care hospitals in Taiwan: Association with hospital antimicrobial usage. PLoS One 2012;7:e37788.  Back to cited text no. 4
    
5.
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. 5
    
6.
Howard A, O'Donoghue M, Feeney A, Sleator RD. Acinetobacter baumannii: An emerging opportunistic pathogen. Virulence 2012;3:243-50.  Back to cited text no. 6
    
7.
Melsen WG, Rovers MM, Groenwold RH, Bergmans DC, Camus C, Bauer TT, et al. Attributable mortality of ventilator-associated pneumonia: A meta-analysis of individual patient data from randomised prevention studies. Lancet Infect Dis 2013;13:665-71.  Back to cited text no. 7
    
8.
Kollef MH, Shorr A, Tabak YP, Gupta V, Liu LZ, Johannes RS. Epidemiology and outcomes of health-care-associated pneumonia: Results from a large US database of culture-positive pneumonia. Chest 2005;128:3854-62.  Back to cited text no. 8
    
9.
Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB. Nosocomial bloodstream infections in US hospitals: Analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 2004;39:309-17.  Back to cited text no. 9
    
10.
Bloodstream Infection Event (Central Line-Associated Bloodstream Infection and Non-central Line Associated Bloodstream Infection). Centers for Disease Control and Prevention. Available from: http://www.cdc.gov/nhsn/pdfs/pscmanual/4psc_clabscurrent.pdf. [Last accessed on 2016 Oct 20].  Back to cited text no. 10
    
11.
David D, Samuel P, David T, Keshava SN, Irodi A, Peter JV. An open-labelled randomized controlled trial comparing costs and clinical outcomes of open endotracheal suctioning with closed endotracheal suctioning in mechanically ventilated medical intensive care patients. J Crit Care 2011;26:482-8.  Back to cited text no. 11
    
12.
Manchanda V, Sanchaita S, Singh N. Multidrug resistant Acinetobacter. J Glob Infect Dis 2010;2:291-304.  Back to cited text no. 12
    
13.
Fournier PE, Richet H. The epidemiology and control of Acinetobacter baumannii in health care facilities. Clin Infect Dis 2006;42:692-9.  Back to cited text no. 13
    
14.
Garnacho J, Sole-Violan J, Sa-Borges M, Diaz E, Rello J. Clinical impact of pneumonia caused by Acinetobacter baumannii in intubated patients: A matched cohort study. Crit Care Med 2003;31:2478-82.  Back to cited text no. 14
    
15.
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.  Back to cited text no. 15
    
16.
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.  Back to cited text no. 16
    
17.
Robenshtok E, Paul M, Leibovici L, Fraser A, Pitlik S, Ostfeld I, et al. The significance of Acinetobacter baumannii bacteraemia compared with Klebsiella pneumoniae bacteraemia: Risk factors and outcomes. J Hosp Infect 2006;64:282-7.  Back to cited text no. 17
    
18.
Grupper M, Sprecher H, Mashiach T, Finkelstein R. Attributable mortality of nosocomial Acinetobacter bacteremia. Infect Control Hosp Epidemiol 2007;28:293-8.  Back to cited text no. 18
    
19.
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.  Back to cited text no. 19
    
20.
Joly-Guillou ML. Clinical impact and pathogenicity of Acinetobacter. Clin Microbiol Infect 2005;11:868-73.  Back to cited text no. 20
    
21.
Kollef MH, Silver P, Murphy DM, Trovillion E. The effect of late-onset ventilator-associated pneumonia in determining patient mortality. Chest 1995;108:1655-62.  Back to cited text no. 21
    
22.
Yang YS, Lee YT, Huang TW, Sun JR, Kuo SC, Yang CH, et al. Acinetobacter baumannii nosocomial pneumonia: Is the outcome more favorable in non-ventilated than ventilated patients? BMC Infect Dis 2013;13:142.  Back to cited text no. 22
    
23.
Loh LC, Yii CT, Lai KK, Seevaunnamtum SP, Pushparasah G, Tong JM. Acinetobacter baumannii respiratory isolates in ventilated patients are associated with prolonged hospital stay. Clin Microbiol Infect 2006;12:597-8.  Back to cited text no. 23
    
24.
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. 24
    
25.
Jamulitrat S, Arunpan P, Phainuphong P. Attributable mortality of imipenem-resistant nosocomial Acinetobacter baumannii bloodstream infection. J Med Assoc Thai 2009;92:413-9.  Back to cited text no. 25
    
26.
Veeraraghavan B, Pragasam AK, Bakthavatchalam YD, Anandan S, Swaminathan S, Sundaram B. Colistin-sparing approaches with newer antimicrobials to treat carbapenem-resistant organisms: Current evidence and future prospects. Indian J Med Microbiol 2019;37:72-90.  Back to cited text no. 26
[PUBMED]  [Full text]  
27.
Wang J, Pan Y, Shen J, Xu Y. The efficacy and safety of tigecycline for the treatment of bloodstream infections: A systematic review and meta-analysis. Ann Clin Microbiol Antimicrob 2017;16:24.  Back to cited text no. 27
    
28.
Neonakis IK, Spandidos DA, Petinaki E. Confronting multidrug-resistant Acinetobacter baumannii: A review. Int J Antimicrob Agents 2011;37:102-9.  Back to cited text no. 28
    
29.
Gurjar M. Colistin for lung infection: An update. J Intensive Care 2015;3:3.  Back to cited text no. 29
    
30.
Kim YK, Lee JH, Lee HK, Chung BC, Yu SJ, Lee HY, et al. Efficacy of nebulized colistin-based therapy without concurrent intravenous colistin for ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii. J Thorac Dis 2017;9:555-67.  Back to cited text no. 30
    
31.
Humphries RM, Abbott AN, Hindler JA. Understanding and Addressing CLSI Breakpoint Revisions: a Primer for Clinical Laboratories. Journal of Clinical Microbiology [Internet] 2019;57. Available from: https://jcm.asm.org/content/57/6/e00203-19. [Last accessed on 2020 Jun 05].  Back to cited text no. 31
    
32.
Satlin MJ, Lewis JS, Weinstein MP, Patel J, Humphries RM, Kahlmeter G, et al. Clinical and laboratory standards institute (CLSI) and European committee on antimicrobial susceptibility testing (EUCAST) position statements on polymyxin B and colistin clinical breakpoints. Clin Infect Dis 2020.  Back to cited text no. 32
    
33.
Ito A, Sato T, Ota M, Takemura M, Nishikawa T, Toba S, et al.In vitro antibacterial properties of cefiderocol, a novel siderophore cephalosporin, against gram-negative bacteria. Antimicrob Agents Chemother 2018;62.  Back to cited text no. 33
    
34.
Piperaki ET, Tzouvelekis LS, Miriagou V, Daikos GL. Carbapenem-resistant Acinetobacter baumannii: In pursuit of an effective treatment. Clin Microbiol Infect 2019;25:951-7.  Back to cited text no. 34
    
35.
B I, Y D, Ra B, Dl P. New Treatment Options Against Carbapenem- Resistant Acinetobacter baumannii Infections [Internet]. Antimicrobial agents and chemotherapy 2018. Available from: https://pubmed.ncbi.nlm.nih.gov/30323035/. [Last accessed on 2020 Jun 05].  Back to cited text no. 35
    
36.
Avery LM, Abdelraouf K, Nicolau DP. Assessment of theIn Vivo Efficacy of WCK 5222 (Cefepime-Zidebactam) against Carbapenem-Resistant Acinetobacter baumannii in the Neutropenic Murine Lung Infection Model. Antimicrob Agents Chemother [Internet] 2018;62. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6201064/. [Last accessed on 2020 Jun 05].  Back to cited text no. 36
    
37.
Bhagwat SS, Periasamy H, Takalkar SS, Palwe SR, Khande HN, Patel MV. The novel β-lactam enhancer zidebactam augments thein vivo pharmacodynamic activity of cefepime in a neutropenic mouse lung Acinetobacter baumannii infection model. Antimicrobial agents and chemotherapy. 2019 Apr 1;63:e02146-18.  Back to cited text no. 37
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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2004 - Indian Journal of Medical Microbiology
Published by Wolters Kluwer - Medknow

Online since April 2001, new site since 1st August '04