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Helio S Sader

Publications and source records attributed to Helio S Sader.

At least 19 recordsLinked to original sources
PubMed2026

Aztreonam-avibactam Activity against Enterobacterales from Asia Pacific and Latin American Medical Centres: Summary of 5 years of Surveillance prior to Clinical Use (2020-2024).

OBJECTIVES: To assess the in vitro activity of aztreonam-avibactam against Enterobacterales from the Asia Pacific region (APAC) and Latin America (LATAM) during a 5-year period prior to its approval for clinical use in these regions. METHODS: 12,039 Enterobacterales isolates were consecutively collected in 2020-2024 from 17 medical centres in APAC (n=7,369) and 10 in LATAM (n=4,670) then susceptibility tested by broth microdilution. Carbapenem-resistant Enterobacterales (CRE) and isolates with elevated aztreonam-avibactam MICs (>4 mg/L) were submitted to whole genome sequencing. RESULTS: Aztreonam-avibactam was active against 99.9% of Enterobacterales from APAC and LATAM and exhibited potent activity against CRE isolates (MIC50/90, 0.25/2 mg/L; 97.3% susceptible in APAC and MIC50/90, 0.25/0.5 mg/L; 99.4% susceptible in LATAM). Cefiderocol was active against 91.2% of CREs from APAC and LATAM. Ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam showed limited activity against CRE isolates from LATAM (53.5% to 64.8% susceptibility) and APAC (27.3% to 38.8% susceptible). The occurrence of carbapenemases varied clearly among the countries evaluated. In general, metallo-β-lactamases (MBLs) prevailed in APAC and KPCs predominated in LATAM, but with great variability among countries within a region. Decreased susceptibility to aztreonam-avibactam was largely due to PBP3 alterations plus the production of CMY and/or CTX-M β-lactamases among Escherichia coli, and decreased membrane permeability associated with KPC production among Klebsiella pneumoniae. CONCLUSIONS: The results of this investigation provide a baseline for monitoring the activity of aztreonam-avibactam in APAC and LATAM and emphasize the importance of surveillance programs to monitor the emergence of resistance markers.

Aztreonam-avibactam↗
PubMed2026

Activity of Aztreonam-avibactam and Ceftazidime-Avibactam against Enterobacterales and Pseudomonas aeruginosa causing infections in patients hospitalized in hematology, oncology, and transplant units from United States medical centres (2019-2024).

Immunosuppression increases the risks and severity of infections and is associated with a higher incidence of infection with multidrug-resistant (MDR) pathogens. We evaluated the antimicrobial susceptibility of Enterobacterales and Pseudomonas aeruginosa from patients hospitalized in hospital units where the frequency of immunosuppressed patients is very high. Bacterial isolates were consecutively collected (1/patient) from 75 US medical centres in 2019-2024 and susceptibility tested by broth microdilution. Enterobacterales (n = 2,407) and P. aeruginosa (n = 485) from patients hospitalized in hematology, oncology, and transplant units were evaluated. Carbapenem-resistant Enterobacterales (CRE) were screened for β-lactamases by whole genome sequencing. Enterobacterales were mainly from bloodstream infection (BSI; 53.6%) and urinary tract infection (19.9%) and P. aeruginosa were mainly from BSI (37.9%) and pneumonia (35.0%). Aztreonam-avibactam, ceftazidime-avibactam, and meropenem-vaborbactam were highly active against Enterobacterales (99.9-99.4% susceptible), including MDR isolates (99.6-98.1% susceptible), but only aztreonam-avibactam exhibited good activity against CRE (95.8% susceptible). Ceftolozane-tazobactam showed good activity against Escherichia coli (95.7% S) and Klebsiella pneumoniae (92.8% S), but limited activity against Enterobacter cloacae species complex (75.9% susceptible). All (100.0%) carbapenemase (CBase)-producing CRE isolates were aztreonam-avibactam-susceptible while 77.4% were ceftazidime-avibactam-susceptible and 67.7% were meropenem-vaborbactam-susceptible. The most common CBases were KPC (41.7%), NDM (12.5%), and OXA-48 types (10.4%). Metallo-β-lactamases represented 23.5% of CBases and were identified in 16.7% of CREs. The most active agents against P. aeruginosa were ceftazidime-avibactam (95.7% susceptible), ceftolozane-tazobactam (94.8% susceptible), and tobramycin (91.5% susceptible). Piperacillin-tazobactam and meropenem were active against 81.4% and 82.5% of P. aeruginosa, respectively, and aztreonam-avibactam inhibited 78.6% of P. aeruginosa at ≤8 mg/L.

Humans↗
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

Bactericidal activity of cefepime and ceftriaxone tested against Streptococcus pneumoniae.

The bactericidal activities of cefepime and ceftriaxone were assessed by testing a contemporary collection of 50 Streptococcus pneumoniae strains. Minimum inhibitory and bactericidal concentrations (MIC and MBC, respectively) of cefepime and ceftriaxone were determined, and time-kill studies were performed on 14 selected strains (10 penicillin-resistant, 2-intermediate, and 2-susceptible). Cefepime and ceftriaxone showed essentially identical potency (MIC50, 1 microg/mL and MIC90, 2 microg/mL, for both compounds) and MBC values (MBC50, 1 microg/mL for both). MBC/MIC ratios were < or = 4 for cefepime and < or = 8 for ceftriaxone on 48 (96.0%) strains, and 2 strains (4.0%) displayed MBC/MIC ratios > or = 32 (tolerance) to the 2 cephalosporins. Time-kill curves corroborated the MBC/MIC studies. Cefepime and ceftriaxone bactericidal activity (> or = 3 log10 CFU/mL reduction in inoculum) was demonstrable after 24 h of exposure to 8x MIC for 13 (92.9%) of 14 strains, whereas 1 strain showed approximately 2 log10 CFU/mL reduction. In conclusion, our results indicate that cefepime and ceftriaxone exhibit comparable potency and bactericidal activities when tested against contemporary pneumococcal strains with varying penicillin susceptibility patterns. Both parenteral cephems offer alternative therapeutic choices for the treatment of invasive pneumococcal infections.

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

Multicenter studies of tigecycline disk diffusion susceptibility results for Acinetobacter spp.

Acinetobacter sp. isolates having multidrug resistance (MDR) patterns have become common in many medical centers worldwide, limiting therapeutic options. A five-center study tested 103 contemporary clinical Acinetobacter spp., including MDR strains, by reference broth microdilution and disk diffusion (15-mug disk content) methods against tigecycline. Applying U.S. Food and Drug Administration tigecycline breakpoint criteria for Enterobacteriaceae (susceptibility at < or =2 microg/ml [< or =1 microg/ml by the European Committee on Antimicrobial Susceptibility Testing]; disk diffusion breakpoints at > or =19 mm and < or =14 mm) to Acinetobacter spp. led to an unacceptable error rate (23.3%). However, an adjustment of tigecycline disk diffusion breakpoints (susceptible/resistant) to > or =16/ < or =12 mm reduced intermethod errors to an acceptable level (only 9.7%, all minor).

Acinetobacter↗
PubMed2006

Emergence of serine carbapenemases (KPC and SME) among clinical strains of Enterobacteriaceae isolated in the United States Medical Centers: report from the MYSTIC Program (1999-2005).

Among 8885 Enterobacteriaceae tested in the 1999 to 2005 period as part of the USA Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program, 51 strains with increased imipenem and meropenem MIC values (> or =2 microg/mL) were detected. bla(KPC) was identified from 28 Klebsiella pneumoniae from 3 medical centers in the New York City area (8 ribotypes), 2 Klebsiella oxytoca from Arkansas (same ribotype), 7 Citrobacter freundii (6 from New York [5 ribotypes] and 1 from Delaware), 4 Enterobacter spp. from New York (2 species, different ribotypes), 3 Escherichia coli (2 from New York and 1 from Ohio, same ribotype), and 1 Serratia marcescens (New York). Sequencing confirmed KPC-2 or -3 in all of the strains. S. marcescens strains harboring SME-1 (2 isolates, same ribotype) and SME-2 (1 isolate) were identified from medical centers in Illinois and Washington state, respectively. Our results indicate that bla(KPC-2/3) has emerged widely (New York City area, Arkansas, Delaware, and Ohio) among Enterobacteriaceae isolated in the MYSTIC Program participant sites (2000-2005) and continues to be isolated from multiple species, as a result of clonal expansion and horizontal gene transfer. The escalating occurrence (0.35%) of serine carbapenemases could compromise the role of carbapenems and other beta-lactams in USA clinical practice although observed in only a few locations to date.

Academic Medical Centers↗
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

Update on the cefdinir spectrum and potency against pathogens isolated from uncomplicated skin and soft tissue infections in North America: are we evaluating the orally administered cephalosporins correctly?

The spectrum and potency of cefdinir, an orally administered cephalosporin, was reevaluated for the uncomplicated skin and soft tissue infection (uSSTI) indication using contemporary isolates from 2004 to 2005. Cefdinir continues to have high rates of susceptibility against methicillin-susceptible staphylococci (100.0%), beta-hemolytic streptococci (groups A and B; 100.0%), viridans group streptococci (88.9%), Escherichia coli (93.2%), and Klebsiella pneumoniae (90.0%). No diminished activity was detected since the last evaluation (1997-2002 isolates), and cefdinir remains significantly more potent (4- to 16-fold) than cephalexin, even when using surrogate agents of cephalexin susceptibility that were suspect for estimating true clinical utility. Activity greater than cephalexin (4-fold) was also noted for cefdinir against community-associated methicillin-resistant Staphylococcus aureus isolates. Cefdinir should be considered as a viable option for the therapy uSSTI caused by indicated species.

Administration, Oral↗
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

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

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↗