Alan H. Mutnick

Occurrence and antimicrobial susceptibility patterns of pathogens isolated from skin and soft tissue infections: report from the SENTRY Antimicrobial Surveillance Program (United States and Canada, 2000)

A total of 1,404 bacterial isolates were recovered from skin and soft tissue infections (SSTIs) from hospitalized patients in 24 sites in the United States (US) and 5 Canadian medical centers as part of the SENTRY Antimicrobial Surveillance Program. Isolates were collected between October and December, 2000. The rank order of pathogens was: Staphylococcus aureus (45.9%), Pseudomonas aeruginosa (10.8%), Enterococcus spp. (8.2%), Escherichia coli (7.0%), Enterobacter spp. (5.8%) and Klebsiella spp. (5.1%). The same order was observed in the US and Canada. Of note, almost 30% of S. aureus were oxacillin-resistant. Vancomycin resistance among enterococci was low (7.8%) representing a marked decrease from earlier SENTRY Program reports. Several antimicrobial agents remained very active against P. aeruginosa and Enterobacteriaceae isolates. In particular amikacin, cefepime, and the carbapenems (imipenem and meropenem) showed an excellent spectrum of activity (>95% susceptible). Extended-spectrum beta-lactamase production was observed in both E. coli (7.1%) and Klebsiella spp. (11.3%). Cefepime remained highly active, even against ceftazidime-resistant isolates of Enterobacter spp. The results of this study have identified the most common causes of SSTIs in hospitalized patients in North America, and can be used to make informed decisions concerning standards of empiric treatment for SSTIs in this region.

Linezolid Resistance since 2001: SENTRY Antimicrobial Surveillance Program

BACKGROUND: The oxazolidinone class of antimicrobials has demonstrated remarkable activity against gram-positive cocci. Linezolid has proven to be a first-line therapeutic option for vancomycin-resistant strains. Linezolid clinical trial results and subsequent published case reports cite rare resistance emerging in patients receiving prolonged therapy. OBJECTIVE: To report the initial linezolid-resistant organisms from cases obtained through the SENTRY Antimicrobial Surveillance Program, after screening >40 000 gram-positive cocci without resistance between 1998 and 2000. METHODS: During 2001–2002, 8 resistant strains (from 8 different patients) located in 6 states from 7 different participating SENTRY institutions in the US were identified among bloodstream, respiratory, skin and soft tissue, and urinary tract infection isolates of Enterococcus faecalis, Enterococcus faecium, Staphylococcus epidermidis, and Streptococcus oralis. Resistance was detected by reference broth microdilution methods and confirmed by identical results using Etest (AB BIODISK, Solna, Sweden) and the standardized disk diffusion method. RESULTS: Minimum inhibitory concentration (MIC) and disk diffusion tests showed elevated MICs (≥8 μg/mL) and small inhibitory zone diameters (≤15 mm) for all strains to both linezolid and the investigational oxazolidinone AZD2563. Vancomycin resistance was detected in 2 of the 8 linezolid-resistant strains. All enterococci and the viridans-group streptococcus (S. oralis) strain showed resistance to erythromycin. E. faecium strains were resistant to penicillins, but susceptible to quinupristin/dalfopristin. Only 3 of the patients had previously received the drug. CONCLUSIONS: Linezolid resistance remains rare, with only 8 isolates among 9833 (0.08%) monitored isolates identified between January 1, 2001, and June 30, 2002. Resistance, however, was no longer limited to enterococci. Clinical laboratories should test linezolid more widely to detect emerging resistance, especially for patients receiving oxazolidinone therapy. Longitudinal surveillance programs are warranted to detect a trend in the development of resistance, determine the molecular mechanism of resistance, and recommend alternative therapies or epidemiologic interventions.

Pathogen of occurrence and susceptibility patterns associated with pneumonia in hospitalized patients in North America: results of the SENTRY Antimicrobial Surveillance Study (2000).

Antimicrobial selection for patients diagnosed with pneumonia is a major therapeutic challenge and dilemma to the clinical practitioner. In the community setting, patients usually receive empiric oral therapy based upon multiple patient risk factors and locally prevalent pathogen susceptibilities. For patients admitted to the hospital with pneumonia, or who acquire pneumonia while in the hospital, therapy can be initially empiric and then become directed once culture and susceptibility results are known. The SENTRY Antimicrobial Surveillance Program since 1997, has monitored pathogen frequency and antimicrobial susceptibilities in hospitalized patients with pneumonia in North America. In this Study 2,712 pathogens were studied from 30 medical centers (25 in the United States and 5 in Canada). Over 30 species of organisms were recovered with Staphylococcus aureus comprising 28.0% of all isolates and with four other species (Pseudomonas aeruginosa 20.0%, Streptococcus pneumoniae 9.1%, Klebsiella spp. 7.5% and Haemophilus influenzae 7.3%) constituted 71.9% of isolates submitted. Methicillin (oxacillin)-resistant S. aureus accounted for 43.7% of all S. aureus isolates. Antimicrobials demonstrating significant (>80%) activity against S. aureus were: chloramphenicol (81.6%), tetracycline (91.4%), rifampin (96.4%) and quinupristin/dalfopristin (99.7%); and no isolate was resistant to glycopeptides or linezolid. North American isolates of P. aeruginosa were most susceptible to amikacin (93.7%) > tobramycin (90.2%) > meropenem (89.1%) > imipenem = piperacillin/tazobactam (85.6%) > piperacillin (82.1%) > cefepime (80.5%). Overall, 32.1% of S. pneumoniae were penicillin non-susceptible while erythromycin susceptibility was only 74.8%. Fluoroquinolones and recent generation cephalosporins retained excellent activity (gatifloxacin [99.2%] > levofloxacin = cefepime [98.8%] > ceftriaxone [97.2%]) against S. pneumoniae. Klebsiella spp. were 100.0% susceptible to the carbapenems (meropenem and imipenem) but extended spectrum beta-lactamases were detected at a rate of 5.4%. The beta-lactamase-positive rate in H. influenzae was 28.6% in North America (71.4% ampicillin-susceptible). The SENTRY Antimicrobial Surveillance Program continues to identify important North American patterns of pathogen frequency and resistance. Additionally, the provision of multi-year longitudinal data and associated reports allow for comparisons, which function as critical tools for effective patient management and antimicrobial interventions.

Antimicrobial susceptibility patterns of β-hemolytic and viridans group streptococci: report from the SENTRY Antimicrobial Surveillance Program (1997–2000)

Susceptibility patterns of 15 antimicrobial agents were assessed for 3,400 isolates of beta-hemolytic (betahS) and viridans group (VgS) streptococci in the four regions of the SENTRY Antimicrobial Surveillance Program: Asia-Pacific (APAC), Europe (EU), Latin America (LA) and North America (NA). In 1997 through 2000, SENTRY Program monitors tested strains by reference broth microdilution methods and results were interpreted using National Committee for Clinical Laboratory Standards criteria. Among the betahS processed, 81.9% of strains were either Streptococcus pyogenes (n = 650) or S. agalactiae (n = 1,190). The VgS were generally classified as unspeciated alpha-hemolytic streptococci (n = 512; 44%) or S. mitis (n = 254; 22%). Seven quinolones, two beta-lactams, erythromycin (ER), clindamycin (CM), quinupristin/dalfopristin (Q/D), vancomycin (VA), teicoplanin (TP) and linezolid (LZ) were tested. Rank order of susceptibility for betahS isolates was: ceftriaxone (CTX) = Q/D = VA = TP = LZ (100.0%) > gatifloxacin (GATI) = trovafloxacin (TROV, 99.8%) > levofloxacin (LEVO; 99.7%) > penicillin (PEN; 99.3%) > grepafloxacin (GREPA; 97.4%) > CM (94.4%) > ER (85.5%). ER versus betahS had the highest MIC(90) values (2 microg/ml) and the lowest susceptibility rates across all regions (range, 81.4% in NA to 97.3% in LA). Among the VgS, susceptibility rank order was: VA = TP = LZ (100.0%) > Q/D (99.1%) > GATI = LEVO = TROVA (98.0%) > GREPA (96.5%) > CTX (92.8%) > CM (90.3%) > PEN (68.6%) > ER (64.5%). Macrolide resistance in both streptococcal species groups of the M-phenotype was highest in the Americas, with erm-patterns predominating in EU and APAC regions. BMS284756 among the monitored new agents showed a four- to eight-fold greater potency versus these streptococcal isolates when compared to the other six tested quinolones. Like Streptococcus pneumoniae, these other streptococci appear to have acquired numerous resistances and require continued surveillance to direct adequate therapies.

Spectrum and potency evaluation of a new oxazolidinone, linezolid: report from the SENTRY Antimicrobial Surveillance Program, 1998-2000.

Resistance (R) among Gram-positive cocci has escalated in the last two decades to levels necessitating the development and use in the newer drug classes, oxazolidinones (linezolid) and streptogramins (quinupristin/dalfopristin [Q/D]). The SENTRY Antimicrobial Surveillance Program has monitored these classes before, during and after their release by various regulatory agencies. Over 30,000 Gram-positive strains were tested against >30 drugs by reference broth microdilution methods between 1998-2000 in four geographic regions (Asia-Western Pacific [APAC], Europe [EU], Latin America [LA], North America [NA]). The tested strains were 23,188 staphylococci; 5,103 enterococci and 2,045 streptococci. Among staphylococci, linezolid was active against all isolates (MICs, < or =4 microg/ml) regardless of susceptibility patterns of other antimicrobial agents. Similar results were noted for vancomycin (includes one VISA from Hong Kong), teicoplanin, and Q/D (<1% R). Gatifloxacin had the widest spectrum among fluoroquinolones (FQ) against Staphylococcus aureus (1.5-9.2% R) and coagulase-negative staphylococci (0.8-4.0%). Linezolid was also active against all enterococci (MIC50 and (90,) 2 microg/ml). Q/D was active against only 75.3% of vancomycin-resistant enterococci (VRE). The VRE rate was highest in NA (12.4%) > EU (3.2%) > LA (1.6%) > APAC (1.3%). Among streptococci, linezolid was consistently active (MIC(90,) 1 microg/ml) as were the glycopeptides and Q/D. Variable penicillin-R (MIC, > or = 2 microg/ml) was observed among regions: EU (32.5%) > APAC (15.1%) > LA (13.8%) > NA (9.6%), and macrolide-R was higher in EU (40.3%). Ciprofloxacin-R at > or =4 microg/ml in streptococcal strains was noted world wide highest in viridans group streptococci (18.4-25.6%). Linezolid remained active (MIC, < or =4 microg/ml) against all Gram-positive species strains tested in the SENTRY Program (1998-2000). Q/D, glycopeptides and newer FQ compounds were generally less effective in vitro. It remains a prudent practice to continue surveillance programs to detect emerging resistance patterns and recognize significant regional variations in the oxazolidinone susceptibilities.

Geographic variations and trends in antimicrobial resistance among Enterococcus faecalis and Enterococcus faecium in the SENTRY Antimicrobial Surveillance Program (1997-2000).

In the 1990s, the Enterococcus emerged as an important pathogen because of increasing prevalence and acquired resistances to glycopeptides and other agents. The seriousness of this problem can vary markedly worldwide and within nations; the SENTRY Antimicrobial Surveillance Program documents these differences. Over 8,000 enterococci were processed in the program (1997-2000) and the Enterococcus faecalis (EF; 4,034 strains) and Enterococcus faecium (EFM; 1,123 strains) isolates are tabulated. All strains were processed by three regional monitors using reference dilution methods. Identification to species was performed by participants and confirmed by the central laboratories. EF occurrence was greater than EFM by ratios of 3:1 to 5:1 in the Asia-Pacific (APAC), European (EU), and North American (NA) regions; the ratio was 17:1 in Latin America (LA). EF and EFM represented approximately 80-90% of all isolated enterococci. Glycopeptide-resistant enterococci (GRE) rates varied from nil for EF in APAC and LA to 43 to 54% in EFM in NA. A slight increase in GRE was noted in NA (EFM only). Van A phenotypes predominated all regions. The most recent (2000) rank order of % GRE by region was: for NA (13%) > LA (4%) > EU (3%) > APAC (1%). In NA potential therapeutic agents were (% S): ampicillin (81%), chloramphenicol (87%), quinupristin/dalfopristin (20%), ciprofloxacin (39%), gatifloxacin (51%), nitrofurantoin (83%) and linezolid (>99%). Resistances in enterococci continue to be documented worldwide, but rates within endemic areas like NA appears to be stabilizing. Van A resistance patterns predominate and therapeutic options continue to present dilemmas, although some of the older agents remain usable as primary therapy or as alternatives to the newer agents such as the oxazolidinones.

Geographic variations in garenoxacin (BMS284756) activity tested against pathogens associated with skin and soft tissue infections: report from the SENTRY Antimicrobial Surveillance Program (2000)

The antimicrobial activity of garenoxacin, a des-(6)F quinolone (formally BMS284756 and T-3811), was evaluated against 2,537 skin and soft tissue infection (SSTI) isolates from the SENTRY Antimicrobial Surveillance Program. Strains isolated in 2000 from Europe, North and Latin America were tested at a central laboratory using reference broth microdilution methods. The rank order of the seven most frequent SSTI pathogens was: Staphylococcus aureus (39.9%), Pseudomonas aeruginosa (12.1%), Escherichia coli (9.7%), Enterococcus spp. (7.7%), Klebsiella spp. (5.8%), Enterobacter spp. (5.6%) and coagulase-negative staphylococci (CoNS; 4.2%). Garenoxacin exhibited a four-fold greater activity (MIC(90), 0.06 microg/ml) compared to levofloxacin (MIC(90), 0.25 microg/ml) against oxacillin-susceptible S. aureus; and oxacillin-resistant staphylococci were more susceptible to garenoxacin (>/=90.5%) at </=4 microg/ml than ciprofloxacin or levofloxacin. Enterococcus spp. were more susceptible to garenoxacin and gatifloxacin (MIC(50), 0.5 microg/ml) than ciprofloxacin or levofloxacin (MIC(50), 2 microg/ml). All tested quinolones inhibited 64.7 to 69.7% of P. aeruginosa isolates, and the rank order of potency slightly favored ciprofloxacin (MIC(50), </=0.25 microg/ml). Similar susceptibility rates for the four quinolones were observed against E. coli (85.8-87.0%), Enterobacter spp. (90.8-94.3%) and Klebsiella spp. (89.8-95.2%) with the greatest levels of resistance recorded in Latin America for E. coli and Enterobacter spp. The occurrence of extended spectrum beta-lactamase-producing isolates (predominantly K. pneumoniae) was documented in all three monitored regions (Latin America > Europe > North America). Continued development of garenoxacin as a treatment of pathogens that commonly cause SSTIs appears to be warranted.

Contemporary evaluation of the in vitro activity and spectrum of cefdinir compared with other orally administered antimicrobials tested against common respiratory tract pathogens (2000-2002)

Cefdinir is an oral cephalosporin approved by the Food and Drug Administration in 1997 for the treatment of acute exacerbation of chronic bronchitis, pharyngitis-tonsillitis, community-acquired pneumonia, acute maxillary sinusitis, and uncomplicated skin and skin structure infections in adults and adolescents, and acute otitis media, pharyngitis-tonsillitis, and uncomplicated skin and skin structure infections in children. Although cefdinir showed similar activity to other cephalosporins in the early studies, very limited data has been generated over the last decade. In this report, we summarize the contemporary in vitro activity and spectrum of cefdinir in comparison to numerous other orally administrated antimicrobials available for treatment of community-acquired respiratory infections. A total of 8,326 non-duplicate recent clinical isolates, including Haemophilus influenzae (3,438), Moraxella catarrhalis (1,688), and Streptococcus pneumoniae (3,200), were collected from 35 medical centers in North America during 2000 through 2002, and susceptibility tested by reference broth microdilution methods. Pneumococcal susceptibility patterns for beta-lactams and macrolides were also analyzed according to the year of isolation and the age group of the patients. Cefdinir had the greatest activity against H. influenzae among the cephalosporins tested with susceptibility rates of 97.1 to 99.0%. All of the agents tested had complete or near complete activity against M. catarrhalis. Against S. pneumoniae, cefdinir and other cephalosporins showed similar susceptibility patterns, but improved rates were observed in 2002 (78.5-79.4%) when compared to the previous monitored period (71.8-74.5%). This increase in susceptibility was mainly because of a declining the occurrence of high-level penicillin resistance (MIC >/=2 microg/ml) across all age groups. Macrolide resistance also decreased among S. pneumoniae in 2002 when compared to 2000 through 2001; however, resistance to levofloxacin continued to increase from 0.9% in 2000 to 1.4% in 2002. These results indicate a significant change in emerging beta-lactam resistance patterns (including cefdinir) with a decrease possibly influenced by greater pneumococcal vaccine use in children and the elderly. These rates of increased susceptibility could sustain and enhance the clinical activity of orally administered beta-lactams such as cefdinir.

CANCER Resistance Surveillance Program: Initial Results from Hematology–Oncology Centers in North America

OBJECTIVE The CANCER (Chemotherapy Alliance for Neutropenics and the Control of Emerging Resistance) surveillance program was initiated to collect culture data on antimicrobial and antifungal agents in hospitals treating neutropenic patients in North America, as a means to monitor the development of microbial resistance. METHODS A total of 2042 isolates from bloodstream, respiratory, urinary, and cutaneous infections in 2000–2001 were submitted by 33 oncology centers, clinics, and hospitals in North America, sent to a central laboratory, and tested by National Committee for Clinical Laboratory Standards methods against 42 different antimicrobials. RESULTS Staphylococcus aureus, Escherichia coli, coagulase-negative staphylococci, Enterococcus spp., and Klebsiella spp. represented the most frequently isolated pathogens during the initial benchmark year. The incidence of extended-spectrum β-lactamase–producing phenotypes ranged from 1.6% to 4.6% among E. coli and Klebsiella spp. Amikacin, tobramycin, polymyxin B, and piperacillin/tazobactam provided the highest susceptibility rates against Pseudomonas aeruginosa isolates. Yeast bloodstream isolates demonstrated complete susceptibility to amphotericin B, but 14% of strains were considered to have high-level fluconazole resistance. CONCLUSIONS Elevated resistance rates when compared to general hospital strains were not observed in the CANCER program during the baseline year of this novel longitudinal, resistance surveillance program. The prevalence of gram-positive pathogens, although representing more than 50% of all bacterial isolates, was slightly lower than that reported previously by other investigators. Continued evaluation for antimicrobial resistance as well as changes in the prevalence of gram-positive pathogens requires the use of longitudinal surveillance programs such as the CANCER program. Such initiatives allow the development of therapeutic strategies for coping with changes in resistance and pathogen prevalence in this dynamic at-risk patient environment.

Impact of Modified Nonmeningeal Streptococcus pneumoniae Interpretive Criteria (NCCLS M100-S12) on the Susceptibility Patterns of Five Parenteral Cephalosporins: Report from the SENTRY Antimicrobial Surveillance Program (1997 to 2001)

ABSTRACT The revised interpretive criteria for Streptococcus pneumoniae recently published in the NCCLS M100-S12 informational supplement provide two sets of breakpoints for some cephalosporins: one set for meningeal infection isolates and a new set for nonmeningeal infection isolates. The net effect of these changes was to increase the reported rates of susceptibility of S. pneumoniae to the more active parenteral cephalosporins, such as cefepime, cefotaxime, and ceftriaxone, by 9.1 to 13.0%, bringing their in vitro rates much closer to those of amoxicillin (modified in an earlier NCCLS publication). These revised breakpoints will assist the rational prescribing of antimicrobial agents for the treatment of pneumococcal infections for specific types of infection and establish a greater correlation with clinical outcomes.