Indian Pediatrics - Editorial

Letters to the Editor

Indian Pediatrics 2004; 41:97-98

Extended Spectrum of b-Lacta-mase Mediated Resistance to Third Generation Cephalosporins Among Klebsiellae pneumoniae in Neonatal Septicemia

Neonatal septicemia is caused by variety of bacterial specie(1), of which Klebsiella pneumoniae is the predominant organism. Several out breaks of infection caused by K. pneumoniae isolates that are simultaneously resistant to broad-spectrum cephalosporins and aminoglycosides have been reported. Some of these multidrug resistant isolates produce "Extended Spectrum b-Lactamases" (ESbLs) that are able to hydrolyze expanded spectrum cephalosporins (e.g., ceftriaxone, cefotaxime and ceftazidime) aztonam, and related oxyamino-b-lactums(2,3). Studies carried out in various part of India have reported prevalence of ESbL producing klebsiella isolates (3,4). The present study was conducted with an objective to examine the incidence of ESbL producing strains and multidrug resistant strains of K. pneumoniae isolated from 828 cases noeonatal septicemia from various neonatal care unit hospitals in Gulbarga.

Out of 828 cases studied, growth of bacteria was obtained in 346 (41.78%) blood samples. The most predominant organism was K. pneumoniae 96 (27.74%), followed by staphylococcus aureus 78 (22.54%), coagu-lase negative S. aureus (18.78%), E. coli 48 (13.87%) and other less frequent isolates. Antimicrobial susceptibility testing and double disk diffusion synergy testing was done to detect ESbL on all 96 isolates. Table I shows antibiotic resistance pattern of K.pneumonia isolates. All the 96 isolates were found to be resistant to a minimum of 3 antibiotics, hence these were considered multidrug resistant. 87.5% of the isolates showed resistance or decreased susceptibility to at least one of the 3GC and 64.6% to all the 3GC. All the isolates were found sensitive to imipenem. ESbL production was detected in 13 isolates against ceftazidime, ceftriaxone and cefotaxime, and this ESbL production and resistance to the 3GC was transferred to the recipient E. coli K12J62-2 strain (obtained from CMC, Vellore).

TABLE I

Antibiotic Resistance Pattern of 96 Klebsiella Pneumoniae Isolates

	Sensitive		Resistance
Antibiotic (µg)	No.	Per cent	No.	Per cent
Ampicillin (30)	01	1.04	95	98.95
Amikacin (10)	08	8.33	88	91.66
Ceftazidime (30)	34	35.14	62	64.59
Ceftriaxone (30)	08	8.33	88	91.66
Cefotacime (30)	12	12.50	84	87.50
Cefuroxime (30)	19	19.79	77	80.20
Co-trimoxazole (30)	16	16.66	80	83.33
Cefhaloridine (30)	07	7.29	89	92.70
Gentamicin (10)	15	15.62	81	84.37
Imipenem (30)	96	100.00	00	0.00

ESbL mediated resistance to 3GC was found in 13.54% of our isolates. During the past decade, ESbL producing K.pneumoniae have emerged as one of multidrug resistant organism(3). The incidence of ESbL producing Klebsiella isolates in the United States has been reported to be 5%, in France and England 14-16%, from different clinical specimens(4,5). There are few reports available from India in which ESbL positively in various specimen ranges from 6.6-53%(2,3). However, the percentage of 3GC resistant strains may be much higher, because the conventional disc diffusion criteria used in the routine laboratory underestimate the incidence of these isolates. There are no reports available in India to compare the incidence of ESbL producing strains from neonatal septicemia.

In our study, ESbL production in all the 13 isolates were co-transferred to E.coli indi-cating plasmid mediated ESbL production(5). These conjugative plasmid responsible for the dissemination of resistance to other members of gram negative bacteria in hospitals and in the community. In addition to resistance to 3GC 91.66% of the isolates showed resistance to amikacin, 84.37% to gentamicin and 83.33% to cotrimaxozole. In this study, resistance to 3GC was found to co-exist with resistance to other antibiotics. Since all the isolates showed multidrug resistace, the therapeutic strategies to control infections due to Klebsiella has to be carefully formulated.

Approximately 30% of the ESf3L pro-ducers appear falsely sensitive or moderately sensitive to 3GC in routine susceptibility testing. It is known that the minimum inhibitory concentration (MIC) for ESbL producing organisms is higher than that for non-ESbL producers of the same species. However, the MIC may not reach the breakpoint values for resistance and is thus reported as sensitive in routine disk diffusion susceptibility test(6).

The present study highlights the incidence of ESbL producing Klebsiella isolates among neonates in Gulbarga. Patients with septicemia due to these isolates are unlikely to respond to the penicillins, cephalosporins and aztreonam, since these organisms may not appear resistant to these antimicrobial agents by conventional disc diffusion criteria. Hence, microbiology laboratories should look for ESbL production routinely and explicitly report their presence in order to avoid the undesired effects of multidrug resistance and also appropriate therapy can be instituted.

Acknowledgement

We want to thank the Dean, M.R. Medical College, Gulbarga; the District Surgeon, Government General Hospital, Gulbarga; the Medical Superintendent, Sangameshwar Hospital, Gulbarga; and Dr. Srikanth SW, Professor, Department of Pediatrics, M.R. Medical College for their kind cooperation extended in obtaining the clinical samples, and Gulbarga University, Gulbarga, for the facilities.

Vinod Kumar C.S.,
Neelagund Y.F.,
From the Department of PG Studies &
Research in Microbiology,
Gulbarga University,
Gulbarga 585 106, India.

References

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2. Abigail S, Mathai E, Jesudasan MV, John TJ. Ceftazidime resistance among Klebsiella pneumoniae in south India. Indian J Med Res 1995; 102: 53-55.

3. Jerestin BH, Vandana Agarwal, Pathak M, Saoji AM. Extended spectrum b-lactamase mediated resistance to third generation cephalosporins in Klebsiella pneumoniae in Nagpur, Central India. Indian J Med Res 1997; 105: 158-161.

4. Jacoby GA. Antimicrobial resistant pathogens in the 1990s. Annu Rev Med 1996; 47. 169-179.

5. Sirot D. Extended-spectrum plasmid-mediated betalactamases. Antimicrob Agents Chemother 1995; 36: 19-34.

6. Paterson DL, Gottberg A V, Mohapatra S. In vitro susceptibility and clinical outcome of bacteremia due to ESbL producing K. pneu-moniae . Clin Infect Dis 1998; 27: 956-960.