Emergence  of Unusual Gram - Negative Bacteria Among Cancer Patients in a Tertiary Care Cancer Centre at North Kerala.

Murugesan S

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OJHAS Vol. 17, Issue 4: (October-December 2018)

Original Article
Emergence of Unusual Gram - Negative Bacteria Among Cancer Patients in a Tertiary Care Cancer Centre at North Kerala

Authors:
Saravanan Murugesan, Parthiban Rudrapathy, Sajani Samuel,
Microbiology Division, Department of Clinical Laboratory Services and Translational Research, Malabar Cancer Centre, Thalassery, Kannur, Kerala - 670103.

Address for Correspondence
Dr. Saravanan Murugesan,
Lecturer, Microbiology Division,
Department of Clinical Laboratory Services and Translational Research,
Malabar Cancer Centre,
Thalassery, Kannur,
Kerala – 670103.
E-mail: microbiosaravanan@gmail.com.

Citation
Murugesan S, Rudrapathy P, Samuel S. Emergence of Unusual Gram - Negative Bacteria Among Cancer Patients in a Tertiary Care Cancer Centre at North Kerala. Online J Health Allied Scs. 2018;17(4):7. Available at URL: https://www.ojhas.org/issue68/2018-4-7.html

Submitted: Dec 12, 2018; Accepted: Jan 10, 2019; Published: Jan 30, 2019

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This work is licensed under a Creative Commons Attribution-No Derivative Works 2.5 India License

Abstract: Patients with cancer are at a high risk of infection and often the focus of the infection is not apparent. Blood- stream infections (BSIs) have been the leading complications in such patients. Bacteria are the primary causative agents of BSIs. However, in recent years, unusual gram-negative bacteria i.e. Stenotrophomonas, Burkholderia, Elizabethkingia, etc., have emerged as potential human pathogens in cancer patients. Hence, the current study was performed to analyze the unusual GNB and their antibiotic susceptibility profile in BSIs among cancer patients in a tertiary care cancer centre. This retrospective study was conducted at a tertiary care cancer centre at North Kerala. We analyzed microbiological profile of blood cultures received in the Microbiology Division from January 2016 to December 2017. All the blood cultures were processed by using automated blood culture system (Bactec 9050). The positive cultures were analyzed by automated identification and susceptibility systems (ViteK 2 compact). During the 2-year period, a total of 4154 blood cultures were done out of which 385 (9.2%) cultures yielded growth. Overall, 15 different species (n = 27/385; 7%) of unusual GNB pathogens was found from 385 positive cases. Burkholderia cepacia complex (n = 4) is the most common species followed by Pseudomonas putida (n = 3), Chryseobacterium gleum (n = 3), etc. This study revealed the emergence of unusual GNB as potential drug-resistant nosocomial pathogens in patients with cancer.
Key Words: Unusual Gram-negative bacteria, Cancer patients, Antibiotic resistance

Introduction:

Bloodstream Infections (BSIs) are a major cause of life-threatening complications in patients with malignancies which is associated with delay in chemotherapy, longer hospital stay, higher mortality rate and increased healthcare costs (1,2). Although, members of the family Enterobacteriaceae constitute majority of these infections, unusual Gram negative bacilli (GNB) like Burkholderia species, Stenotrophomonas species, Elizabethkingia species etc. are increasingly identified mainly due to improvement in diagnostic testing (3-5). These unusual GNBs are usually pan drug resistant and generally colonise the hospital environment. Owing to the temporal variation of occurrence of unusual GNB infections in immuno compromised patients and the changing pattern of antibiotic susceptibility profiles, periodic surveillance is required.

Hence, the current study was performed to analyze the likely etiologic agents and the antibiotic sensitivity profile of unusual GNB causing BSIs among cancer patients in a tertiary care cancer centre.

Methods

We analyzed the microbiological profile of blood cultures received in the Microbiology Division from January 2016 to December 2017. The samples included peripheral blood, blood drawn through catheters and catheter tip from patients with clinical malignancy. This study was approved by Institutional Review Board (1616/IRB-SRC/13/MCC/23-1-2018/8).

Microbiological and susceptibility results of all patients were retrieved from the microbiology laboratory database. All blood cultures during the study period were processed by the Bactec 9050 automated blood culture system (Becton Dickinson) according to manufacturer’s protocol. The positive signals from blood cultures when detected were immediately Gram stained and cultured on Blood agar and MacConkey agar for confirmation. After performing culture, Bacterial identification and susceptibility was done by using BD PhoenixTM (Becton Dickinson) from January 2016 to October 2017 and thereafter by using VITEK2 Compact system (Biomerieux, France).

As there are no established Clinical and Laboratory Standards Institute (CLSI) breakpoints for few unusual GNB (6), the interpretive breakpoints for Enterobacteriaceae and Pseudomonas were used. The isolates were further tested against piperacillin-tazobactam 100/10 µg, gentamicin 10 µg, amikacin 30 µg, ceftazidime 30 µg, cefepime 30 µg, chloramphenicol 30 µg, meropenem 10 µg, levofloxacin 5 µg, minocycline 30 µg and trimethoprim/sulfamethoxazole 1.25/23.75 µg. Antibiotic discs were obtained from HiMedia Lab (Mumbai, India). Strains of S. aureus ATCC 25923, E. coli ATCC 25922 and P. aeruginosa ATCC 27853 were used for quality control (QC).

Results

During the study period, a total of 4154 blood cultures were received by the microbiology division, out of which there were 385 (9.2%) positive blood cultures. A total of fifteen unusual GNB pathogens (n = 27/385; 7%) were found in our study from 385 bacterial pathogens (Table I). Two patients had blood cultures positive for two species of unusual GNB. The first patient had bacteremia caused by Sphingobacterium multivorum from central line and Comomonas testosteroni from peripheral line. The second patient had bacteremia caused by Burkholderia cepacia from central line and Sphingobacterium multivorum from peripheral line.

Out of the 27 unusual GNB, Burkholderia cepacia complex (n = 4) is the most common species followed by Pseudomonas putida (n = 3), Chryseobacterium gleum (n = 3), Elizabethkingia meningoseptica (n = 2), etc. The list of etiological agents was given in Table 1.

Table 1: Distribution of unusual pathogens according to tumor types
Type of tumor	*B. cepacia*	*C. gleum*	*P. putida*	*E. meningoseptica*	*S. plymuthica*	*S. multivorum*	*S. paucimobilis*	*S. maltophila*	*C. testostereni*	*C. violaceum*	*P. agglomerans*	*B. gladioli*	*C. farmerii*	*P. multocida*	*A. faecalis*
Lung cancer		1		1						1
Gastric cancer			1					1			1
Lymphoma	1	1
Breast cancer													1		1
Pancreatic cancer			1		1
Rectal cancer					1	1			1
Colon cancer	1					1		1				1
Sarcoma	1	1
Osteosarcoma							1
Ovarian cancer				1			1
Non hodgkins lymphoma	1
AML Relapse			1
Squamous cell carcinoma														1
Total	4	3	3	2	2	2	2	2	1	1	1	1	1	1	1

Details of antimicrobial susceptibility are shown in Table 2. Majority of the isolates were sensitive to co-trimoxazole. Two isolates of B. cepacia complex (n = 2/4; 50%), E. meningoseptica (n = 2/2; 100%) and C. gleum (n = 3/2; 66.6%) were found to be multidrug resistance (MDR) respectively.

Table 2: Antimicrobial susceptibility of unusual Gram negative pathogens
Bacterial species (n)	Amikacin	Gentamicin	Levofloxacin	Ceftazidime	Cefepime	Chloramphenicol	Meropenem	Minocycline	Co-trimoxazole	Piperacillin-tazobactum
	Number of resistant isolates (percentage of resistant)
B. cepacia complex (n = 4)	-	-	2 (50)	3 (75)	-	3 (75)	4 (100)	1 (25)	2 (50)	-
C. gleum (n = 3)	3 (100)	3 (100)	1 (33)	3 (100)	-	-	3 (100)	3 (100)	0 (0)	3 (100)
P. putida (n = 3)	0 (0)	-	1 (33)	1 (33)	-	-	0 (0)	-	2 (66)	1 (33)
E. meningoseptica (n = 2)	1 (50)	1 (50)	2 (100)	2 (100)	2 (100)	-	2 (100)	-	1 (50)	2 (100)
S. plymuthica (n = 2)	0 (0)	0 (0)	1 (50)	-	2 (100)	-	0 (0)	-	1 (50)	0 (0)
S. multivorum (n = 2)	1 (50)	2 (100)	0 (0)	2 (100)	2 (100)	-	2 (100)	-	0 (0)	1 (50)
S. paucimobilis (n = 2)	0 (0)	0 (0)	0 (0)	-	1 (50)	-	0 (0)	-	0 (0)	1 (50)
S. maltophila (n = 2)	-	-	1 (50)	2 (100)	-	0 (0)		1 (50)	0 (0)	2 (100)
B. gladioli (n = 1)	-	-	1 (100)	0 (0)	-	-	0 (0)	0 (0)	1 (100)	0 (0)
C. farmerii (n = 1)	0 (0)	1 (100)	1 (100)	-	1 (100)		0 (0)		0 (0)	0 (0)
C. violaceum (n = 1)	1 (100)	1 (100)	0 (0)	-	0 (0)	-	1 (100)	0 (0)	0 (0)	0 (0)
P. agglomerans (n = 1)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	-	0 (0)	-	0 (0)	0 (0)

Discussion

To our knowledge, this is the first study conducted in Kerala to report the unusual GN pathogens causing BSIs among cancer patients. This retrospective study disclosed several important findings. Fifteen different species (n = 27/385; 7%) of unusual GNB was found in our study. These are very problematic because of their ubiquitous distribution in diverse environmental sources and their antimicrobial resistance (5). The problem of infection with multidrug resistant organisms is further compounded by the immunocompromised status of cancer patients due to the use of chemotherapy, immunosuppression, catheterization and sub optimal nutrition (2). The distribution of unusual GNB reported in the study was more diverse than previous studies (2,4,7).

In this study, among the unusual GNB isolated, B. cepacia complex was the predominant isolate followed by C.gleum, P. putida and E. meningoseptica. B. cepacia is a pathogen usually causing infection in immunocompromised patients and their transmission is reported to be through medical devices used in Intensive Care Unit (ICU) (3). Co-trimoxazole is the drug of choice for the treatment of infections caused by B. cepacia along with ceftazidime and meropenem alone or in combination with other antibiotics. Two isolates of B. cepacia complex (n = 2/4; 50%) were found to be MDR.

C. gleum (n = 3) and P. putida (n = 3) were noted as the second leading causative pathogen in this study. C. gleum iscommonly found on moist hospital surfaces, like wash basins and dressing trolleys and can cause severe nosocomial infections especially in immunocompromised, critically ill patients (8). P. putida causes infections such as pneumonia, catheter infections, bacteremia, etc. All the isolates of C. gleum (n = 3) were found to be MDR which was not consistent with previous report (10). There are no published reports of C. gleum causing BSIs in cancer patients. Three isolates of P. putida were found to be susceptible to amikacin, meropenem, whereas one isolate showed resistance to ceftazidime, levofloxacin, cotrimoxazole, piperacillin-tazobactum.

Recently, S. maltophilia has arisen as a crucial nosocomial pathogen responsible for high mortality rate (10). All the isolates were found to be resistant to ceftazidime, whereas all the isolates were found to be susceptible to co-trimoxazole. Co-trimoxazole is a first line drug for the treatment of S. maltophilia infections owing to its good susceptibility and clinical outcomes in the treated patients. According to our susceptibility result, however, co-trimoxazole appeared to be the most promising therapeutic option which was consistent with the previous reports (4,10).

Polymicrobial BSIs (PBSIs) is a frequent and difficult to treat complication in cancer patients and is responsible for high mortality rates. Cholangitis, neutropenic enterocolitis, abdominal infection and perirectal infection were more frequent in patients with PBSIs. In this study, two patients were found to be PBSIs from rectal and colon cancer respectively. Physicians should identify patients at risk for PBSIs and provide empiric antibiotic therapy that covers the most frequent pathogens involved in these infections, including MDR strains of unusual GNB (11).

Conclusion

Overall, the present surveillance study revealed different unusual GNBs as causative agents in BSIs among cancer patients with their antibiotic susceptibility profile. Periodic surveillance of aetiologic agents and their susceptibility pattern is required for successful empiric treatment of BSIs in immune compromised patients.

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