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H S Sader

Publications and source records attributed to H S Sader.

At least 73 records · Page 4Linked to original sources

The use of molecular techniques in the epidemiology and control of infectious diseases.

The ability to identify specific strains within a given species of pathogen is an important aid in the rational development of effective measures to prevent and control nosocomial infections. The efforts of both microbiologist and hospital epidemiologic are facilitated greatly by the availability of the newer molecular epidemiologic typing techniques. Although these methods clearly have limitations, they generally are a significant improvement over the more conventional typing methods, many of which are too cumbersome, insensitive, and time-consuming to be of practical value for epidemiologic evaluations. Based on current experience, the molecular typing methods that appear to be the most practical and useful for both large and small scale epidemiologic studies are the DNA-based methods of REAP and PFGE. Many questions remain concerning the appropriate role of molecular typing methods in the clinical microbiology laboratory. Often, molecular typing may be performed more efficiently in a reference laboratory. In contrast, selected methods such as plasmid analysis are well within the scope of clinical microbiology laboratories and may be an important adjunct to the hospital infection control effort. Given the limitations of the available methods and the complex nature of patients at risk for nosocomial infections, it is imperative that these methods be employed with clear epidemiologic objectives in mind. Typing should always include unrelated as well as epidemiologically related isolates and, whenever possible, all organisms should be typed under identical conditions, preferably within the same test run. In addition, results are most effectively used to supplement rather than to replace hypotheses and questions thoughtfully developed by the clinician or epidemiologist. Ideally, typing is performed independently by the laboratory to avoid bias, but the results are applied collaboratively to ensure that both the potential insights and the unavoidable ambiguities presented by the results are clearly appreciated. Additional studies based upon sound epidemiologic principles will help clarify the role of the various molecular typing methods as epidemiologic markers and advance our understanding of the epidemiology of nosocomial infections.

Bacterial Infections↗

In vitro antimicrobial activity of cefpirome against ceftazidime-resistant isolates from two multicenter studies.

The in vitro activity of cefpirome against ceftazidime-resistant (MIC > 16 mg/l) isolates from two multicenter studies was analyzed. The first investigation carried out in the USA, was an in vitro comparison of cefpirome and five third-generation cephalosporins in which more than 6,000 isolates were evaluated, including 97 Enterobacteriaceae and 1,509 staphylococci resistant to ceftazidime. The second study was a multicenter international study (> 5,000 strains total) in which 160 ceftazidime-resistant gram-negative bacilli and 509 staphylococci from five countries (Australia, France, Germany, Italy and UK) were tested against cefpirome. The results from the US trial indicated that only 0.8% of enteric bacilli were resistant to cefpirome compared to 4.9% and 4.7% resistant to ceftazidime and cefoperazone, respectively. In the international trial, cefpirome was also active against ceftazidime-resistant, class I beta-lactamase producing enteric bacilli (75% susceptibility, MIC50 of 4 mg/l) especially against Citrobacter spp., Enterobacter spp. and Morganella morganii. Cefpirome was 8- to 64-fold more active than ceftazidime against seven different staphylococcal species. The antimicrobial activity of cefpirome against routine clinical isolates and those organisms resistant to third-generation cephalosporins was highly consistent within a nation (USA) and among various developed countries.

Bacterial Infections↗

Prevalence of important pathogens and the antimicrobial activity of parenteral drugs at numerous medical centers in the United States. II. Study of the intra- and interlaboratory dissemination of extended-spectrum beta-lactamase-producing Enterobacteriaceae.

The incidence of extended-spectrum beta-lactamases (ESBL)-producing Klebsiella pneumoniae and Escherichia coli has been increasing rapidly, and they are probably even more prevalent than is currently recognized because of difficulties in their detection by the clinical microbiology laboratory. In addition, several outbreaks associated with these multiresistant strains have been reported. In the present study we evaluated 30 clinical isolates (27 K. pneumoniae from 11 hospitals and three E. coli from three hospitals) that were resistant or intermediately susceptible to ceftazidime and/or cefuroxime. The main objective of the study was to evaluate the intra- and interhospital dissemination of ESBL-producing strains. The isolates were tested for susceptibility to ceftazidime, cefuroxime, gentamicin, and ofloxacin, and the ability of various susceptibility testing methods to detect resistance to these beta-lactams was evaluated. The production of ESBL was assessed by the disk approximation synergy test, and typing was performed by pulsed-field gel electrophoresis (PFGE) of chromosomal DNA. ESBL production was demonstrated in 15 K. pneumoniae (from seven hospitals) and in one E. coli strain. Most ESBL-producing isolates demonstrated cross resistance with gentamicin and ofloxacin. Chromosomal DNA analysis by PFGE exhibited a great genomic variability among ESBL-producing isolates. Our results also indicated the occurrence of both intra- and interhospital dissemination of these multiresistant strains.

Bacteriological Techniques↗

Update of lomefloxacin in vitro activity and spectrum. A multicenter trial testing contemporary pathogens following Food and Drug Administration validation guidelines. Lomefloxacin Activity Study Group.

The United States Food and Drug Administration recently recommended that the antimicrobial product package insert (PPI) subsection on microbiology be annually validated with regard to the compound's spectrum and potency. To address this request, a nine-laboratory trial was organized to test (two methods) lomefloxacin, a newer fluoroquinolone, and nine comparison drugs against PPI-listed pathogens (1934 strains). A broad geographic sampling (nine medical centers) was achieved, and lomefloxacin was determined to be active [minimum inhibitory concentration (MICs), < or = 2 micrograms/ml for > or = 90% of strains] for all PPI-listed species except Pseudomonas aeruginosa, Citrobacter freundii, and Providencia rettgeri (42%-87% inhibited). Comparison fluoroquinolones also had a similarly compromised spectrum of activity against these species. Additional organism species, including Neisseria gonorrhoeae, N. meningitidis, Salmonella enteriditis, and Shigella species, should be added to the lomefloxacin PPI (MIC90s, 0.03-0.25 microgram/ml) following data generated in this study. These in vitro results indicate that lomefloxacin remains active against the vast majority of clinically "indicated" species, and that it has a spectrum compatible with other marketed fluoroquinolones for these tested pathogens, monitored in 1994.

Anti-Bacterial Agents↗

Evaluation of interhospital spread of methicillin-resistant Staphylococcus aureus in Sao Paulo, Brazil, using pulsed-field gel electrophoresis of chromosomal DNA.

To evaluate the interhospital spread of methicillin-resistant Staphylococcus aureus (MRSA) clone in Sao Paulo, we analyzed the restriction fragment length polymorphisms (RFLP) of chromosomal DNA from isolates from nine Sao Paulo hospitals. Restriction digestion of genomic DNA was performed with SmaI and the fragments were separated by pulsed-field gel electrophoresis. Only six different RFLP patterns were demonstrated among 30 MRSA isolates. Isolates possessing an identical RFLP pattern were demonstrated in eight of the nine Sao Paulo hospitals evaluated. Our results documented the widespread dissemination of a single clone of MRSA in several hospitals. Furthermore, the small clonal variability among multidrug-resistant MRSA coupled with the wide spread of this clone could make the intrahospital epidemiological evaluation of RMSA outbreaks very difficult.

Brazil↗

Nosocomial transmission of Serratia odorifera biogroup. 2: Case report demonstration by macrorestriction analysis of chromosomal DNA using pulsed-field gel electrophoresis.

OBJECTIVES: To investigate a cluster of Serratia odorifera in a cardiothoracic surgery unit (CTSU) and to evaluate the applicability of three typing methods for this species. DESIGN: During a surveillance surgical wound study, S odorifera was isolated from two patients in the CTSU. The patients' hospital charts were reviewed for the details of surgery and for common personnel, procedures, or medications. Cultures were obtained of water, soap, and unit dose medications from the CTSU, the operating room, and the surgical intensive care unit. The isolates' antibiograms, biotypes (Vitek identification card and API 20E), and patterns of chromosomal DNA (chrDNA) by pulsed-field gel electrophoresis (PFGE) were examined. S odorifera isolates from our organism collection were used as controls. SETTING: A 900-bed university hospital with a 22-bed CTSU. RESULTS: ChrDNA patterns of isolates from the two patients were identical, suggesting a possible nosocomial source. However, no source of organisms or mode of transmission was identified. Neither biotype nor antibiogram were useful for epidemiologically typing S odorifera, and PFGE was necessary to discriminate among isolates. CONCLUSIONS: Although rarely isolated, S odorifera and other non-marcescens Serratia species may cause nosocomial outbreaks. PFGE of chrDNA seems to be a reliable method for epidemiologically typing this species.

Aged↗

Evaluation and characterization of multiresistant Enterococcus faecium from 12 U.S. medical centers.

Forty-two Enterococcus faecium isolates resistant to ampicillin, penicillin, gentamicin, streptomycin, vancomycin, and teicoplanin (VanA phenotype) from 12 U.S. medical centers were analyzed by pulsed-field gel electrophoresis of chromosomal DNA. The isolates were tested for susceptibility to 12 alternative drugs. The results indicated both intrahospital and interhospital diversity among multiresistant vanA enterococcal isolates. Furthermore, the finding of isolates with identical pulsed-field gel electrophoresis patterns in different centers strongly suggests some interhospital clonal transmission.

DNA, Bacterial↗

Antimicrobial activity of the new carbapenem biapenem compared to imipenem, meropenem and other broad-spectrum beta-lactam drugs.

The in vitro activity of biapenem was compared to that of imipenem, meropenem and other broad-spectrum beta-lactams. A total of 716 isolates from recent cases of clinical septicemia and an additional 137 stock strains possessing known beta-lactamases or other well-characterized resistance mechanisms were tested. The minimal concentrations inhibiting 90% of strains (MIC90) of Enterobacteriaceae species were for biapenem 0.03 to 1 mg/l and for imipenem 0.25 to 2 mg/l. No member of the Enterobacteriaceae was found to be resistant to biapenem. Biapenem and meropenem were the most active drugs against Pseudomonas aeruginosa, with an MIC90 of 1 mg/l. Biapenem was more active than ceftazidime against most gram-negative and gram-positive bacteria tested. Biapenem was as potent as imipenem against anaerobic bacteria (including Bacteroides fragilis), with an MIC90 of 0.25 mg/l. High MICs of biapenem were demonstrated for Xanthomonas maltophilia, oxacillin-resistant Staphylococcus spp. and Enterococcus spp. These species have demonstrated resistance to other carbapenems and to most of the newer cephalosporins. The results of this study, coupled with previously documented favorable qualities of biapenem, endorse further investigation of this broad-spectrum antibacterial agent for clinical use.

Anti-Bacterial Agents↗

Epidemiologic typing of multiply drug-resistant Pseudomonas aeruginosa isolated from an outbreak in an intensive care unit.

From June to August 1991, there was an outbreak of Pseudomonas aeruginosa infections in an intensive care unit in a general hospital in Sao Paulo, Brazil. We obtained 14 isolates from 14 patients, 11 from tracheal aspirate, and 3 from surgical wound exudates. These strains were typed by serotyping, pyocin typing, and pulsed-field electrophoresis (CHEF) of chromosomal DNA (chrDNA), and the different typing methods were analyzed. These three methods demonstrated seven identical strains. We also performed an extensive antibiogram (33 drugs) in all 14 isolates. The incidence of resistance to aminoglycosides, extended-spectrum beta-lactams, and quinolones was very high among the seven identical isolates; however, the antibiogram profile differed significantly among the isolates. Our results suggest that a unique strain caused several cross-transmitted infections during this period of time, and the emergence of antimicrobial resistance has been occurring before and after the establishment of the epidemic strain by selective drug use. The chrDNA fingerprinting proved to be versatile and precise for epidemiologic investigations of P. aeruginosa infections.

Brazil↗

In vitro comparison activity of OPC-17116, a new fluoroquinolone, against more than 5,000 recent clinical isolates from five medical centers.

The in vitro activity of OPC-17116, a new fluoroquinolone, was compared with those of ciprofloxacin, ofloxacin and cefixime. A total of 5,231 fresh clinical isolates from five geographically separate US medical centers were tested. The primary results of this study are: 1. OPC-17116 is very active against Enterobacteriaceae [MIC90s, 0.015-1 microgram/ml, except Providencia rettgeri (MIC90, > 8 micrograms/ml)], 2. among nonenteric Gram-negative bacilli (e.g. Xanthomonas maltophilia, MIC90, 2 micrograms/ml) and Gram-positive cocci (e.g. oxacillin-susceptible staphylococci, MIC90s, 0.12-0.5 microgram/ml) OPC-17116 demonstrated higher activity than ciprofloxacin or ofloxacin, 3. the quinolones were more active than cefixime against most of the species tested, especially against Gram-positive and non-enteric Gram-negative organisms. The results of this study, associated with prior documented favorable qualities, support continued investigation of OPC-17116 for clinical use.

Anti-Infective Agents↗

Oxacillin- and quinolone-resistant Staphylococcus aureus in Sao Paulo, Brazil: a multicenter molecular epidemiology study.

OBJECTIVE: To investigate the possibility of interhospital spread of multiresistant Staphylococcus aureus in Sao Paulo, Brazil. DESIGN: We evaluated 13 nosocomial S aureus strains selected because of resistance to oxacillin and ciprofloxacin. SETTING: The strains were collected between March 1991 and September 1991 from four different hospitals in Sao Paulo. Two were teaching hospitals, and two were private hospitals. PATIENTS: Each strain was isolated from a different patient. All patients were hospitalized when the strains were isolated. INTERVENTIONS: The strains were typed by restriction endonuclease analyses of plasmid DNA (REAP) using EcoRI, HindIII, RsaI, and AluI and by extended antibiogram profile (34 drugs). RESULTS: All strains had identical plasmid and antibiogram profile. They demonstrated the same plasmid pattern as previously described in one of the hospitals studied. CONCLUSIONS: Our results suggest the dissemination of a unique oxacillin- and quinolone-resistant strain of S aureus in several hospitals of Sao Paulo, Brazil.

Bacterial Typing Techniques↗

In vitro activity of OPC-17116 compared to other broad-spectrum fluoroquinolones.

The in vitro activity of OPC-17116 was compared to that of five similar fluoroquinolones (ciprofloxacin, enoxacin, norfloxacin, ofloxacin and temafloxacin). A total of 700 isolates from recent cases of clinical bacteremia were tested. Fifty additional stock strains with well-characterized resistance mechanisms were also processed. The minimal concentrations inhibiting 90% of strains (MIC90) of Enterobacteriaceae species were for OPC-17116 0.015-0.5 micrograms/ml and for ciprofloxacin 0.015-0.25 micrograms/ml. Moraxella catarrhalis, Haemophilus influenzae and Neisseria gonorrhoeae were very susceptible to OPC-17116 (MIC90 0.015 micrograms/ml) thus being fourfold more active than ciprofloxacin. For all beta-hemolytic streptococci and pneumococci OPC-17116 MICs were less than or equal to 0.5 micrograms/ml. The most resistant enteric bacilli were among the Citrobacter freundii and Providencia rettgeri strains (MIC90 0.5 micrograms/ml). Pseudomonas aeruginosa strains were comparably susceptible to OPC-17116 (MIC90 0.5 micrograms/ml). Low pH and CO2 incubation had an adverse effect on OPC-17116 MICs, and resistance development was documented among current clinical isolates of staphylococci, pseudomonas and some Enterobacteriaceae.

Anti-Infective Agents↗

Cefotaxime is extensively used for surgical prophylaxis.

Cefotaxime, a broad-spectrum third-generation cephalosporin, has been extensively used worldwide for chemotherapy of serious infections. Based on the characteristics of its antimicrobial spectrum, low incidence of allergy, and lack of adverse effects, cefotaxime has been used successfully for prophylaxis of a number of different surgical procedures. Extensive data have been accumulated for single-dose or short-course cefotaxime prophylaxis regimens. These cefotaxime regimens have been demonstrated to be very effective and inexpensive. For this article, over 11,500 published cefotaxime prophylaxis cases are reviewed (10,500 control cases) and 98 references are cited. Single-dose cefotaxime was clearly indicated for hysterectomies, cesarean sections, upper gastrointestinal cases, bone and joint operations, biliary tract procedures, transurethral resections, open urologic surgeries, and some vascular procedures. Short-course (3-4 doses) may be required for colorectal resections, cardiac surgeries, head and neck surgeries, organ transplants, specific pediatric surgical cases, and for some patients with compromised immune function, regardless of origin. Cefotaxime has reduced wound morbidity of contaminated abdominal operations to < 10%. This change from multiple-dose regimens to the single-dose or short-course regimens, enabled by cefotaxime use, decreases the risk of inducing or selecting bacterial resistance; the change would generate a significant reduction in hospital costs. Surgeons should not hesitate to employ cefotaxime and other third-generation cephalosporins with proven limited-dose indications to greatly benefit their patients and the hospital environment.

Cefotaxime↗

In vitro activity of cefpodoxime compared with other oral cephalosporins tested against 5556 recent clinical isolates from five medical centers.

A multicenter study was conducted in which the in vitro activity of cefpodoxime (the active metabolite of the prodrug ester cefpodoxime proxetil) was compared with those of cefixime, cefuroxime, cefaclor, cefadroxil, and clarithromycin against 5556 recent clinical isolates. Cefpodoxime demonstrated potent activity against members of the Enterobacteriaceae, in particular against species generally resistant to the established oral cephalosporins such as Proteus vulgaris [minimum inhibitory concentration (MIC)50, 0.12 microgram/ml], Providencia rettgeri (MIC50, 0.015 microgram/ml), and Serratia marcescens (MIC50, 2 micrograms/ml). Cefpodoxime was very effective against the fastidious organisms most frequently associated with respiratory infections, such as Streptococcus pneumoniae (MIC90, 0.12 microgram/ml), Haemophilus influenzae (MIC90, 0.12 microgram/ml), and Moraxella catarrhalis (MIC90, 1 microgram/ml). In contrast to other orally administrated third-generation cephalosporins (cefixime or ceftibuten), cefpodoxime demonstrated reasonable activity against oxacillin-susceptible staphylococci, with MIC50 ranging from 1 to 2 micrograms/ml. All cephalosporins tested demonstrated poor activity against Pseudomonas spp., Xanthomonas spp., Enterococcus spp., and oxacillin-resistant staphylococci. Cefpodoxime had the widest spectrum of activity of all tested oral cephalosporins.

Administration, Oral↗

[Evaluation of in vitro activity of new fluoroquinolones, cephalosporins and carbapenems against 569 gram-negative bacteria].

OBJECTIVE: Evaluation of the in vitro activity of new fluoroquinolones, cephalosporins and carbapenems against gram-negative bacteria. MATERIAL AND METHOD: A total of 569 clinical isolates were obtained from inpatients at São Paulo Hospital--UNIFESP/EPM in June and July of 1992. The species distribution was as follows: Enterobacter sp. (62), Escherichia coli (308), Klebsiella pneumoniae (27), Klebsiella sp. (9), Proteus mirabilis (23), Pseudomonas aeruginosa (88), Pseudomonas sp. (4), Serratia sp. (30) and other gram-negatives (7). Susceptibility tests were performed by broth microdilution. The antimicrobials agents tested were: ciprofloxacin, ofloxacin, levofloxacin, grepafloxacin, DU 6859-alpha, ceftazidime, cefepime, FK 037, imipenem, meropenem and biapenem. RESULTS: DU 6859-alpha showed the highest anti-microbial activity among the fluoroquinolones. It was two- to four-fold more active than ciprofloxacin against some species. The potency and antimicrobial spectrum were similar between the fourth-generation cephalosporins against Enterobacteriaceae, except for Enterobacter sp. strains which were more susceptible to cefepime than they were to cefetazidime or FK 037. When testing Pseudomonas aeruginosa, ceftazidime was slightly more active than the other cephalosporins. Against Enterobacteriaceae and Pseudomonas aeruginosa strains, meropenem was more active than imipenem or biapenem. In addition, the percentage of strains, susceptible to meropenem was higher than the percentage susceptible to the other cerbapenems against these species. CONCLUSION: The new antimicrobial agents demonstrated in vitro activity higher than that of agents commercially available. However, more studies are necessary to further evaluate the in vivo activity and the clinical benefit of these compounds.

Anti-Infective Agents↗

[Sensitivity pattern of 117 clinical isolates of Staphylococcus aureus from 12 hospitals].

OBJECTIVE: To evaluate the antimicrobial susceptibility pattern of oxacillin susceptible (OSSA) and resistant Staphylococcus aureus (ORSA) isolates to other antimicrobial agents that can be used for the treatment of staphylococcal infections. MATERIAL AND METHOD: We evaluated 117 clinical S. aureus isolates from several São Paulo hospitals. Clinical isolates from Campinas, SP and from João Pessoa, PB, were also included. The in vitro susceptibility testing was performed by broth microdilution as described by the National Committee for Clinical Laboratory Standards (NCCLS). The minimum inhibitory concentration (MIC) was evaluated for 24 antimicrobial agents, including beta-lactams, fluoroquinolones, aminoglycosides, glycopeptides, macrolides, lincosamides and streptogramins. Both commercially available and experimental drugs were included in the study. Cross-resistance among fluoroquinolones was evaluated by susceptibility testing 24 isolates to 10 fluoroquinolones. RESULTS: The antimicrobial agents that showed the highest in vitro activity were the glycopeptides, the streptogramin RP-59.500, and the mupirocin (100% susceptibility). Eighty-seven percent of the OSSA and only 38% of the ORSA isolates were susceptible to ciprofloxacin (MIC50 0.25 microgram/mL and > 4 micrograms/mL, respectively). Cross-resistance among fluoroquinolones were noted even for the experimental drugs. Two fluoroquinolones remained active against ciprofloxacin-resistant isolates, clinafloxacin and WIN-57.273. However, the ciprofloxacin-resistant isolates had MICs eight-to 64-fold higher than the ciprofloxacin-susceptible isolates, suggesting that the MICs may continue to increase when these fluoroquinolones become commercially available. CONCLUSION: Our results showed a high rate of antimicrobial resistance among S. aureus from the Brazilian hospitals. Very few drugs can still be used for the treatment of staphylococcal infections.

Anti-Bacterial Agents↗

[Evaluation of antimicrobial sensitivity of 87 clinical isolates of vancomycin-resistant enterococci].

OBJECTIVES: 1) To evaluate the antimicrobial susceptibility pattern of vancomycin-resistant enterococci to the antimicrobial agents that are commonly used to treat enterococci infections and to some alternative drugs. 2) To evaluate the accuracy of E test for susceptibility testing enterococci. MATERIAL AND METHOD: We evaluated 87 clinical VRE isolates that were selected from a previous study which analyzed 1936 clinical isolates collected and processed in 97 US medical centers in the last quarter of 1992. The isolates were identified to the species level by using the API 20S System, the Vitek gram-positive identification cards and a modified version of the conventional method proposed by Facklam and Collins. The in vitro susceptibility testing was performed by broth microdilution, E test and disk diffusion methods, following the criteria described by the National Committee for Clinical Laboratory Standards (NCCLS). The VRE isolates were tested against antimicrobial agents commonly used to treat enterococci infections (vancomycin, teicoplanin, ampicillin, penicillin, gentamicin and streptomycin) and against ten potential alternative drugs (chloramphenicol, doxycycline, sparfloxacin, ciprofloxacin, clinafloxacin, erythromycin, spectinomycin, trospectomycin, trimetoprim-sulfametoxazol and novobiocin). RESULTS: Our results showed a high rate of resistance to ampicillin and penicillin (86%). High level resistance to gentamicin and streptomycin was demonstrated by 82% and 85% respectively. Although teicoplanin and vancomycin belong to the same antibiotic group (glycopeptide), 29% of VRE were susceptible to teicoplanin. Among the alternative drugs, trospectomycin, doxycyclin and chloramphenicol showed the highest in vitro activity, with 94%, 92% and 82% susceptibility respectively. In addition, erythromycin, trimetoprim-sulfametoxazol and ciprofloxacin showed the highest rates of resistance (98%, 83% and 69%, respectively). CONCLUSION: The treatment options for infections caused by vancomycin-resistant enterococci seem to be very narrow since a small percentage of those isolates were susceptible to the other antimicrobial agents commonly used to treat these infections and only a few of the alternative drugs tested showed good in vitro activity. Many regimens using various antibiotic combinations have been tested against VRE, most of them with fluoroquinolones. However further studies are necessary to evaluate the clinical role of these antibiotic combinations.

Anti-Bacterial Agents↗