Mondell L. Beach

Survey of Infections Due to Staphylococcus Species: Frequency of Occurrence and Antimicrobial Susceptibility of Isolates Collected in the United States, Canada, Latin America, Europe, and the Western Pacific Region for the SENTRY Antimicrobial Surveillance Program, 1997–1999

Between January 1997 and December 1999, bloodstream isolates from 15,439 patients infected with Staphylococcus aureus and 6350 patients infected with coagulase-negative Staphylococcus species (CoNS) were referred by SENTRY-participating hospitals in the United States, Canada, Latin America, Europe, and the Western Pacific region. S. aureus was found to be the most prevalent cause of bloodstream infection, skin and soft-tissue infection, and pneumonia in almost all geographic areas. A notable increase in methicillin (oxacillin) resistance among community-onset and hospital-acquired S. aureus strains was observed in the US centers. The prevalence of methicillin (oxacillin)-resistant S. aureus varied greatly by region, site of infection, and whether the infection was nosocomial or community onset. Rates of methicillin resistance were extremely high among S. aureus isolates from centers in Hong Kong and Japan. Uniformly high levels of methicillin resistance were observed among CoNS isolates. Given the increasing multidrug resistance among staphylococci and the possible emergence of vancomycin-resistant strains, global strategies are needed to control emergence and spread of multiply resistant staphylococci.

Survey of Bloodstream Infections Due to Gram-Negative Bacilli: Frequency of Occurrence and Antimicrobial Susceptibility of Isolates Collected in the United States,Canada, and Latin America for the SENTRY Antimicrobial Surveillance Program, 1997

During 1997, a total of 4,267 nosocomial and community-acquired bloodstream infections due to gram-negative organisms were reported from SENTRY hospitals in Canada (8 sites), the United States (30 sites), and Latin America (10 sites). Escherichia coli was the most common isolate (41% of all gram-negative isolates), followed by Klebsiella species (17.9%), Pseudomonas aeruginosa (10.6%), and Enterobacter species (9.4%). For all gram-negative isolates combined, the most active antimicrobials tested were meropenem, imipenem, and cefepime. The quinolones levofloxacin (MIC90, 2 microg/mL), ciprofloxacin (MIC90, 1 microg/mL), gatifloxacin (MIC90, 2 microg/mL), sparfloxacin (MIC90, 2 microg/mL), and trovafloxacin (MIC90, 2 microg/mL) were also active against most isolates. Bloodstream infection isolates from Latin America were uniformly more resistant to all classes of antimicrobial agents tested than were isolates from Canada or the United States. Resistance phenotypes consistent with extended-spectrum beta-lactamase production were also most common among E. coli and Klebsiella species from Latin America. Further investigation of the reasons for regional differences in resistance patterns is needed, as is ongoing surveillance to detect resistance trends and to guide antimicrobial use.

Survey of blood stream infections attributable to gram-positive cocci: frequency of occurrence and antimicrobial susceptibility of isolates collected in 1997 in the United States, Canada, and Latin America from the SENTRY antimicrobial surveillance program

The SENTRY Antimicrobial Surveillance Program was established in January, 1997 to monitor the predominant pathogens and antimicrobial resistance patterns of nosocomial and community-acquired infections via a network of sentinel hospitals in the United States (30 sites), Canada (eight sites), Latin America (10 sites), and Europe (24 sites). During the first 12-month study period (January to December, 1997), a total of 9519 blood stream infections (BSI) were reported by SENTRY participants in the U.S. (6150), Canada (1727), and Latin America (1642). The Gram-positive cocci, Staphylococcus aureus, coagulase-negative staphylococci (CoNS), enterococci, and streptococci accounted for 53.9% (5131 infections) of all BSI (56.5% U.S., 55.7% Canada, and 42.9% Latin America). The staphylococci, Enterococcus spp., S. pneumoniae, beta-hemolytic streptococci, and viridans group streptococci accounted for 6 of the top 11 BSI pathogens in the U.S. and Canada, whereas only S. aureus (1st), CoNS (3rd), and Enterococcus spp. (9th) were among the top 11 pathogens in Latin American hospitals. The results of this survey affirm the importance of Gram-positive cocci as causes of BSI in both North America and Latin America and demonstrate that important antimicrobial resistance exists among isolates of staphylococci, streptococci, and enterococci from all three geographic regions. This includes oxacillin-resistance among S. aureus (26.9% U.S., 29.2% Latin America, and 4.0% Canada) and CoNS (71.5% U.S., 68.4% Latin America, and 65.6% Canada), penicillin resistance among viridans group streptococci (48.5% U.S., 45.1% Canada, and 33.3% Latin America) and pneumococci (36.1% U.S., 27.5% Canada, and 65.6% Latin America), high-level resistance (HLR) to aminoglycosides among enterococci (27.2 to 70.1% U.S., 33.3 to 75.7% Canada and 16.7 to 51.5% Latin America), and macrolide resistance among beta-hemolytic streptococci (12.4 to 14.2% U.S., 10.5 to 12.3% Canada, and 0.0 to 4.0% Latin America), viridans group streptococci (32.4 to 39.7% U.S., 22.5-35.2% Canada, and 20.0% Latin America), and pneumococci (10.0 to 10.6% U.S., 9.8-10.8% Canada, and 9.4-18.7% Latin America). BSI isolates of Gram-positive cocci from the U.S. and Latin America were considerably more resistant than those from Canada. New agents with Gram-positive activity will be essential for optimal treatment of BSI attributable to Gram-positive cocci in both North and Latin America.

In vitro antimicrobial activity of GAR-936 tested against antibiotic-resistant gram-positive blood stream infection isolates and strains producing extended-spectrum β-lactamases

GAR-936, a new, semisynthetic glycylcycline, has shown good antibacterial activity against a wide range of clinically important Gram-positive and -negative aerobic bacteria including Streptococcus pneumoniae, Hemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, most Enterobacteriaceae, Staphylococcus aureus and Enterococcus spp. The purpose of this study was to determine the activity of GAR-936 against a range of Gram-positive and -negative bloodstream isolates including many strains producing extended-spectrum beta-lactamases (ESBLs). Six hundred four bloodstream isolates of Gram-positive cocci collected as part of the SENTRY surveillance program were selected for their geographic diversity. GAR-936 was also tested against an additional 176 Gram-negative cocci isolates (Klebsiella pneumoniae, 98 strains; Escherichia coli, 78 strains), 96 of which were ESBL-producers. Broth microdilution testing was used to determine the susceptibility of the selected organisms and a range of comparator antimicrobial agents whose choice was based on their activities against the selected pathogens and included a mix of both newer and older agents. Presence of an ESBL-producing strain was confirmed using the clavulanate test. GAR-936 demonstrated impressive activity against all 604 strains of Gram-positive cocci, with an MIC range of <or=0.015-1 microg/mL, and MIC(90)s ranging from <or=0.05 microg/mL for S. pneumoniae to 0.25 for S. aureus and coagulase-negative staphylococci. MICs against the 176 Gram-negative isolates were higher (range 0.06-4 microg/mL), with MIC(90)s of 0.25-1 microg/mL. The activity of GAR-936 was relatively unaffected by the presence of ESBLs. The activity of GAR-936 was particularly impressive against Gram-positive cocci when compared against the test results for vancomycin and the newer antimicrobial agents, linezolid and quinupristin/dalfopristin. The MIC(90)s for GAR-936 were significantly lower than the comparator agents for all species tested with particularly impressive results against S. pneumoniae and enterococci.

Trends in antimicrobial susceptibility of bacterial pathogens isolated from patients with bloodstream infections in the USA, Canada and Latin America

From January through June of 1998, 4579 bloodstream infections (BSI) due to bacterial pathogens were reported from SENTRY hospitals in Canada, the USA and Latin America. Staphylococcus aureus, Escherichia coli, and coagulase-negative staphylococcus (CoNS) were the most common pathogens, together accounting for 55.2% of all BSI during this time period. Compared with the 5794 BSI reported from SENTRY from January through June of 1997, no major change was seen in the frequencies of occurrence of the most common bacterial causes of BSI. Between 1997 and 1998, the major change in antimicrobial resistance was an increase in oxacillin-resistance in both S. aureus and CoNS in all regions. These data demonstrate widespread antimicrobial resistance in Canada, Latin America and the USA, with a notable increase in oxacillin-resistance among staphylococci. Ongoing surveillance remains essential, and will enhance efforts to limit the scope of this worldwide problem.

Contemporary in vitro spectrum of activity summary for antimicrobial agents tested against 18 569 strains non-fermentative Gram-negative bacilli isolated in the SENTRY Antimicrobial Surveillance Program (1997/2001)

The frequency of occurrence and antimicrobial susceptibility patterns of 18569 non-fermentative Gram-negative bacilli consecutively collected as part of the SENTRY Antimicrobial Surveillance Program were summarized. The isolates were tested by the broth microdilution method in three coordinator laboratories using common reagents and reference methodologies. The most frequently isolated pathogen was Pseudomonas aeruginosa (11968 isolates; 64.5%) followed by Acinetobacter spp. (3468 isolates; 18.7%) and Stenotrophomonas maltophilia (1488 isolates; 8.0%). The lowest resistance rates for P. aeruginosa documented were for amikacin (8%), meropenem (10%) and cefepime (10%), and all fluoroquinolones tested showed similar resistance rates (22-24%). The most active compounds against Acinetobacter spp. were the carbapenems, imipenem (11% resistance) and meropenem (12% resistance) followed by cefepime (31% resistance) and gatifloxacin (32% resistance). Very few compounds showed reasonable in vitro activity against S. maltophilia, with the most active antimicrobial agents being trimethoprim/sulphamethoxazole, gatifloxacin and levofloxacin (5-6% resistance). Resistance surveillance among these organisms remains necessary to guide empirical antimicrobial therapy, especially for these less frequently isolated and difficult to test pathogens.

Bacterial pathogens isolated from patients with skin and soft tissue infections: frequency of occurrence and antimicrobial susceptibility patterns from the SENTRY Antimicrobial Surveillance Program (United States and Canada, 1997)

As part of the SENTRY Antimicrobial Surveillance Program, 1562 bacterial isolates were recovered from hospitalized patients with skin and soft tissue infections (SSTIs) in 30 United States (U.S.) and 8 Canadian medical centers between October and December, 1997. The overall rank order of recovery of the six most common pathogens was Staphylococcus aureus (42.6%) > Pseudomonas aeruginosa (11.3%) > Enterococcus spp. (8.1%) > Escherichia coli (7.2%) > Enterobacter spp. (5.2%) > beta-hemolytic streptocci (5.1%). With one exception, essentially the same order was observed in both the U.S. and Canada. The single exception was the Enterococcus group, which were the third most common isolate in the U.S. (9.6%), but the seventh most common isolate in Canada (3.7). Of note, 24.0% of S. aureus isolates were oxacillin resistant; vancomycin was uniformly active. Vancomycin resistance among Enterococcus spp. (16.5%) was observed only in the U.S. Several antimicrobial agents remained broadly active for SSTI isolates of P. aeruginosa, including meropenem, amikacin, tobramycin, and piperacillin with or without tazobactam. Imipenem resistance (MICs, > or = 8 micrograms/mL) was observed in 11.9% of isolates of P. aeruginosa and ceftazidime, and cefepime had equivalent activity (85.2% and 85.8% susceptible, respectively). Numerous beta-lactams, aminoglycosides and fluoroquinolones were broadly active against E. coli SSTI isolates (i.e. < 5% resistance). Extended-spectrum beta-lactamase production was uncommon both with E. coli and Klebsiella spp. in both nations. Cefepime, imipenem, and meropenem; the aminoglycosides; and fluoroquinolones were conspicuously more active against Enterobacter spp. than other agents tested. High-level, stably derepressed Amp C beta-lactamase production was commonly observed in this group (26.8%), but cefepime generally retained activity against these ceftazidime-resistant organisms. The results of this study serve to define the most common bacterial causes of SSTIs in North America, elucidate patterns of antimicrobial resistance and can be used as a basis for making initial empiric antimicrobial management decisions in hospitalized patients with such infections.

Geographic variations in activity of broad-spectrum β-lactams against Pseudomonas aeruginosa: summary of the worldwide SENTRY Antimicrobial Surveillance Program (1997–2000)

With reports of increasing resistance to antimicrobial agents among Pseudomonas aeruginosa clinical isolates worldwide, the activities of cefepime and eight other broad-spectrum beta-lactams against 6969 isolates collected during 1997-2000 from the four regions of the SENTRY Antimicrobial Surveillance Program. P. aeruginosa isolates were tested by the reference broth microdilution method against nine beta-lactam antimicrobial agents (aztreonam, cefepime, ceftazidime, imipenem, meropenem, piperacillin +/- tazobactam, ticarcillin +/- clavulanate), three aminoglycosides (amikacin, gentamicin, tobramycin), and two fluoroquinolones (ciprofloxacin, levofloxacin). The strains were contributed by more than 100 medical centers. National Committee for Clinical Laboratory Standards criteria were used to identify susceptible and resistant isolates. P. aeruginosa strains from Latin America were generally the most resistant to all classes of antimicrobials, compared with strains from other regions. The beta-lactams exhibited a wide range of potency, with carbapenems most active (meropenem, 80-91% susceptible; imipenem, 76-88% susceptible). Piperacillin/tazobactam was the most active penicillin (77-80% susceptible), and cefepime (67-83% susceptible) had an average 2% (range, 0.7-3.5%) greater susceptibility rate than ceftazidime (66-80% susceptible) across all regions. The rank order of beta-lactam activity according to percent resistant isolates in North American P. aeruginosa strains was: meropenem (4.8% resistant) > cefepime (6.8%) > imipenem (8.6%) > piperacillin/tazobactam (10.3%) > piperacillin (12.9%). Only 2.3% and 6.5% of isolates were resistant to amikacin or tobramycin, respectively, and nearly 16% of P. aeruginosa strains were resistant to ciprofloxacin. Compared with other geographic regions, strains of P. aeruginosa remain most susceptible in North America. In all regions, aminoglycosides in combination with carbapenems, cefepime, or piperacillin/tazobactam would provide more potential antipseudomonal activity than fluoroquinolone combinations for wide-spectrum empiric regimens.

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.

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

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