Modification in prescribing practices for third-generation cephalosporins and ciprofloxacin is associated with a reduction in meticillin-resistant Staphylococcus aureus bacteraemia rate.

To decrease the incidence of hospital infections caused by meticillin-resistant Staphylococcus aureus (MRSA), an educational intervention study was performed in which the use of intravenous ciprofloxacin and third-generation cephalosporins was discouraged. The effect was assessed by observing the MRSA bacteraemia rate both within the hospital and the intensive care unit for 18 months before, and 16 months after, the two-month intervention programme. MRSA bacteraemia rate throughout the hospital was reduced by 62.9% (P<0.001) by the end of the study and MRSA colonisation rate was reduced by 38.4% (not significant). There was no concomitant decrease in episodes of bacteraemia caused by meticillin-susceptible Staphylococcus aureus (MSSA) during the study period. There was a fall in hospital dispensing of both ciprofloxacin (80.4%) and third-generation cephalosporins (75.2%). The overall incidence of MRSA bloodstream infections within critical care was reduced (4.200 vs 0.272 per 1000 occupied bed-days) but this was not significant.

Dihydropteroate synthase and novel dihydrofolate reductase gene mutations in strains of Pneumocystis jirovecii from South Africa.

Dihydropteroate synthase (DHPS) gene mutations have raised concerns about emerging sulfonamide resistance in Pneumocystis jirovecii. DHPS and dihydrofolate reductase (DHFR) gene products were amplified in clinical specimens from South African patients. One of 53 DHPS genes sequenced contained the double mutation Thr55Ala Pro57Ser. DHFR gene mutations detected were Ala67Val and the new mutations Arg59Gly and C278T.

National surveillance programme on susceptibility patterns of respiratory pathogens in South Africa: moxifloxacin compared with eight other antimicrobial agents.

AIMS: The susceptibility patterns of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae, and Streptococcus pyogenes isolated from specimens submitted to 12 private laboratories in South Africa were determined. METHODS: Minimum inhibitory concentration (MIC) determinations were performed on the isolates in the microbiology laboratory at Tygerberg Hospital according to the recommendations of the National Committee for Clinical Laboratory Standards (NCCLS). RESULTS: According to the NCCLS breakpoints, 24% of 729 S pneumoniae isolates were sensitive, 30% intermediate, and 46% resistant to penicillin. Rates of macrolide resistance were high, with 61% of the pneumococci being resistant to clarithromycin and azithromycin. Co-trimoxazole resistance was also high, with 28% of pneumococcal strains being sensitive, 21% intermediate, and 51% resistant. beta Lactamase was produced by 7% of 736 H influenzae isolates and 91% of 256 M catarrhalis isolates. The quinolones, moxifloxacin and levofloxacin, were universally active against all isolates tested, which included S pneumoniae, H influenzae, M catarrhalis, K pneumoniae, and S pyogenes. CONCLUSIONS: Haemophilus influenzae and S pneumoniae were the most commonly isolated organisms. Resistance to penicillin was one of the highest reported in the world (76%) in S pneumoniae, as was macrolide resistance in pneumonocci, although surprisingly, only 14% of S pyogenes were resistant. The quinolones, moxifloxacin and levofloxacin, were active against all organisms tested, including the penicillin and macrolide resistant strains and moxifloxacin was more active than levofloxacin against pneumococci.

Pneumocystis pneumonia.

Pneumocystis jiroveci is a common cause of pneumonia in South African patients with AIDS. Sulphonamide resistance may become a problem in South Africa, as patients are treated with prophylactic co-trimoxazole when their CD4 counts fall below 200 cells/microliter. Failure of prophylaxis and treatment has been observed, possibly due to infection with sulphonamide-resistant strains. Sulphonamide resistance has been reported elsewhere, and is due to point mutations at codons 55 and 57 of the dihydropteroate synthase gene. Strain typing is useful for molecular epidemiological purposes.

A two year global evaluation of the susceptibility of Candida species to fluconazole by disk diffusion.

The in-vitro activity of fluconazole against 46,831 yeast isolates collected over a two-year period from 57 laboratories in 33 countries worldwide was assessed using a disc diffusion method. Candida albicans was the organism isolated most frequently, accounting for 68.6% of the total number of isolates. C. glabrata, C. tropicalis, C parapsilosis and C. krusei and Cryptococcus neoformans represented 9.9, 4.7, 4.3, 1.9, and 1.4% of isolates respectively during the 2 year period and rates varied markedly between countries. In 1999 data blood isolates represented 4.9% of all isolates and intensive care unit isolates represented 9.9%. In both the 1998 and 1999 data, 99% of C. albicans were fully susceptible (S) to fluconazole, and 95.6% of all species of yeasts tested were S or susceptible-dose dependent (S-DD) to fluconazole. No emerging trends of resistance were noted with any of the Candida spp. tested as 96% of all isolates retained susceptibility (S or S-DD) to this agent.

Incidence of high-level gentamicin resistance in enterococci at Johannesburg Hospital.

OBJECTIVE: To document the incidence of high-level gentamicin resistance (HLGR) in enterococcal isolates at Johannesburg Hospital. DESIGN: Survey of laboratory isolates. SETTING: Academic hospitals. BACTERIAL STRAINS: Consecutive samples of enterococcal isolates. MAIN OUTCOME MEASURE: The incidence of HLGR in enterococcal isolates. RESULTS: The incidence of HLGR was 26.5% of Enterococcus faecalis isolates and 20% of E. faecium isolates grown during the study period. CONCLUSIONS: High-level gentamicin resistance is common among enterococci isolated at Johannesburg Hospital, and this observation must be considered in defining strategies for the management of invasive enterococcal infections in the future.

Comparative in vitro activity of piperacillin/tazobactam against gram-negative bacilli.

OBJECTIVE: To describe the in vitro activity of piperacillin/tazobactam against clinical isolates of Gram-negative bacteria, compared with other antibacterial agents. DESIGN: Survey of susceptibility of clinical isolates of Gram-negative bacilli. SETTING: Academic hospitals of the University isolates of the Witwatersrand teaching complex. BACTERIAL STRAINS: 180 selected clinical isolates of Gram-negative bacilli. MAIN OUTCOME MEASURES: Minimum inhibitory concentrations (MICs) determined by agar dilution using techniques according to the recommendations of the National Committee for Clinical Laboratory Standards. RESULTS: Ciprofloxacin, biapenerm, imipenem, cefepime and cefpirome were all highly active against most of the Enterobacteriaceae. All the ampicillin-resistant strains of Enterobacteriaceae were susceptible to piperacillin/tazobactam, MIC90 values being 4/4 mg/l for Klebsiella and Proteus/Providencia spp., 8/4 mg/l for Citrobacter and Serratia spp., and 16/4 mg/l for Escherichia coli. All the agents, with the exception of ampicillin (MIC90 4 mg/l) and chloramphenicol (MIC90 4 mg/l), were highly active against the Haemophilus influenzae isolates tested. All Bacteroides fragilis strains were susceptible to piperacillin/tazobactam (MIC90 8/4 mg/l), as well as to co-amoxiclav (MIC90 4/2 mg/l), biapenem and imipenem (MIC90s 0.5 mg/l). The Pseudomonas spp. tested included strains resistant to piperacillin/tazobactam, ceftazidime, 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 most active agent against the Acinetobacter isolates investigated. CONCLUSIONS: The in vitro spectrum of activity of piperacillin/tazobactam against the majority of isolates was comparable to those of the other new agents tested.

Comparative in vitro activity of several antimicrobial agents against selected clinical isolates.

A comparison between the in vitro activities of ceftazidime, cefotaxime, ceftriaxone, ampicillin, piperacillin, gentamicin, tobramycin and netilmicin was performed on selected clinical isolates. The activity of the agents was assessed by means of minimum inhibitory concentration determinations, and time-kill studies. The third generation cephalosporins were active against all members of the Enterobacteriaceae excluding some Enterobacter species. Their activity against these bacteria was generally comparable and greater than that of piperacillin. Netilmicin was the most active of the aminoglycosides tested against members of the Enterobacteriaceae; however, aminoglycoside-resistant strains were encountered. Ceftazidime was the most active of the third generation cephalosporins against the non-fermenters (e.g. Pseudomonas and Acinetobacter spp), its inhibitory activity also being greater than that of piperacillin. Using a time-kill study, ceftazidime also demonstrated greater bactericidal activity than piperacillin against an isolate of Pseudomonas aeruginosa. The aminoglycoside demonstrating the greatest activity against the non-fermenters was tobramycin.

Serotype and antimicrobial susceptibility patterns of Haemophilus influenzae isolates from inpatients and outpatients in Johannesburg.

During the 6-month period July 1987-January 1988, 934 isolates of Haemophilus influenzae were collected from 6 laboratories in Johannesburg. On the basis of counter-immuno-electrophoresis, 30 of the isolates were serotype b, with 9 of 36 (25%) cerebrospinal fluid isolates being type b. Overall, 11.7% of the isolates produced beta-lactamase. The prevalence of resistance based on a disc diffusion test was ampicillin 14%, chloramphenicol 2.3%, cefaclor 4.4%, erythromycin 84.9%, tetracycline 4.7% and co-trimoxazole 9.7%. Problems were encountered with the disc diffusion testing of augmentin- and minimum inhibitory concentrations (MICs) were determined. The MICs of 40 isolates were compared with their zone diameters. Good correlation between these two methods of antimicrobial susceptibility testing was found with all the antimicrobials tested excluding augmentin (correlation coefficient 0.1234) and cefaclor (correlation coefficient -0.2473).

In vitro selection of bacteria resistant to LY146032, a new cyclic lipopeptide.

Isolates of Streptococcus pneumoniae, Enterococcus faecalis, Enterococcus faecium, and coagulase-positive and -negative staphylococci were investigated for their abilities, in vitro, to develop resistance to LY146032. Exposure of the organisms to incremental concentrations of LY146032 resulted in MICs 8- to 32-fold higher than those for the original isolates. After three passages on antibiotic-free medium, the high MICs were maintained for the coagulase-negative staphylococci and pneumococci, with a twofold decrease observed for the enterococci and a fourfold decrease observed for Staphylococcus aureus. The frequency of spontaneous emergence of resistance was highest with S. pneumoniae (1.2 X 10(-6) at 16 times the original MIC) and lowest with S. aureus (7.0 X 10(-10) at 8 times the original MIC). For bacteria For bacteria surviving time-kill studies MICs were also higher than were those for the original isolates. Exposure to LY146032 in vitro selected for strains with decreased susceptibilities to the antimicrobial agent. However, the emergence of resistance in vivo is unpredictable and can be evaluated only after prolonged clinical use of the drug.

In vitro susceptibility of upper respiratory tract pathogens to 13 oral antimicrobial agents.

An in vitro comparison of the activities of 13 oral antimicrobial agents against clinical isolates of bacteria commonly responsible for causing upper respiratory tract infections was performed. With regard to Haemophilus influenzae, beta-lactamase-negative strains were susceptible to amoxycillin, augmentin, cefaclor, erythromycin, trimethoprim, cotrimoxazole and tetracycline, with CL 284,635 being the most active agent. With the exception of amoxycillin these drugs were also active against beta-lactamase-producing strains. CL 284,635 was also very active against Branhamella catarrhalis isolates, including beta-lactamase-producing strains, but was less active against the Gram-positive bacteria tested. Cefadroxil, cephradine and cephalexin were mainly active against Gram-positive pathogens. Based on minimum inhibitory concentration determinations, cefaclor, augmentin and co-trimoxazole would be appropriate drugs for the treatment of those cases of otitis media and sinusitis where H. influenzae and Streptococcus pneumoniae are important pathogens provided they are susceptible to these agents.

In vitro activity of A-56619 (difloxacin), A-56620, and other new quinolone antimicrobial agents against genital pathogens.

The in vitro activities of two new carboxyquinolones, A-56619 (difloxacin) and A-56620, were compared with those of ciprofloxacin, norfloxacin, and ofloxacin against genital tract pathogens. All the quinolones were highly active against Neisseria gonorrhoeae. A-56619 had the lowest MICs against Chlamydia trachomatis (MIC range, 0.125 to 0.25 micrograms/ml) and Haemophilus ducreyi (MIC for 90% of isolates tested, 0.1 micrograms/ml).

Bacterial meningitis in Johannesburg--1980-1982.

A 2-year retrospective study of aetiology, age distribution, seasonal variation and antimicrobial sensitivity patterns of bacteria isolated from patients with meningitis in five Johannesburg hospitals for White, Black, Coloured and Asian patients was performed. Neisseria meningitidis was isolated most frequently, followed by Streptococcus pneumoniae, Haemophilus influenzae, Escherichia coli and Streptococcus group B. In the Black population 73% of the meningococcal infections occurred in patients over 3 years of age, and the majority of these infections were caused by serogroup A organisms. Virtually all (93%) of the H. influenzae infections occurred in children of less than 3 years of age. Of the isolates tested, 16% of the meningococci, 4,5% of the H. influenzae and 47% of the pneumococci were resistant to sulphadiazine, ampicillin and penicillin respectively.

In vitro susceptibility and cross-resistance of South African isolates of Neisseria gonorrhoeae to 14 antimicrobial agents.

One hundred isolates of Neisseria gonorrhoeae obtained from patients attending clinics in Johannesburg, South Africa, were tested by a broth dilution technique for their minimal inhibitory concentrations (MICs) of benzyl penicillin G, ampicillin, cefoxitin, cefuroxime, cefotaxime, ceftriaxone, ceftazidime, tetracycline, minocycline, doxycycline, spectinomycin, rosaramicin, chloramphenicol, and rosoxacin. None of the isolates tested produced beta-lactamase. The MICs of penicillin ranged from less than or equal to 0.007 to 0.5 micrograms/ml. The isolates were also very susceptible to rosaramicin (minimal concentration at which 50% of isolates were inhibited [MIC50] = 0.02 micrograms/ml) and to the new cephalosporins (cefotaxime MIC50 less than 0.007 micrograms/ml, ceftriaxone MIC50 less than 0.007 micrograms/ml, and ceftazidime MIC50 less than 0.007 micrograms/ml). By using regression analysis, good correlation was observed between the MICs of penicillin and those of the other agents, with the exception of ceftriaxone, spectinomycin, and rosaramicin. The MICs and the minimal bactericidal concentrations were within a log2 concentration of each other.