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Biomedical subjects

M A Pfaller

Publications and source records attributed to M A Pfaller.

477 records · Page 27Linked to original sources

Application of genomic DNA subtyping by pulsed field gel electrophoresis and restriction enzyme analysis of plasmid DNA to characterize methicillin-resistant Staphylococcus aureus from two nosocomial outbreaks.

Pulsed-field gel electrophoresis (PFGE) and restriction enzyme analysis of plasmid DNA (REAP) were applied to study the epidemiologic relationship among methicillin-resistant Staphylococcus aureus (MRSA) isolates from outbreaks in two hospitals in São Paulo, Brazil: 82 MRSA isolates, 73 from a university hospital and nine from a general adult intensive care unit of a private hospital, were collected from 62 patients: 95% of the MRSAs were also resistant to gentamicin and ciprofloxacin. REAP subtyping of both collections identified six different subtypes: 55 (72.6%) MRSAs from the university hospital and nine isolates from the private hospital shared the same epidemic REAP subtype. Discrimination by restriction of genomic DNA with Sma I followed by PFGE enabled the identification of 14 DNA subtypes. Based on the combined REAP-genomic DNA subtype, the predominant subtype in the university hospital was A/A (44 isolates) whereas the epidemic subtype in the private hospital was A/M (seven isolates). The application of two typing methods showed better discrimination among MRSAs than did either method alone.

Bacterial Typing Techniques↗

Proposed quality control guidelines for National Committee for Clinical Laboratory Standards Susceptibility Tests using the veterinary antimicrobial agent tiamulin.

Quality control guidelines for standardized antimicrobial susceptibility test methods are critical for the continuing accuracy of these clinical tests. In this report, quality control limits were proposed for the veterinary antimicrobial agent tiamulin with minimum inhibitory concentration (MIC) ranges of three or four log(2) dilution steps in two different medium formulations. Disk diffusion zone diameter ranges were proposed for tiamulin tested against Actinobacillus pleuropneumoniae ATCC 27090 (12-18 mm) and Staphylococcus aureus ATCC 25923 (25-32 mm). The data from eight participating laboratories produced 100% of results within proposed MIC limits (8-32 microg/mL), and 95.8-97.0% of zones were found within suggested zone diameter QC guidelines. These proposed QC ranges should be validated by in-use results from veterinary clinical laboratories.

Actinobacillus Infections↗

Cefditoren in vitro activity and spectrum: a review of international studies using reference methods.

Cefditoren, a broad-spectrum orally administered cephalosporin ester, has documented in vitro efficacy against many Gram-positive and -negative pathogens and stability against clinically important beta-lactamases. We have reviewed the microbiology and the pharmacokinetic/pharmacodynamic literature regarding the spectrum and potency of this newer agent against the major etiologic agents of community-acquired respiratory infection, (Streptococcus pneumoniae, Hemophilus influenzae and Moraxella catarrhalis), as well as the Enterobacteriaceae and non-enteric Gram-negative bacilli, staphylococci, and other aerobic and anaerobic Gram-positive cocci. The level of cefditoren activity against S. pneumoniae (MIC(90,) 0.5 microg/mL) was superior to all marketed oral cephalosporins and at least equal to amoxicillin +/- clavulanate. H. influenzae (MIC(90,) 0.016-0.03 microg/mL) and M. catarrhalis (MIC(90,) 0.06-0.5 microg/mL) were also very susceptible to cefditoren. In contrast to cefixime and ceftibuten, cefditoren was active against oxacillin-susceptible staphylococci (MIC(90,) < or = 1 microg/mL) at a level comparable to cefuroxime axetil, cefaclor or cefprozil. Enterococci, Pseudomonas aeruginosa and most anaerobes (Gram-negative) were not cefditoren-susceptible, but most Enterobacteriaceae, beta-haemolytic and viridans group streptococci were highly susceptible. Furthermore, an overview of key in vitro susceptibility testing methods and issues including disk diffusion testing and Etest (AB BIODISK, Solna, Sweden) method accuracy, interpretive criteria, and pharmacodynamic considerations for the selection of a breakpoint concentration are provided. The rapid bactericidal nature of the antibacterial activity of cefditoren, its post antibiotic effect, penicillin binding protein targets, and extent of beta-lactamase stability are all favorable qualities. In conclusion, this orally administered (BID) beta-lactam possesses promise for use against commonly isolated problematic respiratory tract pathogens such as penicillin-non-susceptible pneumococci and beta-lactamase-positive M. catarrhalis or H. influenzae. Success in the clinical trials will further define the role of cefditoren in this era of emerging resistant bacterial pathogens.

Cephalosporins↗

Neisseria meningitidis with decreased susceptibility to penicillin: report from the SENTRY antimicrobial surveillance program, North America, 1998-99.

The purpose of this study was to estimate the prevalence of Neisseria meningitidis with decreased susceptibility to penicillin (MIC, >0.06 microg/mL) in North America (NA). Antimicrobial susceptibility testing by Etest (AB BIODISK, Solna, Sweden) was performed on 53 invasive clinical isolates obtained from 11 SENTRY Antimicrobial Surveillance Program participants in NA (9 states, 2 provinces) during 1998-99. All strains were markedly susceptible to ciprofloxacin (MIC(90), 0.008 microg/mL) and cefotaxime (MIC(90), < or = 0.002 microg/mL). Only 54.7% were susceptible to trimethoprim-sulfamethoxazole (TMP/SMX) at < or = 0.5/9.5 microg/mL. One strain was resistant to rifampin (MIC, > 32 microg/mL) and 16 isolates (30.2%) were relatively resistant to penicillin with MICs ranging from 0.094 to 0.25 microg/mL. No beta-lactamase production was detected. The serogroup distribution was 40% Y, 28% B, 24% C, 2% W-135, and 6% of strains were nongroupable. The prevalence of N. meningitidis with decreased susceptibility to penicillin in NA appears higher than previous reports.

Anti-Bacterial Agents↗

Antifungal dynamics of LY 303366, an investigational echinocandin B analog, against Candida ssp.

Two isolates each of Candida albicans, Candida tropicalis, and Candida glabrata were selected for time-kill curve testing against LY 303366 at concentrations ranging from 0.125 x MIC to 16 x MIC. RPMI 1640 buffered morpholinepropanesulfonic acid (MOPS) was utilized as growth medium. Samples were obtained at predetermined time points over 24 hours and streaked for colony count determination. Against C. albicans (one strain) and C. glabrata isolates, LY 303366 exhibited fungicidal (> or = three log10 reduction in CFU) activity. In contrast, fungistatic activity was observed with LY 303366 against C. albicans (one strain) and C. tropicalis isolates at all of the multiples of the MIC tested. With the exception of one C. glabrata strain, the rate and extent of activity against test isolates was not enhanced with concentrations exceeding the MIC. Our data indicate that maximal antifungal activity with LY 303366 may be achieved by optimizing the time of fungal exposure to the drug. Additionally, these data suggest that use of the current interpretive endpoint for MICs in RPMI may underestimate the antifungal activity of LY 303366. Thus, the MIC endpoint may need to be re-evaluated, or perhaps an alternative media, such as antibiotic medium #3, should be utilized for determination of LY 303366 MICs.

Anidulafungin↗

Molecular approaches to diagnosing and managing infectious diseases: practicality and costs.

As molecular techniques for identifying and detecting microorganisms in the clinical microbiology laboratory have become routine, questions about the cost of these techniques and their contribution to patient care need to be addressed. Molecular diagnosis is most appropriate for infectious agents that are difficult to detect, identify, or test for susceptibility in a timely fashion with conventional methods.

Clinical Laboratory Techniques↗

Piperacillin/tazobactam (YTR 830) combination. Comparative antimicrobial activity against 5889 recent aerobic clinical isolates and 60 Bacteroides fragilis group strains.

Piperacillin combined with tazobactam (formerly YTR 830) was tested at a ratio of 8:1 against 5889 aerobic isolates and 50 strains from the Bacteroides fragilis group. Imipenem was the most active agent tested against Enterobacteriaceae (99.3% at less than or equal to 4 micrograms/ml), ceftazidime was most effective against nonenteric Gram-negative bacilli (80.7% at less than or equal to 8 micrograms/ml), and piperacillin/tazobactam possessed a superior spectrum against Gram-positive cocci (92.2% at less than or equal to 16/2 micrograms/ml). Against all aerobic strains, piperacillin/tazobactam had a spectrum (90.3% at less than or equal to 16/2 micrograms/ml) comparable to imipenem (93.6% at less than or equal to 4 micrograms/ml) and was distinctly greater than that of ticarcillin/clavulanic acid (73.3% at less than or equal to 16/2 micrograms/ml) and ceftazidime (75.5% at less than or equal to 8 micrograms/ml). Against the B. fragilis group isolates, all piperacillin/tazobactam MICs were less than or equal to 64/8 micrograms/ml. This activity was superior to piperacillin alone (MIC:50, 8-64 micrograms/ml) and cefoxitin (MIC50, 4-64 micrograms/ml). Piperacillin/tazobactam appears to be a promising parenteral antimicrobial combination, with a spectrum effective against a wide variety of clinical pathogens.

Bacteria, Aerobic↗

Legionnaires' disease associated with a hospital water system. A five-year progress report on continuous hyperchlorination.

In 1981, sixteen cases of nosocomial legionellosis occurred among 456 patients admitted to a new hematology-oncology unit (35 per 1000 admissions). Monoclonal antibody typing and restriction endonuclease plasmid analysis identified a unique strain (09,04) of Legionella pneumophila serogroup 1 isolated from both patients and water outlets. Continuous hyperchlorination of the hot and cold water began in January 1982, and chlorine levels of 3 to 5 mg/L have been maintained most recently. Water samples have been consistently negative for Legionella for more than five years. Four sporadic cases of nosocomial legionellosis have occurred in the hematology-oncology unit during the same period (one per 1000 admissions) associated with a different strain of L pneumophila serogroup 1 (09,00). The environmental reservoir(s) of L pneumophila serogroup 1 in these cases has not been identified. Levels of trihalomethanes (potential carcinogens) were high (greater than 100 micrograms/L) when chlorine levels of hot water exceeded 4 mg/L. Some corrosion damage to the water distribution system has occurred: the average number of leaks per month increased steadily from zero in 1982 to 5.2 in 1986. The chlorinator installation costs were +75,800, and annual operation expenses were +12,500. Continuous hyperchlorination is a promising but still experimental technique for control of nosocomial legionellosis. In our experience, epidemic disease has been controlled, but sporadic cases have continued to occur.

Chlorine↗

Update on clinical antifungal susceptibility testing for Candida species.

With the emergence of fungi as important nosocomial pathogens, increasing reports of antifungal resistance, and expanding drug therapy options, the need for clinically relevant antifungal susceptibility testing is evident. Over the last decade, the National Committee for Clinical Laboratory Standards (NCCLS) worked to standardize procedures for in vitro susceptibility testing of Candida species against fluconazole, itraconazole, 5-fluorocytosine, and amphotericin B. With the establishment of a reproducible methodology, correlation of antifungal susceptibility in vitro with clinical outcome is a priority. The NCCLS proposed susceptibility breakpoints for the three agents against Candida species, with breakpoints for amphotericin B forthcoming. These breakpoints could provide useful guidance in some clinical situations involving azole or 5-fluorocytosine therapy; however, routine susceptibility testing of fungal isolates should be discouraged.

Antifungal Agents↗