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Community-acquired methicillin-resistant Staphylococcus aureus infections in discharging ears.

OBJECTIVES: Although community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections have recently become an increasing problem in various fields of medicine, they have rarely been studied in the ear. The purpose of this study was to determine the prevalence of community-acquired MRSA infections in discharging ears and to compare the epidemiology of MRSA with that of other pathogens. MATERIAL AND METHODS: Between August 2000 and February 2002, 248 isolates recovered from 221 discharging ears of patients with 3 disease entities (chronic otitis media, acute otitis externa and granular myringitis) were prospectively analyzed using bacteriology. The isolates analyzed using bacteriology were divided into three groups: MRSA, methicillin-susceptible S. aureus (MSSA) and non-SA. RESULTS: S. aureus was found in 108 (43.5%) isolates and MRSA in 27. Therefore, the percentage of MRSA among the S. aureus isolates was 25.0% (27/108). The prevalence of community-acquired MRSA infections in discharging ears was 12.2% (27/221) and the MRSA strains were highly susceptible to vancomycin, teicoplanin, fusidic acid and minocycline. The MRSA-infected patients were older than those infected with other groups of pathogens. Also, MRSA infections appeared to be more common in chronic otitis media than in acute otitis externa or granular myringitis. CONCLUSIONS: Community-acquired MRSA represents an increasing problem. In this study, MRSA strains were highly susceptible to vancomycin, teicoplanin, fusidic acid and minocycline.

Acute Disease↗

Antimicrobial resistance of Clostridium difficile isolates in a tertiary medical center, Israel.

The antimicrobial susceptibilities of 49 Clostridium difficile isolates obtained from patients with C. difficile-associated diarrhea to metronidazole, vancomycin, rifampicin, fusidic acid, doxycycline, and linezolid were determined by the disc diffusion and Etest (Biodisk, Solna, Sweden). Random amplification of polymorphic DNA-PCR amplification assay was performed for studying clonality of isolates. Resistance to metronidazole was found in 2% (1/49 isolates; MIC > or = 256 microg/mL) of isolates and resistance to linezolid in 2% (1/49 isolates; MIC = 24 microg/mL). One isolate showed combined resistance to fusidic acid (by disc diffusion test) and rifampicin (MIC > or = 32 microg/mL). All isolates were sensitive to doxycycline and vancomycin. Molecular typing revealed an absence of clonality among the resistant isolates, whereas the sensitive isolates were monoclonal. Resistance of C. difficile to metronidazole and other antimicrobials including linezolid exists in our institution. This finding should promote exploration of this problem in Israel and clarify the impact of resistance on outcome.

Adolescent↗

In vitro susceptibility of Corynebacterium group D2 and Corynebacterium jeikeium to twelve antibiotics.

The in vitro susceptibility of 83 Corynebacterium group D2 strains and 44 Corynebacterium jeikeium strains to 12 antimicrobial agents was determined by an agar dilution technique using Mueller-Hinton agar supplemented with Tween 80 (0.025%). All strains of Corynebacterium group D2 were highly sensitive to fusidic acid, pristinamycin, teicoplanin and vancomycin (geometric mean MICs 0.047, 0.048, 0.338 and 0.396 mg/l respectively). Most of the strains were resistant to other antibiotics tested (ciprofloxacin, erythromycin, gentamicin, lincomycin, rifampin and tetracycline). However, a few strains were highly sensitive (MICs less than or equal to 0.2 mg/l). The overall pattern of susceptibility of 44 strains of Corynebacterium jeikeium was similar; the geometric mean MICs of fusidic acid, pristinamycin, vancomycin and teicoplanin were 0.234, 0.235, 0.557 and 0.652 mg/l respectively.

Anti-Bacterial Agents↗

Scope of urinary pathogens isolated in the Public Health Bacteriology Laboratory, Harare: antibiotic susceptibility patterns of isolates and incidence of haemolytic bacteria.

OBJECTIVES: To determine the scope of urinary pathogens isolated in the Public Health Bacteriology Laboratory, their antibiotic susceptibility patterns and the incidence of haemolytic bacteria in Harare. DESIGN: Prospective study. Patients of different age groups attending various clinics in Parirenyatwa Hospital, Harare, between October 1995 and April 1996 were enrolled for the study. SETTING: A laboratory based study at the Bacteriology Unit, Public Health Laboratories, Harare. SUBJECTS: 1,760 urine specimens obtained from male and female patients suspected of having UTI. RESULTS: Out of a total number of 1,760 urine specimens screened only 473 (26.9pc) were positive for UTI pathogens. Four hundred and nineteen (88.5pc) and 46 (9.7pc) of the 473 positive UTI pathogens were Gram negative and Gram positive bacteria respectively. Eight (1.7pc) of the positive isolates were Candida spp. The commonest pathogen isolated was Escherichia coli (40.5pc), followed by Klebsiella spp. (22.1pc) and Proteus spp. (7.2pc). Of the positive isolates 184 (38.9pc) and seven (1.5pc) were beta- and alpha-haemolytic respectively. Of E. coli isolates 72pc were beta-haemolytic. Sex distribution showed that 53pc and 47pc of the UTI pathogens were isolated from males and females respectively. E. coli was more predominant in females (51.3pc). Antibiotic susceptibility patterns revealed that 100pc of strains of E. coli, Proteus spp., Serratia spp., Salmonella spp., Morganella spp., Staphylococcus aureus and coagulase negative staphylococci (CNS) were sensitive to Ciprofloxacin. Urinary isolates were markedly resistant to Tetracycline, Carbenicillin, Cotrimoxazole, Ampicillin and Nitrofurantoin. Fusidic acid and Clindamycin were active against staphylococcal species. CONCLUSION: We conclude that E. coli is the commonest UTI pathogen and that 72pc of strains were beta-haemolytic. We suggest the use of Ciprofloxacin as the drug of choice for the treatment of UTI caused by both Gram positive and Gram negative UTI pathogens. Nitrofurantoin and Gentamycin are in addition recommended for E. coli while Fusidic acid and Clindamycin may be useful for staphylococcal species.

Adolescent↗

Fitness of antibiotic resistant Staphylococcus epidermidis assessed by competition on the skin of human volunteers.

BACKGROUND: Antibiotic resistance typically confers a biological fitness cost on bacteria that can be manifested as a decreased growth rate in culture media and experimental animals. However, there are limited experimental data on the relative fitness of resistant and susceptible bacteria during growth in their natural environment. OBJECTIVE: We have developed a human competition model to investigate the relative fitness of antibiotic-resistant and -susceptible bacteria. MATERIALS AND METHODS: A non-epidemic Staphylococcus epidermidis strain was isolated from skin, and a rifampicin-resistant (RifR) clone was selected. The RifR marker was used to distinguish the inoculated strains from the resident population of coagulase-negative staphylococci. The RifR strains were further selected for resistance to ciprofloxacin (CipR) and fusidic acid (FusR). A 1:1 mix of susceptible and resistant bacteria was applied on the forearms of 12 volunteers. Competition was monitored by sampling bacteria from skin and determining their relative numbers. RESULTS: Resistance to ciprofloxacin due to parC mutations did not decrease the growth rate in vitro, and the CipR/CipS ratio was close to 1 during day 1 and 3 in the in vivo competition experiments. In contrast, fusidic acid resistance due to fusA mutations resulted in a decrease in the growth rate in vitro and a considerable loss of fitness in the competition. The FusR/FusS ratio diminished from 1.3 to 0.023 in 3 days. CONCLUSIONS: These data show that human volunteers can be used as a simple and relevant model to study the biological cost of resistance.

Drug Resistance, Bacterial↗

The changing pattern of antibiotic susceptibilities of Bacteroides fragilis in Kuwait.

The susceptibility of 340 distinct strains of Bacteroides fragilis isolated during 1981 to 1988, to eight antimicrobial agents was determined. These included isolates from infected hospitalized patients (127), infected out-patients (89), faecal isolates from uninfected patients hospitalized for greater than 10 days (48) and from normal subjects in the community (76). All strains were susceptible to metronidazole with a MIC of 1 mg/l. The least effective antibiotics were ampicillin, fusidic acid, erythromycin and tetracycline. There was no significant difference in antibiotic sensitivities between strains causing community-acquired and those causing hospital-acquired infections. However faecal isolates from hospitalized patients were significantly more resistant to ampicillin (P less than 0.05), cefoxitin (P less than 0.005) and clindamycin (P = 0.001) than community faecal isolates. During the study period there was a rise in resistance to clindamycin (P less than 0.005), cefoxitin, erythromycin and fusidic acid (P less than 0.001) and tetracycline (P less than 0.05). Antimicrobial resistance of B. fragilis is rising and long periods of hospitalization seem to play an important role in its development.

Anti-Bacterial Agents↗

Synergism between the GTPase activities of EF-Tu.GTP and EF-G.GTP on empty ribosomes. Elongation factors as stimulators of the ribosomal oscillation between two conformations.

A remarkable positive cooperativity between the GTPase activities of EF-Tu and EF-G on empty ribosomes from Escherichia coli has been discovered. This cooperativity implies a decrease of the corresponding apparent KM values of the empty ribosome for either elongation factor: from more than 10 microM to 0.5 microM for EF-Tu.GTP by the addition of 0.25 microM EF-G and from 0.7 microM to 0.5 microM for EF-G.GTP by the addition of 3 microM EF-Tu. In a further analysis of this phenomenon, the effects of various specific antibiotics were studied: thiostrepton, fusidic acid, tetracycline, pulvomycin and kirromycin appeared to inhibit the synergistic effect, whereas streptomycin was found to stimulate it. Even in the present minimal system the ribosomes respond to the above-mentioned antibiotics in a way surprisingly similar to that in the coupled system with mRNA and tRNAs. The cooperativity seems not to be due to a simultaneous binding of the two elongation factors to the ribosome as revealed by studying the effects of fusidic acid and kirromycin, and by band-shift experiments by means of gel electrophoresis under non-denaturing conditions. Our experimental data and the kinetic analysis of alternative models provide evidence that EF-Tu.GTP and EF-G.GTP interact sequentially with empty ribosomes that oscillate between two different conformations, one for each elongation factor. Apparently, ribosomes have an intrinsic property for oscillation as normally observed during protein synthesis with a frequency paced by the events of tRNA binding and translocation.

Allosteric Regulation↗

Aerobic bacteria isolated from blood cultures of patients and their antibiotic susceptibilities in Harare, Zimbabwe.

OBJECTIVE: To assess the extent of involvement of different types of gram positive and gram negative bacteria and incidence of monomicrobial and polymicrobial cases in patients with bacteremia but without a record of the underlying clinical conditions of the patients. Antibiotic susceptibility patterns of isolates were also determined to guide clinicians in the management of such bacteremic cases especially where routine sensitivity testing is not performed. DESIGN: Case series. SETTING: The study comprised patients attending different clinics in Parirenyatwa Hospital, Harare. SUBJECTS: A total of 817 blood cultures from patients, comprising 469 and 348 males and females respectively. There were no records of the underlying clinical conditions of the patients. MAIN OUTCOME MEASURES: Prevalence rates of organisms and their antibiograms using standard techniques and Kirby-Bauer disc diffusion method. RESULTS: Results obtained revealed that only 303(37.1%) of the 817 total samples screened were positive for either monomicrobial or polymicrobial bacteremia. Two hundred and eighteen (71.9%) and 85 of positive cultures were Gram positive and Gram negative bacteria respectively. Coagulase negative staphylococci (CNS) strains were the predominant organisms isolated (42.9%). Other organisms isolated were Staphylococcus aureus (11.6%), Escherichia coli (6.9%), Salmonella spp. (8.3%), Klebsiella spp. (5.3%), whereas Pseudomonas aeruginosa, Haemophilus influenzae, Enterobacter and Micrococcus species each accounted for less than 4%. Antibiogram patterns showed multiple resistance of S. aureus and CNS to Penicillin, Erythromycin and Methicillin. All isolates of S. pyogenes (10), S. pneumoniae (18) and Micrococcus spp (10). were susceptible to penicillin. Ciprofloxacin, Clindamycin, Fusidic acid and Gentamycin were highly active against gram positive organisms except that Gentamycin was inactive against S. pneumoniae. Ceforoxime, Erythromycin and Ceftriazone also showed good activities against Gram positive organisms. All (10) isolates of P. aeruginosa were susceptible to Polymyxin B, Carbenicillin and Ciprofloxacin. Ciprofloxacin, Norfloxacin and Gentamycin were highly active against all Gram negative bacteria. CONCLUSION: For infections due to both Gram positive and Gram negative bacteria, Ciprofloxacin and Gentamycin would be appropriate for therapy whereas Fusidic acid and Clindamycin may, in addition, be recommended for Gram positive organisms. It is also concluded that a prevalence rate of 37.1% of bacteremic cases existed in the sampled population and that monomicrobial cases were more predominant.

Bacteremia↗

Comparative susceptibility of clinical group A, B, C, F, and G beta-hemolytic streptococcal isolates to 24 antimicrobial drugs.

A total of 312 clinical beta-hemolytic streptococcal isolates (Streptococcus pyogenes, group A = 63; Streptococcus agalactiae, group B = 145; group C = 50; group F = 27; group G = 27) were examined for susceptibility to 23 and 24 antimicrobial drugs with the Bauer-Kirby agar disk diffusion and the agar dilution method, respectively. Sheep blood Mueller-Hinton agar served as the reference medium. Wilkins-Chalgren agar supported optimal growth of group A and B, but not of all group C, F, and G streptococci. The group A streptococci were susceptible to all beta-lactam antibiotics, clindamycin, chloramphenicol, rifampin, teicoplanin, and vancomycin, but resistant to cotrimoxazole, fusidic acid, and, except for 2 strains, to fosfomycin. Resistance (R)/intermediate susceptibility (I) rates (R/I%) to ciprofloxacin (0/2%), ofloxacin (1/2%), erythromycin (1.6/0%), and clarithromycin (0/1%) were low. Higher resistance rates were noted with tetracyclines (doxycycline 23.8/15.9%; tetracycline 39.7/3.2%). Among the group B streptococcal isolates, one strain was resistant against oxacillin and of intermediate susceptibility to penicillin G and cefoxitin. All isolates were susceptible to teicoplanin and rifampin. Conversely, all group B isolates were resistant to cotrimoxazole and fusidic acid; 69% and 51% of these isolates were susceptible to fosfomycin and rifampin, respectively. R/I rates of the group B streptococcal isolates were low for ciprofloxacin and ofloxacin (0/0.7%), clindamycin (0.7/0%), erythromycin (1.4/ 3.5%), clarithromycin (1.4/0%), and chloramphenicol (0.7/0%). Resistance to tetracyclines was significant (doxycycline: 72.4/2.1%; tetracycline; 74.5/1.4%). Among the non-A, non-B beta-hemolytic streptococci, 2 group C strains were resistant to oxacillin and showed intermediate susceptibility to penicillin G. All isolates were susceptible to third and fourth-generation cephalosporins, imipenem, chloramphenicol, rifampin, teicoplanin, and vancomycin. R/I rates to the other antimicrobial drugs were: ciprofloxacin (3.9/1.9%), ofloxacin (2.9/1.9%), clindamycin (2.9/1%), erythromycin (5.8/0%), clarithromycin (3.8/2.9%), and cotrimoxazole (16.4/3.9%). Resistance against tetracyclines was more frequent (doxycycline: 18.3/2.9%; tetracycline: 20.2/6.7%). On the basis of various minor discrepancies between MIC and disk diffusion test results, it is proposed that the current NCCLS inhibition zone (diameter, mm) criteria indicative of intermediate susceptibility of beta-hemolytic streptococci be changed for the following antimicrobial drugs: ampicillin: 22-27 mm (only for group A and B beta-hemolytic streptococci); ciprofloxacin: 16-18 mm; clindamycin: 15-18 mm; doxycycline: 17-19 mm; tetracycline: 17-19 mm, and erythromycin: 14-19 mm.

Anti-Bacterial Agents↗

Sensitivity of Staphylococcus aureus, isolated from skin infections in 1994, to 19 antimicrobial agents.

The most common pathogen causing skin infections is Staphylococcus aureus and the incidence of multiply resistant strains of S. aureus has been increasing. The in vitro susceptibility of 130 isolates of S. aureus to 19 antimicrobial agents: ampicillin (ABPC), methicillin, cefaclor, cefpodoxime proxetil, gentamicin, erythromycin, clindamycin, minocycline, vancomycin, fusidic acid, norfloxacin, ofloxacin, enoxacin, ciprofloxacin, lomefloxacin, tosufloxacin, sparfloxacin, nadifloxacin and grepafloxacin, was evaluated by agar dilution tests. The S. aureus isolates were isolated from 130 patients with skin infections in 1994. The proportion of methicillin-resistant S. aureus isolates among the strains isolated was 19.2%. The concentration needed to inhibit 50% of the isolates was 3.13 mg/ml or less for all of the drugs, but the concentration needed to inhibit 90% of isolates was over 12.5 micrograms/ml, except in the cases of minocycline, vancomycin, fusidic acid, tosufloxacin and nadifloxacin. Tosufloxacin and nadifloxacin had the lowest minimum inhibitory concentrations. None of the S. aureus strains was resistant to nadifloxacin.

Anti-Bacterial Agents↗

The antibiotic sensitivity patterns of Bacillus anthracis isolated from the Kruger National Park.

Forty-four isolates of Bacillus anthracis made from carcasses and soil in different localities of an endemic anthrax area in the Kruger National Park, South Africa, were tested by standard disc diffusion for their susceptibility to 18 different antibiotics. These were ampicillin, penicillin G, sulphatriad, streptomycin, clindamycin, gentamicin, fusidic acid, trimethoprim, sulphamethoxazole, chloramphenicol, erythromycin, methicillin, tetracycline (2 different concentrations), novobiocin, cefotaxime, netilmicin, cefamandole and cefoxitin. All the isolates were susceptible to ampicillin, streptomycin, chloramphenicol, erythromycin, tetracycline, methicillin and netilmicin. More than 90% of the isolates were sensitive to clindamycin, gentamicin and cefoxitin, whereas only 84.1% of the isolates were sensitive to penicillin G, 86.4% to novobiocin and 68.18% to cefamandole. Complete resistance in 100% of the isolates was encountered with trimethoprim and sulphamethoxazole, with 95.45% for sulphatriad. Moderate sensitivity occurred with penicillin G (15.9% of the isolates), clindamycin (6.8%), novobiocin (13.6%), fusidic acid (84.1%), cefotaxime (100%), cefamandole (31.8%) and cefoxitin (6.8%). The relevance of the findings to the therapeutic uses of different types of antibiotic in human clinical cases referred to in the literature is discussed.

Animals↗

Antibiotic treatment for Clostridium difficile-associated diarrhea in adults.

BACKGROUND: Clostridium difficile (C. difficile) is recognized as a frequent cause of antibiotic-associated diarrhea and colitis. OBJECTIVES: The aim of this review is to establish the efficacy of antibiotic therapy for C. difficile-associated diarrhea (CDAD), to identify the most effective antibiotic treatment for CDAD in adults and to determine the need for stopping the causative antibiotic during therapy. SEARCH STRATEGY: MEDLINE (1966 to 2003), EMBASE (1980 to 2003), Cochrane Central Database of Controlled Trials and the Cochrane IBD Review Group Specialized Trials Register were searched using the following search terms: "pseudomembranous colitis and randomized trial"; "Clostridium difficile and randomized trial"; "antibiotic associated diarrhea and randomized trial". SELECTION CRITERIA: Only randomized, controlled trials assessing antibiotic treatment for CDAD were included in the review. Probiotic trials are excluded. The following outcomes were sought: initial resolution of diarrhea; initial conversion of stool to C. difficile cytotoxin and/or stool culture negative; recurrence of diarrhea; recurrence of fecal C. difficile cytotoxin and/or positive stool culture; patient response to cessation of prior antibiotic therapy; sepsis; emergent surgery: fecal diversion or colectomy; and death. DATA COLLECTION AND ANALYSIS: Data were analyzed using the MetaView statistical package in Review Manager. For dichotomous outcomes, relative risks (RR) and 95% confidence intervals (CI) were derived from each study. When appropriate, the results of included studies were combined for each outcome. For dichotomous outcomes, pooled RR and 95% CI were calculated using a fixed effect model, except where significant heterogeneity was detected, at which time the random effects model was used. Data heterogeneity was calculated using MetaView. MAIN RESULTS: Of eleven studies identified, two were subsequently excluded because patients were stool positive for C. difficile, but did not have diarrhea or because the study was not a randomized controlled trial. All of the remaining nine studies involved patients with diarrhea who recently received antibiotics for an infection other than C. difficile. The definition of diarrhea ranged from at least two loose stools per day with an associated symptom such as rectal temperature > 38(o)C, to at least six loose stools in 36 hours. In terms of symptomatic cure, metronidazole, bacitracin and fusidic acid were not shown to be less effective than vancomycin. Teicoplanin may be slightly more effective than vancomycin with a relative risk of 1.21 [95% CI 1.00 to 1.46] and a p-value of 0.06. In terms of initial symptomatic resolution, vancomycin is more effective than placebo with a relative risk of 6.75 [95% CI 1.16 to 48.43] and a p-value of 0.03. This result should be interpreted with caution given the small number of patients in this comparison (12 in the vancomycin group and nine in the placebo group) and the poor methodological quality of the trial. Metronidazole, bacitracin, teicoplanin, fusidic acid and rifaximine are as effective as vancomycin for initial symptomatic resolution. The other secondary outcomes measured in this review: surgery, sepsis and death occurred infrequently in all of the studies. AUTHORS' CONCLUSIONS: Current evidence leads to uncertainty whether mild CDAD needs to be treated. Patients with mild CDAD may resolve their symptoms as quickly without treatment. The only placebo-controlled study shows vancomycin's superior efficacy. However, this result should be treated with caution due to the small number of patients enrolled and the poor methodological quality of the trial. The Johnson study of asymptomatic carriers also shows that placebo is better than vancomycin or metronidazole for eliminating C. difficile in stool during follow-up. If one does decide to treat, then two goals of therapy need to be kept in mind: improvement of the patient's clinical condition and prevention of spread of C. difficile infection to other patients. Given these two considerations, one should choose the antibiotic that brings both symptomatic cure and bacteriologic cure. In this regard, teicoplanin appears to be the best choice because the available evidence suggests that it is better than vancomycin for bacteriologic cure and has borderline superior effectiveness in terms of symptomatic cure. Teicoplanin is not readily available in the United States, which must be taken into account when making treatment decisions in that country.

Adult↗

Comparative pulsed-field gel electrophoresis typing of gentamicin-resistant and -susceptible methicillin-resistant Staphylococcus aureus strains isolated in France between 1991 and 1998. Changes in antibiotic susceptibility.

Using macrorestriction of genomic DNA and pulsed-field gel electrophoresis, we examined 504 non-redundant, infection-causing human isolates of methicillin-resistant Staphylococcus aureus susceptible (G(S): 238 isolates) or resistant to gentamicin (G(R): 266 isolates). The strains were isolated at Albert Chenevier Hospital (Créteil, France) between 1 January 1991 and 31 December 1998. Their susceptibility to erythromycin, lincomycin, tetracycline, rifampicin, fusidic acid and fosfomycin was also studied. Seventy-six genotypes were identified (percentage similarity<80). Ten types, each containing at least eight strains, predominated. G(R) strains showed higher genetic polymorphism than G(S) strains: the 266 G(R) isolates belonged to 67 genotypes, five of which predominated (44, 42, 38, 30 and 15 isolates); the 238 G(S) isolates belonged to only 18 types, four of which predominated (112, 83, 11 and 10 isolates). Fifty-six percent of G(R) strains (34 Gt) were resistant to erythromycin, lincomycin, tetracycline and rifampicin, and were isolated at relatively stable frequencies. Resistance to five antibiotics studied (susceptible to fusidic acid) was observed among 16.5% of G(R) strains. The frequency of strains with this profile diminished from 30% in the early 1990s to 10% in 1998. One hundred and twenty-six G(S) isolates were susceptible to all six antibiotics; this profile was only found from 1993 onwards, and was increasingly frequent (60% of G(S) strains in 1996). Resistance to erythromycin and lincomycin only was found in 70 G(S) isolates; this profile accounted for approximately half the isolates in 1992/1993 and only one-third in 1998. These results, obtained over an eight-year period, show an overall increase in antibiotic susceptibility. They confirm the spread of two major clones of MRSA-G(S) and support the hypotheses that G(S) strains derive from G(R) strains that have lost the aac6'-aph2" gene; and that G(S) strains are genetically related to those that were present before the use of gentamicin and persisted at a low frequency until 1992-1993.

Anti-Bacterial Agents↗

Assessment of the palatability of antistaphylococcal antibiotics in pediatric volunteers.

OBJECTIVE: To evaluate the palatability of four commonly prescribed antistaphylococcal antibiotics, cloxacillin, cephalexin, erythromycin, and fusidic acid, in volunteer children. DESIGN: A single-blind taste test of four flavored antibiotic suspensions commonly used in the treatment of skin infections in pediatric patients. SETTING: University teaching hospital. PARTICIPANTS: Twenty healthy volunteer children with a mean age of 9.2 +/- 2.0 SD years (range 6-12). MAIN OUTCOME MEASURES: The taste of each antibiotic was rated by the children on a 10-cm visual analog scale incorporating a facial hedonic scale. The children were also asked which antibiotic they thought tasted the best and which tasted the worst. RESULTS: Taste scores were as follows: cloxacillin 1.4 +/- 1.8 cm, cephalexin 6.5 +/- 2.7 cm, erythromycin 6.8 +/- 3.0 cm, and fusidic acid 6.3 +/- 2.4 cm. The taste rating of cloxacillin was significantly lower compared with the other three antibiotics (p = 0.001). Cloxacillin was chosen as having the worst taste by a significant proportion of the children (18 of 20). None of the antibiotics was clearly best tasting. CONCLUSIONS: Given similar effectiveness, taste considerations may be important in the decision as to which antibiotic to prescribe. The perception that cloxacillin is poor tasting to children is supported by this study, which suggests that when compliance with oral medication is critical for successful treatment, prescription of cloxacillin suspension should be avoided.

Anti-Bacterial Agents↗

A new UK strain of epidemic methicillin-resistant Staphylococcus aureus (EMRSA-17) resistant to multiple antibiotics.

An extensive outbreak in a hospital on the south coast of England in 2000, involving a multi-resistant strain of methicillin-resistant Staphylococcus aureus (MRSA) phenotypically similar to a strain periodically seen in several hospitals in that region since 1996, prompted a study to characterize the strain and determine the extent of its spread. Sixty-nine isolates with related phage patterns obtained between 1997 and 2000 from 19 hospitals were selected for study. Of these, 55 isolates had an identical PFGE profile (designated F1), and eight shared five other PFGE profiles (designated F2-F6), which differed from that of F1 by no more than three bands and were considered related. Six isolates had PFGE profiles that differed from F1-F6 by 9-18 bands and were considered to be distinct strains. The 63 isolates of profiles F1-F6 were considered to comprise a single strain and were phenotypically identical, being urease positive and resistant to multiple antibiotics including methicillin, ciprofloxacin, erythromycin, fusidic acid, rifampicin, gentamicin, kanamycin, neomycin, streptomycin and tetracycline, with or without high- or low-level mupirocin resistance. Borderline resistance to teicoplanin was also commonly noted. All but one of these 63 isolates contained the gene sea, with five also carrying the genes seg and sei, and two carrying tst. The isolates of this strain had been referred from 13 different hospitals, seven of which were on or near the south coast, four from London, one from the Midlands and one from the north of England. The isolates were thus considered to comprise an epidemic MRSA (EMRSA) strain, which has been designated EMRSA-17. The six non-EMRSA-17 isolates identified in the study were sensitive to fusidic acid and rifampicin, and came from six geographically diverse hospitals including three in Northern Ireland.

Cross Infection↗

Elution of six antibiotics bonded to polyethylene vascular grafts sealed with three proteins.

The elution of six antistaphylococcal antibiotics from vascular polyethylene grafts sealed with albumin, gelatin, or collagen were studied in an in vitro system. The antibiotics tested were pefloxacin, vancomycin, teicoplanin, fusidic acid, pristinamycin, and rifampicin. The grafts were impregnated by simple soaking in antibiotic (1 mg/ml). The data were fitted to an exponential model and antibiotic half-lives (t1/2) were calculated from the regression lines. All the antibiotics tested were bound to the protein sealants. Antibiotic release varied with the type of antibiotic and the sealant. Rifampicin was eluted most slowly, particularly with albumin- and gelatin-sealed grafts, with t1/2 at 4-5.5 hr and antibiotic activity was still found at 48 hr. The glycopeptides were also eluted more slowly from albumin or gelatin sealant than from collagen. Although large quantities of glycopeptides were initially bound, they were quickly eluted (t1/2 = 30-44 min) and there was no residual antibiotic activity at 24 hr. Pefloxacin, pristinamycin, and fusidic acid bound to collagen or gelatin sealants were the most rapidly eluted, with t1/2 of 3-14 min, but they were eluted more slowly from albumin-sealed grafts, with t1/2 of 22-90 min. In vitro studies can be useful for evaluating the binding of antibiotics to protein-sealed grafts before animal experiments or human testing.

Albumins↗

Successful oral pristinamycin therapy for osteoarticular infections due to methicillin-resistant Staphylococcus aureus (MRSA) and other Staphylococcus spp.

OBJECTIVES: Oral treatment regimens for multiresistant methicillin-resistant Staphylococcus aureus (MRSA) infections are limited. In Australia, rifampicin plus fusidic acid is the usual treatment regimen following glycopeptide therapy but many patients are intolerant of this; some isolates are resistant; new oxazolidinones are expensive for routine use. Pristinamycin is a possible alternative and we report our experience with this agent. METHODS: The Department of Microbiology and Infectious Diseases, South Western Area Pathology Service treats patients drawn from the South Western Sydney Area Health Service that houses approximately 800,000 people and contains approximately 2000 acute care public hospital beds. Patients prescribed pristinamycin between 1 September 2000 and 31 January 2000 were identified from hospital pharmacy records. A retrospective chart review was performed. Accepted clinical definitions of osteomyelitis and septic arthritis were used. RESULTS: Twenty-seven patients were identified with osteoarticular infections. Twenty-four cases involved Staphylococcus aureus (multiresistant MRSA in 21 cases); three involved Staphylococcus epidermidis sensu stricto; four cases involved multiple organisms. Nineteen cases received pristinamycin monotherapy; the others received various combinations (fusidic acid with five; other antibiotics with three). Therapy was generally well tolerated; no haematological or biochemical toxicity was detected. Seven patients had minor gastrointestinal disturbance; and one developed rash. Four patients required dose reduction. Only four patients ceased pristinamycin due to intolerance. Treatment outcome was evaluated in 23 cases; cure was effected in 16 cases, five were successfully suppressed and two failed. There were no deaths. CONCLUSIONS: Oral pristinamycin is well tolerated and an important additional agent to treat osteoarticular infections with multiresistant MRSA and other staphylococci.

Administration, Oral↗

Trends in antibiotic susceptibility patterns and epidemiology of MRSA isolates from several hospitals in Riyadh, Saudi Arabia.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA), is associated with high morbidity and mortality rates with rapid development of resistance. METHODS: A total of 512 MRSA isolates were procured from 6 major hospitals in Riyadh, Saudi Arabia and antibiotic susceptibilities and MICs were documented against several antibiotics and vancomycin. SPSS version 10 was used for statistical analysis. RESULTS: The prevalence of MRSA in the study hospitals ranged from 12% to 49.4%. Mean patient age was 44 years with males constituting 64.4% and females 35.6%. Approximately 41.5% of the isolates came from patients in the extreme age groups. MIC for vancomycin was in the susceptible range for all isolates ranging from 0.25 to 3 ug/ml. The overall susceptibility of MRSA to the various antibiotics tested was: fusidic acid 4.3%, sulfamethoxazole/trimethoprim 33.8%, gentamicin 39.6%, mupirocin 77.0%, gatifloxacin 78.9%, chloramphenicl 80.7%, linezolid 95.1%, quinupristin/dalfopristin 100%. Some differences were noted in the resistance of isolates among the participating hospitals reflecting antibiotic usage. On the whole, inpatient isolates (accounting for 77.5% of the isolates) were more resistant than outpatient isolates (22.5%) except for linezolid. Quinupristin-dalfopristin and linezolid are the most effective antibiotics tested against inpatient isolates while quinupristin-dalfopristin and gatifloxacin seem to be the most effective against outpatient isolates. Approximately one forth of the isolates are no longer susceptible to mupirocin used for eradication of the carrier state reflecting resistance developing after widespread use. Trends over time show a tendency towards decreased susceptibility to gatifloxacin and linezolid with increasing susceptibility to gentamicin and sulfamethoxazole/trimethoprim. CONCLUSION: Quinupristin/dalfopristin and linezolid are two valuable additions to our antimicrobial armamentarium, but resistance has already been described. To preserve their value, their use should be limited to those rare cases where they are clearly needed. Fusidic acid, the local antibiotic, gentamicin and trimethoprim/sulfamethoxazole should not be relied upon for treatment of MRSA infections, at least empirically as the percentage of susceptible isolates is very low.

Adult↗