|Year : 2003 | Volume
| Issue : 1 | Page : 52-55
In vitro activity of cefpirome: A new fourth generation cephalosporin
Department of Microbiology, Sri Venkateswara Institute of Medical Sciences, Tirupati - 517 507, AP, India
Department of Microbiology, Sri Venkateswara Institute of Medical Sciences, Tirupati - 517 507, AP, India
This study was carried out to find the efficacy of Cefpirome in an Indian setting in a tertiary care referral hospital. A total of 516 bacterial isolates from various clinical specimens were tested against cefpirome (Cpo) and compared against the activities of three other cephalosporins, namely cefazolin (Cz), cefuroxime (Cu), and cefotaxime (Ce) as representative of the other three generations. Preliminary testing was done by Kirby Bauer technique. In the gram positive group of organisms (Staphylococcus aureus and coagulase negative staphylococci); 96 strains out of 177 (54.2%) were resistant to Cpo compared to 61.0% for Cz and 72.3% for Cu. In the Enterobacteriaceae group, 66.0% of the isolates were resistant to Cpo compared to 63.2% for Ce; while for Pseudomonas and other non-fermentors, the corresponding figures were 70.7% and 50.0% for Cpo and Ce respectively. The MIC for the strains resistant to Cpo were found to be >16mg/L to >256mg/L. This study highlights that Cpo did not have superior activity against the organisms isolated in our laboratory. However, since its activity against gram positive and gram negative organisms is comparable to those of Cz and Ce respectively, it may be useful for mixed infections for empirical therapy.
|How to cite this article:|
Chaudhury A. In vitro activity of cefpirome: A new fourth generation cephalosporin. Indian J Med Microbiol 2003;21:52-5
|How to cite this URL:|
Chaudhury A. In vitro activity of cefpirome: A new fourth generation cephalosporin. Indian J Med Microbiol [serial online] 2003 [cited 2019 Sep 19];21:52-5. Available from: http://www.ijmm.org/text.asp?2003/21/1/52/8319
Cephalosporins have been classified, first as marketing strategy and subsequently for convenience, into different generations depending upon their activity against gram positive and gram negative organisms. Cefpirome is a new C-3' quaternary ammonium cephalosporin which bears a 2,3- cyclopentano pyridinium at the C-3 position of the cephem nucleus and has been classified as a fourth generation cephalosporin., It is considered to be highly active against both gram negative organisms including Pseudomonas aeruginosa and gram positive organisms including staphylococci. It is stable to both plasmid and chromosomal b- lactamases and has been shown to induce less class I b- lactamase resistance than other cephalosporins.,, Ever since its introduction in the early years of 1980s, numerous reports have come in from Europe, USA, South America , and Asia regarding its superiority to third generation cephalosporins and its unique efficacy against both gram- positive, and negative organisms. In this respect, its use as monotherapy in mixed infections has also been advocated., It has been introduced in India in 1999, but there have been no reports regarding its usefulness in Indian setting. This study was undertaken to find out the in-vitro efficacy of Cefpirome against the commonly encountered gram-negative bacteria and Staphylococci vis-à-vis other commonly used cephalosporins, in a tertiary care hospital in south India.
| ~ Materials and Methods|| |
A total of 516 strains of Staphylococcus aureus, coagulase negative staphylococci (CONS), Pseudomonas aeruginosa, members of the Enterobacteriaceae family, and gram negative non fermentative organisms were included in the study. The isolates were from various clinical specimens like urine, blood, pus, sputum, and various body fluids including CSF. Identification of the isolates was done by conventional techniques., The isolates were stock cultured in semi solid nutrient agar and preserved at 4-8°C and subcultured only twice. Antibiotic sensitivity testing was done by Kirby Bauer technique on Mueller Hinton agar. Cefazolin (30 µg), cefuroxime (30 µg), and cefotaxime (30 µg) discs were obtained from Hi Media (India), and cefpirome (30 µg) discs were obtained from Oxoid (UK). Interpretation was done as per NCCLS guidelines. For cefpirome, inhibition zone size of >18 mm was taken as sensitive. E.coli ATCC 25922, S.aureus ATCC 25923, and P. aeruginosa ATCC 27853 were used as sensitive controls according to the nature of the isolates. MIC of the strains resistant to cefpirome was determined by agar dilution method.9 Cefpirome sulphate (Hoechst Marion Roussel) 1.191 gram equivalent to 1 g of cefpirome was used to make oubling dilutions of the drug ranging from 1 mg/L - 256 mg/L. A value of > 8 mg/L was taken as resistant.
| ~ Results|| |
The distribution of the isolates is shown in [Table - 1]. Of the total 516 isolates, majority (209, 40.5%) belonged to the Enterobacteriaceae family, followed by staphylococci (177, 34.3%). Pseudomonads and other non fermentative gram negative bacilli (NFGNB) constituted the rest 25.2% isolates. Streptococci, enterococci, and Haemophilus spp. were not included in this study.
[Table - 2] shows the sensitivity of the isolates to cefpirome. The overall sensitivity of the gram positive and gram negative isolates to this agent was 36.5%. The gram positive group as a whole was more sensitive (47.5%) compared to the gram negative group (29.2%). Staphylococcal isolates from urine and blood were comparatively more sensitive to cefpirome compared to the isolates from pus and body fluids, which was also true for the enterobacteria.
A comparative activity of clinically important cephalosporins with respect to cefpirome is depicted in [Table - 3]. The activity of the first generation agent cefazolin is shown against gram positive organisms; second generation cefuroxime against both gram positive and gram negative (except Pseudomonas spp.); and the third generation cefotaxime against all gram negative isolates. For S.aureus, cefpirome has shown similar activity as cefazolin (56.8% vs. 58.4% resistance); but superior to cefuroxime (76.8% resistance). For CONS, cefpirome emerges as a better agent (sensitivity-52 %) compared to the other two. When tested against members of the Enterobactericeae family and NFGNB, cefpirome has shown no clear advantage over the third generation agent cefotaxime. On the other hand, cefpirome has shown significantly inferior activity to P.aeruginosa compared to cefotaxime with resistance frequency of 67.7% and 39.8% respectively.
The MIC of the staphylococci ranged from 16-64mg/L with MIC90 value of 32mg/L. For Gram negative isolates, MIC ranged from 16 256 mg/L and the MIC90 was > 128mg/L for the enterobacteria and P.aeruginosa; and 64 mg/L for the resistant NFGNB.
| ~ Discussions|| |
Antibiotic resistance is not a new problem in India or in the world. What is alarming is the apparent failure of newly introduced and potent agents in settings where resistance is widespread. Generally resistance rates are low after a new antibacterial agent is introduced; resistance then appears and increases until it reaches a steady state level. We have shown in this study that, high frequency of resistance to a newly introduced agent was already present. This again may not be surprising because cefpirome belongs to the cephalosporin group of agents which are the targets of unusually potent ß -lactamases which can confer resistance to a large number of agents having similar parent structure. In the 1980s and 1990s, reports from North America, Europe, and Japan have revealed an uniformly higher efficacy of cefpirome as compared to the other ß-lactams including the cephalosporins. This scenario may be imperceptibly changing in the light of two recent reports. The first one from Thailand found 13.4% resistance to cefpirome in all gram negative organisms tested. In a more recent report from Japan,14 216 strains of P.aeruginosa were studied of which 41.7% were resistant to cefpirome with MIC90 value of 50 µg/mL. In the same study, fewer strains (15.7%) were found resistant to the third generation cephalosporin - ceftazidime, which corroborates partly to our findings for P.aeruginosa (39.8% resistant to cefotaxime compared to 67.7% to cefpirome). This is the first study in India comparing the efficacy of cefpirome with other cephalosporins. Recent studies from India have highlighted the high levels of resistance to the various other cephalosporins. In one recent study, 43.6% of Salmonella More Details typhi were found resistant to cefotaxime.15 In another more recent study16 with various Citrobacter spp., resistance to different third generation cephalosporins (cefotaxime, ceftriaxone, and ceftazidime) ranged from 70.4%-82.2%. Our study also found similar high resistance (63.1%) of the Enterobacteriaceae members against cefotaxime.
The last two decades have not really witnessed the discovery of any truly new antibacterial drug. The newer agents which have been marketed are basically molecules belonging to some of the existing group with some alteration in the structure. With such an approach, it is not surprising that these “new” agents do not remain effective for long particularly in the backdrop of widely existent antibiotic resistance. Pre-launch multicentric in vivo and in vitro evaluation of new antibiotics is sadly lacking in India. No effort is made by the pharmaceutical companies to find out the real efficacy of these drugs in this country using accurate quantitative methods like E-test or equivalent. On the other hand, reports from developed countries are highlighted which probably have no bearing in the setting where the agents are to be used. As a result, very often these agents are used by the clinicians with the mistaken belief that “highly potent broad spectrum” are being prescribed. This, in part, is also due to a lack of effective antimicrobial resistance surveillance agency in India leading to improper monitoring of antibiotic resistance.
| ~ References|| |
|1.||Seibert G, Limbert M, Winkler I, Dick T. The antimicrobial activity in vitro and beta-lactamase stability of the new cephalosporin HR 810 in comparison to five other cephalosporins and two aminoglycosides. Infection 1983;11:275-279. |
|2.||Jones RN, Pfaller MA, Allen SD, Gerlach EH, Fuchs PC, Aldridge KE. Antimicrobial activity of cefpirome: an update compared to third generation cephalosporins against nearly 6000 recent clinical isolates from five medical centres. Diagn Microbiol Infect Dis 1991;14:361-364. |
|3.||Ludo V, for the International study group. Epidemiology and sensitivity of 8625 ICU and haematology/ oncology bacterial isolates in Europe. Scand J Infect Dis- suppl 1993;91:14-24. |
|4.||Jacoby GA, Carreras I. Activities of beta-lactam antibiotics against Escherichia coli strains producing extended spectrum beta-lactamases. Antimicrob Agents Chemother 1990;34:858-862. |
|5.||Stobberingh EE, Houben AW. Inducing capacity and selection of resistant variants of cefpirome (HR 810) in comparison with other beta-lactam compounds. Chemotherapy 1988;34:490-496. |
|6.||Wolff M for The Cefpirome Pneumonia Study Group. Comparison of strategies using cefpirome and ceftazidime for empiric treatment of pneumonia in intensive care patients. Antimicrob Agents Chemother 1998;42:28-36. |
|7.||Wilson WR. The role of fourth generation cephalosporins in the treatment of serious infectious diseases in hospitalised patients. Diagn Microbiol Infect Dis 1998;31:473-477. |
|8.||Chaudhury A. Experience with cefpirome- a newly introduced cephalosporin in India. Abstr A1. Clinical Laboratory 2001;47:594. |
|9.||Koneman EW, Allen SD, Janda WM, Schreckenberger PC, Winn WC Jr. (Eds.) Colour Atlas and Textbook of Diagnostic Microbiology. 5th ed. (Lippincott, USA) 1997. |
|10.||Collee JG, Fraser AG, Marmion BP, Simmons A. (Eds.) Mackie & McCartney Practical Medical Microbiology. 14th Ed. (Churchill Livingstone, London) 1996. |
|11.||National Committee for Clinical Laboratory Standards. Performance standards for antimicrobial disk susceptibility tests; Approved Standards, 7th ed. 2000,20:1. |
|12.||Austin DJ, Kristinsson KG, Anderson RM. The relationship between the value of antimicrobial consumption in human communities and the frequency of resistance. Proc Natl Acad Sci USA 1999;96:1152-1156. |
|13.||Biedenbach DJ, Johnson DM, Jones RN. In vitro evaluation of cefepime and other broad spectrum beta-lactams in eight medical centres in Thailand. The Thailand Antimicrobial Resistance Study group. Diagn Microbiol Infect Dis 1999;35:325-331. |
|14.||Niitsuma K, Saitoh M, Kojmabara M, Kashiwabara N, Aoki T, Tomizawa M, Maeda J, Kosenda T. Antimicrobial susceptibility of Pseudomonas aeruginosa isolates in Fukushima Prefecture. Jpn J Antibiot 2001;54:79-87. |
|15.||Sanghavi SK, Mane MP, Niphadkar KB. Multidrug resistance in Salmonella typhi. Indian J Med Microbiol 1999;17:88-90. |
|16.||Patil MA, Lakshmi V. Antibiotic resistance among Citrobacter spp. from different clinical specimens. Indian J Med Microbiol 2000;18:25-29. |