|Year : 2022 | Volume
| Issue : 3 | Page : 97-101
Antibiotic stewardship and microbiological aspects of ventilator-associated pneumonia in patients undergoing cardiac surgery
K Supraja1, Thangam Menon2, Mullasari Ajit Sankardas3, Anusha Rohit4, S Sharmila1, SM Subathra1
1 Department of Pulmonology, The Madras Medical Mission, Chennai, Tamil Nadu, India
2 Department of Microbiology, Saveetha Dental College and Hospitals, Chennai, Tamil Nadu, India
3 Department of Cardiology, The Madras Medical Mission, Chennai, Tamil Nadu, India
4 Department of Microbiology, The Madras Medical Mission, Chennai, Tamil Nadu, India
|Date of Submission||29-May-2022|
|Date of Decision||19-Jul-2022|
|Date of Acceptance||28-Aug-2022|
|Date of Web Publication||01-Mar-2023|
Dr. K Supraja
No. 4 A, Dr. JJ Nagar, The Madras Medical Mission, Chennai - 600 037, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Purpose: Infections are a serious threat in the postoperative period in cardiac surgical patients. Ventilator-associated pneumonia (VAP) is caused by multidrug-resistant organisms resulting in high mortality. Our aim is to study the prevalence of VAP, the organism associated with it and the appropriate management. Materials and Methods: Three thousand consecutive patients who underwent cardiac surgery were included and followed from admission till discharge. All baseline characteristics and intra- and postoperative details were collected. Data on microbiological sampling were noted. The duration of ventilation and time point at which samples were sent, microbiological growth, its sensitivity, and antibiotics used were analyzed. The reassessment of the need for antibiotics at the end of 48 h of sending culture and switching based on the sensitivity (antibiotic time-out) was also captured. Results: Forty-eight patients had VAP (12.78 per 1000 ventilator days); 38 patients had culture-proven growth. The most common organism in our setting was Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. The resistance to β-lactams, cephalosporins, and carbapenems was high. Dual and triple antibiotic therapies were noted in 64% of patients. Failure to adhere to antibiotic time-out was associated with mortality in patients when it was adhered and not adhered (27% vs. 74%, respectively) (<0.015). Conclusions: The incidence of VAP in our setting is very low. However, VAP remains a serious threat and carries a high mortality. A high degree of suspicion, timely diagnosis, usage of appropriate antibiotics based on local antibiogram, and following antibiotic time-out will help to reduce the intensive care stay and mortality.
Keywords: Cardiac surgery, pneumonia, ventilator
|How to cite this article:|
Supraja K, Menon T, Sankardas MA, Rohit A, Sharmila S, Subathra S M. Antibiotic stewardship and microbiological aspects of ventilator-associated pneumonia in patients undergoing cardiac surgery. J Assoc Pulmonologist Tamilnadu 2022;5:97-101
|How to cite this URL:|
Supraja K, Menon T, Sankardas MA, Rohit A, Sharmila S, Subathra S M. Antibiotic stewardship and microbiological aspects of ventilator-associated pneumonia in patients undergoing cardiac surgery. J Assoc Pulmonologist Tamilnadu [serial online] 2022 [cited 2023 Mar 21];5:97-101. Available from: https://www.japt.in//text.asp?2022/5/3/97/370805
| Introduction|| |
Hospital-acquired infections are a major threat to the recovery of patients undergoing cardiac surgery. The most common infections are deep sternal wound infections, bloodstream infections, urinary tract infections, and pneumonia. These infections are an important cause of morbidity, mortality, and translate into prolonged intensive care unit (ICU) stay and hospital stay, and further increase the cost of health care.,
Ventilator-associated pneumonia (VAP) is defined as “pulmonary infection developing 48 h or more after initiation of mechanical ventilation.” The prevalence of VAP in cardiac surgical patients was 6.37% (2.1%–13%), the incidence of new-onset VAP was 35.2%, and 21.27 episodes per 1000 mechanical ventilation days. VAP is associated with high mortality rate ranging between 24% and 76% with a 15%–45% attributable mortality.,,
The majority of organisms involved in VAP are gram-negative bacilli, namely, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, and Escherichia More Details coli; gram-positive organism such as Staphylococcus aureus was also documented. The distribution of organisms depends on the ICU and the institution. Hence, antibiotics administered should be based on local antibiogram and sensitivity. Early administration of antibiotics reduces the severity of VAP and avoids prolonged stay in ICU, but should be tailored based on antibiotic sensitivity tests to avoid drug resistance.
Our aim in this study was assessing the microbiological aspects of organisms producing VAP. Our objective was to understand the usage of antibiotics by physicians and whether stewardship is diligently followed, length of stay (LOS) in ICU and in the hospital.
| Materials and Methods|| |
This prospective observational study was carried out in the Madras Medical Mission, a tertiary-level cardiac center with 250 beds in Chennai, India. The Department of Cardiac Surgery annually performs approximately 2000 adult cardiac operations. It is a certified Green OT with five operating rooms. A 26-bedded ICU with a 12-bedded step-down ICU is dedicated exclusively to the postoperative care of patients who have undergone cardiac surgery. During 2 years (December 2017–December 2019), all consecutive patients undergoing cardiac surgery who were potentially eligible were included in the study. Patients were excluded if they were younger than 18 years, if they had undergone heart transplantation, had an active infection and if unwilling to consent to participate. The Institutional ethics committee approved the study. All patients, preoperatively, provided informed written consent both for their heart surgery and for their participation in the study.
Study design, endpoint, and data collection
The type of the study was a prevalence study. Consecutive sampling was adopted and all patients undergoing cardiac surgery during the study period were enrolled. Patients were evaluated for ventilator-associated events such as a change in positive end-expiratory pressure, change in FIO2, new onset of fever, increasing white blood cell count, purulent secretions, change of antibiotics, and requirement of culture for diagnosis of infection were all documented. Samples which fulfilled the criteria for VAP by definition were included in the analysis.
The diagnosis and sending of respiratory microbiological samples and treatment protocol were left to the discretion of the treating physician and the investigator did not have any say on this. A study coordinator collected data on a daily basis of the study patients in ICU and followed them until discharge or death. Patients fulfilling the criteria for VAP were then analyzed for the pattern of organism and sensitivity. Further, the antibiotics were used, and the dose duration was documented and analyzed.
Data were collected from the patient chart and noted in preformatted questionnaire. This was then entered into Epi Info software by two independent persons to minimize typographical errors.
All definitions were selected at the beginning of the original study design.
VAP was defined as “on or after day 3 of mechanical ventilation and within 2 days of worsening of oxygenation, one of the following criteria was met:
- Purulent respiratory secretions – The presence of 3+ or 4+ PMNL in gram stain in secretions from the lung, trachea, or bronchi
- Positive culture of sputum, endotracheal aspirate, bronchoalveolar lavage (BAL), lung tissue, or protected brush specimen (excluding Candida, normal respiratory flora, coagulase-negative Staphylococcus species, Enterococcus)
- Microbiological samples sent before 48 h of ventilation were excluded from etiological analysis
- Reintubation done within 24 h was accounted as part of current ventilation”.
Sampling of the lower respiratory tract was done by endotracheal aspiration (ETA) and/or bronchoalveolar lavage. For ETA, we obtained undiluted tracheal secretions, if unproductive; irrigation with 5 mL of Ringer's lactate solution was done. A bacterial count of 105 colony-forming unit (CFU) per milliliter for ETA and 104 CFU per milliliter and above was considered positive for BAL. Bacterial counts of 10^3 in BAL were reported with caution if numerous polymorphonuclear leukocytes were seen along with intracellular organisms. Standard microbiological techniques were used for culture and organisms were identified and susceptibility testing was done with a combination of Vitek® 2 Compact (bioMérieux, France), broth microdilution and modified Kirby–Bauer disk diffusion method based on the Clinical and Laboratory Standards Institute (CLSI) M 100 guidelines., Episodes with > one pathogenic microorganism were considered polymicrobial.
Eight isolates were subjected to testing for carbapenemases by the Gene Xpert Carba-R assay (Cepheid, USA) to check for the presence of IMP, OXA-48, NDM, VIM, and KPC from the isolates directly. Results were obtained in 1 h as against 18–24 h for the susceptibility results.
Epi Info™ 126.96.36.199 by the Centers for Disease Control and Prevention was used for data entry.
| Results|| |
Of the 3000 patients, 48 (1.6%) developed VAP. The mean duration to develop VAP was 115 h following intubation. Twenty-six (54%) cases occurred in <4 days. Positive microbial isolates with significant counts were obtained for 38 (79%) persons. The total number of organisms isolated was 45. Respiratory samples from the endotracheal tube and bronchial and tracheal aspirations were included in the study.
The organism recovered from the respiratory secretions was isolated in the Vitek® 2 Compact system. The profile of the organisms is included in [Table 1]. The common pathogens isolated were K. pneumoniae, A. baumannii, and P. aeruginosa. Gram-positive organisms were not common in our setting. The minimum number of organisms required to create an antibiogram is 30 in accordance with CLSI M39-A4, Analysis and Presentation of Cumulative Antimicrobial Susceptibility Test data. Hence, no organisms individually qualify. However, looking at each organism along with the susceptibility profiles, the following can be concluded [Table 2], [Table 3], [Table 4].
|Table 1: Microorganisms isolated from ventilator-associated pneumonia cases|
Click here to view
Antibiotic susceptibility was done using a combination of Vitek® 2 Compact, Kirby–Bauer disk diffusion, and broth microdilution for all organisms isolated. Depict the susceptibility pattern of the most common pathogens. Only 31.5% of the K. Pneumoniae showed susceptibility to the third-generation cephalosporins with an extended-spectrum β-lactamase rate of 68.5%. These isolates also showed an increased resistance to carbapenems with only 31.5% of the 19 isolates showing susceptibility. The antibiotic susceptibility profile of the eight A. baumannii was very interesting as 75% showed susceptibility to gentamicin, 50% to co-trimoxazole, 25% to amikacin, and 12.5% to minocycline. All other antibiotics were resistant in all the patients. P. aeruginosa was isolated in seven patients and showed 57% susceptibility to ceftazidime and 43% susceptibility to all other antibiotics tested. Other organisms like E. coli were isolated in only three patients and all isolates showed susceptibility to carbapenems and aminoglycosides.
Carbapenemase resistance testing was done for eight isolates depending on the economic affordability of the patient. Carbapenemase genes (Oxa-48 and NDM) were detected in five isolates. Oxa-48 was the most common type of carbapenemase gene in 4 of the isolates and one isolate had a combination of Oxa-48 and NDM genes. No resistance mechanism was detected in 3 isolates.
The initial antibiotic used for surgical antibiotic prophylaxis (SAP) was cefuroxime (85.41%) with mean duration of antibiotic prophylaxis of 2.46 days. Cefoperazone sulbactam was used in 10.41% of patients, with mean duration of 4.4 days of antibiotic prophylaxis (in patients undergoing valve surgery). The antibiotic usage pattern is shown in [Table 2]. All 48 patients were on the SAP antibiotics before sending cultures. Twenty-two patients were on dual and nine were on triple antibiotics and the mean duration of antibiotics was 8.7 days. Based on cultures, 27 required escalation of therapy and it was done in 12 cases. Switching to oral antibiotics when appropriate was not done for this cohort of patients.
Antibiotic timeout is defined as the evaluation of ongoing antibiotic treatment needed after 48 h of sampling cultures. In our cohort, it was followed only in 11/38 patients. The mortality in the group where antibiotic time out was followed was 27% (3/11) compared to 74.04% (20/27) in the other group. There was a strong association between failure to follow antibiotic timeout with mortality (P < 0.015).
| Discussion|| |
The spectrum of microbial infection varies in each ICU. There is limited data on the incidence of VAP in cardiac surgical ICUs from the Indian subcontinent. We closely monitored 3000 patients who underwent cardiac surgery from admission till discharge. Of these, 48 (1.6%) patients fit into the criteria of VAP (as per our study definition mentioned in methodology). This is less in comparison with similar studies done in India and Western countries., The reason for the low prevalence of VAP can be as follows: (a) More than one-third of patients underwent off-pump surgery and the average duration of ventilation was 16 h when compared to on-pump where it was 24 h; (b) early extubation of patients whenever feasible; (c) preoperative optimizing of patients with preexisting lung disease to help them wean off the ventilator faster.
In our study, the predominant pathogens isolated include K. pneumoniae, A. baumannii, and P. aeruginosa similar to Western literature that shows Enterobacterales and P. aeruginosa implicated in VAP.
Our isolates showed increased resistance to multiple antibiotics and many isolates were multidrug resistant. For example, among the K. pneumoniae isolated, only 68.5% were susceptible to meropenem and beta-lactam beta-lactamase inhibitors like piperacillin/tazobactam. Treatment options for A. baumannii were very few with only gentamicin being susceptible in 75% of the isolates. P. aeruginosa showed 57% susceptibility to ceftazidime but 43% of isolates were susceptible to all other antibiotics tested. E. coli showed good susceptibility to carbapenems and aminoglycosides but all organisms showed poor susceptibility to fluoroquinolones and third-generation cephalosporins. Imipenem and aminoglycosides exhibited excellent activity against gram-negative organisms.
Carbapenemase resistance testing was done in eight patients, of which five had resistance detected (four OXA-48 resistant and one OXA-48 and NDM resistant) and in three patients no resistance was noted. This information throws light on the significance of the prevalent resistance of organisms causing pneumonia and the need to aggressively treat with appropriate antibiotics to prevent death.
The initial SAP antibiotic used was cefuroxime and the mean duration was 2.46 days, and in 10.41% of patients, cefoperazone sulbactam was used with a mean duration of 4.4 days as compared to the 48 h recommended by the hospital SAP policy. The other drugs used either alone or in combination as dual or triple antibiotics are amikacin, cefuroxime, piperacillin/tazobactam, teicoplanin, carbapenems and colistin. All 48 cases had exposure to antibiotics before sending cultures to the laboratory. Despite antibiotic treatment, 38 had significant growth. VAP is associated with prolonged ICU and hospital stay and increased mortality.,,, In our study, mortality was 56%, the mean duration of stay in ICU was 14.9 days and total hospital stay was 22 days.
In this study, we investigated the appropriateness of using antibiotics after sending cultures to the laboratory [Table 5]. Twenty-two patients were on dual and nine on the triple antibiotic cover around the time of sending cultures. Antibiotic escalation was required in 27 patients based on sensitivity and was done in only 9 (33%) patients. Continuation of same and de-escalation of antibiotic was required in five and six patients, respectively, and was done only in one patient in both categories. This failure to switch antibiotics (especially escalation) at the appropriate time was associated with increased mortality. The mortality in the group where antibiotic time was followed and not followed was 27% (3/11) and 74% (20/27), respectively. We noted a strong association between failure to follow antibiotic timeout with increased mortality (P < 0.015). This finding highlights the importance of antibiotic tailoring once the sensitivity is identified. In all 48 patients, antibiotic switch to oral antibiotics was not done after the initial course of appropriate antibiotics.
| Conclusions|| |
In summary, VAP is caused by highly resistant bacteria, resulting in significant increase in ICU stay and hospital stay. It is important to send cultures at the appropriate time and change antibiotics according to susceptibility results. This will greatly reduce the cost of treatment and help reduce preventable loss of life and reduce LOS. Antibiotic time-out should be done at the end of 48 h of sending samples to the microbiology laboratory to ensure optimal patient care.
We would like to thank Antara Patra for secretarial assistance.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]