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 ~  Abstract
 ~  Patients and methods
 ~  Results
 ~  Discussion
 ~  Box: Microbiolog...
 ~  References

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Year : 2004  |  Volume : 22  |  Issue : 4  |  Page : 255-257

Learning from an outbreak: ESBL- the essential points

Department of Clinical Microbiology, Pondicherry Institute of Medical Sciences, Kalapet, Pondicherry 605 014, India

Date of Submission18-Nov-2003
Date of Acceptance13-Mar-2004

Correspondence Address:
Department of Clinical Microbiology, Pondicherry Institute of Medical Sciences, Kalapet, Pondicherry 605 014, India

 ~ Abstract 

Extended spectrum beta-lactamase (ESBL) producing strains of Klebsiella pneumoniae have emerged as important nosocomial pathogens. The present report describes an outbreak of ESBL positive K.pneumoniae in a neonatal intensive care unit of a tertiary care center in southern India. The clinical and microbiological significance of multiresistant gram negative ESBL producers have been discussed in light of this outbreak by multi-resistant gram negative bacilli. The review also offers some practical guidance regarding infection control and therapeutic options.

How to cite this article:
Shanmuganathan C, Ananthakrishnan A, Jayakeerthi S R, Kanungo R, Kumar A, Bhattacharya S, Badrinath S. Learning from an outbreak: ESBL- the essential points. Indian J Med Microbiol 2004;22:255-7

How to cite this URL:
Shanmuganathan C, Ananthakrishnan A, Jayakeerthi S R, Kanungo R, Kumar A, Bhattacharya S, Badrinath S. Learning from an outbreak: ESBL- the essential points. Indian J Med Microbiol [serial online] 2004 [cited 2020 Oct 1];22:255-7. Available from:

Extended spectrum beta-lactamase (ESBL) producing strains of Klebsiella pneumoniae have emerged as important agents in the list of nosocomially acquired neonatal pathogens.[1] ESBL producing strains are resistant to third generation cephalosporins, and hence pose a formidable challenge in management of infected neonates. The present report describes an outbreak of ESBL producing K. pneumoniae septicaemia in a nursery, which occurred over a period of 20 days resulting in death of 8 out of 10 neonates affected.

 ~ Patients and methods Top

In the neonatal intensive care unit of JIPMER Hospital preterm babies, neonates with birth asphyxia and those born following prolonged rupture of membranes (>24 hours) constitute the major admissions. Diagnosis of neonatal septicaemia was made based on clinical and a positive blood culture.
Antibiotic susceptibility was carried out by disk diffusion technique using NCCLS criteria. Samples were collected from linen, humidifier, incubator, oxygen hood, cradle, feeding trolley, tap, breast pump, breast milk storage bottles and refrigerator as soon as the outbreak was detected. A screening for ESBL production was done by disc approximation technique using ceftazidime (30 g) and amoxycillin/clavulanic acid (20/10 g).

 ~ Results Top

The outbreak started with the isolation of K. pneumoniae from a preterm baby with severe respiratory distress and within a period of three weeks ten neonates developed K.pneumoniae septicaemia.
Eight of the ten (8 male, 2 female) septicaemic neonates were preterm (80% <37 weeks) with low birth weight (80% <2500 gm). Other important predisposing factors identified were, low Apgar score (80%, <5 at 1st minute) and prolonged rupture of membrane (20%, >24 hrs). First clinical manifestation occurred at a mean of 2.5 + 0.23 days after admission. Main presenting complaint was respiratory distress associated with lethargy and feeding difficulties. Disseminated intravascular coagulation was seen in four and necrotizing enterocolitis was seen in three of the neonates.
Empiric treatment included a combination of I.V cefotaxime (50mg/kg q 12h) and amikacin (7.5mg/kg q 12h). Subsequent to culture and sensitivity of these isolates the treatment was changed to a combination of ciprofloxacin (15mg/kg q12h) and amikacin (7.5mg/kg q 12h). Condition of six neonates worsened and they expired within three days of clinical diagnosis. Two of the septicaemic neonates recovered while the other two expired due to fulminant illness.
Isolation of the septicaemic neonates was done to control spread of K.pneumoniae in the neonatal intensive care unit. Subsequent screening of the environment yielded K.pneumoniae from breast pump, breast milk storage bottle and refrigerator.
Antibiotic susceptibility testing of all clinical and environmental isolates showed a similar antibiogram. All the strains were also found to produce ESBL. E-test of the clinical and environmental isolates using aztreonam strips showed an MIC of >256 g/ mL for all isolates barring one (from refrigerator) which was sensitive with an MIC of 0.047 g /mL.
The breast pump and the milk storage bottle were identified as the most probable source responsible for the outbreak. Sterilization of breast pump and storage bottles subsequently controlled the outbreak. Surveillance during the following six months did not yield any K.pneumoniae from clinical samples.

 ~ Discussion Top

ESBL positive Klebsiella pneumoniae has been incriminated in hospital acquired infections. This organism colonizes the bowel and skin and is probably transmitted via medical staff hands.[2],[3] Neonatal septicaemia due to ESBL producing K.pneumoniae was reported to produce 25% mortality in one study.[4] Nosocomial K.pneumoniae infection is associated with a high mortality in neonates and antimicrobial therapy in infections has been complicated by the emergence of multi-resistant strains. These organisms remain susceptible to only a few antimicrobial agents, some of which are not recommended for use in children.[5] Laboratory antibiogram influenced the subsequent treatment regime of ciprofloxacin and amikacin combination, which could save two of the neonates. Reporting of ESBL production by the organism helped the clinician in modifying the therapeutic strategy. Environmental isolates monitored for detection of ESBL producing K. pneumoniae identified the source to be the breast pump and breast milk storage bottles. Sterilization of the breast pump and ensuring the prevention of stored breast milk contamination helped in controlling the infections. Most breast pump pieces can be sterilized (disinfected) by steaming, microwave or boiling.
ESBL producing K.pneumoniae evolve due to mutation in the class A TEM and SHV beta-lactamases.[4] TEM 1, SHV 2 and SHV 5 are the common types of beta lactamases produced by these strains. ESBL producers are resistant to 3rd generation cephalosporins and aztreonam (monobactam). Cross-resistance to other unrelated antibiotics may occur and resistance is transferable in association with plasmid (Box).
In the present study, we have used antibiotic sensitivity profiles as the typing method. Although not comparable to molecular methods in discriminatory power, antibiogram typing is one of the simplest and widely used method of bacteriological typing which can easily be applied in clinical laboratories for preliminary screening.

 ~ Box: Microbiology of ESBL3 Top

ESBLs are enzymes capable of hydrolysing penicillins, broad-spectrum cephalosporins and monobactams
ESBLs are derived from TEM and SHV-type enzymes
ESBLs are often located on plasmids that are transferable in association with a large plasmid (>98 mDa) from strain to strain and between bacterial species
The activity of ESBLs may be chromosomal or plasmid mediated
Detection of ESBL is difficult based on routine susceptibility testing performed by a clinical microbiology laboratory
Methods of ESBL detection include double disk test, use of E-test ESBL strips, combined disc method, VITEK ESBL cards (bioMerieux).
ESBLs are either inhibited by beta-lactamase inhibitors such as clavulanic acid or are inhibitor resistant
It is clinically important to detect ESBL production by Klebsiellae or E. coli even when cephalosporin MICs are in the susceptible range (= 8 microg/ml). Apparently susceptible organisms may be ESBL producers
ESBL-producing organisms must be reported as resistant to aztreonam and all cephalosporins (with the exception of cephamycins - e.g. cefotetan, cefoxitin, latamoxef)
ESBL producing organisms pose unique challenges to clinical microbiologists, clinicians, infection control professionals and pharmaceuticals.[6],[7],[8] Methods of controlling spread of ESBL in the hospital depends on altering infection control practices to limit the dissemination of these bacterial species, which may be more effective than attempts to control only antibiotic resistant isolates. 

 ~ References Top

1.Kuruvilla KA, Pillai S, Jesudasan M, Jana AK. Bacterial profile of sepsis in a neonatal unit in South India. Indian Pediatr 1998;35:851-858.  Back to cited text no. 1    
2.Ananthakrishnan AN, Kanungo R, Kumar A, Badrinath S. Extended spectrum Beta lactamase producers among surgical wound infections and burns patients in JIPMER. Indian J Med Micrbiol 2000;18(4):160-165.  Back to cited text no. 2    
3.Podschun R, Ullmann U. Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy, typing methods, and pathogenicity factors. Clin Microbiol Rev 1998; 11(4):589-603.  Back to cited text no. 3    
4.Siu LK, Lu, PL, Hsueh PR, Lin FM, Chang SC, Luh KT, Ho M, Lee CY. Bacteremia due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in a pediatric oncology ward: clinical features and identification of different plasmids carrying both SHV-5 and TEM-1 genes. J Clin Microbiol 1999; 37(12):4020-4027.  Back to cited text no. 4    
5.Du B, Long Y, Liu H, Chen D, Liu D, Xu Y, Xie X. Extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae bloodstream infection: risk factors and clinical outcome. Intensive Care Med 2002;28(12):1718-1723.  Back to cited text no. 5    
6.Rupp ME, Fey PD. Extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae: considerations for diagnosis, prevention and drug treatment. Drugs 2003;63(4):353-365.  Back to cited text no. 6    
7.Wong-Beringer A. Therapeutic challenges associated with extended-spectrum, beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae. Pharmacotherapy 2001;21(5):583-592.  Back to cited text no. 7    
8.Tan BH, Tan AL. Community-acquired bacteremia with an ESBL-producing Escherichia coli strain-a case report. Int J Infect Dis 2002;6(4):318-319.  Back to cited text no. 8    
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2004 - Indian Journal of Medical Microbiology
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