Biomedical subjects

M A Pfaller

Publications and source records attributed to M A Pfaller.

At least 109 records · Page 6Linked to original sources

PubMed2001

Use of penicillin MICs to predict in vitro activity of other beta-lactam antimicrobial agents against Streptococcus pneumoniae.

Linear regression analysis was used to compare penicillin MICs determined with 3,129 recent clinical isolates of Streptococcus pneumoniae to MICs obtained with nine other beta-lactam antimicrobial agents. A strong correlation between penicillin MICs and those obtained with other beta-lactams was demonstrated. It may be possible to test penicillin and use MICs obtained with penicillin to predict MICs of other beta-lactam antimicrobials for Streptococcus pneumoniae.

Anti-Bacterial Agents↗

PubMed2001

Comparison of the Vitek Gram-Positive Susceptibility 106 card and the MRSA-screen latex agglutination test for determining oxacillin resistance in clinical bloodstream isolates of Staphylococcus aureus.

The Vitek automated susceptibility testing system with a modified Gram-Positive Susceptibility (GPS) 106 Card (bioMerieux Vitek, Inc., Hazelwood, Mo.) and a rapid slide latex agglutination test (MRSA-Screen; Denka Seiken Co., Ltd., Tokyo, Japan) were evaluated for their ability to detect oxacillin resistance in Staphylococcus aureus. The oxacillin-salt agar screen (OS) test, the reference broth microdilution method, and the detection of the mecA gene by PCR were compared with the commercial products. A total of 200 contemporary (1999) bloodstream infection isolates were collected from the SENTRY Antimicrobial Surveillance Program, representing diverse geographic areas throughout the world. Among the 99 mecA-positive isolates, 3 isolates were found negative by the MRSA-Screen. Another two isolates did not grow on OS plates and had MICs of 0.5 and 2 microg/ml with the Vitek GPS card. All 101 mecA-negative isolates were also found negative by the MRSA-Screen and were categorized as susceptible by the GPS card. Overall, the MRSA-Screen, GPS card, and OS test had sensitivities of 96.9, 98.0, and 98.0% and specificities of 100.0, 100.0, and 98.0%, respectively. MRSA-Screen was a rapid (</=15 min) and simple test to perform, and the GPS card provided results in <8 h. Both methods were sensitive and specific for detecting staphylococcal oxacillin resistance in the clinical microbiology laboratory.

Bacteremia↗

PubMed2001

Comparison of the Vitek gram-positive susceptibility 106 card, the MRSA-Screen latex agglutination test, and mecA analysis for detecting oxacillin resistance in a geographically diverse collection of clinical isolates of coagulase-negative staphylococci.

The Vitek automated susceptibility testing system with a modified gram-positive susceptibility (GPS) 106 card (bioMerieux Vitek, Inc., Hazelwood. Mo.) and a rapid slide latex agglutination test (MRSA-Screen test; Denka Seiken Co., Ltd., Tokyo, Japan) were evaluated for their abilities to detect oxacillin resistance in coagulase-negative staphylococci (CoNS). The reference broth microdilution method and the detection of the mecA gene by PCR ("gold standard" reference result) were used to compare the results obtained with the commercial products. A total of 123 clinical isolates consisting of eight species were selected from U.S. surveillance collections. Among the mecA-positive isolates (95 strains), 30 isolates were initially negative on the MRSA-Screen test read at 3 min. When the agglutination reaction was extended for 10 min, 26 of the 30 isolates became positive. For a different four isolates, the oxacillin MIC was < or =0.25 microg/ml on the Vitek GPS 106 card. Among the mecA-negative isolates (28 strains), for two Staphylococcus warneri, two S. lugdunensis, and two S. saprophyticus strains MICs were > or =0.5 microg/ml by the reference broth microdilution method. Four of these isolates were also categorized as resistant with the Vitek GPS 106 card and two isolates were positive by the MRSA-Screen test. Overall, the MRSA-Screen test, GPS 106 card, and reference broth microdilution method had sensitivities of 95.7 (result at 10 min), 95.7, and 100%, respectively, and specificities of 92.8, 85.7, and 78.5%, respectively. Although the MRSA-Screen test required a slight procedural modification, both commercial methods achieved a sensitivity and specificity at detecting oxacillin resistance in CoNS at a level that was acceptable for clinical laboratory use.

Bacterial Proteins↗

PubMed2001

Evaluation of Etest method for determining posaconazole MICs for 314 clinical isolates of Candida species.

The performance of the Etest for posaconazole (SCH 56592) susceptibility testing of 314 isolates of Candida spp. was assessed against the National Committee for Clinical Laboratory Standards (NCCLS) microdilution broth method. The NCCLS method employed RPMI 1640 broth medium, and MICs were read after incubation for 48 h at 35 degrees C. MICs were determined by Etest for all 314 isolates with RPMI agar containing 2% glucose (RPG agar) and were read after incubation for 48 h at 35 degrees C. The Candida isolates included C. albicans (n = 174), C. glabrata (n = 57), C. tropicalis (n = 31), C. parapsilosis (n = 39), C. krusei (n = 5), C. guilliermondii (n = 6), and C. lusitaniae (n = 2). The Etest results correlated well with reference MICs. Overall agreement was 95%, and agreements for individual species were as follows: C. krusei, 100%; C. albicans, 98%; C. tropicalis, 97%; C. glabrata, 93%; C. parapsilosis, 85%; C. guilliermondii, 83%; and C. lusitaniae, 50%. The problem of trailing end points was minimized with RPG agar, and good agreement with broth dilution MICs was obtained when discernible growth within an established ellipse was ignored. The Etest method using RPG agar appears to be a useful method for determining posaconazole susceptibilities of Candida species.

Antifungal Agents↗

PubMed2001

Evaluation of Etest method for determining caspofungin (MK-0991) susceptibilities of 726 clinical isolates of Candida species.

The performance of the Etest for testing the susceptibilities to caspofungin (MK-0991) of 726 isolates of Candida spp. was assessed against the National Committee for Clinical Laboratory Standards (NCCLS) microdilution broth method. The NCCLS method employed RPMI 1640 broth medium, and MICs were read after incubation for 48 h at 35 degrees C. MICs were determined by Etest for all 726 isolates with RPMI agar containing 2% glucose (RPG) and were read after incubation for 48 h at 35 degrees C. The Candida isolates included Candida albicans (n = 486), Candida glabrata (n = 96), Candida tropicalis (n = 51), Candida parapsilosis (n = 47), Candida krusei (n = 11), Candida lusitaniae (n = 2), and Candida guilliermondii (n = 33). In addition, a subset of 314 isolates were also tested by Etest using Casitone agar (CAS) and antibiotic medium 3 agar (AM3). The Etest results obtained using RPG correlated well with reference MICs. Overall agreement was 94% with RPG, 82% with CAS, and 79% with AM3. When RPG was used, agreement ranged from 79% for C. parapsilosis to 100% for C. krusei, C. lusitaniae, and C. guilliermondii. When CAS was used, agreement ranged from 0% for C. lusitaniae to 100% for C. glabrata. With AM3, agreement ranged from 0% for C. lusitaniae to 100% for C. guilliermondii. All three media supported growth of each of the Candida species. Etest results were easy to read, with sharp zones of inhibition. In most instances (75%) where a discrepancy was observed between the Etest and the reference method, the Etest MIC was lower. The Etest method using RPG appears to be useful for determining caspofungin susceptibilities of Candida species.

Anti-Bacterial Agents↗

PubMed2001

Comparison of results generated by serotyping, pulsed-field restriction analysis, ribotyping, and repetitive-sequence PCR used to characterize penicillin-resistant pneumococci from the United States.

One hundred forty-seven isolates of Streptococcus pneumoniae with high-level penicillin resistance collected during a national surveillance program in the United States were characterized by serotyping, pulsed-field restriction analysis, ribotyping, and repetitive-sequence (BOX element) PCR. The results generated by each method were compared by frequency of association to examine whether relationships existed between the various typing methods and statistically to determine association with the geographic source of the isolate or the age of the patient from whom the isolate was obtained. When the data were examined by pairwise analysis of individual strain classifications produced by each typing method, no statistically significant relationships between strain type, geographic location, or patient age were identified, suggesting that distinct clones of penicillin-resistant S. pneumoniae have been widely distributed throughout the United States. However, we did observed shared expression of two or three typing markers at a high frequency (>50%) among clusters of strains, indicating a certain level of concordance between the various typing methods used to classify penicillin-resistant S. pneumoniae.

Adolescent↗

PubMed2001

International surveillance of bloodstream infections due to Candida species: frequency of occurrence and in vitro susceptibilities to fluconazole, ravuconazole, and voriconazole of isolates collected from 1997 through 1999 in the SENTRY antimicrobial surveillance program.

A surveillance program (SENTRY) of bloodstream infections (BSI) in the United States, Canada, Latin America, and Europe from 1997 through 1999 detected 1,184 episodes of candidemia in 71 medical centers (32 in the United States, 23 in Europe, 9 in Latin America, and 7 in Canada). Overall, 55% of the yeast BSIs were due to Candida albicans, followed by Candida glabrata and Candida parapsilosis (15%), Candida tropicalis (9%), and miscellaneous Candida spp. (6%). In the United States, 45% of candidemias were due to non-C. albicans species. C. glabrata (21%) was the most common non-C. albicans species in the United States, and the proportion of non-C. albicans BSIs was highest in Latin America (55%). C. albicans accounted for 60% of BSI in Canada and 58% in Europe. C. parapsilosis was the most common non-C. albicans species in Latin America (25%), Canada (16%), and Europe (17%). Isolates of C. albicans, C. parapsilosis, and C. tropicalis were all highly susceptible to fluconazole (97 to 100% at < or =8 microg/ml). Likewise, 97 to 100% of these species were inhibited by < or =1 microg/ml of ravuconazole (concentration at which 50% were inhibited [MIC(50)], 0.007 to 0.03 microg/ml) or voriconazole (MIC(50), 0.007 to 0.06 microg/ml). Both ravuconazole and voriconazole were significantly more active than fluconazole against C. glabrata (MIC(90)s of 0.5 to 1.0 microg/ml versus 16 to 32 microg/ml, respectively). A trend of increased susceptibility of C. glabrata to fluconazole was noted over the three-year period. The percentage of C. glabrata isolates susceptible to fluconazole increased from 48% in 1997 to 84% in 1999, and MIC(50)s decreased from 16 to 4 microg/ml. A similar trend was documented in both the Americas (57 to 84% susceptible) and Europe (22 to 80% susceptible). Some geographic differences in susceptibility to triazole were observed with Canadian isolates generally more susceptible than isolates from the United States and Europe. These observations suggest susceptibility patterns and trends among yeast isolates from BSI and raise additional questions that can be answered only by continued surveillance and clinical investigations of the type reported here (SENTRY Program).

Antifungal Agents↗

PubMed2001

In vitro evaluation of BI 397, a novel glycopeptide antimicrobial agent.

BI 397, a semi-synthetic amide derivative of the experimental glycopeptide, MDL 62,476 (A40926), has excellent in vitro activity against a wide range of Gram-positive organisms. In this extensive study, 630 contemporary (1998-2000) Gram-positive isolates were selected from various resistance surveillance studies for their resistance patterns to fluoroquinolones, macrolides-lincosamides-streptogramins, beta-lactams and glycopeptide agents. The BI 397 spectrum of activity was similar to that of other glycopeptides with a MIC90 of < or =0.5 microg/ml for all tested isolates with the exception of vancomycin-resistant enterococci Van A; (MIC90, 32 microg/ml). BI 397 was more potent than vancomycin and teicoplanin against Staphylococcus aureus (2- to 8-fold), beta-haemolytic streptococci (equal to >16-fold), viridans group streptococci (equal to >32-fold), and Corynebacterium spp. including C. jeikeium (8- to >16-fold). BI 397 was also more active than quinupristin/dalfopristin against all Gram-positive organisms tested with the exception of oxacillin-susceptible S. aureus, against which it had equal activity. BI 397 has little activity against Haemophilus influenzae (MIC90, 64 microg/ml) or other Gram-negative bacilli (MIC90, >64 microg/ml). BI 397 exhibited bacteriostatic activity (like the vancomycin control) versus most species, but was bactericidal against tested Streptococcus pneumoniae. In vitro testing conditions with blood supplemented or free protein containing media elevated BI 397 MIC results, and the 30-microg disk seems acceptable for further disk diffusion test development. Animal pharmacokinetic data published elsewhere suggest that BI 397 may be dosed less frequently than teicoplanin and the results of early studies in humans are awaited with interest, especially when treating teicoplanin-refractory coagulase-negative staphylococci.

Anti-Bacterial Agents↗

PubMed2001

In vitro antifungal susceptibility testing.

With the rising frequency of fungal infections, as well as increasing reports of resistance to antifungal agents, it is imperative that clinically applicable antifungal susceptibility testing be available. In 1997 the National Committee for Clinical Laboratory Standards published standard guidelines for antifungal susceptibility testing of Candida sp and Cryptococcus neoformans with amphotericin B, flucytosine, fluconazole, itraconazole, and ketoconazole. Although the methods are standard, they are time consuming, can be difficult to interpret, and are approved only for testing limited organisms and drugs. Modifications to the methods and alternative approaches have been proposed to make these tests more convenient and efficient, applicable to a greater number of species, and appropriate for performing in the clinical laboratory.

Antifungal Agents↗

PubMed2000

Outbreak of severe Pseudomonas aeruginosa infections caused by a contaminated drain in a whirlpool bathtub.

During a 14-month period, 7 patients with hematological malignancies acquired serious infections caused by a single strain of multiply resistant Pseudomonas aeruginosa. A case-control study, culture surveys, and pulsed-field gel electrophoresis implicated a whirlpool bathtub on the unit as the reservoir. All case patients and 32% of control patients used this bathtub (P=.003). The epidemic strain was found only in cultures of samples taken from the bathtub. The drain of the whirlpool bathtub, which was contaminated with the epidemic strain, closed approximately 2.54 cm below the drain's strainer. Water from the faucet, which was not contaminated, became contaminated with P. aeruginosa from the drain when the tub was filled. The design of the drain allowed the epidemic strain to be transmitted to immunocompromised patients who used the whirlpool bathtub. Such tubs are used in many hospitals, and they may be an unrecognized source of nosocomial infections. This potential source of infection could be eliminated by using whirlpool bathtubs with drains that seal at the top.

Adult↗

PubMed2000

Nosocomial bloodstream infections caused by Acinetobacter species in United States hospitals: clinical features, molecular epidemiology, and antimicrobial susceptibility.

We examined the clinical and epidemiological features of nosocomial bloodstream infections (BSIs) caused by Acinetobacter species and observed from 1 March 1995 through 28 February 1998 at 49 United States hospitals (SCOPE National Surveillance Program). Acinetobacter species were found in 24 hospitals (49%) and accounted for 1.5% of all nosocomial BSIs reported. One hundred twenty-nine isolates were identified either as A. baumannii (n=111) or other Acinetobacter species (n=18). Patients with A. baumannii BSI, compared with patients with nosocomial BSI caused by other gram-negative pathogens, were more frequently observed in the intensive care unit (69% vs. 47%, respectively; P<.001; odds ratio [OR] 2.4; 95% confidence interval [CI] 1.6-3.7) and were more frequently receiving mechanical ventilation (58% vs. 30%, respectively; P<.001; OR 3.2; 95% CI 2.1-4.8). Crude mortality in patients with A. baumannii BSI was 32%. Molecular relatedness of strains was studied by use of polymerase chain reaction-based fingerprinting. Clonal spread of a single strain occurred in 5 hospitals. Interhospital spread of epidemic A. baumannii strains was not observed. The most active antimicrobial agents against A. baumannii (90% minimum inhibitory concentration values) were imipenem (1 mg/L; 100% of isolates susceptible), amikacin (8 mg/L; 96%), tobramycin (4 mg/L; 92%), and doxycycline (4 mg/L; 91%). Thirty percent of isolates were resistant to > or =4 classes of antimicrobials and were considered to be multidrug resistant.

Acinetobacter↗

PubMed2000

Respiratory tract pathogens isolated from patients hospitalized with suspected pneumonia: frequency of occurrence and antimicrobial susceptibility patterns from the SENTRY Antimicrobial Surveillance Program (United States and Canada, 1997).

Thirty-seven sentinel hospitals (29 in the United States [US]; eight in Canada) collected bacterial isolates from hospitalized patients with a diagnosis of pneumonia. The antimicrobial susceptibility patterns of these pathogens were determined to more than 60 agents (40 reported) using the reference broth microdilution method described by the National Committee for Clinical Laboratory Standards. The five most frequently recorded species among the 2757 isolates collected during the study were (no. tested/%): Staphylococcus aureus (632/22.9%), Pseudomonas aeruginosa (498/18. 1%), Haemophilus influenzae (284/10.3%), Klebsiella spp. (240/8.7%), and Streptococcus pneumoniae (213/7.7%). There was a significant difference in the susceptibility to antimicrobials between the US and Canada for S. aureus to oxacillin (50.1% versus 93.8% susceptible, respectively), gentamicin (78.7% versus 97.8%), and fluoroquinolones (49.5 to 53.0% versus 89.8 to 94.9%). Amikacin (92. 8% susceptible) was the most active antimicrobial agent against P. aeruginosa, and meropenem was the most potent beta-lactam. Against H. influenzae, most drugs retained a high level of activity, whilst against the S. pneumoniae, only the newer fluoroquinolones (gatifloxacin, levofloxacin, sparfloxacin) remained highly effective in vitro. Only two antimicrobial agents (imipenem and meropenem) were >99% active against the Klebsiella spp. and Enterobacter spp. isolated in this survey (possess extended spectrum beta-lactamases or hyperproduction of Amp C cephalosporins); cefepime (95.6-100.0% susceptible) was significantly more active than other cephalosporins tested. Clonal, epidemic outbreaks of multiply resistant strains were very rare in monitored hospitals. In conclusion, important differences exist between the US and Canada in the susceptibility patterns of some respiratory tract pathogens to commonly used antimicrobial agents with Canadian strains generally being more susceptible to currently available antimicrobial agents.

Anti-Bacterial Agents↗

PubMed2000

Frequency of occurrence and antimicrobial susceptibility patterns for pathogens isolated from latin american patients with a diagnosis of pneumonia: results from the SENTRY antimicrobial surveillance program (1998).

The correct empiric choice of antimicrobial therapy in the treatment of pneumonia in hospitalized patients has established itself as a major therapeutic challenge to clinicians. Selection of an inappropriate antimicrobial agent could lead to increased rates of mortality and morbidity. Characteristics of pathogens responsible for this infection such as species prevalence, overall antimicrobial resistance rates, and mechanisms of detected resistance could serve as an invaluable resource to clinicians in making such therapeutic selections. This report addresses the aforementioned problems/needs by analysis of 712 strains isolated from the lower respiratory tract of patients hospitalized with a diagnosis of pneumonia in 10 Latin American medical centers in the SENTRY Antimicrobial Surveillance Program (1998). The four most frequently isolated pathogens (no/% of total) were: Pseudomonas aeruginosa (191/26.8%), Staphylococcus aureus (171/24.0%), Klebsiella spp. (86/12.1%), and Acinetobacter spp. (75/10.5%); representing nearly 75.0% of all isolates. More than 40 antimicrobial agents (23 reported) were tested against these isolates by reference broth microdilution methodology, and susceptibility profiles were established. The nonfermentative Gram-negative bacteria (P. aeruginosa and Acinetobacter spp.) exhibited high levels of resistance to the agents tested. Amikacin (77.5% susceptible) was the most active drug tested against P. aeruginosa 50.0% against the Acinetobacter spp. isolates. Based on published interpretive criteria, over 22.0% of the Klebsiella spp. and 12.5% of the Escherichia coli were classified as extended spectrum beta-lactamase (ESBL) producers. Of the cephalosporin class compounds tested against the Klebsiella spp. and E. coli isolates, cefepime demonstrated the highest rates of susceptibility (84.9% and 91.7%, respectively). This compound also fared well against the Enterobacter spp. isolates, inhibiting 88.2% of the isolates tested, many of which were resistant to ceftazidime and ceftriaxone. Resistance to oxacillin among the S. aureus isolates was nearly 50. 0%, with vancomycin, teicoplanin, and the streptogramin combination quinupristin/dalfopristin inhibiting all isolates. Several clusters of multiply resistant organisms were also observed, and further characterization by ribotyping and pulsed-field gel electrophoresis established possible patient-to-patient spread. The results of this study indicate that rates of resistance among respiratory tract pathogens continue to rise in Latin America, with specific concerns for the high prevalence of nonfermentative Gram-negative bacteria isolated, oxacillin resistance rates in S. aureus, and the epidemic dissemination of multiply-resistant strains in several medical centers. International surveillance programs (SENTRY) should assist in the control of escalating antimicrobial resistance in this geographic area.

Anti-Bacterial Agents↗

PubMed2000

In vitro activity of selected cephalosporins and erythromycin against staphylococci and pneumococci isolated at 38 North American medical centers participating in the SENTRY Antimicrobial Surveillance Program, 1997-1998.

The SENTRY Antimicrobial Surveillance Program employs a worldwide network of hospitals to monitor the predominant bacterial and fungal pathogens and antimicrobial susceptibility patterns associated with nosocomial and community-acquired bloodstream, respiratory tract, wound, and urinary tract infections. The purpose of this analysis of SENTRY data is to extract information on the current North American susceptibility patterns of pneumococci and oxacillin-susceptible staphylococci from the comprehensive SENTRY program database. Clinical isolates were provided by 30 centers in the United States (grouped into five regions) and eight centers in Canada. Susceptibility testing was performed at a central reference laboratory using broth microdilution methods and interpretive criteria specified by the National Committee for Clinical Laboratory Standards. Of 34 530 North American bacterial isolates tested during 1997 and 1998, 565 (1.6%) were oxacillin-susceptible, coagulase-negative staphylococci (CoNS). Cefazolin, cefepime, and ceftriaxone all had excellent activity against these CoNS (97.3%-99. 3% susceptible), and 90.4% were susceptible to ceftazidime. A total of 4404 isolates (12.8%) were oxacillin-susceptible Staphylococcus aureus. Overall, 98.9% to 99.2% were susceptible to cefazolin, cefepime, and ceftriaxone; ceftazidime did not have acceptable activity against these S. aureus. Streptococcus pneumoniae accounted for 1665 (4.8%) of North American SENTRY isolates. A total of 1212 isolates (72.8%) were fully susceptible to penicillin (MIC </= 0.06 microg/ml), 250 (15%) were penicillin intermediate (MIC 0.12-1 microg/ml), and 203 (12.2%) were penicillin resistant (MIC >/= 2 microg/ml). The rate of penicillin susceptibility was highest in Canada, and lowest in the South Central and South East regions of the United States. Cefepime, cefuroxime, ceftazidime, and erythromycin all demonstrated excellent efficacy (94%-99.8% susceptibility) against fully penicillin-susceptible isolates of S. pneumoniae. Among pneumococci with intermediate penicillin resistance, 88% were susceptible to cefepime, 92% to cefotaxime, and only 14% to ceftazidime. None of the antimicrobial agents in this analysis demonstrated adequate activity against fully penicillin-resistant pneumococci. In summary, the fourth-generation cephalosporin, cefepime, demonstrated consistently excellent efficacy against oxacillin-susceptible staphylococci and most pneumococci, and remains an appropriate choice for empiric therapy of serious infections.

Anti-Bacterial Agents↗

PubMed2000

Antimicrobial activity and in vitro susceptibility test development for cefditoren against Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus species.

Cefditoren, a third generation orally administered aminothiazolyl cephalosporin, has demonstrated bactericidal activity against many Gram positive and negative bacterial pathogens and stability against clinically important beta-lactamases. Cefditoren was compared to cefaclor, cefixime, and penicillins against 1 435 recently isolated strains of streptococci (312 Streptococcus pneumoniae, 165 viridans group streptococci, 142 beta-haemolytic streptococci), Haemophilus influenzae (521 strains), and Moraxella catarrhalis (295 strains). Streptococcus pneumoniae and viridans group streptococci had penicillin nonsusceptible rates of 37.8 and 35.8%, respectively. Cefditoren (MIC(90) in microg/ml/% susceptible) activity against all tested H. influenzae (0.03/100) and M. catarrhalis (0.06-0.5/100) was comparable to cefixime and significantly greater than cefaclor. Cefditoren (MIC(90), 0.5 microg/ml) was 4- to 128-fold more active than comparison beta-lactams against the pneumoococci and was the most potent beta-lactam (including penicillin) versus beta-haemolytic streptococci. Cefditoren pharmacokinetics demonstrate a T(1/2) of 1.5-2 h and C(max) values of 2.8 and 4.6 microg/ml, respectively with 200 or 400 mg doses of cefditoren pivoxil; plasma concentrations exceed 1 microg/ml for 4 to 6 hours (33-50% of dosing interval). Consequently, a susceptible MIC of </= 1 microg/ml or </= 2 microg/ml was proposed with zone diameter correlates of >/= 18 and >/= 15 mm (5-microg disk) for all cited fastidious species tested. Categorical agreement between MIC and disk tests was 94.6 to 100% with a correlation coefficient (r) range of 0.50 to 0.90 for streptococci. H. influenzae intermethod comparison results using the same interpretive criteria were in complete agreement, but exhibited a low r = 0.39. Cefditoren clearly possesses the most potent activity among currently studied oral cephalosporins or penicillin against commonly isolated bacterial pathogens causing bronchitis, pneumonia, sinusitis, or pharyngitis and was active against nearly all penicillin-resistant streptococci at </= 0.5 microg/ml. Expanded clinical investigations seem warranted.

Cefaclor↗

PubMed2000

Comparison of the activity of two broad-spectrum cephalosporins tested against 2,299 strains of Pseudomonas aeruginosa isolated at 38 North American medical centers participating in the SENTRY Antimicrobial Surveillance Program, 1997-1998.

Pseudomonas aeruginosa is an important nosocomial pathogen. Resistance to certain beta-lactam antimicrobial agents among P. aeruginosa is increasing. The SENTRY Antimicrobial Surveillance Program was designed to employ a network of hospitals in the United States, Canada, Latin America, and Europe to monitor the predominant bacterial and fungal pathogens and antimicrobial susceptibility patterns associated with community-acquired and nosocomial bloodstream, respiratory tract, wound, and urinary tract infections. The purpose of this analysis of SENTRY results was to extract information on the current North American susceptibility pattern of P. aeruginosa for two antipseudomonal cephalosporins, ceftazidime, and cefepime. Clinical isolates were provided by 30 centers in the United States (grouped into five regions) and eight centers in Canada. Susceptibility testing was performed at a central reference laboratory by using broth microdilution methods and interpretive criteria specified by the National Committee for Clinical Laboratory Standards. Of the 34, 530 North American bacterial isolates tested during 1997 and 1998, 2299 (6.7%) were P. aeruginosa. There were no substantial differences in regional rates of P. aeruginosa susceptibility to ceftazidime (range 78.8-81.9%) or cefepime (range 80.0-83.4%) The percentage of resistant isolates among the 1784 United States isolates was 13.3% for ceftazidime versus 7.1% for cefepime (p < 0.05). It is essential to continue surveillance of the in vitro efficacy of these and other beta-lactam agents against P. aeruginosa because of the clinical importance of these safe and broad-spectrum cephems used alone or in combination in current clinical practice.

Cefepime↗

PubMed2000

Occurrence of single-point gyrA mutations among ciprofloxacin-susceptible Escherichia coli isolates causing urinary tract infections in Latin America.

To detect if isolates susceptible to quinolones already carry mutations in the gyrA and parC genes, we selected 12 ciprofloxacin-susceptible Escherichia coli strains collected from patients with urinary tract infections in Latin America in 1998, as part of ongoing SENTRY Antimicrobial Surveillance Program. The isolates studied exhibited minimal inhibitory concentrations (MICs) for ciprofloxacin between < or = 0.015 microg/mL and 0.5 microg/mL. The molecular characterization of quinolone resistance was determinated by amplification of the gyrA and parC by PCR followed by sequencing of the respective amplicons. We observed that E. coli isolates exhibiting MIC, < or = 0.06 microg/mL for ciprofloxacin did not show mutations in either topoisomerase. On the other hand, all isolates with MIC between 0.12 microg/mL and 0.5 microg/mL demonstrated single mutation in the gyrA gene. The most frequent mutation occurred at position 83, where the amino acid serine was replaced by leucine. No mutations in the parC gene were observed. To preserve the potency and prevent the development of resistance, we suggest that quinolone usage should be rational, especially in the treatment of urinary tract infections, and in the prophylaxis of immunosupressed patient populations.

Anti-Infective Agents↗

PubMed2000

In vitro pharmacodynamic characteristics of flucytosine determined by time-kill methods.

Two Candida albicans isolates, three non-albicans Candida isolates (Candida glabrata, Candida krusei, and Candida tropicalis), and one Cryptococcus neoformans isolate were evaluated by time-kill methods to characterize the relationship of flucytosine concentrations to antifungal activity and the duration of the post-antifungal effect (PAE). Against Candida and Cryptococcusisolates, flucytosine at concentrations > 1 x MIC exhibited fungistatic (</=99% reduction in CFU) activity over a 24-h time-period. The rate and extent of fungistatic activity of flucytosine against all isolates was generally not increased when 5-FC concentrations exceeded 4 x MIC. A notable PAE was detected for flucytosine against both Candida and Cryptococcus species that persisted 2 to 4 h. These in vitro data suggest that flucytosine is predominately a concentration-independent fungistatic agent at clinically achieved serum concentrations. This pharmacodynamic characteristic coupled with the persistent PAE and the relatively long half-life of flucytosine in humans (> 5 h), suggests lower daily dosing may possible without loss of antifungal efficacy.

Antifungal Agents↗