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Thomas R Fritsche

Publications and source records attributed to Thomas R Fritsche.

At least 19 recordsLinked to original sources
PubMed2007

Activity of dalbavancin tested against Staphylococcus spp. and beta-hemolytic Streptococcus spp. isolated from 52 geographically diverse medical centers in the United States.

Dalbavancin is a lipoglycopeptide antimicrobial agent with a potency significantly better than that of vancomycin when tested against staphylococci and streptococci. These two pathogens are common causes of skin and skin structure infections (SSSIs), and dalbavancin has been approved for the treatment of moderate to severe SSSIs. This study generated susceptibility data for staphylococci and beta-hemolytic streptococci from 52 U.S. medical centers that locally tested dalbavancin, vancomycin, and other antimicrobial class representatives to assess the potency of dalbavancin and the overall contemporary activities of commonly prescribed agents. Locally generated data showed that oxacillin-resistant staphylococci (57.0% overall) had slightly higher dalbavancin MIC(90) values (0.19 microg/ml) than oxacillin-susceptible strains (0.125 microg/ml). This potency was 8- to 16-fold greater than that for vancomycin. beta-Hemolytic streptococci had MIC(90) values ranging between 98% against staphylococci. Erythromycin resistance was high for staphylococci (30.6 to 94.1%) with inducible clindamycin resistance rates of 26.0% and 55.0% for oxacillin-susceptible and -resistant Staphylococcus aureus, respectively. Beta-hemolytic streptococci had a 20.2% erythromycin resistance rate and a 60% inducible clindamycin resistance rate but were highly susceptible to other tested agents. Etest reading errors were apparent and skewed results towards slightly higher dalbavancin MICs, requiring further education on how to interpret Etest method results for this compound. Current disk diffusion breakpoint criteria for oxacillin susceptibility for S. aureus showed a very-major-error rate of 2.3% and only a 0.9% minor-error rate when cefoxitin was used to predict oxacillin susceptibility. Dalbavancin demonstrated excellent potency and activity (100% susceptibility at proposed breakpoints) against common causes of SSSI pathogens in this U.S. multicenter study sample.

Anti-Bacterial Agents↗
PubMed2006

Comparative activities of cefepime and piperacillin/tazobactam tested against a global collection of Escherichia coli and Klebsiella spp. with an ESBL phenotype.

Cefepime exhibits more stability to hydrolysis by extended-spectrum beta-lactamases (ESBLs) compared with other cephalosporins, and piperacillin/tazobactam may be active against these pathogens because of the enzyme inhibitory activity of tazobactam. Thus, we evaluated the in vitro activity of these 2 antimicrobials against a large collection of isolates with an ESBL phenotype. A total of 50,637 clinical isolates (34,367 Escherichia coli and 16,270 Klebsiella spp.) collected from more than 80 medical centers (1998-2004) were tested by reference broth microdilution methods, and isolates with an ESBL phenotype (MIC, > or = 2 microg/mL for aztreonam or ceftazidime or ceftriaxone) were submitted to a clavulanate inhibition test (confirmation of ESBL production). Among isolates from North America, 3.9% of E. coli and 8.6% of Klebsiella spp. showed an ESBL phenotype, whereas among isolates from the rest of the world (ROW) (Europe, Latin America, and Asia), 7.7% of E. coli and 28.3% of Klebsiella spp. exhibited this pattern. Confirmation rates varied from 21.6% of E. coli in North America to 52.8% of Klebsiella spp. in the row Among E. coli from North America, cefepime (90.3% susceptibility) was generally more active than piperacillin/tazobactam (82.7%), especially among ESBL-not-confirmed (97.0% versus 85.5%). Cefepime also showed reasonable activity against Klebsiella spp. from North America (89.4% susceptibility). In general, isolates from North America exhibited higher susceptibility rates to both beta-lactams compared with isolates from the ROW, and ESBL-not-confirmed strains showed generally higher susceptibility rates than ESBL-confirmed organisms.

Anti-Bacterial Agents↗
PubMed2006

Occurrence of plasmidic AmpC type beta-lactamase-mediated resistance in Escherichia coli: report from the SENTRY Antimicrobial Surveillance Program (North America, 2004).

Among 1429 Escherichia coli isolates collected as part of the SENTRY Antimicrobial Surveillance Program (2004) from 30 North American medical centres, 65 (4.5%) were screen-positive for an extended-spectrum beta-lactamase (ESBL). Among the strains with a negative ESBL confirmatory test (n=26; clavulanic acid inhibition), a CMY-2 enzyme was detected in 13 isolates (50.0%), FOX-5 in 3 isolates (11.5%) and DHA-1 in 1 isolate (3.8%). These AmpC-producing E. coli were cephamycin (cefoxitin)-resistant but susceptible to cefepime (minimum inhibitory concentration (MIC) < OR =0.12-4 mg/L). Clearly, the ESBL tests recommended by the Clinical and Laboratory Standards Institute identify only a fraction of E. coli with elevated beta-lactam MIC values as ESBL-producing strains; the majority of the remaining strains would be potentially responsive to some other beta-lactams, directed by accurately performed and interpreted susceptibility methods.

Academic Medical Centers↗
PubMed2006

Contemporary causes of skin and soft tissue infections in North America, Latin America, and Europe: report from the SENTRY Antimicrobial Surveillance Program (1998-2004).

The morbidity and cost for cure associated with skin and soft tissue infections (SSTIs) have recently become more complicated because of the increasing prevalence of multidrug-resistant pathogens associated with this healthcare problem. The SENTRY Antimicrobial Surveillance Program has been monitoring SSTI since 1997, and now presents data from 3 continents over a 7-year period (1998-2004). Isolates were tested by reference broth microdilution methods at a central laboratory using the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) methods and interpretative criteria. The predominant pathogens included Staphylococcus aureus (ranked 1st in all geographic regions), Pseudomonas aeruginosa, Escherichia coli, and Enterococcus spp. A considerable variation in the methicillin (oxacillin)-resistant S. aureus rate was noted between countries and continents, with the overall rate highest in North America (35.9%) compared with Latin America (29.4%) and Europe (22.8%). Vancomycin-resistant Enterococcus spp. increased in Europe (4.1%) and North America (6.2%) during the period, but remained low and relatively unchanged in Latin America. Among the P. aeruginosa isolates tested, susceptibility to imipenem was much lower in Latin America (65.3%) compared with the other regions (80.7-88.7%), and resistance being associated with an increase in metallo-beta-lactamase-producing strains in Latin America and in some European countries. Multidrug-resistant strains of P. aeruginosa were also more of a concern in Latin America (24.7%) compared with Europe (10.8%) or North America (3.2%). Latin America also had the highest occurrence of extended-spectrum beta-lactamase-producing isolates among E. coli (15.1%) and Klebsiella spp. (48.0%) when compared with other regions. Continued surveillance of pathogen prevalence and antimicrobial resistance patterns should provide information that is important to improve empiric care particularly in the hospital environment.

Anti-Bacterial Agents↗
PubMed2006

Comparisons of parenteral broad-spectrum cephalosporins tested against bacterial isolates from pediatric patients: report from the SENTRY Antimicrobial Surveillance Program (1998-2004).

A contemporary collection of 12737 strains from pediatric patients (<18 years) isolated over a 7-year period (1998-2004) from 52 sentinel hospitals in North America was tested to determine the comparative antimicrobial potency of broad-spectrum parenteral cephalosporins and selected comparator agents. Most of the strains (84.1%) were isolated from blood stream or respiratory tract infections. The rank order of the top 10 pediatric pathogens analyzed was Streptococcus pneumoniae (15.5%) >Haemophilus influenzae (14.6%) >Staphylococcus aureus (13.8%) >Moraxella catarrhalis = coagulase-negative staphylococci (8.0%) >Escherichia coli (7.8%) >Pseudomonas aeruginosa (5.2%) >Klebsiella spp. (4.8%) >Enterococcus spp. (4.7%) > beta-hemolytic streptococci (4.4%). Both cefepime and ceftriaxone (MIC(90), 1 microg/mL; 93.9% and 93.7% susceptible, respectively) were highly active against S. pneumoniae. However, the S. pneumoniae strains showed reduced susceptibility to ceftazidime (56.6%), as well as penicillin (56.6%) < trimethoprim-sulfamethoxazole (57.1%) < erythromycin (66.2%) < tetracycline (71.4%). beta-Hemolytic streptococci showed 100.0% susceptibility to penicillin, cefepime, and ceftriaxone. Cefepime and ceftriaxone exhibited high activity against oxacillin (methicillin)-susceptible S. aureus, (MIC(90), 4 microg/mL; 100.0% and 99.8% susceptible, respectively), whereas ceftazidime (MIC(90), 16 microg/mL) was active against only 86.7% of strains. H. influenzae strains showed complete susceptibility to cefepime, ceftriaxone, and levofloxacin (MIC(90), < or =0.5 microg/mL; 100.0%), and 34.0% of H. influenzae and 99.2% of M. catarrhalis strains produced beta-lactamase. Although the 3 cephalosporins tested (cefepime, ceftriaxone, and ceftazidime) were very active (98.6-99.6% susceptible) against E. coli, cefepime (99.0% susceptible) was slightly more active than ceftriaxone and ceftazidime (96.4% and 95.1% susceptible, respectively) against Klebsiella spp. Cefepime was also the most active beta-lactam agent tested against Enterobacter spp. (MIC(90), 2 microg/mL; 99.3% susceptible), whereas the susceptibility rates of other broad-spectrum beta-lactams (ceftriaxone, ceftazidime and piperacillin-tazobactam) were significantly lower (78.4-81.5%). Against P. aeruginosa, imipenem and piperacillin-tazobactam showed the highest susceptibility rates (94.4% and 93.3%, respectively), whereas imipenem and cefepime showed the lowest resistance rates (1.4% and 2.3%, respectively). Our results indicate that cefepime was the most broad-spectrum cephalosporin analyzed and remains a very potent alternative for the treatment of contemporary pediatric infections in North America.

Adolescent↗
PubMed2006

Influence of patient age on the frequency of occurrence and antimicrobial resistance patterns of isolates from hematology/oncology patients: report from the Chemotherapy Alliance for Neutropenics and the Control of Emerging Resistance Program (North America).

The Chemotherapy Alliance for Neutropenics and the Control of Emerging Resistance Program (CANCER) monitored the susceptibility of pathogens recovered in hematology/oncology centers from 2000 to 2002. A total of 3970 isolates from 32 hospitals (26 United States, 6 Canada) were analyzed at a central location (JMI Laboratories, North Liberty, IA) for trends in pathogen occurrence and reference antimicrobial susceptibility profiles. The top 5 ranking pathogens were Staphylococcus aureus (19.3%), coagulase-negative staphylococci (CoNS) (14.1%), Escherichia coli (13.4%), Enterococcus spp. (10.2%), and Klebsiella spp. (9.5%). A total of 35.5% of S. aureus and 78.8% of CoNS were resistant to oxacillin, whereas 22.0% of Enterococcus spp. were resistant to vancomycin. E. coli and Klebsiella spp. were highly susceptible (>90%) to piperacillin/tazobactam, 3rd-generation cephalosporins, and ciprofloxacin, but 3.9% and 2.4% of these species, respectively, met screening criteria for extended spectrum beta-lactamase production. Enterobacter spp. were less susceptible to piperacillin/tazobactam, ceftazidime, and ceftriaxone (83.7-88.2%) because of Amp C production and were most inhibited by cefepime and imipenem. Amikacin and polymyxin B were very active against Pseudomonas aeruginosa (97.4-97.7% susceptible). Prevalence of S. aureus, E. coli, Enterobacter spp., and Klebsiella spp. increased significantly (+48% to 98%) with age, whereas CoNS and viridans group streptococci decreased markedly (-62% to 69%) with advancing age. The isolation of Gram-positive pathogens declined (55% to 47%) with age (< or =14 to > or =65 years). Fluoroquinolones generally exhibited decreased susceptibility with increased age against nearly all listed pathogens. Oxacillin resistance rates for S. aureus increased with age (6-46%) as did vancomycin resistance rates for enterococci (nil in < or =14 years group to 18-24% in adults). Pathogens infecting neutropenic patients did not reflect greater resistance than those found in the general hospitalized patients. Gram-positive organisms were only slightly more predominant (53.4%), and cited age-related variations in pathogen occurrence and/or susceptibility patterns by species must be considered for empiric regimes for hematology and oncology patients.

Adolescent↗
PubMed2006

Evaluation of dalbavancin in combination with nine antimicrobial agents to detect enhanced or antagonistic interactions.

Dalbavancin is a potent, once-weekly administered lipoglycopeptide that is active against a broad spectrum of Gram-positive species. Synergy studies were performed with dalbavancin and each of nine antimicrobial agents (90 tests in total) representing nine antimicrobial classes using the broth microdilution checkerboard method to establish in vitro interactive categories. Antagonism was not observed between dalbavancin and any of the antimicrobials tested. However, dalbavancin was synergistic or partially synergistic with oxacillin for staphylococci, including methicillin-resistant strains, vancomycin-intermediate Staphylococcus aureus and enterococci, a significant finding that warrants further investigation to establish its potential clinical relevance.

Anti-Infective Agents↗
PubMed2006

Antimicrobial susceptibility pattern comparisons among intensive care unit and general ward Gram-negative isolates from the Meropenem Yearly Susceptibility Test Information Collection Program (USA).

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program is a global, longitudinal antimicrobial resistance surveillance network of greater than 100 medical centers worldwide monitoring the susceptibility of bacterial pathogens to carbapenems and other broad-spectrum agents. Between 1999 and 2002, 15 US medical centers referred up to 200 nonduplicate isolates from clinical infections to a central processing laboratory. During this 4-year period, the antimicrobial activity of 11 broad-spectrum agents was assessed against 5389 bacterial isolates using Clinical and Laboratory Standards Institute (formerly National Committee for Clinical Laboratory Standards)-recommended methods with interpretive criteria. Analysis of the MIC results for pathogens isolated from patients hospitalized in intensive care units (ICUs) were compared to results from pathogens isolated in non-ICU settings. Among Enterobacteriaceae (3884 strains), the carbapenems (imipenem and meropenem) demonstrated the highest susceptibility rates (> or =98.7%) and with only a 1% increase in resistance for ICU isolates compared to non-ICU organisms. Other antimicrobial agents tested demonstrated consistently higher susceptibility rates against Enterobacteriaceae isolates from ICU (89.7-98.7%) and non-ICU (93.2-99.9%) areas. For the nonfermentative Gram-negative bacilli, the rank order of the most active agents having lowest percentage resistance rates were tobramycin (15.5%) < cefepime < imipenem < piperacillin/tazobactam < ceftazidime < meropenem (21.9%) for ICU isolates, and meropenem (7.8%) < cefepime < imipenem < piperacillin/tazobactam < ceftazidime < tobramycin (12.9%) among non-ICU strains. All tested agents showed lower susceptibility rates (range, 1.0-15.3%) and higher resistance rates (range, 0.1-15.1%) for both Enterobacteriaceae and nonfermentative Gram-negative bacilli among the ICU isolates compared to the non-ICU isolates (except for ciprofloxacin against Enterobacteriaceae). Continued surveillance of these broad-spectrum antimicrobial agents in both ICU and general hospital wards appears warranted to monitor the occurrence and spread of antimicrobial resistance in pathogens causing serious infections in these care areas and the possible emergence of resistance mechanisms that could compromise empiric carbapenem therapy.

Anti-Bacterial Agents↗
PubMed2006

Antimicrobial activity of cefepime tested against ceftazidime-resistant Gram-negative clinical strains from North American Hospitals: report from the SENTRY Antimicrobial Surveillance Program (1998-2004).

To assess the effect of ceftazidime resistance on the activity of other antimicrobial agents, 3030 ceftazidime-resistant Gram-negative bacilli (GNB) isolates (of a total of 42061 GNB) were tested against a panel of more than 30 agents. Ceftazidime resistance was observed in 40.3% of Acinetobacter spp., 16.9% of Pseudomonas aeruginosa, and 5.7% of Enterobacteriaceae isolates. The highest rates of ceftazidime resistance among the enteric GNB were observed with Enterobacter spp. (20.9%) >Citrobacter spp. (15.3%) > indole-positive Proteae (10.1%). Overall, 90% of ceftazidime-resistant Enterobacteriaceae and 30% of ceftazidime-resistant P. aeruginosa remained susceptible to the "4th-generation" cephalosporin, cefepime. The activities (% susceptible) of other antimicrobials tested against ceftazidime-resistant Enterobacteriaceae and P. aeruginosa, respectively, were as follows: amikacin, 90% and 88%; ciprofloxacin, 63% and 46%; gentamicin, 59% and 67%, imipenem, 99% and 65%; levofloxacin, 69% and 44%; and piperacillin/tazobactam only 40% and 12%. Ceftazidime-resistant GNB exhibited high rates of resistance to other antimicrobials. Cefepime was very active against ceftazidime-resistant enteric GNB (AmpC enzyme producers), especially Enterobacter spp. (94.3% susceptible), Citrobacter spp. (96.7% susceptible), and indole-positive Proteae (89.6% susceptible), and showed activity similar to that of ceftazidime against all P. aeruginosa and Acinetobacter spp. isolated in North American medical centers. Continued resistances surveillance monitoring will be necessary to assess the effectiveness of widely used broad-spectrum antimicrobials as novel resistance mechanisms emerge.

Anti-Bacterial Agents↗
PubMed2006

Emergence of multidrug-resistant Streptococcus pneumoniae: report from the SENTRY Antimicrobial Surveillance Program (1999-2003).

Emerging resistance among Streptococcus pneumoniae to penicillin, erythromycin, clindamycin, tetracyclines, and trimethoprim-sulfamethoxazole continues to compromise orally administered therapy for community-acquired respiratory tract infections. Concern also exists that multidrug-resistant (MDR) S. pneumoniae and Haemophilus influenzae strains could develop fluoroquinolone resistance (FQR). S. pneumoniae (2379 strains), H. influenzae (2456), and Moraxella catarrhalis (901) studied as part of the SENTRY Antimicrobial Surveillance Program in 2003 were tested by reference MIC methods against 16 antimicrobials. In addition, 592 strains of S. pneumoniae from 1999 to 2003 were assessed for trends in MDR occurrences. H. influenzae beta-lactamase production varied from 11.6% in Latin America to 27.3% in North America, whereas beta-lactamase rates for M. catarrhalis remained stable at 94.7-95.6%. Penicillin resistance (MIC, > or =2 microg/mL) in S. pneumoniae was 14.7%, 12.7%, and 15.9% for Europe, Latin America, and North America, respectively. MDR S. pneumoniae increased from 5.7% (1999) to 6.3% (2003) in North America, but no FQR increase to new agents (gatifloxacin) was detected in the 2001-2003 MDR S. pneumoniae isolates. Five epidemic clusters of FQR S. pneumoniae (levofloxacin MIC, >32 microg/mL) strains have been reported by our group previously in Italian medical centers in 2002-2004. Unlike the strains described here, those strains were susceptible to beta-lactams, trimethoprim-sulfamethoxazole, chloramphenicol, and rifampin, and resistant to macrolide-lincosamide-streptogramin B agents and tetracycline (not meeting MDR criteria). Excluding these clones from Italy, overall FQR rates did not significantly vary from the prior years' experience across the regions (North America > Europe > Latin America). In conclusion, MDR and FQR S. pneumoniae continue to occur across all geographic regions monitored with some detectable clonality. The monitoring of emerging resistance as part of surveillance programs is useful in differentiating sporadic from clonal resistances, an important distinction when assessing prospective public health interventions or empiric therapy recommendations.

Anti-Bacterial Agents↗
PubMed2006

Antimicrobial activity of a novel peptide deformylase inhibitor, LBM415, tested against respiratory tract and cutaneous infection pathogens: a global surveillance report (2003-2004).

OBJECTIVES: To evaluate the spectrum of activity and potency of LBM415, the first of the peptide deformylase inhibitor (PDFI) class to be developed for treatment of community-acquired respiratory tract infections and uncomplicated skin and soft tissue infections (uSSTI), against a large, contemporary international collection of targeted pathogens collected during 2003-2004. METHODS: A total of 21,636 isolates were tested by reference broth microdilution methods as part of a longitudinal international antimicrobial resistance surveillance study. Characteristics of the organism collection included resistance to oxacillin among 35.0% of Staphylococcus aureus and 76.0% of coagulase-negative staphylococci (CoNS); resistance to penicillin (MIC > or = 2 mg/L) among 18.0% of Streptococcus pneumoniae; vancomycin resistance among 20.0% of Enterococcus spp. and ampicillin resistance among 22.0% of Haemophilus influenzae. RESULTS: LBM415 displayed potent activity against staphylococci, streptococci, Enterococcus faecium and Moraxella catarrhalis, with > or = 99.0% of strains being inhibited at < or = 4 mg/L; 97.0% of Enterococcus faecalis isolates and 92.0% of H. influenzae isolates were also inhibited at this concentration. Seventy-seven percent of Burkholderia cepacia and 82.0% of Stenotrophomonas maltophilia were inhibited at < or = 8 mg/L. No differences in LBM415 activity against S. aureus, CoNS, S. pneumoniae, Enterococcus spp. and H. influenzae were detected for subsets susceptible or resistant to antimicrobials such as oxacillin, penicillin, ampicillin, macrolides, vancomycin and fluoroquinolones. While regional differences were apparent with some comparator agents, sensitivity to LBM415 did not vary significantly among strains from the various geographic areas sampled. One isolate of S. aureus displayed high-level resistance to LBM415 owing to multiple sequence changes in resistance phenotype genes (defB and fmt), despite the absence of the compound in clinical practice. This isolate remained susceptible to all other antimicrobials tested except for penicillin. CONCLUSIONS: With few differences detected among strains from various geographic regions, the first PDFI class agent to enter clinical development has consistently demonstrated a broad spectrum of activity against commonly isolated pathogens associated with uncomplicated respiratory and cutaneous infections. These compounds represent a significant therapeutic advance owing to their novel mechanism of action and antibacterial spectrum, including activity against resistant organisms, should pharmacokinetic and pharmacodynamic parameters support their continued development. Given the detection of a pre-existing PDFI-resistant isolate of S. aureus as demonstrated here, surveillance for resistance among the PDFI-targeted pathogens following introduction of this class of agent into clinical usage will be an important component of future studies.

Amidohydrolases↗
PubMed2006

Activity of gatifloxacin tested against isolates from pediatric patients: report from the SENTRY Antimicrobial Surveillance Program (North America, 1998-2003).

The SENTRY Antimicrobial Surveillance Program has monitored the activity of antimicrobial agents worldwide since 1997. The increasing number of clinical failures with established anti-infectives (penicillins, other beta-lactams, macrolides) among pediatric patients has stressed the importance for alternative therapeutic options. Ciprofloxacin has been recently approved for expanded use as treatment of complicated urinary tract infections in children, and gatifloxacin has been used successfully in clinical trials in selected children with severe or refractory otitis media. We evaluated the activity of gatifloxacin against strains isolated from children < 7 years of age and compared this to the general patient population (all ages included) using the SENTRY Program database. A total of 59826 North American isolates were collected, of which 4641 were from children (< 7 years old); all isolates were tested using reference broth microdilution methods. In contrast to the general population (GP), gatifloxacin resistance rates were very low among isolates from this younger patient group. Gatifloxacin susceptibility rates were > 84% for all pathogens evaluated in younger patients. All Streptococcus pneumoniae strains from children < 7 years old were susceptible to gatifloxacin, and susceptibility among the Enterobacteriaceae species was > 98%. The greatest difference in susceptibility rates between the younger children and the GP was observed among nonfermentative gram-negative bacilli (95.0-100% versus 64.8-83.7%, respectively) and Enterococcus faecalis (94.7% versus 58.4%). Gatifloxacin susceptibilities of Pseudomonas aeruginosa and Acinetobacter spp. isolates from the pediatric population were > or = 95% (> 97% for ciprofloxacin) compared to the GP at only 64.8-69.1%. In conclusion, gatifloxacin remains very active against bacterial isolates from children < 7 years, indicative of the limited exposure of this population to fluoroquinolones. Continued resistance surveillance will be necessary to monitor the activity of the fluoroquinolone class as they are introduced for specific clinical indications into the pediatric age groups, especially if re-studied against S. pneumoniae (refractory otitis media) and P. aeruginosa (cystic fibrosis associated pneumonia).

Adolescent↗
PubMed2006

Clonal occurrences of multidrug-resistant Gram-negative bacilli: report from the Meropenem Yearly Susceptibility Test Information Collection Surveillance Program in the United States (2004).

The Meropenem Yearly Susceptibility Test Information Collection Program is a global, longitudinal resistance surveillance network of more than 100 medical centers worldwide monitoring the susceptibility of bacterial pathogens to carbapenems and other broad-spectrum agents. Between 1999 and 2004, a total of 10-16 US medical centers referred up to 200 nonduplicate isolates from clinical infections to a central processing laboratory. Over this 6-year period, the antimicrobial activity of 12 broad-spectrum agents was assessed against 15990 bacterial isolates using Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) reference methods. Analysis of the MIC results by year within organism species and/or organism groups revealed a continued decrease in fluoroquinolone susceptibility (ciprofloxacin and levofloxacin), especially among indole-positive Proteae (-22.1%), Escherichia coli (-17.0%), Enterobacter species (-10.0%), and Proteus mirabilis (-7.6%) isolates. Antibiogram analysis of strains demonstrating multidrug resistance from the same institutions were further characterized by automated ribotyping and pulsed-field gel electrophoresis to determine clonality. In 2004, a total of 165 selected multidrug-resistant (MDR) strains produced 64 different ribotypes with the largest representing 31 Escherichia coli isolates from 6 medical centers. Other clusters were also identified within single medical centers among Enterobacter cloacae (6 strains), Providencia stuartii (5 strains), and Morganella morganii (4 strains). A significant clonal outbreak encompassing 40 Acinetobacter baumannii isolates from 3 centers in a single endemic region was identified in 1999 and has persisted through 2004. Continued surveillance of these broad-spectrum antimicrobial agents against MDR pathogens appears warranted to monitor the incidence and spread of resistant clones causing serious infections. Possible emergence of resistance mechanisms via clonal dissemination proves to be among the principle threats that compromise carbapenem therapy, where meropenem maintains the broadest spectrum of coverage.

Anti-Bacterial Agents↗
PubMed2006

Activity of gemifloxacin tested against Neisseria gonorrhoeae isolates including antimicrobial-resistant phenotypes.

The antigonococcal potency of gemifloxacin and 5 reference comparator antimicrobials was determined for a selected collection of gonococcal isolates. The 250 Neisseria gonorrhoeae strains were inclusive of (1) 50 historic strains from Japan with elevated fluoroquinolone minimal inhibitory concentration values (QRNG) and (2) 200 contemporary strains from clinical specimens in 2004 (176 from 6 sentinel sites in the United States and 24 bacteremic isolates from the SENTRY Antimicrobial Surveillance Program). The rank order of potency of the tested antimicrobials for the entire collection was: ceftriaxone (MIC(90) = 0.06 microg/mL) > gemifloxacin (1 microg/mL) > tetracycline (2 microg/mL) > ciprofloxacin = levofloxacin = penicillin (4 microg/mL). The activity of gemifloxacin was not affected by penicillinase production; however, its activity was decreased for penicillin-resistant strains. Cross-resistance between gemifloxacin and the older fluoroquinolones was present, and the gemifloxacin MIC90 value was higher for the ciprofloxacin-resistant strains compared with the ciprofloxacin-susceptible strains (2 versus 0.016 mug/mL, respectively). More than 20.0% of the recent clinical strains were resistant to penicillin, tetracycline, and ciprofloxacin with >30.0% of gonococci resistant to ciprofloxacin in Washington State and Hawaii. The historic QRNG strains from the Far East were predominantly of intermediate susceptibility (88.0%) to ciprofloxacin, with a gemifloxacin MIC90 value of only 0.25 microg/mL. The bacteremic gonococcal strains were exquisitely susceptible to the 3 quinolones tested (ciprofloxacin, levofloxacin, and gemifloxacin, MIC90 at < or = 0.03 microg/mL) and ceftriaxone (MIC90 = 0.06 microg/mL). In summary, the potency of gemifloxacin was competitive and positioned between that of ceftriaxone and older quinolones or penicillin or tetracycline, irrespective of the gonococcal resistance phenotype. Gemifloxacin should be considered for further development as a therapeutic option to treat uncomplicated infections due to emerging strains resistant to penicillins, tetracycline, and some older fluoroquinolones.

Anti-Bacterial Agents↗
PubMed2006

Spectrum and potency of dalbavancin tested against 3322 Gram-positive cocci isolated in the United States Surveillance Program (2004).

Dalbavancin is an injectable, next generation lipoglycopeptide with an extended serum elimination half-life. Once-weekly dosing has been successful for treatment of skin and skin structure (SSSI) and catheter-related bloodstream infections (CR-BSI). Concurrent with clinical trails, dalbavancin resistance surveillance was initiated in 2003, and results are reported here for the 2004 United States (USA) component. A total of 3322 Gram-positive cocci were tested by reference broth microdilution methods. Organism species tested included: Staphylococcus aureus (2102; 49% oxacillin-resistant), coagulase-negative staphylococci (CoNS; 255, 82% oxacillin-resistant), beta-hemolytic streptococci (241), viridans group streptococci (46), and Streptococcus pneumoniae (678). Dalbavancin (MIC90,0.06-0.12 microg/mL) was comparable in spectrum, but superior in potency to vancomycin (MIC90,1-2 microg/mL) against staphylococci. Dalbavancin MIC90 values against the tested streptococci was 0.03 microg/mL. Dalbavancin was more active against tested SSTI pathogens than comparator agents having complete susceptibility rates (100.0%) similar to vancomycin. Vancomycin, (16- to 32-fold), linezolid (8- to 32-fold), daptomycin (4- to 32-fold), and quinupristin/dalfopristin (4- to 32-fold) were less active than dalbavancin. In conclusion, dalbavancin exhibited greater potency than comparison glycopeptides or lipopeptides, streptogramin combinations, and oxazolidinones against Gram-positive pathogens associated with SSSI or CR-BSI. Dalbavancin wild-type MIC distributions remain unchanged compared with prior sampled years (2002-2003) in the USA.

Anti-Bacterial Agents↗
PubMed2006

Microbiologic characterization of isolates from a dalbavancin clinical trial for catheter-related bloodstream infections.

Dalbavancin, a new-generation semisynthetic lipoglycopeptide in phase 3 clinical development, has been documented to be more active than vancomycin or teicoplanin against Gram-positive bacteria, including multidrug-resistant strains, by in vitro testing and in animal models. The human pharmacokinetics of dalbavancin predicts efficacy at weekly dosing intervals. In a phase 2 open-label clinical trial, dalbavancin exhibited superiority when compared with vancomycin against catheter-related bloodstream infection (CR-BSI). The majority of pathogens identified in this study as in clinical practice were coagulase-negative staphylococci (CoNS), necessitating rigorous characterization of duplicate isolates to rule out contaminants and to validate cases for study evaluations. At follow-up for the intent-to-treat population, overall pathogen eradication was 92.3% for dalbavancin and 75.9% for vancomycin. We describe the details of organisms isolated, their epidemiologic/genetic characterization, susceptibility patterns against glycopeptides, and the eradication rates by organism group. In conclusion, dalbavancin was active against all isolated pathogens associated with CR-BSI (CoNS, Staphylococcus aureus and Enterococcus faecalis; all MIC results, < or = 0.25 microg/mL) and achieved significant (P < 0.05) clinical success when compared with vancomycin.

Anti-Bacterial Agents↗
PubMed2006

Prevalence and antimicrobial susceptibility patterns among gastroenteritis-causing pathogens recovered in Europe and Latin America and Salmonella isolates recovered from bloodstream infections in North America and Latin America: report from the SENTRY Antimicrobial Surveillance Program (2003).

Gastroenteritis-causing pathogens are the second leading cause of morbidity and mortality worldwide. Complicating the clinical diarrhoea syndrome is the emergence of antimicrobial resistance among the responsible bacterial pathogens. The reported increases in fluoroquinolone resistance in Salmonella, Shigella and Campylobacter have been extremely worrisome considering the primary role of ciprofloxacin as a treatment. In this study, 1479 bacterial isolates from gastroenteritis infections were collected in Europe and Latin America, which included Salmonella spp. (834; 56%), Shigella spp. (311; 21%), Campylobacter spp. (182; 12%) and Aeromonas spp. (72; 5%). The fluoroquinolones displayed the greatest activity against these pathogens, with only three non-Campylobacter spp. strains being non-susceptible using current Clinical and Laboratory Standards Institute (CLSI) breakpoint criteria. Whilst ciprofloxacin resistance in European and Latin American Salmonella was only 0.2% and 0.0%, respectively, a total of 16.2% and 12.9% of isolates were resistant to nalidixic acid, indicating possible first-step gyrA mutations. Among confirmed extended-spectrum beta-lactamase-producing Salmonella strains, CTX-M genes were detected in 15 originating from Russia. Erythromycin and azithromycin were the most potent agents tested against Campylobacter spp. (values of minimum inhibitory concentration for 90% of the organisms, 0.5 mg/L and 0.12 mg/L, respectively), with erythromycin displaying the highest susceptibility (91.1%). Salmonella isolates from bloodstream infections displayed antibiograms that were nearly identical to strains causing gastroenteritis. Considering the role that antimicrobial therapy plays in the management of moderate to severe bacterial gastroenteritis, global surveillance and local/national public health programmes can provide critical data illuminating the dissemination of resistance and guidance for empirical therapy.

Aeromonas↗