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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 6  |  Issue : 4  |  Page : 232-236

Burkholderia cepacia complex bacteremia in pediatric intensive care unit in a tertiary care hospital in North India


1 Department of Microbiology, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
2 Department of Medical Microbiology, PGIMER, Chandigarh, India
3 Department of Paediatrics, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh, India

Date of Submission02-Aug-2018
Date of Decision15-Aug-2018
Date of Acceptance30-Sep-2018
Date of Web Publication21-Nov-2019

Correspondence Address:
Neha Kaushal
Department of Microbiology, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/cjhr.cjhr_118_18

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  Abstract 


Introduction: Burkholderia cepacia complex (BCC) is a nonfermentative Gram-negative bacillus, now increasingly recognized as an important human pathogen causing hospital-acquired infections. Furthermore, it is a rare cause of sepsis in pediatric age group. Objective: The study aimed to determine the pattern of BCC infection in pediatric intensive care unit (PICU), to explore the antibiotic sensitivity profile, and to identify the source of BCC if any within the PICU. Materials and Methods: The study was conducted in the Department of Microbiology and Pediatrics, JNMC, AMU, Aligarh, for a period of 8 months from January 2017 to August 2017. Matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) was done in the Department of Microbiology, PGI, Chandigarh. All the blood cultures received in the enteric laboratory were screened. The isolates were then identified by standard biochemical techniques, and antimicrobial sensitivity was determined by Kirby–Bauer disc diffusion method as per the Clinical and Laboratory Standards Institute guidelines. Identity was confirmed by MALDI-TOF. As the increasing number of BCC infections was being reported, additional samples were collected from the PICU to identify the source. Results: The study involved 35 cases of blood culture-proven septicemia due to BCC among patients admitted in PICU. The first clustering of cases was noted in January 2017 affecting 6 babies. Six months later in August 2017, a second cluster of cases was noted affecting 24 babies. BCC was isolated in 35 samples. Among 30 patients, 20 were infants (including 13 neonates). Ceftriaxone (100%), minocycline (95%), chloramphenicol (85%), and co-trimoxazole (84.6%) were the most effective drugs followed by levofloxacin (79.1%), meropenem (71.4%), and ceftazidime (48.3%). None of the isolates was found to be sensitive to colistin, polymyxin B, cefepime, and tobramycin. BCC was also isolated from samples of Diurese-Nierenszintigraphie (DNS) and injection fentanyl used in PICU which could have possibly served as a source for further infection. Conclusion: BCC is an important cause of bacteremia with high fatality. It possesses the intrinsic resistance to many potent antibiotics. Proper and timely identification can help reduce the mortality, and implementation of infection control measures is essential.

Keywords: Bacteremia, Burkholderia, PICU


How to cite this article:
Kirmani S, Khan F, Kaushal N, Shahid M, Taneja N, Ahmed A. Burkholderia cepacia complex bacteremia in pediatric intensive care unit in a tertiary care hospital in North India. CHRISMED J Health Res 2019;6:232-6

How to cite this URL:
Kirmani S, Khan F, Kaushal N, Shahid M, Taneja N, Ahmed A. Burkholderia cepacia complex bacteremia in pediatric intensive care unit in a tertiary care hospital in North India. CHRISMED J Health Res [serial online] 2019 [cited 2019 Dec 14];6:232-6. Available from: http://www.cjhr.org/text.asp?2019/6/4/232/271324




  Introduction Top


Aerobic nonfermenting Gram-negative bacilli (NFGNB) including organisms such as Pseudomonas spp., Acinetobacter spp., Alcaligenes spp., Stenotrophomonas maltophilia, and Burkholderia cepacia complex (BCC) are a taxonomically diverse group of organisms that either do not utilize glucose as a source of energy or utilize it oxidatively.[1] Among the NFGNBs, BCC is the fourth most common worldwide.[2] BCC is emerging as an important cause of bloodstream infections worldwide, particularly immune compromised patients with hematological malignancies and patients admitted in intensive care unit (ICUs).[3] Besides bacteremia, this organism has been reported to colonize the lungs of patients with cystic fibrosis and to cause a variety of human infections such as septic arthritis, urinary tract infections, peritonitis, and respiratory tract infections.[4],[5] BCC has the ability to survive and multiply in the diverse range of hospital environments such as soil, water, detergent solutions, intravenous (IV) fluids, and antiseptic solutions. They may be isolated from instruments such as ventilator machine, humidifiers, mattresses, and other equipment as well as from the skin of health-care workers.[6]

BCC is intrinsically resistant to many β-lactam drugs, aminoglycosides, colistin, and polymyxin B, the first-line therapeutics of choice against pseudomonal infections.[7] The high level of intrinsic resistance in this organism, coupled with the lack of newer or effective antibiotics, makes treatment options very difficult.[5] Reports of cases of B. cepacia nosocomial infections are rare, probably due to the lack of specific laboratory tests in routine testing in most hospitals, so B. cepacia has been ambiguously reported as NFGNB or simply Pseudomonas spp. This was the case in the routine microbiology laboratory in our department before this study. This also explains the lack of reports about the prevalence of B. cepacia infections in India and many other countries.[5],[8],[9] Therefore, the present study aimed to determine the pattern of BCC infection in pediatric ICU (PICU), to explore the antibiotic sensitivity profile, and to identify the source of BCC if any within the PICU in our tertiary care hospital.


  Materials and Methods Top


The study was conducted in the Department of Microbiology and Pediatrics, JNMC, AMU, Aligarh, for a period of 8 months from January to August 2017. As the increasing number of cases due to BCC was reported, all the samples of blood culture in the enteric laboratory were screened. Blood samples were collected under strict aseptic precautions before starting antimicrobial therapy and inoculated immediately in brain–heart infusion broth and were plated on sheep blood agar and MacConkey agar after 24 and 48 h of incubation. The negative result was followed up by examining the broth daily and doing a final subculture at the 6th day. Isolates were identified by standard biochemical techniques, and further antimicrobial sensitivity was determined by Kirby–Bauer disc diffusion method as per the Clinical and Laboratory Standards Institute guidelines. Wayson staining was also done for identification.

Identification/microbiological analysis

They are Gram-negative, nonfermenting, motile bacilli. On blood agar, opaque and glistening gray-colored colonies were seen. On MacConkey agar, nonlactose-fermenting colonies were seen which were catalase and oxidase positive. On performing Wayson staining, typical bipolar pattern was seen [Figure 1]. Identity was later confirmed by matrix-assisted laser desorption/ionization-time-of-flight which was done in the Department of Microbiology, PGI, Chandigarh. Relevant clinical data were also collected.
Figure 1: Morphology of Burkholderia cepacia complex on Wayson staining

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To identify the source of pathogen, additional samples of common products and equipment were collected from the PICU such as injection dopamine, injection fentanyl, DNS solution, tincture of iodine, cidex, spirit, betadine, paraffin, spirit, IV fluid (dextrose solution), and commonly used antibiotic solutions. An outbreak was suspected, and strict infection control measures were instituted to prevent the spread of infection.

Ethical approval

The permission was taken from Institutional Ethics Committee prior to starting the project. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.


  Results Top


The study included 35 cases of blood culture-proven septicemia due to BCC, among patients admitted to PICU. BCC had affected 30 babies in 8 months. The first clustering of cases was noted in January 2017 affecting 6 babies. Six months later, in August 2017, the second clustering of cases was noted affecting 24 babies.

BCC was isolated in 35 samples collected from 30 children. Among the 30 patients, 20 were infants (including 13 neonates). Five children were in the age group of 1–2 years, 2 each in 2–3 years and more than 5 years' age group, and 1 was in 3–4 years' age group [Table 1]. Males dominated females with a ratio of 2:1.
Table 1: Age-wise distribution of patients infected with Burkholderia cepacia complex

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Twenty-one out of 30 children were preterm including 11 neonates. The ratio of normal vaginal delivery to cesarean section was 2:1. Nineteen children were having low birth weight at the time of delivery. All the children had IV catheter in place. Three children (including 2 neonates) had to be intubated [Table 2].
Table 2: Distribution of factors associated with Burkholderia cepacia complex infection

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Respiratory distress (76.9%) was the most common clinical feature noted followed by decreased food intake (69.2%), fever (61.5%), and decreased activity (53.8%) [Table 3].
Table 3: Clinical features among the patients infected with Burkholderia cepacia complex

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Among the 20 patients who were followed up, 8 expired, 3 were referred to higher centers, and 9 improved after treatment.

Out of 35 samples, BCC was isolated after 24 h of incubation in 27 samples, while in the remaining 8 samples, it was isolated after 72 h of incubation.

On performing antimicrobial sensitivity, ceftriaxone (100%), minocycline (95%), chloramphenicol (85%), and co-trimoxazole (84.6%) were found to be the most effective drugs followed by levofloxacin (79.1%), meropenem (71.4%), and ceftazidime (48.3%). None of the isolates was found to be sensitive to colistin, polymyxin B, cefepime, and tobramycin [Table 4].
Table 4: Sensitivity pattern of Burkholderia cepacia complex species

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BCC was also isolated from samples of DNS and injection fentanyl used in PICU which could have served as source for further infection. Strict infection control measures were instituted to prevent the spread of infection.


  Discussion Top


BCC is being increasingly recognized as an important nosocomial pathogen of humans that causes serious problems in clinical settings because of its high transmissibility between hospitalized patients and its multiple drug resistance.[10],[11],[12] BCC bacteremia should be considered in febrile patients with nosocomial infections, especially those who have an indwelling catheter, are on ventilators, have cystic fibrosis, or have immune dysfunction.

Among the 30 patients, the maximum number of BCC isolates (20, 66.7%) was obtained from infants out of which 13 were neonates. Males dominated females with a ratio of 2:1.

BCC being low virulent, infections are mostly seen in high-risk patients only. Many of our patients had several predisposing factors. The most frequent risk factors were invasive procedures such as IV catheters (100%) and mechanical ventilation (10%) which might have enhanced the susceptibility of already compromised patients due to preterm delivery (70%) and low birth weight (63.3%) in the pediatric ICU. In our study, other risk factors associated with the BCC isolated patients included prolonged hospital stay (66.7%) and prolonged ICU stay (53.3%) which were in concordance with the risk factors mentioned in the study by Mohankumar andShailaja 2016.[2] In the present study, respiratory distress (76.9%) was the most common clinical feature noted followed by decreased food intake (69.2%), fever (61.5%), and decreased activity (53.8%). Among the 20 patients who were followed up, 8 expired, 3 were referred to higher centers, and 9 improved after treatment.

BCC exhibits a broad range of resistance to many antimicrobial agents in vitro. The high level of antibiotic resistance limits the therapeutic options. In the current study, according to the results of antibiotic susceptibility testing by the disk diffusion method, isolates of BCC were most susceptible to ceftriaxone (100%) followed by minocycline (95%), chloramphenicol (85%), and co-trimoxazole (84.6%), followed by levofloxacin (79.1%), meropenem (71.4%), piperacillin–tazobactam (71.4%), and ceftazidime (48.3%). All strains (100%) were resistant to polymyxin, colistin, cefepime, and tobramycin.

Gautam et al. tested 30 isolated strains of BCC and they found that their isolates were susceptible to piperacillin–tazobactam (86.7%), levofloxacin (83.3%), ceftazidime (80%), and tetracycline (76.7%). Among these 30 isolates, maximum resistance was against meropenem (36.7%) and co-trimoxazole (23.3%).[9]

Disbay et al. tested 39 nosocomial strains. They reported that their B. cepacia isolates were most resistant to ceftazidime (61.5%), followed by amikacin and ciprofloxacin (53.8%) each, then meropenem (48.7%), co-trimoxazole (56.4%), and piperacillin–tazobactam (38.4%).[13]

In a study conducted by Nancy et al., 2014, according to the results of antibiotic susceptibility testing by the disk diffusion method, isolates of BCC were most susceptible to meropenem (88.5%), followed by ceftazidime (60%), tobramycin (40%), chloramphenicol (37.1%), piperacillin/tazobactam (25.7%), and tetracycline (5.8%). All strains (100%) were resistant to both co-trimoxazole and ciprofloxacin.

Comparing the results of our study to those three studies, we observed that our strains were more sensitive to meropenem (71.4%) than (51.3%) in Dizbay et al. and (36.7%) in Gautam et al., but our strains were less sensitive to ceftazidime (48.3%) than those of Gautam et al. (80%) and Omar et al. (60%), yet the least sensitivity to ceftazidime was reported by Dizbay et al. (38.5%). No discrepancies are observed as regards to piperacillin–tazobactam, where BCC strains in the study of Gautam et al. and Dizbay et al. were more sensitive to this antibiotic as those tested in our study showing 86.7%, 61.6%, and 71.4% sensitivity, respectively, except that shown by Omar et al. study (25.7%).[14]

Those variations of antibiotic susceptibility results between different countries are probably explained by the different antibiotic policies used.[15],[16] These findings also emphasize even more the need to isolate and test reliably more strains of BCC to review the therapeutic measures.

BCC in the present study showed a lower sensitivity of 84.6% for co-trimoxazole. These findings are in accordance to the study by Fehlberg et al., 2016, who have mentioned a high sensitivity of 97.6% of this antibiotic.[17] Similarly, a sensitivity of 48.3% for ceftazidime is in contrast to the sensitivity of 85% in the study by Kauser et al., 2018 and 93.9% in the study of Fehlberg et al., but Fehlberg et al. had reported a low sensitivity of 30.5% to chloramphenicol as compared to 85% in our study and in the study by Kauser et al., 2018.[7] In our study, a lower sensitivity of 71.4% was achieved for meropenem which matches the study of Kauser et al., 2018, but higher a sensitivity of 100% was reported by Chawla et al., 2013.[6]

Recently, there have been several outbreaks of this organism in PICU setups worldwide. In our study, the first clustering of cases was noted in January 2017 affecting 6 babies. Six months later, in August 2017, a second outbreak was noted affecting 24 babies. An outbreak of.B. cepacia septicemia occurred in the Neonatal Unit (NU) of Kuala Terengganu Hospital, Malaysia, over a 9-week period in 2001 affecting 23 babies and two died. A second outbreak lasting 8 days occurred a year later, affecting 5 babies.[18] In India, in the year 2001–2006, the case fatality rate of Burkholderia was reported as 40 in a study conducted in Chandigarh.[19]

As the increasing number of BCC infections was being observed, a surveillance study was conducted, and samples were collected from the products and equipment used in the PICU such as injection dopa, injection fentanyl, DNS solution, tincture of iodine, cidex, spirit, betadine, paraffin, spirit, IV fluid (dextrose solution), and commonly used antibiotic solutions. We could isolate BCC from DNS and injection fentanyl used in the ICU. Other studies have reported B. cepacia in nosocomial outbreaks due to contaminated disinfectants,[20],[21] nebulizer solutions,[22] medical devices,[23],[24] IV solutions due to contamination of lipid emulsion stoppers,[25] and from moisturizing body milk.[26]

Continuous environmental surveillance and strict infection control policies have to be taken in the health-care setting in order to prevent infections with this saprophyte which is seen ubiquitously including the hospital premises. Isolates of BCC should be considered as nonpathogenic unless proven otherwise. Appropriate isolation procedures rather than antimicrobial therapy should be used to control the spread of BCC colonization among patients.


  Conclusion Top


As more infections by B. cepacia are being reported, this opportunistic pathogen is emerging as a major risk factor to patients and health-care facilities across the world. Due to its ability to thrive in the diverse range of environments, and being one of the most antimicrobial-resistant organisms encountered in the clinical laboratory, BCC contributes to increased morbidity and mortality in hospitalized patients. Various outbreaks and pseudo-outbreaks of BCC septicemia have also been documented in these patients. Through this report, we are highlighting that B. cepacia is a not-so-uncommon organism in causing ICU sepsis in pediatric age group. Clinicians, especially from the tropics and the developing nations, must be made aware as to how to detect and combat this emerging infection with a potentially fatal outcome.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Mohankumar A, Shailaja TS. Epidemiology of Burkholderia complex infections in a tertiary care centre. Int J Recent Trends Sci Technol 2016;18:405-8.  Back to cited text no. 2
    
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Braunwald E, Hauser SL, Longo DL, Jameson JL, Ramphal R, Fauci AS, et al. Infections due to Pseudomonas species and related organisms. In: Fauci AS, editors. Harrison's Principles of Internal Medicine. 17th ed., Ch. 145. USA: McGraw-Hill Medical; 2008. p. 949-56.  Back to cited text no. 3
    
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Chawla K, Vishwanath S, Munim FC. Nonfermenting gram-negative bacilli other than Pseudomonas aeruginosa and Acinetobacter spp. causing respiratory tract infections in a tertiary care center. J Glob Infect Dis 2013;5:144-8.  Back to cited text no. 6
    
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