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Ronald N Jones

Publications and source records attributed to Ronald N Jones.

At least 37 records · Page 2Linked to original sources
PubMed2006

Delayed resistance selection for doripenem when passaging Pseudomonas aeruginosa isolates with doripenem plus an aminoglycoside.

Doripenem (formerly S-4661), a parenteral carbapenem, was tested in combination with an aminoglycoside (gentamicin) to determine the resistance selection of these codrugs during subinhibitory passaging using 6 Pseudomonas aeruginosa isolates. The organisms were selected based on doripenem and gentamicin MIC values to include isolates with MIC values near the susceptible breakpoints of both compounds and 1 strain highly resistant to gentamicin. Baseline MIC values were established for doripenem (2-8 microg/mL) and gentamicin (4 to >256 microg/mL) using reference broth microdilution methods, and passaging was carried out over 7 consecutive days. Doripenem MIC values increased 2 to >/=8-fold in 4 isolates, whereas 2 strains maintained the baseline doripenem MIC. When the experiment was performed with doripenem plus gentamicin, 3 strains maintained the original doripenem MIC values, 2 strains had a 2-fold increase, and only 1 strain showed a 4-fold increase in the doripenem MIC values. Previous studies have demonstrated doripenem to be more potent than other members in its class when tested against P. aeruginosa. The combination of doripenem and an aminoglycoside may be an effective treatment of infections caused by P. aeruginosa with elevated carbapenem MIC values with lower risk of selecting further resistance.

Aminoglycosides↗
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

Characterization of fluoroquinolone-resistant beta-hemolytic Streptococcus spp. isolated in North America and Europe including the first report of fluoroquinolone-resistant Streptococcus dysgalactiae subspecies equisimilis: report from the SENTRY Antimicrobial Surveillance Program (1997-2004).

Beta-hemolytic streptococci are common bacterial pathogens that can cause serious invasive disease, and although this group of species has remained susceptible to the fluoroquinolone class, resistant strains have been reported. This multicenter investigation determined the rate of fluoroquinolone-resistant beta-hemolytic streptococci using the SENTRY Antimicrobial Surveillance Program network data (1997-2004). Forty-seven surveillance culture isolates of beta-hemolytic streptococci from North America and Europe with elevated levofloxacin MIC results (2 to >32) microg/mL were tested for susceptibility to other fluoroquinolones including ciprofloxacin, garenoxacin, gatifloxacin, gemifloxacin, and moxifloxacin using reference broth microdilution and Etest (BIODISK, Solna, Sweden) methods. Strains were characterized using polymerase chain reaction and sequencing to detect mutations in the quinolone-resistance determining region (QRDR). The beta-hemolytic streptococci isolates with reduced fluoroquinolone susceptibility included the following Lancefield groups: A (Streptococcus pyogenes; 9 strains), B (Streptococcus agalactiae; 24 strains), C and G (14 strains). Vitek and API 20 strep (bioMerieux, Hazelwood, MO) identification systems, as well as conventional biochemical methods and colony morphology, were used to confirm the organism identifications. The overall potency (MIC90 in microg/mL) for the fluoroquinolones against all tested beta-hemolytic streptococci showed the following rank order: gemifloxacin (0.06) > garenoxacin (0.12) > moxifloxacin (0.25) > gatifloxacin (0.5) > levofloxacin = ciprofloxacin (1). The rate of levofloxacin-resistant beta-hemolytic streptococci in the SENTRY program was 0.14% (Europe) and 0.51% (North America) during the study period. All levofloxacin-resistant strains tested by molecular methods had significant mutations in either parC (position 79 or 83) and/or gyrA (position 81 or 85). All but 2 isolates with high-level resistance to levofloxacin (>32 microg/mL) had gyrA mutations. Strains with lower MIC values to levofloxacin (2-4 microg/mL) only had mutations in parC. The increasing rate of fluoroquinolone-resistant streptococci including Streptococcus pneumoniae, viridans group streptococci, and the more recently reported beta-hemolytic streptococci, is becoming a clinical concern due to the morbidity and mortality caused by these pathogens.

Adolescent↗
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

Emergence and epidemiology of fluoroquinolone-resistant Streptococcus pneumoniae strains from Italy: report from the SENTRY Antimicrobial Surveillance Program (2001-2004).

Fluoroquinolones are key antimicrobials in the treatment of more serious pneumococcal infections, especially for treating infections caused by penicillin-resistant strains. Increased use of newer fluoroquinolones should be accompanied by greater surveillance efforts to monitor resistance development as well as clonal dissemination. Streptococcus pneumoniae (n=551) collected from 3 medical centers in Italy (Catania, Genoa, and Rome) over a period of 4 years (2001-2004) as part of the SENTRY Antimicrobial Surveillance Program were susceptibility tested against >30 antimicrobials using reference broth microdilution methods. Mutations in the quinolone resistance-determining region (QRDR) were characterized by PCR and sequencing of parC, parE, and gyrA. Epidemiological relationships among levofloxacin-resistant isolates were determined using ribotyping, PFGE, serotyping combined with antimicrobial resistance profiles augmented by QRDR mutation patterns. Eighty-three (15.1%) isolates showed reduced susceptibility to ciprofloxacin (MIC>or=4 microg/mL) and 31 (5.6%) were resistant to levofloxacin. In 2001, all pneumococcal isolates were susceptible to levofloxacin and resistance rapidly emerged in all 3 medical centers in 2002. The overall rates of levofloxacin resistance in 2002-2004 were the following: Catania 10.9%, Genoa 3.3%, and Rome 6.5%. All resistant strains showed at least one mutation in parC and gyrA. Each isolate from Genoa with a unique resistance phenotype also showed distinct ribotype/PFGE, serotype, and QRDR mutation patterns. All isolates from Catania (n=19) showed an identical ribotype/PFGE pattern (333.3/A1); however, 3 distinct clusters could be identified based on further resistance phenotype, serotypes, and QRDR mutation pattern analysis. Two clusters were documented among isolates from Rome based on ribotype/PFGE. One isolate from Genoa shared ribotype/PFGE (333.3/A1) and serotype (9 not V) results with clusters from the other 2 institutions monitored, indicating clonal dissemination between the geographically diverse cities. In conclusion, fluoroquinolone resistance rates have increased among S. pneumoniae recovered in Italian medical centers evaluated by the SENTRY Program. Although resistance has emerged in many epidemiologically distinct strains, clonal dissemination seems to be a key contributing factor for increasing resistance to fluoroquinolones among pneumococci in this nation.

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

Outcomes evaluation of patients with ESBL- and non-ESBL-producing Escherichia coli and Klebsiella species as defined by CLSI reference methods: report from the SENTRY Antimicrobial Surveillance Program.

As extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae continue to emerge worldwide, selection of empiric treatment modalities is an increasing challenge. Data describing the clinical outcomes associated with different treatment regimens have been limited. Using data from centers with confirmed ESBL- and non-ESBL-producing Escherichia coli and Klebsiella species isolates in North America, Latin America, and Europe, potential risk factors for the occurrence of invasive ESBL- and non-ESBL-producing Enterobacteriaceae infections and factors associated with clinical outcome were evaluated. Of the 175 cases considered evaluable, 77% were ESBL-producing organisms. Underlying comorbidities and potential risk factors were generally similar between ESBL and non-ESBL cases with a statistically greater proportion of ESBL cases requiring gastrostomy or jejunostomy tubes, ventilatory assistance, or care in the intensive care unit before culture (P<or=0.008). Among ESBL cases, carbapenem monotherapy and combination therapy were often selected for treatment (32.6% and 13.3%, respectively). Among non-ESBL cases, fluoroquinolones and beta-lactam/beta-lactamase inhibitor combination agents accounted for the highest proportion of treatment regimens (25.0% and 22.5%, respectively), whereas cephalosporin monotherapy and combination therapy were each used as treatment for 10% of cases. Clinical success was similar between patients with ESBL and non-ESBL-producing isolates (83% and 80%, respectively). Although infections arising from E. coli and Klebsiella species are associated with significant mortality, ESBL production alone did not appear to be an independent risk factor for treatment failure.

Adolescent↗
PubMed2006

In vitro activity of tigecycline, a new glycylcycline, tested against 1,326 clinical bacterial strains isolated from Latin America.

UNLABELLED: The in vitro activity of tigecycline (former GAR-936), a new semisynthetic tetracycline, was evaluated in comparison with tetracycline and other antimicrobial agents. MATERIAL AND METHODS: A total of 1,326 contemporary clinical isolates collected from the Latin American region were collected in 2000-2002 period and tested with microdilution broth according to the CLSI guidelines. The bacterial pathogens evaluated included Staphylococcus aureus (505), Streptococcus pneumoniae (269), coagulase-negative staphylococci (CoNS; 227), Haemophilus influenzae (129), Enterococcus spp. (80), Moraxella catarrhalis (54), beta-haemolytic streptococci (28), viridans group streptococci (26), and Neisseria meningitidis (8) RESULTS: Tigecycline demonstrated excellent activity against all Gram-positive cocci, with 90% of penicillin-resistant S. pneumoniae strains being inhibited at 0.12 microg/mL, while the same isolates had an MIC90 of > 16 microg/mL for tetracycline. All Enterococcus spp. were inhibited at 0.25 microg/mL of tigecycline. Tigecycline (MIC50, 0.25 microg/mL) was eight-fold more potent than minocycline (MIC50, 2 microg/mL) against oxacillin-resistant S. aureus (ORSA); all ORSA were inhibited at < 2 microg/mL of tigecycline. Tigecycline demonstrated excellent activity (MIC50, 0.5 microg/mL) against CoNS with reduced susceptibility to teicoplanin (MIC, 16 microg/mL). Tigecycline also showed high potency against respiratory pathogens such as M. catarrhalis (MIC50, 0.12 microg/mL) and H. influenzae (MIC50, 0.5 microg/mL). No tigecycline resistant isolates were detected when the proposed susceptible breakpoints (< 4 microg/mL) was applied. CONCLUSIONS: This results indicate that tigecycline has potent in vitro activity against clinically important pathogenic bacteria, including Gram-positive isolates resistant to both tetracycline and minocycline.

Anti-Bacterial Agents↗
PubMed2006

Microbiological features of vancomycin in the 21st century: minimum inhibitory concentration creep, bactericidal/static activity, and applied breakpoints to predict clinical outcomes or detect resistant strains.

The results of vancomycin susceptibility tests document that the drug continues to have activity against a wide variety of gram-positive pathogens. The subsequent emergence of vancomycin-resistant enterococci, the persistent failure of vancomycin therapy against strains tested as susceptible, and the more recent discoveries of vancomycin-intermediate or -resistant Staphylococcus aureus strains have compromised the use of vancomycin. Although analyses of surveillance studies fail to demonstrate "minimum inhibitory concentration creep" among populations of wild-type enterococci, streptococci, or staphylococci, enterococci with acquired resistance to vancomycin continue to evolve. The dominantly used automated commercial tests poorly recognize vancomycin-intermediate S. aureus, heteroresistant vancomycin-intermediate S. aureus, and vancomycin-resistant S. aureus isolates, which necessitates the use of expensive supplemental screening tests. Monitoring for appropriate serum levels of vancomycin and determinations of the bactericidal activity of vancomycin appear to best predict clinical outcome, thus creating additional diagnostic burdens for clinical laboratories. Improvements in current test methods with breakpoint criteria and expanded use of the vancomycin bactericidal assays to detect "tolerant" strains will be required to increase the value of vancomycin treatment or to refocus therapy toward the use of newer, alternative agents.

Anti-Bacterial Agents↗
PubMed2006

Contemporary antimicrobial activity of triple antibiotic ointment: a multiphased study of recent clinical isolates in the United States and Australia.

Triple antibiotic ointment (TAO) containing neomycin, polymyxin B, and bacitracin was launched in the 1950s in the United States (USA) as a prescription product and then was used over the counter (OTC) since the 1970s (USA) to prevent superficial wound infections. In Australia, TAO has been restricted to prescription use. This study 1) determined cross-resistance patterns of neomycin compared with other aminoglycosides; 2) determined the level and trend of resistance to TAO and individual components especially versus mupirocin-resistant strains (USA); and 3) established the baseline TAO activity level against pathogens from Australia. A total of 200 strains (> or =50% gentamicin-resistant) from the United States were used for the cross-resistance study including Staphylococcus aureus (110), coagulase-negative staphylococci (CoNS; 50), Pseudomonas aeruginosa (10), Escherichia coli (20), and other Enterobacteriaceae (10) tested against TAO, bacitracin, polymyxin B, neomycin, amikacin, gentamicin, streptomycin, tobramycin, and mupirocin. Fifty gentamicin-resistant isolates from each year (1997-2002) were used to determine the activity of TAO over time. Baseline resistance rates of TAO among 300 Australian isolates (AGARS Program, 2002-2003) were also studied. Reference broth microdilution methods were used in all phases of this study. At a 1:100 dilution of the ointment concentration, TAO inhibited all CoNS, Pseudomonas aeruginosa, and Enterobacteriaceae isolates, and resistance to TAO among Staphylococcus aureus at this concentration was only 5% in the cross-resistance study. Patterns of susceptibility in the United States did not significantly vary from 1997 to 2002. Australian pathogens showed that TAO was 98% active against methicillin-resistant Staphylococcus aureus and 100% for Enterobacteriaceae, methicillin-susceptible S. aureus, CoNS, and P. aeruginosa, the rates equivalent to those observed in the United States. Mupirocin-resistant S. aureus (5%) and CoNS (47%) were all TAO-susceptible. All Gram-negative species were also mupirocin-resistant, but inhibited by neomycin and/or polymyxin B components of TAO. In conclusion, aminoglycoside resistance patterns differ significantly, and none of the commonly tested agents could accurately predict neomycin resistance. TAO resistance was rare in the United States after extensive OTC use and was not adversely influenced by decades of parenteral aminoglycoside use. Australian surveillance showed high levels of TAO susceptibility in sampled isolates as a baseline for possible OTC availability. TAO maintains a wider spectrum of activity compared with mupirocin and was usable against mupirocin-resistant Gram-positive strains.

Administration, Topical↗
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↗