|Year : 2015 | Volume
| Issue : 2 | Page : 286-289
Superbugs causing ventilator associated pneumonia in a tertiary care hospital and the return of pre-antibiotic era!
S Qureshi1, C Agrawal1, M Madan1, A Pandey1, H Chauhan2
1 Department of Microbiology, Subharti Medical College, Delhi-Haridwar Bypass, Meerut - 250 005, Uttar Pradesh, India
2 Department of Anaesthesiology, Subharti Medical College, Delhi-Haridwar Bypass, Meerut - 250 005, Uttar Pradesh, India
|Date of Submission||06-Jan-2014|
|Date of Acceptance||25-Sep-2014|
|Date of Web Publication||10-Apr-2015|
Department of Microbiology, Subharti Medical College, Delhi-Haridwar Bypass, Meerut - 250 005, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
The rise in super bugs causing Ventilator-Associated Pneumonia (VAP) is a major cause of mortality and morbidity despite recent advances in management owing to the looming 'antibiotic apocalypse'. The aetiology and susceptibility pattern of the VAP isolates varies with patient population, type of intensive care unit (ICU) and is an urgent diagnostic challenge. The present study carried out for a period of one year in a tertiary care hospital, enrolled patients on mechanical ventilation (MV) for ≥48 hrs. Endotracheal aspirates (ETA) from suspected VAP patients were processed by semi quantitative method. Staphylococus aureus, members of Enterobacteriaceae were more common in early onset VAP (EOVAP), while Nonfermenting Gram negative bacilli (NFGNB) were significantly associated with late onset VAP (LOVAP). Most of the isolates were multi drug resistant (MDR) super bugs. With limited treatment options left for this crisis situation like the pre-antibiotic era; it is an alarm for rational antibiotic therapy usage and intensive education programs.
Keywords: Endotracheal aspirate, non fermenting gram negative bacilli, superbugs, ventilator associated pneumonia
|How to cite this article:|
Qureshi S, Agrawal C, Madan M, Pandey A, Chauhan H. Superbugs causing ventilator associated pneumonia in a tertiary care hospital and the return of pre-antibiotic era!. Indian J Med Microbiol 2015;33:286-9
|How to cite this URL:|
Qureshi S, Agrawal C, Madan M, Pandey A, Chauhan H. Superbugs causing ventilator associated pneumonia in a tertiary care hospital and the return of pre-antibiotic era!. Indian J Med Microbiol [serial online] 2015 [cited 2019 Dec 14];33:286-9. Available from: http://www.ijmm.org/text.asp?2015/33/2/286/153566
| ~ Introduction|| |
Ventilator associated pneumonia (VAP) is an infection that occurs in approximately 9-27% of intensive care unit (ICU) patients more than 48 hrs after endotracheal intubation and mechanical ventilation (MV). , The lower respiratory tract sample collected by invasive or non-invasive techniques provide an insight into the aetiology. ,
As per the American Thoracic Society (ATS) consensus statement, semi quantitative cultures can be performed on Endotracheal aspirates (ETA) for establishing a definitive diagnosis. The frequency of specific multi-drug resistant (MDR) pathogens causing VAP vary by hospital, patient population, exposure to antibiotics, type of ICU patient and changes over time, emphasizing the need for timely local surveillance data. In view of this rising importance of VAP in ICUs, the present study was conducted to establish the diagnosis, by identifying the causative organisms of VAP and to assess their antimicrobial susceptibility pattern.
| ~ Materials and Methods|| |
A prospective study was conducted over a period of one year from January 2012 to December 2012 in the Department of Microbiology. The study group comprised of patients on MV admitted in medicine and surgical ICUs. All patients above the age of 18 years of either gender on MV for >48 hrs were included in the study.
However any patient on MV for <48 hrs or developing pneumonia within 48 hrs of MV were excluded. VAP was clinically suspected in patients with a clinical pulmonary infection score [CPIS] >6 as developed by Pugin et al.  Endotracheal aspirate was collected prior to start or change of antibiotic therapy and on suspicion of VAP thereafter.Collection was done as per the method described by Dey et al.  An acceptable ETA had <10 squamous epithelial cells/low power field or organisms seen under oil immersion (1000x) in the Gram stain. Presence of 25 or more polymorphonuclear leucocytes per 100x field, together with few squamous epithelial cells implied an excellent specimen.  Cultures were carried out by semi-quantitative method.  Bacterial isolates were identified by conventional standard technique.  Colony Count ≥10 5 cfu/ml was consistent with the definitive diagnosis of VAP and < 10 5 cfu/ml due to colonisation or contamination . Antibiotic sensitivity was performed by Kirby Bauer's disc diffusion method as per Clinical and Laboratory Standards Institute (CLSI) guidelines 2012.  Extended-spectrum beta-lactamases (ESBL) among the members of Enterobacteriaceae was detected by Phenotypic Confirmatory test using ceftazidime (30 μg), alone and in combination with clavulanic acid. MBL enzymes among Nonfermenting gram-negative bacilli (NFGNB) was detected by Combined Disc Test (CDT) using imipenem and EDTA which showed reduced susceptibility to carbapenems and methicillin resistance was detected by cefoxitin screening test. ,
| ~ Results|| |
Out of 347 patients put on mechanical ventilatory support in Surgical Intensive Care Unit (SICU) and Medical Intensive Care Unit (MICU); 154 were enrolled in the study as per inclusion criteria.Clinical pulmonary infection score >6 and significant semi quantitative cultures (colony count ≥10 5 cfu/ml) were found in 38 patients.
The percentage of patients with Early onset VAP (EOVAP) was 47.37% and Late onset VAP (LOVAP) was 52.63%. The present study shows that 94.74% of VAP patients had monomicrobial aetiology and 5.26% had polymicrobial aetiology.
S.aureus and members of Enterobacteriaceae were more common in EOVAP while NFGNB were significantly associated with LOVAP (P < 0.05).
Antibiotic resistance pattern of the isolates in EOVAP and LOVAP [Table 1] and [Table 2]. The rate of isolation of Methicillin-resistant Staphylococcus aureus (MRSA), MBL producers and ESBL producers were 66.7%, 28.57% (Acinetobacter), 37.5% (Pseudomonas) and 75% among the respective isolated organisms.
Prolonged ventilator support (>5 days), stupor and coma along with stress ulcer prophylaxis are the risk factors associated with development of VAP in the present study. Reintubation was found in 6 of our patients out of which 5 developed VAP. The number is less and therefore difficult to comment on the significance of this risk factor. Other co morbid conditions like hypertension, chronic renal failure, were also found but their impact on VAP could not be assessed.
Overall Mortality rate in the VAP patients was 48.57% (17/35) whereas ICU mortality rate was 15.41%. A low mortality rate (29.41%) was found in patients with early onset VAP whereas the mortality was comparatively high 66.67% and also found to be statistically significant (P < 0.05) in patients with late onset VAP.
| ~ Discussion|| |
The classification of VAP into early and late onset helps in predicting the implicated pathogens and guide in the initial empiric therapy with antibiotics. , Early onset VAP was observed in 47.37% patients whereas 52.63% patients had late onset pneumonia. NFGNB such as Acinetobacter and Pseudomonas spp. were significantly (P < 0.01) associated with late onset VAP whereas members of family Enterobacteriaceae and S. aureus were more common in early onset VAP. This was also reflected in the study conducted by Joseph et al.  This different distribution pattern of etiologic agents between early and late-onset VAP is also linked to the frequent administration of prior antimicrobial therapy in many patients with late-onset VAP.
NFGNB (72.73%) were the predominant pathogens causing VAP in the SICU followed by members of Enterobacteriaceae and S. aureus. On the contrary, in the MICU S. aureus 66.67% was followed by members of Enterobacteriaceae 50% and NFGNB 27.27%. The most consistently effective antibiotics are the carbapenems, combination with monobactum, and the polymyxins. Although 78% isolates of Acinetobacter spp. from early onset VAP were sensitive to carbapenems, piperacillin tazobactum and 90% of late onset isolates resistant to the same; the resistance pattern to other drugs in the panel was almost similar in both types. This is an alarm for the judicious use of carbapenems. All the isolates were sensitive to the last resort drug-the polymyxin: It's all we are left with in this era of desperation. Similar pattern was seen in Pseudomonas as well. Presently there is concern about the acquisition of plasmid mediated, metallo beta-lactamases active against carbapenems, penicillins and cephalosporins. , In the present study, 28.57% % isolates of Acinetobacter spp., and 37.5% of Pseudomonas aeruginosa were MBL producing strains. A total of 75% of the isolates were ESBL producers in the present study. Resistance to third generation cephalosporin was found to coexist with resistance to two or more antibiotics such as ciprofloxacin, gentamicin, chloramphenicol, amikacin and cotrimoxazole. Studies from literature report MRSA more common in late onset VAP.  In our set up to 66.67% (P < 0.05) MRSA isolates were from early onset VAP due to their probable association with diabetes mellitus, coma, renal failure; with history of prior hospitalisation and prior antibiotic therapy.
A comparison of antibiograms of early and late onset VAP pathogens clearly highlights that late onset VAP was associated with higher rates of infection with carbapenems resistant MDR Acinetobacter spp., Pseudomonas spp., Carbapenem resistant Enterobacteriaceae (CRE):  The 'nightmare bacteria' and MRSA. But the resistance of the NFGNB to the other antibiotics was almost the same in both early and late onset VAP comparable to other studies. , Many of the early onset VAP cases had the risk factors such as prior antibiotic therapy and current hospitalisation for 5 days or more or referrals from nursing homes, for infection with MDR pathogens. That could be the reason for the almost similar patterns of antibiotic susceptibility of isolates from early and late onset VAP. Even the ATS guidelines supports the same reasoning by suggesting that patients with early-onset VAP who have received prior antibiotics or who have had prior hospitalisation within the past 90 days are at greater risk for colonisation and infection. The overall mortality rate in the VAP patients was 48.57% in our ICU setting which was in accordance with previous studies like Goel et al., 45.28%.  However it was difficult to comment on the attributable mortality due to VAP. The present study also demonstrated a statistically significant (P < 0.05) mortality rate in late onset type associated with the grotesque battle against the deadly superbugs.
As in the present study only small number of patients with VAP in a single centre were studied, could be considered a limitation of our study. In addition, we recognise that the findings of this study may not necessarily reflect the situations in other similar centres in India. Hence, further multi-centred studies with larger patient numbers could be carried out to confirm our findings, in particular the high incidence of MDR superbugs.
To conclude 'the drug pipeline for new weapons against deadly superbugs is on life support, and novel solutions are required to resuscitate it-now'. Hand hygiene and rational use of antibiotics still remain the best defence to fight against these resilient foes.
| ~ References|| |
American Thoracic Society; Infectious Diseases Society of America. Guidelines for the Management of Adults with Hospital acquired, ventilator associated and Healthcare associated Pneumonia. Am J Respir Crit Care Med 2005;171:388-416.
Craven E, Chroneou A. Nosocomial Pneumonia In: Mandell G, Bennette Dolin R, editors. Principles and Practice of Infectious Diseases. 7 th
ed. London: Elsevier Churchill Livingstone 2005. p. 3717-24.
Camargo LF, De Marc FV, Barbas CS, Hoelz C, Bueno MA, Rodrigues M Jr, et al
. Ventilator associated pneumonia: Comparison between quantitative and qualitative cultures of tracheal aspirates. Crit Care 2004;8:R422-30.
Pugin J, Auckenthaler R, Mili N, Janssens JP, Lew PD, Suter PM. Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and non-bronchoscopic "blind" bronchoalveolar lavage fluid. Am Rev Respir Dis 1991;143:11-21.
Dey A, Bairy I. Incidence of multidrug-resistant organisms causing ventilator-associated pneumonia in a tertiary care hospital: A nine months′ prospective study. Ann Thorac Med 2007;2:52-7.
Forbes BA, Sahm DF, Weissfeld AS. Bailey and Scott′s Diagnostic Microbiology. Infections of the lower respiratory tract. 12 th
ed. St. Louis Missouri: Mosby Elsevier; 2007. p. 811.
Koneman E, Allen SD, Winn W, Janda W, Procop G, Shrechenberger P, et al
. Role of Microbiology Laboratory in the Diagnosis of Infectious Disease. Guidelines to Practise and Management. In: Color Atlas and Textbook of Diagnostic Microbiology. 6 th
ed. Philadelphia: Lippincott Williams and Willkins; 2006. p. 30.
Colle JG, Miles RS, Watt B. Tests for the Identification of bacteria. In: Colle JG, Fraser AG, Marmion BP, Simmons A, editors. Mackie and McCartney: Practical Medical Microbiology. 14 th
ed. New Delhi: Churchill Livingstone; 2007. p. 131-9.
Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing; Twenty second Informational Supplement (M100-S22). Wayne: Clinical and Laboratory Standards Institute; 2012.
Pandya NP, Prajapati SB, Mehta SJ, Kikani KM, Joshi PJ. Evaluation of various methods for detection of metallo-ß-lactamase (MBL) production in gram negative bacilli. Int J Biol Med Res 2011;2:775-7.
Chawla R. Epidemiology, etiology, and diagnosis of hospital-acquired pneumonia and ventilator-associated pneumonia in Asian countries. Am J Infect Control 2008;36 (4 Suppl):S93-100.
Goel V, Hogade SA, Karadesai SG. Ventilator associated pneumonia in a medical intensive care unit: Microbial aetiology, susceptibility patterns of isolated microorganisms and outcome. Indian J Anaesth 2012;56:558-62.
Joseph NM, Sistla S, Dutta TK, Badhe AS, Parija SC. Ventilator-associated pneumonia in a tertiary care hospital in India: Incidence and risk factors. J Infect Dev Ctries 2009;3:771-7.
[Table 1], [Table 2]