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Logo of mjafiGuide for AuthorsAbout this journalExplore this journalMedical Journal, Armed Forces India
 
Med J Armed Forces India. 1994 July; 50(3): 193–195.
Published online 2017 June 27. doi:  10.1016/S0377-1237(17)31058-4
PMCID: PMC5529726

IN VITRO COMPARATIVE ACTIVITY OF EIGHT ANTIPSEUDOMONAL AGENTS

Abstract

Five hundred and thirty strains of Pseudomonas aeruginosa isolated from indoor patients were tested against three chemical groups comprising eight antibiotics. High degree of resistant strains ranging from 38.0% to 61.8% were seen against carbenicillin, piperacillin and gentamicin. However amikacin, ciprofloxacin, ceftazidime, netilmicin and norfloxacin showed comparatively better activity with resistant strains ranging from 7.8% to 22.8%. A notably higher rate of resistance was seen in urinary isolates.

KEY WORDS: Pseudomonas, Beta-lactams, Aminoglycosides, Quinolones

Introduction

Pseudomonas aeruginosa, a widely distributed organism, is a major human pathogen. The organism is invasive, toxigenic and produces infections in patients with abnormal host defences. It is currently recognised as one of the leading causes of severe hospital associated infections [1]. In the recent years, an increased frequency of resistant strains to several antibiotics has been experienced [2]. In view of this a study was conducted where hospital associated strains of Pseudomonas aeruginosa were tested in vitro against three broad groups of beta-lactams, aminoglycosides and quinolones and their comparative activity was evaluated.

Material and Methods

Five hundred and thirty isolates of Pseudomonas aeruginosa were recovered from clinical samples of patients admitted in Army Hospital Delhi Cantt during 1991–92. Of these 272 isolates were from urine, 177 from pus and skin swabs, 45 from blood and 36 from sputum and others. The samples were received from various critical care units including renal transplant centre, burn centre and neonatal units. Different enriched and selective media were used and Pseudomonas aeruginosa strains were confirmed by Gram stain, growth on oxidative fermentative media, pigment production and oxidase reaction. The isolates from significant bacteriuria samples were grouped as urinary isolates. The other group was from pus and other body fluids samples. All the isolates were tested against eight antibiotics : carbenicillin, piperacillin, ceftazidime, gentamicin, netilmicin, amikacin, ciprofloxacin and norfloxacin taken from three chemical groups of beta-lactams, aminoglycosides and quinolones. Mueller-Hinton medium was used for antibiotic sensitivity testing carried out by Stokes' comparative method [3].

The antibiotic disc concentration of each drug procured from HiMedia Laboratories and M/s Fulford (India) Ltd was as follows : carbenicillin and piperacillin 100 µg each; ceftazidime and netilmicin 30 pg each; and gentamicin, amikacin, ciprofloxacin and norfloxacin 10 pg each.

Results

The chemical group and antibiotic wise resistant pattern of the organism is shown in the Table 1. A notable higher rate of resistant organisms was seen in urinary isolates as compared to isolates from pus and other body fluids. Very high rates of resistant strains, i.e. 38.0% to 61.8% were seen against carbenicillin, gentamicin and piperacillin. The other antibiotics like amikacin, ciprofloxacin, ceftazidime, netilmicin and norfloxacin showed better activity with resistant organsims ranging from 7.8% to 22.8%.

TABLE 1
Resistance profile of Pseudomonas aeruginosa in hospital infections.

Discussion

Pseudomonas aeruginosa is an important hospital associated pathogen causing a high degree of morbidity and mortality [1, 2]. The organism is increasingly becoming resistant to many antibiotics [2]. The most common group of drugs being used against the pathogen are beta-lactams, aminoglycosides and quinolones. The common beta-lactams in use are carbenicillin, piperacillin and cephalosporins. The major mechanism of resistance to beta-lactams found in Pseudomonas aeruginosa is expression of beta-lactamase [4], which is usually chromosomal and/or plasmid mediated. The well tried aminoglycosides have been in use against pseudomonal species for several years. The antibiotics of the group in use are gentamicin, amikacin, netilmicin, sisomicin, kanamycin and streptomycin. The resistance mechanism of this group to pseudomonas is mainly due to penetration barrier and enzymatic modification of the drugs [4].

The quinolones consist of potent antibacterials like nalidixic acid, norfloxacin, ciprofloxacin, ofloxacin and many others. All these drugs are highly active against Gram negative and positive organisms and are well tried against Pseudomonas aeruginosa. Two major mechanisms of resistance of Pseudomonas to quinolones are altered target (DNA gyrase) and reduced antibiotic uptake [5, 6].

In our study, in vitro activity of eight antip-seudomonal agents has been evaluated. The overall percentage of resistant strains from urinary isolates was more as compared to the strains from pus and other body fluids (Table 1). This was also experienced in a recent similar study [7]. In the broad group beta-lactams, ceftazidime showed least resistant strains ranging from 12.4% to 21.7% (p < 0.001) as compared to 38.0% to 61.9% in carbenicillin and 43.6% to 44.9% in piperacillin (Table 1). In the aminoglycoside group, amikacin showed the least number of resistant strains ranging from 7.8% to 11.0% (p < 0.001 & < 0.05) as against 14.7% to 19.9% in netilmicin and 57.4% to 59.6% in gentamicin. Ciprofloxacin showed better results in quinolones with isolates resistant percentage of 10.1 to 18.8 as compared to 14.7% to 22.8% in norfloxacin. However, this fell short of statistical significance.

Previous studies in India and abroad have shown variable percentages of resistant organisms to different anti-pseudomonal agents [7, 8, 9]. In a recently conducted study in India, Sugandhi and Shivananda [9] have experienced that most of the pseudomonal strains were resistant to commonly used drugs like carbenicillin (55%) and gentamicin (84%) but the strains showed very little resistance to ciprofloxacin, 4% and 0% to netilmicin. Fujita et al [10] in 1991 reported 21% strains resistant to piperacillin, 22% to ceftazidime, 26% to amikacin and 33% to ofloxacin. The results in our study are fairly comparable with the studies mentioned, though the percentage of resistant strains to various drugs is some times different. This may be due to extensive use of these drugs in the community and also production of various enzymes inactivating the drugs or reduction of uptake of the antibiotic by the pathogen [5, 6].

The analysis of data indicates broad guidelines in that, drugs showing maximum efficacy (amikacin and ciprofloxacin) be reserved for life threatening infections. Netilmicin and ceftazidime may be used as standard antipseudomonal agents. The use of carbenicillin, piperacillin and gentamicin should be restricted for sometime allowing time for the antimicrobial susceptibility profile to change before reintroducing these drugs. At that time the earlier drugs may be withdrawn.

REFERENCES

1. Baltch AL, Griffin PE. Pseudomonas aeruginosa bacteremia: A clinical study of 75 patients. Am J Med Sci. 1977;274:119–129. [PubMed]
2. Marshall WF, Keating MR, Anhalt JP. Xanthomonas maltophilia: an emerging nosocomial pathogen. Mayo Clin Proc. 1989;64:1097–1104. [PubMed]
3. Stokes EJ, Wentworth PM. Antibiotic sensitivity test by disc diffusion method. Assn of Clinical Pathologists. Broadsheet No. 55. 1972 (revised)
4. Sanders CC. The chromosomal beta-lactamases. In: Bryan LE, editor. Microbial resitance to drugs. Springer Verlag; Berlin: 1989. pp. 129–149.
5. Hirai K, Suzue S, Irikura T, Iyobe S, Mitsuhashi S. Mutations producing resistance to norfloxacin in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1987;30:248–253. [PMC free article] [PubMed]
6. Piddock LJV, Wijnands WJA, Wise R. Quinolone/Ureidopenicillin cross resistance. Lancet. 1987;II:907. [PubMed]
7. Jain S, Sarkar R. Antimicrobial resistance among Gram negative bacilli to newer aminoglycosides and beta-lactams. Indian J Pathol Microbiol. 1991;34:280–286. [PubMed]
8. Martin MA, Pfaller MA, Rojas PB. In vitro susceptibility of nosocomial Gram negative blood pathogens to quinolones and other antibiotics – a statistical approach. J Antimicrob Chemother. 1989;23:353–361. [PubMed]
9. Sugandhi PR, Shivananda PG. Bacteraemia due to non-fermenting Gram negative bacilli in immunocompromised patients. Indian Journal of Medical Microbiology. 1993;11:95–99.
10. Fujita J, Negayama K, Takegama K. Activity of antibiotics against resistant Pseudomonas aeruginosa. J Antimicrob Chemother. 1992;29:539–546. [PubMed]

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