13. Kronvall G. Aingertz S. Nystrom S. Rylander M. Theodorsson E. Comparison of 30 Ilg and 120 Ilg gentamicin disks for the pr~ic!ion of gentamicin resistance in Enterococcus faecalis. APM/S 1991; 99: 887-892. Comparative in vitro 14. Snl!ll JJS. Etown DFJ. Perry SF. George R. Antimicrobial susceptibility testing 01 enterococei: results 01 a survey conduCted by the United Kingdom National External OUality Assessment Scheme for Microbiology. J Atlrimicrob Chemother activity of piperacillinl 1993; 32: 401-411. 15. Stevens PJ. Hutchinson NA. Holliman RE. High-level gentamicin resistance in enterOCOCCal and streptococcal isolates from blood cullure. Med Lab Sci 1992; against Gram­ 49: t6-19. t6. Leelel'"q R. 8ismuth R. DUl:aI J. New high-content disks for determination of high­ level aminogtycoside resistance in clinical isolates of Enterococcus faecalis. Eur negative bacilli J C/in Microbia//nfect Dis t992; 11: 356-360. 17. Pal1erson JE. Zervos MJ. Susceptibility and bactericidal activity stud1es of four ~·'actamase producing enterococci. Antimicrob Agents Chemother 1989; 33: Lynne D. Liebowitz, Keilh P. Klugman 251-253. 18. Hodel-Christian SL. Murray BE. Comparison of gentamicin resistance transposon Tn5281 with regions encoding gentamicin resistance in Enterococcus faeca/is isolates from diverse geographic locations. Antimicrab Agents Chemather 1992; Objective. To describe the in vitro activity of piperacillinl 36: 2259--2264. 19. Zervas MJ. Mikesell TS, Schaberg DR. Hetel'"ogeneity of p1asmids determining tazobactam against clinical isolates of Gram-negative high-level resistance to gentamicin in clinical isolates of Streptococcus faecalis. Antimicrob Agents Chemother 1986; 30: 78-81. bacteria, compared with other antibacterial agents. 20. Aice LB, EUopoulos GM, Wennerstein C, Goldmann D, Jacoby GA. Moellering AC. ChromosomaUy mediated J)-lactamase production and gentamicin resistancf! in Design. Survey of susceptibility of clinical isolates of Enterococcus faeea/is. Antimicrob Agents Chemother 1991; 35: 272·276. Gram-negative bacilli. 21. Kaufhold A. Pobie1$ki A. Horaud T. Ferrieri P. Identical genes confer high-Ievf!! resistance 10 gentamicin upon Enterococcus faecalis. Enterococcus faecium and Setting. Academic hospitals of the University of the Streptococcus agaJactlaa. Ant,m}crob Agents Chemother t992; 36: 1215-t218. 22. Woodford N. Monison 0, Cookson B, George RC. Comparison ot high-level Witwatersrand teaching complex. genlamicin-resistant Enterococcus faecium isolates trom different continents. Antimicrob Agents Chemothef t993; 37: 681-684. Bacterial strains_ 180 selected clinical isolates of Gram­ 23. lsmaeel NA. Clinical isolates of enterococei with high-level resistance to currently avaHable aminoglycosides. J Hosp Infect 1992; 20: 35-42. negative bacilli. 24. Thai LA. Cho.... JW, Pal1erson JE. er al. Molecular characterization of highly Main outcome measures. Minimum inhibitory gentamicin·resistant Enterococcus faecalis isolates lacking streptomycin resistance. Anomicrob Agents Chemother 1993; 37: 134-137. concentrations (MICs) determined by agar dilution using 25. Aosenthal SL Freundlich LF. An aminoglycoside disk sensitivity test for use with enterococci. J Antimicrob Chemother 1982; 10: 459-462 techniques according to the recommendations of the 26. Vandenbroucke-Grauls CMJE. The threat of multi-resistant micro-organisms. Eur J C/in MicrObia/Infect DJs 1993; 12: suppl 1. S27-S30. National Committee for ClinicaJ Laboratory Standards. 27. Watanakunakorn C. Patf!! A. Comparison of patif!nts with enterococcal Results. Ciprofloxacin, biapenem, , bact~emiadue to strains with and without high-le-Vel res/stance to gentamicin. C/in Infect Chs 1993; 17: 74-78. and were aJl highly active against most of the 28. Guiney M. Urwin G. Frequency and antimicrobial susceptibihty of cHOIcar isolates of enterococci. Eur J Clin Microblo/lnfect Dis 1993; 12: 362-366. Enterobacteriaceae. All the -resistant strains of 29 MMWR. Nosocomial enterococci resistant to - United States. 1989­ 1993. MMWR 1993; 42: 597-599. Enterobacteriaceae were susceptible to piperacillinl 30. Soyce JM. Opal SM. Chow JW, et al. Outbreak of multidrug re-sistant Enterococcus faeciurn with uansferable vanB class vancomycin resistance. J Clin tazobactam, MICSll vaJues being 4/4 mgll for Klebsiella and Microbiol1994; 32.: 1148-1153. Proteus/Providencia spp., 8/4 mg/l for Citrobacter and Accepted 2 July 1996. Serratia spp_, and 16/4 mg/1 for Escherichia coli. All the

agents, with the exception of ampicillin (MIC90 4 mgll) and chloramphenicol (MICoo 4 mg/l), were highly active against the HaemophiJus influenzae isolates tested. All Bacteroides fragiJis strains were susceptible to piperacillinllazobaclam (MICoo 8/4 mgll), as well as 10

co-amoxiclav (MIC90 4/2 mg/I), biapenem and imipenem (MIC.,s 0.5 mg/l). The Pseudomonas spp. lested included strains resistant to piperacillinltazobactam, , biapenem, gentamicin, tobramycin and ciprofloxacin. Cefepime was the most active agent against Pseudomonas isolates, with 90% of the strains being susceptible to this agent, while biapenem was the mast active agent against the Acinetobacter isolates investigated. Conclusions. The in vitro spectrum of activity of !tazobactam against the majority of isolates was comparable to those of the other new agents tested.

S Afr Med J 1996; 86: 1276-1280.

South African Institute for Medical Research and University of the Witwatersrand, Johannesburg

Lynne D. Uebowitz. asc. (?HARM.). M.B. S.CH.• 0 T.M.&H.. F.F PATH.. FA.C. PlUM.• PH.O.

Keith P. Klugman.1.l5. a.CH.. D.T.MAH.. M.R.C.PATH.. F.C.PATH~ PH-O

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Piperacillin is an that is active against ciprofloxacin, the (biapenem and imipenem), , other Gram-negative bacteria and and the new (cefepime and cefpirome). some Gram-positive bacteria. However, it is inactivated by PiperacillinJtazobactam demonstrated good activity against many a-lactamases and bacteria with acquired resistance to most of the Enterobacteriaceae isolates tested, including the ampicillin are therefore also piperacillin-resistant. Piperaciltin ampicillin-resistant strains. The MIC911 values were 4/4 mgfl is now being marketed in combination with the a-Iactamase for Klebsiella and Providencia spp., 8/4 mg/l for Citrobacter, antagonist tazobactam. This drug is active against plasmid­ Proteus and Serratia spp., an.d 16/4 for Escherichia coIL mediated TEM, SHV and extended-spectrum (3-lactamases, However, when the percentages of Enterobacteriaceae as well as the f3-lactamases produced by staphylococci and strains falling into the sensitive, moderately sensitive or Bacteroides tragi/is. It is not very active against class I resistant ranges based on NCCLS breakpoints were chromosomally mediated a-Iactamases produced by compared, none of the isolates tested fell into the resistant Enterobacter c!oacae, Citrobacter freundii, indole-positive range for piperacillin/tazobactam, cefepime and biapenem. Proteus spp., Serratia marcescens, and P. aeruginosa. In this One Serratia isolate was resistant to ciprofloxacin, and 1 study the in vitro activity of piperacillinltazobactam was E. coli isolate was resistant to cefpirome and the third­ compared with that of ampicillin, co-amoxiclav, , generation cephalosporins tested. There was no significant , cefpirome, cefepime, biapenem, imipenem, difference between the percentage of Enterobacteriaceae gentamicin, tobramycin and ciprofloxacin against selected isolates susceptible to piperacillinltazobactam and the third­ clinical isolates likely to cause infections in the hospital and fourth-generation cephalosporins, carbapenems and setting. ciprofloxacin. All these agents were superior to ampicillin and co-amoxiclav (P < 0.001). Apart from 3 ~-Iactamase-producing strains of H. influenzae which were resistant to ampicillin, and 1 Materials and methods chloramphenicol-resistant isolate, 100% of the H. influenzae strains tested were extremely sensitive to all other agents. This study was performed in late 1993/early 1994 on clinical A number of multiply-resistant Pseudomonas and isolates from patients attending Johannesburg, Hillbrow and Acinetobacter spp. were selected for the study. When MICgo Baragwanath hospitals. The strains were collected and values and percentage sensitivity were compared, cefepime stored in liquid nitrogen until used. reference was the most active agent against the Pseudomonas spp. powders and their sources were as follows: piperacillin/ tested, with only 2 of the isolates being resistant to this tazobactam, biapenem (Lederle); ampicillin, co-amoxiclav agent. The next most active agents were ciprofloxacin and (SmithKline Beecham); cefoxitin, imipenem (Logos); piperacillinltazobactam with 25% of strains being resistant ceftriaxone (Roche); cefpirome (Roussel); cefepime (8ristol­ to ciprofloxacin and 30% resistant to piperacillin/ Myers Squibb); gentamicin, tobramycin (Eli Ully); tazobactam. A different pattern was observed with the azithromycin (Pfizer); ceftazidime (Glaxo); clindamycin Acinetobacter isolates. All strains were fully sensitive to the (Upjohn) and ciprofloxacin (Bayer). Minimum inhibitory carbapenems, biapenem and imipenem, and either fully concentrations (MICs) were determined by an agar dilution sensitive or moderately susceptible to cefepime. Twenty-five method, according to the National Committee for Clinical per cent of the isolates were resistant to piperacillinl Laboratory Standards (NCCLS) recommendations, using tazobactam and ciprofloxacin. In respect of all the non­ Mueller-Hinton agar (Oxoid) for the Enterobacteriaceae and fermentors (Pseudomonas and Acinetobacter spp.), there non-fermentors; Haemophilus Test Medium (Oxaid) for H. was a significantly larger percentage of strains sensitive to influenzae; and Wilkins-Chalgren agar (Oxoid) for B. fragi/is.' cefepime than any of the other agents tested (P < 0.001 in For the determination of piperacillinltazobactam MICs, the comparison with piperacillinltazobactam and P = 0.04 in concentration of tazobactam was maintained at 4 mg/l, comparison with imipenem). Ceftazidime and cefpirome had while that of piperacillin was diluted as normal. significantly fewer strains susceptible than piperacillin/ The significance of differences in proportions of tazobactam, cefepime, the carbapenems and ciprofloxacin. susceptible isolates was calculated using Yates' corrected All the B. fragi/is isolates were resistant to ciprofloxacin, Chi-square or Fisher's exact test where appropriate, by and 1 to clindamycin. The remaining strains were sensitive means of Epi-Info version 6. to all the other tested with the most active agents being metronidazole and the carbapenems.

Results Discussion The resutts of the MIC detenninations and percentage susceptibility based on NCCLS breakpoints for the various Piperacillin, in combination with tazobactam, demonstrated organisms are listed in Tables I - IV. The significance of the good activity against most of the isolates tested. The MIC~, difference in the proportion of all the Enterobacteriaceae and MICgoS and MIC ranges of piperacillinltazobactam and the non-fermentors susceptible to piperacillin/tazobactam in other agents tested against the Enterobacteriaceae were comparison with the other antimicrobial agents is given in similar to those previously reportecp-6 An interesting Tables V and VI. observation was that there were considerably more Against the Enterobacteriaceae tested, which excluded Citrobacter spp. susceptible to piperacillin/tazobactam but Enterobacter spp., the most active agents overall were resistant to co-amoxiclav. does not

SAMJ Volume 86 No. 10 Oetobtr 1996 1277 Table I. Comparative in vitro sensitivity of piperacillin/tazobactam against Enterobacteriaceae Percentage susceptibility Organism Antimicrobial agent MIC. (mgll) MIC. (mgll) MIC range (mgll) S MS R P-value Escherichia coli Piperacillinltazobactam 214 16/4 0.514 - 64/4 90 la 0 (N= 20) Ampicillin > 128 > 128 1 - > 128 25 5 70 < 0.001 Co-amoxiclav 8/4 16/8 1/0.5 - 84/32 75 15 10 NS Cefoxitin 4 8 1 ~ > 128 90 0 10 NS Ceftriaxone 0.06 0.5 ~ 0.007 - 128 95 0 5 NS Cefpirome 0.03 0.5 0.015 - 64 95 0 5 NS Cefepime 0.06 0.5 ~ 0.007 ~ 16 95 5 0 NS Biapenem ~ 0.015 '" 0.015 ~ 0.015 - 1 100 0 0 NS Imipenem 0.25 0.25 0.06 - 8 95 5 0 NS Gentamicin 1 8 0.5 - > 128 85 15 NS Tobramycin 1 8 0.5 - 32 90 10 NS Clprofloxacin 0.015 0.25 ~ 0.007 - 1 100 0 0 NS Klebsiella spp. Piperacillinltazobactam 214 4/4 1/4 - 8/4 lOO 0 0 (N= 20) Ampicillin > 128 > 128 32->128 0 0 100 < 0.001 Co-amoxiclav 4/2 8/4 211 - 16/8 90 'A 0 NS Cefoxitin 2 8 1 - 128 95 0 5 NS Ceftriaxone 2 8 0.03 - 32 90 5 5 NS Cefpirome 0.5 2 0.03 - 4 lOO 0 0 NS Cefepime 0.25 2 0.015 - 4 100 0 0 NS Biapenem 0.06 0.06 ~ 0.03 - 0.12 100 0 0 NS lrnipenem 0.25 0.5 0.12 - 0.5 100 0 0 NS Gentamicin 4 16 0.12-128 50 50 0.001 Tobramycin 16 32 0.25 - 64 35 65 < 0.001 Ciprofloxacin 0.06 0.12 0.015 - 2 95 5 0 NS Citrobacter spp. PiperacWinltazobactam 4/4 8/4 2/4 - 3214 95 5 0 (N=20) Ampicillin 64 > 128 8 - > 128 10 15 75 < 0.001 Co-amoxiclav 16/8 64/32 211 - 128/64 45 10 45 0.002 Cefoxitin 16 128 1 - > 128 45 10 45 NS Ceftnaxone 0.06 0.5 0.03 - 84 95 0 5 NS Cefpirome 0.06 0.12 0.03 - 1 lOO 0 0 NS Cefepime 0.06 0.12 0.015 -0.5 100 0 0 NS Biapenem 0.06 0.25 0.03 - 0.25 100 0 0 NS Gentamicin 0.5 8 0.12-16 80 20 NS Tobramycin 0.25 8 ~ 0.06 - 64 85 15 NS Ciprofloxacin 0.015 0.03 ~ 0.007 - 0.06 100 0 0 NS Proceusl PiperacJllinltazobactam 1/4 4/4 0.5/4 - 3214 95 5 0 Providencia spp. Ampicillin 128 > 128 8 - > 128 10 25 65 < 0.001 (N= 20) Co-amoxiclav 16/8 32116 1/0.5 - 84/32 30 30 40 < 0.001 Cefoxitin 84 > 128 1 - > 128 30 5 65 <0.001 Ceftriaxone 0.06 0.5 0.03 - 16 95 5 0 NS Cefpirome 0.06 0.06 ~ 0.03 - 0.25 lOO 0 0 NS Cefepime 0.06 0.12 0.015 - 0.25 lOO 0 0 NS Biapenem 0.06 0.12 0.03 - 0.25 lOO 0 0 NS Imipenem 0.5 2 0.12 - 4 100 0 0 NS Gentamicin 2 16 1 - 128 60 40 0.02 Tobramycin 0.5 84 0.12-84 75 25 NS Ciprofloxacin '" 0.003 0.015 ~ 0.003 - 0.06 100 0 0 NS Serratia spp. Piperacillinltazobactam 214 8/4 0.25/4 - 16/4 100 0 0 (N = 20) Ampicillin 64 > 128 8 - > 128 5 5 90 < 0.001 Co-amoxiclav 32116 64/32 211 - > 128/64 5 5 90 < 0.001 Cefoxitin 16 32 4 - 84 45 25 30 < 0.001 Ceftriaxone 0.12 2 0.06 - 8 lOO 0 0 NS Cefpirome 0.06 0.12 '" 0.03 - 1 lOO 0 0 NS Cefepime 0.06 0.12 0.03 - 2 lOO 0 0 NS Biapenem 1 1 0.5 - 2 lOO 0 0 NS Imipenem 1 4 0.5 - 4 lOO 0 0 NS Gentamicin 4 8 1 - 128 80 20 NS Tobramycin 4 16 0.5 - 64 55 45 < 0.001 CJprofloxacin 0.25 0.5 0.06 - 4 95 0 5 NS s "susceptible; MS " mooerately susceplJble; R " resistant; P-vaJue " Significance of the dJlference of m€ proportion of isolates susceptible In companson with plperacllhn/tazobactam; NS " no Significant olfference.

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Table 11. In vitro activity of agents against H. influenzae Percentage susceptibility Organism Antimicrobial agent MIC~ (mgll) MIC~ (mgll) MIC range (mgll) S MS R P-vaJue

H. influenzae Piperacillinltazobactam '" 0.007/4 ~ 0.007/4 '" 0.007/4 - 0.015/4 100 0 0 (N= 20) Ampicillin 0.25 4 :!Si; 0.03 - 4 85 15 NS Co-amoxiclav 0.06/0.03 0.25/0.12 ::so 0.007/0.003 - 0.5/0.25 100 0 0 NS Ceftriaxone ~ 0.0015 ~ 0.0015 '" 0.0015 - 0.07 100 0 0 NS Cefpirome .:<;; 0.007 0.03 '" 0.007 - 0.03 100 0 0 NS Cefepime 0.015 0.015 '" 0.007 - 0.6 100 0 0 NS Blapenem 0.015 0.06 '" 0.007 - 0.25 100 0 0 NS Imipenem 0.03 0.06 ~ 0.015 - 0.12 100 0 0 NS Azlthromycln 0.015 0.25 '" 0.003 - 0.12 100 0 0 NS Chloramphenicol 0.25 4 0.06 - 8 95 5 NS Ciproflaxacin '" 0.015 0.06 os: 0.015 - 0.06 100 0 0 NS

Table Ill. In vitro activity of agents against non-fermentors Percentage susceptibility Organism Antimicrobial agent MIC~ (mgll) MIC~ (mgll) MIC range (mg/I) S MS R P-value

Pseudomonas spp. Piperacillinltazobactam 16/4 >128/4 1/4 - >128/4 70 30 (N = 20) Ceftazidime 16 > 128 2 - .> 128 40 10 50 NS Cefpirome 32 64 4 - > 128 5 20 75 < 0.001 Cefepime 4 8 0.5 - 16 90 10 0 NS Biapenem 8 > 128 1 - .> 128 15 25 60 0.01 Imipenem 32 > 128 2 - > 128 35 25 45 0.06 Gentamicin 16 > 128 2 - > 128 40 60 NS Tobramycin 2 > 128 0.25 - > 128 55 45 NS Ciproftoxacin 16 0.12-64 55 20 25 NS

Acinetobacter spp. Piperaclllin/tazobactam 16/4 > 128/4 ~ 0.0614 - > 128/4 50 25 25 (N= 20) Ceftazidime 32 > 128 2 - > 128 25 15 60 NS Cefpirome 16 64 ,- > 128 20 20 60 NS Cefepime 2 8 0.25 - 8 100 0 0 om Biapenem 0.5 1 "",0.12_-4 100 0 0 0.01 lmipenem 1 4 0.25-4 100 0 0 0.01 Gentamicin 8 > 128 0.5->128 50 50 NS Tobramycin 2 8 0.25 - 128 55 45 NS Ciprofloxacin 128 0.12->128 65 10 25 NS

Table IV. In vitro activity of agents against B. fragilis Percentage susceptibility Organism Antimicrobial agent MIC, (mgll) MIC~ (mgll) MIC range (mgll) S- MS R P-value

B. fragi/is Piperacillinltazobactam 2/4 8/4 0.25/4 - 814 100 0 (N = 20) Co-amoxiclav 1/0.5 4/2 0.25/4 - 4/2 100 0 NS Cefoxitin 16 16 4 - 32 100 0 NS Biapenem 0.25 0.5 0.12 - 1 100 0 NS lmipenem 0.12 0.5 0.03 - 1 100 0 NS Ciprofloxacin 64 128 32-> 128 0 100 < 0.001 Metronidazole 0.5 0.5 0.06 - 1 100 0 NS Clindamycin 0.25 1 0.03 - 8 95 5 NS Chloramphenicol 4 8 2-8 100 0 NS

SAMJ Volume 86 .\'0. 10 Oaobrr 1996 1279 Table V. Significance of difference in proportion of susceptible isolates,'2 and the carbapenems most active against Enterobacteriaceae isolates in comparison with piperacillinl Acinetobacter spp.:2.13 When the activity of the carbapenems, tazobactam biapenem and imipenem was compared in respect of all the Antimicrobial agent P-value Gram-negative bacilli tested, biapenem was at least as Piperacillinltazobactam active as and often more active than imipenem, a finding which is in accordance with previous reports.I! Ampicillin < 0.001 Tazobactam and clavulanic acid have previously been Co-amoxiclav < 0.001 shown to enhance the activity of ~-lactams against Cefoxitin < 0.001 J f)-Iactamase-producing anaerobic Gram-negative bacilli. ,'4 Ceftriaxone NS Although cefoxitin-resistant isolates were not included in this Cefpirome NS study. the MICs of these sensitive strains were similar to Cefepime NS those previously reported, with the carbapenems being the Biapenem NS most active agents_1H5 lmipenem NS Ciprofloxacin NS Conclusion Table VI. Significance of difference in proportion of susceptible non-fermentors in comparison with piperacillinltazobactam PiperacilJinltazobactam may be included in the group of agents useful against most Gram-negative pathogens that Antimicrobial agent P-value cause nosocomial infections in South African patients. Piperacillinltazobactam Ceftazidime 0.02 We wish to acknowledge the immense contribution of the late Jean Saunders to this study and to the antibiotic laboratory Cefpirome < 0.001 work of our unit. This study was sponsored by a grant from Cefepime < 0.001 Lederle Laboratories. Biapenem NS Imipenem NS REFERENCES

Gentamicin NS 1. Jacobs MA. Aronoff sc. Johenrung S, Shlaes OM, Yamahe S. Comparaove actiVities Tobramycin NS 01 the !I-Iactamase inhibitors YTR 830. clavulanate, and combined with ampicillin and broad-spectrllm penlClltins against defined ~-lactarnase-producing Ciprofloxacin NS aerobic Gram-negative bacilli. Anrlmu:rob A~rs Chemother 1989; 29: 980-985. 2. National Committee for Clinical Laboratory Standards. Performance $randards for AlTrlmicrobiaJ $uscepriblbty Testing. VitLanova. Penn.: NCCLS. 1994. 3. At;ar JF, GoIdstein FW, Kitzl$ MO. Susceptibility survey of p,peracillin alone and in the presence of !aZobaetarn. J Anotnlcrob Chemorher 1993; 31: suppl A. 23-28. effectively inhibit the class I chromosomal enzymes 4. FallS RJ, Prior R6_ Comparative in vitro acnvitles of piperacillin-tazobactam and produced by these organisms, and so does not potentlate ueateiltin--elavulanate. Anrmllcrob Agents Chemother 1989; 33; 1268-1274. 5. Mehtar S, Orabu YJ, Blakemore PH. The In Vitro activity of PlperaCltlir\ftazObactam. the activity of amoxycillin against strains that are stably ciprofklxacin, cefo.azidime and ilTUpenem aga.Mt multiple resiStant Gram-negallve derepressed for these enzymes.''; Tazobactam is a weaker cac:teria J Antimicrob Chemother 1990; 25: 915-919. 6. Murray PR, CanueU FH, Lankfon:f RB, and the In Vitro Susceptibility Surveillance inducer of ~-Iactamasesthan clavulanic acid, and has been Group. Multlceflle.- evaluation 01 the In vitro activity of piperaClltin-tazobactalT1 shown to enhance the action of piperacil1in against compared with eleven selected !I-lactam antibiotics and ciprofloKacin a;ainst more than 42 000 aerobic Grarn·posillve and Gram-negative bacteria. Diagn MlcfObiol C. freundii isolates. ID Presumably the strains in our study Infect Ois 1994; 19: 111-120. produced chromosomal ~-lactamases which were induced 7. Schifer V, Shah PM. Ooerr HW. Zleman M. HeH ..... ich S, Siebert G and Srudy Group_ In vitro activity 01 ce/pirome against isolates from patients with urinary tract, lower by clavulanic acid but not by tazobactam. Although respiratory tract and wound infections. J Anrimir;rob Chemother 1992; 29; suppl A. Enterobacter spp., which are known to produce class 1 7·12. 8. Moosdeen F, Keeble J. Williams JO. Inductionlinhibition of chromosomal 1'1-. chromosomal fHactamases, were not included in this study, laCtamases by ~-Iactamase inhibitors. Revlnfe-ct Dis 1966; 8: suppl 5, 5562-5568. 9. Uvermore OM, Akova M, Wu P, Yang Y. Clavulanate and ~·lactamase Induction. J in a multicentre study which evaluated 978 E. aerogenes and Anrimicrob Chemotller 1989; 24: suppl 8, 23-33. 1 789 E. cloacae isolates, their susceptibility rates to 10. Akova M, Yang Y. Uvermore OM. Interactions of tazobactam and clavulanate with inducibly- and constitutively-expressoo Class 1 ~-lactamases. J Antlmlcrob piperacillinltazobactam were 70.7% and 69% respectively./; CfHJmother 1990; 25: 199-208. The fourth-generation cephalosporins, cefepime and 11. Cheng AFS. Ung!KW, Lam AW, Fun; KSC. Wise R. The antilTllcrobl

1280 Volume 86 No. 10 Oerober 1996 SAMJ