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 ~  Abstract
 ~ Introduction
 ~ Subjects and Methods
 ~ Results
 ~ Discussion
 ~ Conclusion
 ~  References
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BRIEF COMMUNICATION
Year : 2016  |  Volume : 34  |  Issue : 3  |  Page : 355-358
 

Reduced susceptibility of carbapenem-resistant Klebsiella pneumoniae to biocides: An emerging threat


Department of Microbiology, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, New Delhi, India

Date of Submission07-Nov-2015
Date of Acceptance28-Jun-2016
Date of Web Publication12-Aug-2016

Correspondence Address:
M Bhatia
Department of Microbiology, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0255-0857.188345

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 ~ Abstract 

Dealing with carbapenem-resistant Klebsiella pneumoniae (CR-Kp) strains, which are generally pan-drug resistant, is an uphill task for health care professionals. Owing to limited therapeutic options and the possibility of development of resistance to commonly used biocides in hospital settings, CR-Kp infections pose a serious threat of emergence of a dreaded pandemic. The aim of the study was to highlight the possibility of emergence of biocide resistance among CR-Kp strains. A case study was conducted in a Super-specialty Hospital in September 2015. A 65-year-old female patient post-laparotomy was admitted to the General Intensive Care Unit of a Super-specialty Hospital. CR-Kp was isolated from the blood and mucus trap samples of this patient. Susceptibility testing of three commonly used biocides in our hospital, namely sodium hypochlorite (4% available chlorine), 5% w/v povidone iodine (0.5% w/v of available iodine) and absolute ethanol (99.9%), respectively, was carried out using K. pneumoniae ATCC 700603 as control. The test isolate showed reduced susceptibility to sodium hypochlorite in comparison to K. pneumoniae ATCC 700603. The possibility of emergence of biocide resistance among CR-Kp strains poses a threat of disrupting our ongoing efforts for implementation of effective infection control measures.


Keywords: Absolute ethanol, carbapenem-resistant Klebsiella pneumoniae, povidone iodine, sodium hypochlorite


How to cite this article:
Bhatia M, Loomba P S, Mishra B, Dogra V, Thakur A. Reduced susceptibility of carbapenem-resistant Klebsiella pneumoniae to biocides: An emerging threat. Indian J Med Microbiol 2016;34:355-8

How to cite this URL:
Bhatia M, Loomba P S, Mishra B, Dogra V, Thakur A. Reduced susceptibility of carbapenem-resistant Klebsiella pneumoniae to biocides: An emerging threat. Indian J Med Microbiol [serial online] 2016 [cited 2020 Sep 18];34:355-8. Available from: http://www.ijmm.org/text.asp?2016/34/3/355/188345



 ~ Introduction Top


Carbapenem-resistant Enterobacteriaceae (CRE), especially carbapenem-resistant Klebsiella pneumoniae (CR-Kp), has been steadily spreading worldwide during the last decade. [1] These strains are generally pan-drug resistant and are associated with very high mortality. Owing to limited therapeutic options and the possibility of development of resistance to commonly used biocides in hospital settings, infections caused by CR-Kp pose a serious threat of emergence of a dreaded pandemic. We hereby present a brief report highlighting these issues.


 ~ Subjects and Methods Top


This study was conducted in a Super-specialty Hospital in September 2015. A 65-year-old female patient post-laparotomy was referred from a tertiary care hospital and admitted in the General Intensive Care Unit (GICU) of our hospital. The patient had persistent high-grade fever and spikes of high blood pressure despite being on treatment with anti-hypertensive drugs, which she had been taking for 4 years. As per the information available from case sheets of the referring hospital, this patient had been subjected to total abdominal hysterectomy with bilateral salpingo-oophorectomy and infra-colic omentectomy for uterine sarcoma associated with intra-abdominal bleeding 2 months ago. She had also received one cycle of chemotherapy post-operatively. Subsequently, the patient developed abdominal distension, vomiting, intractable diarrhoea and breathlessness, for which an abdominal tap was done and intravenous antibiotics (record not available) and fluids were administered. Although ascitic fluid culture was sterile and its biochemical and cytological analysis did not reveal any abnormality, this patient showed only marginal clinical improvement.

On examination at the time of admission of this patient in the GICU of referral hospital, the following parameters were recorded: temperature: 102°F, blood pressure: 130/100 mmHg, pulse rate: 150/min and peripheral capillary oxygen saturation: 99%. Systemic examination did not reveal any abnormality. The following antimicrobials namely doripenem, daptomycin, tigecycline and metronidazole along with intravenous 5% dextrose normal saline, injection perinorm and injection enoxaparin were administered to this patient. However, the patient deteriorated further and developed respiratory distress due to which she was intubated. Blood and mucus trap samples obtained from this patient were sent for culture. K. pneumoniae resistant to ampicillin, amoxicillin-clavulanate, piperacillin-tazobactam, ticarcillin-clavulanate, cefuroxime, cefuroxime axetil, cefepime, ceftriaxone, cefotaxime, ceftazidime, imipenem, meropenem, doripenem, ertapenem, amikacin, gentamicin, netilmicin, tobramycin, colistin, co-trimoxazole, ciprofloxacin and ofloxacin and intermediate sensitive to tigecycline was repeatedly isolated from both these samples. While VITEK-2 automated bacterial identification system (BioMerieux Delhi, India, Pvt., Ltd.) was used to identify and determine susceptibility to several of these aforementioned antibiotics, the susceptibility to cefotaxime, ceftazidime, ofloxacin, netilmicin, tobramycin and ticarcillin-clavulanate was determined using modified Kirby-Bauer disk diffusion method. [2] The susceptibility to doripenem was determined using E-test strip (BioMerieux Delhi, India, Pvt., Ltd.) using K. pneumoniae ATCC 700603 as control strain. Clinical and Laboratory Standards Institute guidelines 2015 were used for interpreting the antibiotic susceptibility results. This isolate was also subjected to tube dilution method suggested by Mazzola et al. [3] for determining minimum inhibitory concentration (MIC) of three commonly used biocides in our hospital namely sodium hypochlorite (4% available chlorine), 5% w/v povidone iodine (0.5% w/v of available iodine) and absolute ethanol (99.9%). Minimum bactericidal concentration (MBC) of these biocides was determined by sub-culturing from each of these tubes onto blood agar plates which were then incubated aerobically at 37°C for 24 h. The highest dilution of biocide at which no growth was obtained on blood agar plates was taken as MBC. Similar tests were also performed on K. pneumoniae ATCC 700603 which was taken as control strain.


 ~ Results Top


The MIC and MBC results of sodium hypochlorite (4% available chlorine), 5% w/v povidone iodine (0.5% w/v of available iodine) and absolute ethanol (99.9%) for test isolate and K. pneumoniae ATCC 700603 are shown in [Table 1]. Reduced susceptibility to sodium hypochlorite was observed in test isolate in comparison to control strain. [Figure 1] and [Figure 2], respectively, depict the E-test based MIC results of doripenem for test isolate and K. pneumoniae ATCC 700603.
Figure 1: E-test demonstrating doripenem resistance (minimum inhibitory concentration ≥4 ƒÊg/ml) in Klebsiella pneumoniae isolated from the blood and mucus trap samples of the patient under study

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Figure 2: E-test demonstrating doripenem susceptibility (minimum inhibitory concentration ≤1 ƒÊg/ml) in ATCC 700603 Klebsiella pneumoniae

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Table 1: Minimum inhibitory concentration and minimum bactericidal concentration results of three commonly used biocides in our hospital for test isolate and Klebsiella pneumoniae ATCC 700603


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 ~ Discussion Top


CRE has been defined as carbapenem non-susceptible and extended-spectrum cephalosporin-resistant Escherichia coli, Enterobacter aerogenes, Enterobacter cloacae complex, K. pneumoniae or Klebsiella oxytoca. Some authorities exclude ertapenem resistance from this definition. [4] According to data published by the Centers for Disease Control and Prevention in the United States, the percentage of CRE increased from 1.2% in 2001 to 4.2% in 2011. [5] The highest increase in proportion, from 1.6% to 10.4%, was observed for Klebsiella spp. during the same period. [5] Since the first reported CR-Kp was identified in 1996, these isolates are emerging as a cause of multidrug-resistant Gram-negative infections in healthcare settings. [6],[7],[8] Production of K. pneumoniae carbapenemase enzymes is the most common mechanism of resistance among these organisms. [8] This species seems to represent a 'reservoir' of resistance, transmittable to other members of the family Enterobacteriaceae, including E. coli and Enterobacter spp. [9]

CR-Kp strains are implicated in nosocomial outbreaks of severe respiratory tract, catheter-related bloodstream, surgical site and urinary tract infections. [10],[11] Reported risk factors for infection with CR-Kp include higher severity of illness, recent solid organ or stem-cell transplant, mechanical ventilation, longer length of stay and prior antimicrobial exposure to cephalosporins, fluoroquinolones and carbapenems. [12],[13],[14] The patient under study had many of these risk factors such as uterine sarcoma, for which she was operated and had received a cycle of chemotherapy, prolonged hospital stay, inadvertent administration of antimicrobial agents and mechanical ventilation. K. pneumoniae isolated from the blood and mucus trap samples of this patient was resistant to all but one antibiotic (tigecycline) to which it was moderately susceptible. Currently available penicillins, cephalosporins and carbapenems do not demonstrate in vitro activity against CR-Kp. There are very few treatment options for infections caused by CR-Kp strains. Tigecycline and colistin are two agents with in vitro activity against CR-Kp, which are currently being used for treatment of bloodstream infections (BSIs) in several countries. [15] However, the low plasma concentrations of tigecycline and the toxicity associated with colistin make these less appealing options for use in BSI. In addition to these concerns, the published outcome data for these two agents in the treatment of CR-Kp BSI are limited. There are published reports on CR-Kp isolates which display in vitro resistance to both tigecycline and colistin. [15] Recently reported in vitro results for combination therapy which includes doripenem, rifampin and polymyxin B are promising, but this combination has not been evaluated in clinical settings. [16] Members of the family Enterobacteriaceae have generally been found to be susceptible to doripenem. In studies conducted by Mendes et al. and Li et al., 98.7% and 98.1% of the isolates belonging to Enterobacteriaceae family were susceptible to doripenem. [17],[18] However, in contrast to these findings, in the present case, K. pneumoniae was resistant to doripenem also. CR-Kp infections are associated with both high morbidity and mortality. [15] Unfortunately, the patient under study also expired due to septicemia and multiorgan failure within 2 weeks of admission to the GICU.

Since CR-Kp infection is a serious problem in hospitals worldwide, posing a serious threat to immunocompromised patients, effective elimination strategies may prevent these drug-resistant bacteria from spreading within hospital environments. Keeping in mind the possibility of this extremely-drug resistant bacterial isolate [19] being less susceptible or completely resistant to commonly used biocides in our hospital, MIC and MBC values of three of these biocides were determined using K. pneumoniae ATCC 700603 as control. Although there was no difference in these values for povidone iodine and absolute ethanol between test and control strains, the test isolate (CR-Kp) had slightly higher MIC and MBC values for sodium hypochlorite in comparison to control strain. In a study conducted by Guo et al., it was concluded that pan-resistant pathogenic CR-Kp strains contained various drug-resistant genes and exhibited relatively high resistance to certain biocides such as ethyl alcohol, chlorhexidine acetate and iodophor. [20]


 ~ Conclusion Top


CR-Kp is emerging as a serious threat in health-care settings worldwide. Treatment options are limited with high morbidity and mortality associated with infections caused by this strain. The possibility of emergence of biocide resistance among these strains poses a genuine threat of disrupting our ongoing efforts for implementation of appropriate and effective infection control measures. Monitoring the biocide resistance rates of such strains should be carried out on a regular basis so that appropriate steps can be taken beforehand to combat the possibility of emergence of a dreaded pandemic.

Acknowledgement

We would like to acknowledge the Department of Anaesthesiology, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, New Delhi, India, Miss Shweta Chaturvedi and Mrs. Divya Sharma, Laboratory Assistants, Department of Microbiology, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, New Delhi, India.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 ~ References Top

1.
Falagas ME, Lourida P, Poulikakos P, Rafailidis PI, Tansarli GS. Antibiotic treatment of infections due to carbapenem-resistant Enterobacteriaceae: Systematic evaluation of the available evidence. Antimicrob Agents Chemother 2014;58:654-63.  Back to cited text no. 1
    
2.
Miles RS, Amyes SG. Laboratory control of antimicrobial therapy. In: Collee JG, Fraser AG, Marimon BP, Simmons A, editors. Mackie & McCartney Practical Medical Microbiology. Reprint. 14 th ed. New Delhi: Elsevier; 2007. p. 151-78.  Back to cited text no. 2
    
3.
Mazzola PG, Jozala AF, Novaes LC, Moriel P, Penna TC. Minimal inhibitory concentration (MIC) determination of disinfectant and/or sterilizing agents. Braz J Pharm Sci 2009;45:241-8. Available from: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502009000200008 and lng=en. [Last cited on 2015 Oct 30].  Back to cited text no. 3
    
4.
Guh AY, Bulens SN, Mu Y, Jacob JT, Reno J, Scott J, et al. Epidemiology of carbapenem-resistant Enterobacteriaceae in 7 US communities, 2012-2013. JAMA 2015;314:1479-87.  Back to cited text no. 4
    
5.
Centers for Disease Control and Prevention (CDC). Vital signs: Carbapenem-resistant Enterobacteriaceae. MMWR Morb Mortal Wkly Rep 2013;62:165-70.  Back to cited text no. 5
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6.
Yigit H, Queenan AM, Anderson GJ, Domenech-Sanchez A, Biddle JW, Steward CD, et al. Novel carbapenem-hydrolyzing beta-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae. Antimicrob Agents Chemother 2001;45:1151-61.  Back to cited text no. 6
    
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Nordmann P, Cuzon G, Naas T. The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria. Lancet Infect Dis 2009;9:228-36.  Back to cited text no. 7
    
8.
Schwaber MJ, Carmeli Y. Carbapenem-resistant Enterobacteriaceae: A potential threat. JAMA 2008;300:2911-3.  Back to cited text no. 8
    
9.
Lombardi F, Gaia P, Valaperta R, Cornetta M, Tejada MR, Di Girolamo L, et al. Emergence of carbapenem-resistant Klebsiella pneumoniae: Progressive spread and four-year period of observation in a cardiac surgery division. Biomed Res Int 2015;2015:871947.  Back to cited text no. 9
    
10.
Mouloudi E, Protonotariou E, Zagorianou A, Iosifidis E, Karapanagiotou A, Giasnetsova T, et al. Bloodstream infections caused by metallo-ß-lactamase/Klebsiella pneumoniae carbapenemase-producing K. pneumoniae among intensive care unit patients in Greece: Risk factors for infection and impact of type of resistance on outcomes. Infect Control Hosp Epidemiol 2010;31:1250-6.  Back to cited text no. 10
    
11.
Sievert DM, Ricks P, Edwards JR, Schneider A, Patel J, Srinivasan A, et al. Antimicrobial-resistant pathogens associated with healthcare-associated infections: Summary of data reported to the National Healthcare Safety Network at the centers for disease control and prevention, 2009-2010. Infect Control Hosp Epidemiol 2013;34:1-14.  Back to cited text no. 11
    
12.
Patel G, Huprikar S, Factor SH, Jenkins SG, Calfee DP. Outcomes of carbapenem-resistant Klebsiella pneumoniae infection and the impact of antimicrobial and adjunctive therapies. Infect Control Hosp Epidemiol 2008;29:1099-106.  Back to cited text no. 12
    
13.
Gasink LB, Edelstein PH, Lautenbach E, Synnestvedt M, Fishman NO. Risk factors and clinical impact of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae. Infect Control Hosp Epidemiol 2009;30:1180-5.  Back to cited text no. 13
    
14.
Ben-Ami R, Rodríguez-Baño J, Arslan H, Pitout JD, Quentin C, Calbo ES, et al. A multinational survey of risk factors for infection with extended-spectrum beta-lactamase-producing Enterobacteriaceae in nonhospitalized patients. Clin Infect Dis 2009;49:682-90.  Back to cited text no. 14
    
15.
Bratu S, Tolaney P, Karumudi U, Quale J, Mooty M, Nichani S, et al. Carbapenemase-producing Klebsiella pneumoniae in Brooklyn, NY: Molecular epidemiology and in vitro activity of polymyxin B and other agents. J Antimicrob Chemother 2005;56:128-32.  Back to cited text no. 15
    
16.
Neuner EA, Yeh JY, Hall GS, Sekeres J, Endimiani A, Bonomo RA, et al. Treatment and outcomes in carbapenem-resistant Klebsiella pneumoniae bloodstream infections. Diagn Microbiol Infect Dis 2011;69:357-62.  Back to cited text no. 16
    
17.
Mendes RE, Rhomberg PR, Bell JM, Turnidge JD, Sader HS. Doripenem activity tested against a global collection of Enterobacteriaceae, including isolates resistant to other extended-spectrum agents. Diagn Microbiol Infect Dis 2009;63:415-25.  Back to cited text no. 17
    
18.
Li Y, Lv Y, Xue F, Zheng B, Liu J, Zhang J. Antimicrobial resistance surveillance of doripenem in China. J Antibiot (Tokyo) 2015;68:496-500.  Back to cited text no. 18
    
19.
Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012;18:268-81.  Back to cited text no. 19
    
20.
Guo W, Shan K, Xu B, Li J. Determining the resistance of carbapenem-resistant Klebsiella pneumoniae to common disinfectants and elucidating the underlying resistance mechanisms. Pathog Glob Health 2015;109:184-92.  Back to cited text no. 20
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