Tigecycline activity tested against antimicrobial resistant surveillance subsets of clinical bacteria collected worldwide (2011)

Tigecycline was approved by the United States Food and Drug Administration in 2005 and has generally retained activity against resistant Gram-positive and Gram-negative organisms. We monitored the in vitro activity of this glycylcycline in 2011 for continued potency worldwide. A total of 22,005 unique clinical isolates were consecutively collected in North America (NA; 9232 isolates), Europe (EU; 6776), Latin America (LA; 2016), and Asia-Pacific region (APAC, 3981) and tested for susceptibility according to the reference broth microdilution method recommendations against tigecycline and numerous comparators. Oxacillin (methicillin) resistance rates in methicillin-resistant Staphylococcus aureus (MRSA) were 49.3%, 30.2%, 42.9%, and 37.8%, and vancomycin resistance rates in enterococci (VRE) were 27.0%, 11.3%, 6.3%, and 4.0% in NA, EU, LA, and APAC, respectively. All MRSA (2839) and >99% of VRE were susceptible to tigecycline. Among Escherichia coli, extended-spectrum β-lactamase (ESBL) rates varied from 12.6% in the NA to 57.4% in APAC, and only one strain was nonsusceptible to tigecycline. Tigecycline was active against ESBL phenotype (96.5–98.4% susceptible) and meropenem-nonsusceptible Klebsiella spp. (94.3–100.0% susceptible). Only 4 of 213 (1.9%) meropenem-nonsusceptible Klebsiella spp. were tigecycline-nonsusceptible, all with tigecycline minimum inhibitory concentration (MIC) of 4 μg/mL (intermediate). Among ceftazidime-nonsusceptible Enterobacter spp., 94.7–98.2% were susceptible to tigecycline. Meropenem-nonsusceptible Acinetobacter spp. varied from 51.2% in NA to 80.9% in APAC; and 83.8% (LA) to 93.9% (APAC) of strains were inhibited at a tigecycline MIC of ≤2 μg/mL. Tigecycline showed potent activity against Stenotrophomonas maltophilia (89.3–98.3% inhibited at ≤2 μg/mL). In summary, tigecycline has sustained potent activity and a broad-spectrum against clinically important bacteria causing infections worldwide, including multidrug-resistant organism subsets.     

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.     

MYSTIC Europe 2007: activity of meropenem and other broad-spectrum agents against nosocomial isolates

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program is a longitudinal antimicrobial surveillance study that has been in existence since 1997 in centers that are actively prescribing meropenem. This report examines the results from the study in Europe in 2007. A total of 5208 isolates were examined for activity (MIC) of meropenem and other broad-spectrum antibacterial comparators. Cumulative susceptibility rates using Clinical and Laboratory Standards Institute criteria against all methicillin-susceptible staphylococci were imipenem (97.7%) > meropenem (97.3%) > piperacillin/tazobactam (96.2%) > tobramycin (94.2%) > gentamicin (92.0%) > ciprofloxacin (84.0%) > ceftazidime (39.8%). Against all species of Enterobacteriaceae, the rates were meropenem (99.4%) > imipenem (98.3%) > tobramycin (92.0%) > gentamicin (89.5%) > ceftazidime (86.2%) > piperacillin/tazobactam (85.5%) > ciprofloxacin (84.2%). Meropenem was most effective against the nonfermenters, although multidrug-resistant Acinetobacter spp. and imipenem-resistant Pseudomonas aeruginosa strains were reported. The continued need for surveillance studies such as MYSTIC is exemplified, and results from these types of surveillance can, hopefully, help in the correct choice of empiric therapy.     

Antimicrobial susceptibility patterns of beta-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.     

Regional Resistance Surveillance Program Results for 12 Asia-Pacific Nations (2011)

The Regional Resistance Surveillance program monitored susceptibility rates and developing resistance by geographic region, including 12 Asia-Pacific (APAC) countries. Reference broth microdilution methods for susceptibility/interpretations were applied, processing 5,053 strains. Among Staphylococcus aureus isolates (37% methicillin-resistant S. aureus [MRSA], highest in South Korea [73%]), linezolid (LZD), tigecycline (TIG), and vancomycin were 100% active, but 33 and 34% of strains were levofloxacin (LEV) or macrolide resistant, respectively. Streptococcus pneumoniae was most resistant to β-lactams and macrolides (45%) but was LZD, LEV, and TIG susceptible (>98%). Extended-spectrum β-lactamase (ESBL) phenotype rates in Escherichia coli and Klebsiella spp. were 48 and 47%, respectively, and were highest in Taiwan, at 75 to 91%. The best anti-ESBL-phenotype agents were amikacin (81 to 96% susceptible), colistin (COL; >98%), TIG (>98%), and carbapenems (81 to 97%). Pseudomonas aeruginosa showed ≥20% resistance to all drugs except COL (99% susceptible). In conclusion, endemic evolving antimicrobial resistances in APAC nations show compromised roles for many commonly used antimicrobials.     

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.     

Antimicrobial susceptibility of Gram-negative organisms isolated from patients hospitalized in intensive care units in United States and European hospitals (2009–2011)

Treatment of infections in the intensive care unit (ICU) represents a great challenge, especially those caused by Gram-negative organisms. Rapid introduction of appropriate antimicrobial therapy is crucial to reduce mortality; resistance rates in the ICU can be elevated due to antimicrobial selection pressure. We evaluated the antimicrobial susceptibility patterns of Gram-negative bacteria isolated from patients hospitalized in ICUs (ICU patients). The isolates were consecutively collected as part of the SENTRY Antimicrobial Surveillance Program from January 2009 to December 2011 and tested for susceptibility to multiple antimicrobial agents at a central laboratory by reference broth microdilution methods. Antimicrobial susceptibility results for 5989 bacterial isolates from ICU patients (3445 from the United States [USA] and 2544 from Europe [EU]) were analyzed and compared to those of 17,244 organisms from non-ICU patients (9271 from USA and 7973 from EU). Escherichia coli, Klebsiella spp., and Pseudomonas aeruginosa were the most frequently isolated organisms from ICU patients, followed by Enterobacter spp., Serratia spp., Haemophilus influenzae, Acinetobacter spp., and Proteus mirabilis. Susceptibility rates were generally lower among ICU isolates compared to non-ICU organisms. E. coli isolates from ICU patients exhibited elevated extended-spectrum β-lactamase (ESBL)-phenotype rates (13.7% in USA and 16.6% in EU); furthermore, only amikacin (90.5–94.8% susceptibility), colistin (99.8–100.0% inhibited at ≤2 μg/mL), imipenem (95.5–96.0%), meropenem (95.4–95.8%), and tigecycline (96.3–98.0%) exhibited good activity against Klebsiella spp. ESBL-phenotype rates have increased among both E. coli and Klebsiella spp. from ICU patients in the USA and in Europe, with the most noticeable increase among Klebsiella spp. from Europe (from 27.5% in 2009 to 41.8% in 2011; P = 0.015 and odds ratio = 0.89 [95% confidence interval, 1.13–3.18]). Meropenem susceptibility among Klebsiella spp. improved slightly in the USA but decreased markedly in Europe from 100.0% in 2009 to 89.7% in 2011. Only colistin (99.4% susceptible) and amikacin (97.3% in USA and 84.9% in EU) exhibited good activity against P. aeruginosa strains from ICU patients. The greatest differences in susceptibility rates between P. aeruginosa strains from ICU and non-ICU patients were observed for the anti-pseudomonal β-lactams, such as ceftazidime, meropenem, and piperacillin/tazobactam. The results of this study (101 medical centers) highlight major antimicrobial coverage problems and trends in antimicrobial resistance for USA and EU ICU patient isolates.     

Antimicrobial Activity of Ceftolozane-Tazobactam Tested against Enterobacteriaceae and Pseudomonas aeruginosa with Various Resistance Patterns Isolated in U.S. Hospitals (2011-2012)

Ceftolozane/tazobactam, a novel antimicrobial agent with activity against Pseudomonas aeruginosa (including drug-resistant strains) and other common Gram-negative pathogens (including most extended-spectrum-β-lactamase [ESBL]-producing Enterobacteriaceae strains), and comparator agents were susceptibility tested by a reference broth microdilution method against 7,071 Enterobacteriaceae and 1,971 P. aeruginosa isolates. Isolates were collected consecutively from patients in 32 medical centers across the United States during 2011 to 2012. Overall, 15.7% and 8.9% of P. aeruginosa isolates were classified as multidrug resistant (MDR) and extensively drug resistant (XDR), and 8.4% and 1.2% of Enterobacteriaceae were classified as MDR and XDR. No pandrug-resistant (PDR) Enterobacteriaceae isolates and only one PDR P. aeruginosa isolate were detected. Ceftolozane/tazobactam was the most potent (MIC_50/90, 0.5/2 μg/ml) agent tested against P. aeruginosa and demonstrated good activity against 310 MDR strains (MIC_50/90, 2/8 μg/ml) and 175 XDR strains (MIC_50/90, 4/16 μg/ml). Ceftolozane/tazobactam exhibited high overall activity (MIC_50/90, 0.25/1 μg/ml) against Enterobacteriaceae and retained activity (MIC_50/90, 4/>32 μg/ml) against many 601 MDR strains but not against the 86 XDR strains (MIC₅₀, >32 μg/ml). Ceftolozane/tazobactam was highly potent (MIC_50/90, 0.25/0.5 μg/ml) against 2,691 Escherichia coli isolates and retained good activity against most ESBL-phenotype E. coli isolates (MIC_50/90, 0.5/4 μg/ml), but activity was low against ESBL-phenotype Klebsiella pneumoniae isolates (MIC_50/90, 32/>32 μg/ml), explained by the high rate (39.8%) of meropenem coresistance observed in this species phenotype. In summary, ceftolozane/tazobactam demonstrated high potency and broad-spectrum activity against many contemporary Enterobacteriaceae and P. aeruginosa isolates collected in U.S. medical centers. Importantly, ceftolozane/tazobactam retained potency against many MDR and XDR strains.     

Antibiotic resistance rates for Pseudomonas aeruginosa clinical respiratory and bloodstream isolates among the Veterans Affairs Healthcare System from 2009 to 2013

Pseudomonas aeruginosa is a major cause of healthcare-associated infections and resistance among isolates is an increasing burden. The study purpose was to describe national resistance rates for clinical P. aeruginosa respiratory and bloodstream cultures and the prevalence of multidrug-resistant (MDR) P. aeruginosa within the Veterans Affairs (VA). MDR was defined as non-susceptibility to at least one drug in at least 3 of the following 5 categories: carbapenems, extended-spectrum cephalosporins, aminoglycosides, and piperacillin/tazobactam. We reviewed 24,562 P. aeruginosa respiratory and bloodstream isolates across 126 VA facilities between 2009 and 2013. Most isolates were collected from inpatient settings (82%). Resistance was highest in fluoroquinolones (33%) and exceeded 20% for all classes assessed (carbapenems, extended-spectrum cephalosporins, aminoglycosides, and piperacillin/tazobactam). Resistance was higher in inpatient settings and in respiratory isolates. Prevalence of MDR was 20% overall (22% for inpatient isolates, 11% outpatient, 21% respiratory, 17% bloodstream). Our findings are consistent with previous surveillance reports.     

Expanded studies of piperacillin/tazobactam formulations: variations among branded product lots and assessment of 46 generic lots

The experience with analyzing the potency of piperacillin/tazobactam generic formulations by a precise multiorganism in vitro assay was expanded to 46 lots (29 manufacturers, 17 countries). Across all generic lots, the range of activity compared with a reference branded lot (RLOT; Zosyn®; Wyeth Pharmaceuticals, Philadelphia, PA) was +10% to −42% (average, −16%). Eight lots of Zosyn® were also tested with a range of +7 to −19 (average, only −6%), and the reproducibility (13 replicates) of the RLOT assay was confirmed (±3%). This ongoing quality assurance project demonstrated wide activity variations in piperacillin/tazobactam generic lots with a consistent trend toward subpotent performance (−16%) compared with the branded product. Generic substitutions within hospital formularies should consider parameters of in vitro activity, in addition to applied chemical analyses and measures of bioavailability to avoid potential adverse clinical consequences.     

Antimicrobial susceptibility of common pathogens isolated from postoperative intra-abdominal infections in Japan

The principle of empirical therapy for patients with intra-abdominal infections (IAI) should include antibiotics with activity against Enterobacteriaceae and Bacteroides fragilis group species. Coverage of Pseudomonas aeruginosa, Enterobacter cloacae, and Enterococcus faecalis is also recommended for hospital-associated IAI. A nationwide survey was conducted to investigate the antimicrobial susceptibility of pathogens isolated from postoperative IAI. All 504 isolates were collected at 26 institutions and referred to a central laboratory for susceptibility testing. Lower susceptibility rates to ciprofloxacin and cefepime were demonstrated in Escherichia coli. Among E. coli, 24.1% of strains produced extended-spectrum β-lactamase (ESBL). Carbapenems, piperacillin/tazobactam, cephamycins/oxacephem, aminoglycosides, and tigecycline had high activity against E. coli, including ESBL-producing isolates. Among E. cloacae, low susceptibility rates to ceftazidime were demonstrated, whereas cefepime retained its activity. P. aeruginosa revealed high susceptibility rates to all antimicrobials tested except for imipenem. Among B. fragilis group species, low levels of susceptibility were observed for cefoxitin, moxifloxacin, and clindamycin, and high susceptibility rates were observed for piperacillin/tazobactam, meropenem, and metronidazole. Ampicillin, piperacillin, and glycopeptides had good activity against E. faecalis. Imipenem had the highest activity against E. faecalis among carbapenems. In conclusion, we suggested the empirical use of antimicrobials with the specific intent of covering the main organisms isolated from postoperative IAI. Piperacillin/tazobactam, meropenem, or doripenem, are appropriate in critically ill patients. Combination therapy of cefepime (aztreonam in patients with β-lactam allergy) plus metronidazole plus glycopeptides, imipenem/cilastatin or cephamycins/oxacephem plus ciprofloxacin plus metronidazole are potential therapeutic options.     

Antibiotic resistance surveillance over a 4-year period (2000–2003) in Turkey: results of the MYSTIC Program

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program is a global study that provides antimicrobial susceptibility data in centers prescribing meropenem. The activity of meropenem and 7 broad-spectrum antimicrobials have been examined against 5208 bacterial isolates from 9 Turkish centers between 2000 and 2003. Cumulative susceptibility rates against all species of Enterobacteriaceae combined were ranked as follows: meropenem (99.3%), imipenem (97.6%), cefepime (80.0%), piperacillin–tazobactam (73.6%), ceftazidime (70.3%), ciprofloxacin (70.1%), cefotaxime (66.9%), and tobramycin (67.2%). The production of extended-spectrum β-lactamases (ESBLs) was detected in 48.7% of Klebsiella pneumoniae and in 19.5% of Escherichia coli isolates. Of ESBL producing K. pneumoniae isolates, 75.7% were resistant to tobramycin, 40.3% to ciprofloxacin, and 48.3% to piperacillin–tazobactam. Only piperacillin/tazobactam and carbapenems were active against more than 50% of Pseudomonas aeruginosa at the National Committee for Clinical Laboratory Standards-susceptible breakpoint, and the carbapenems were the most active compounds against Acinetobacter spp. These data confirm the continued potency of meropenem against Enterobacteriaceae in units where it is actively being prescribed.     

Antimicrobial susceptibility of Pseudomonas aeruginosa isolates obtained from patients in Canadian intensive care units as part of the Canadian National Intensive Care Unit study

The antimicrobial susceptibility profile of 419 clinical isolates of Pseudomonas aeruginosa obtained from intensive care unit patients was determined. Amikacin and piperacillin/tazobactam were the most active antimicrobials evaluated. Fifty isolates (11.9%) were resistant to antimicrobials from > or =3 classes. Ninety-six percent of multidrug-resistant (MDR) isolates remained fully susceptible to colistin (polymyxin E).     

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.     

Reproducibility assessment of tigecycline MIC results by broth microdilution methods using commercially prepared dry-form panels

We assessed the reproducibility of tigecycline and piperacillin/tazobactam MIC results tested by broth microdilution methods on commercially prepared dry-format panels. Fifteen bacterial isolates were tested 3 times daily for 3 days for a total of 9 replicate results per strain. The within-day and between-days reproducibility was 100% for tigecycline at +/-1 log(2) dilution step and >98% for piperacillin/tazobactam at +/-1 log(2) dilution step. Identical MIC results were observed for 84.4% and 78.7% of tests for same-day replicates for tigecycline and piperacillin/tazobactam, respectively. These results demonstrate the excellent reproducibility of in vitro susceptibility tests for both tigecycline and piperacillin/tazobactam using a commercially prepared dry-form broth microdilution MIC panel.     

中国14家教学医院院内菌血症与肺炎和腹腔感染病原菌的抗生素耐药监测

目的 监测2006年10月-2007年10月我国不同地区14家教学医院分离的院内获得病原菌的分布和体外药物敏感性.方法 收集来自于院内菌血症、肺炎和腹腔感染患者标本的病原菌.菌株经中心实验室复核后,采用琼脂稀释法测定29种抗菌药物对菌株的MICs,数据输入WHONET5.4软件进行耐药性分析.结果 本研究共收集到2 660株病原菌.引起菌血症(BSI)的病原菌中分离率位于前3位的分别为大肠埃希菌(30.0%)、肺炎克雷伯菌(12.O%)和金黄色葡萄球菌(11.2%);引起院内获得性肺炎(HAP)的病原菌中分离率位于前3位的分别为铜绿假单胞菌(23.4%)、鲍曼不动杆菌(17.4%)和肺炎克雷伯菌(13.8%);引起腹腔感染(IAI)的病原菌中分离率位于前3位的分别为大肠埃希菌(38.8%)、肺炎克雷伯菌(10.2%)和铜绿假单胞菌(9.2%).对于大肠埃希菌和克雷伯菌,敏感性大于80%的药物包括替加环素(100%)、美罗培南(99.3%～100%)、亚胺培南(98.5%～100%)和哌拉西林/三唑巴坦(83.8%～95.1%),氟喹诺酮类药物的敏感性为12.4%～44.9%.对于肠杆菌属、柠檬酸杆菌属、沙雷菌属,替加环素的敏感性为99.2%-100%,亚胺培南和美罗培南的敏感性为96.6%-100%.另外,敏感性较高的抗菌药物还有阿米卡星(82.8%～96.6%)、哌拉西林/三唑巴坦(73.4%～93.1%)、头孢吡肟(69.O%～82.8%)和头孢哌酮/舒巴坦(72.6%～75.9%),氟喹诺酮类药物的敏感性为55.2%-82.8%.多苇耐药的铜绿假单胞菌和鲍曼不动杆菌的发生率分别为18.7%和54.O%.多黏菌素B对铜绿假单胞菌的敏感性最高(93.5%),其次为阿米卡星和哌拉西林/三唑巴坦(均为75.1%).多黏菌素B对鲍曼不动杆菌的敏感性最高(96.2%),其次为替加环素(92.1%)、亚胺培南(59.4%)、米诺环素(59.4%)和美罗培南(56.5%).金黄色葡萄球菌中MRSA的发生率为64.5%,凝同酶阴性葡萄球菌巾MRSCoN的发生率为82.8%.所有葡萄球菌对替加环素、万古霉素和替考拉宁的均敏感.本次监测中发现9株万古霉素耐药的肠球菌(VRE),VRE发生率为4.3%.结论 替加环素、碳青霉烯类、哌拉西林/三唑巴坦、阿米卡星和头孢吡肟对医院分离的肠杆菌科菌保持较高的抗菌活性;多黏菌素B对铜绿假单胞菌和鲍曼不动杆菌均体现出高抗菌活性,鲍曼不动杆菌对替加环素的敏感率达92.1%;替加环素、万古霉素和替考拉宁对院内革兰阳性球菌保持高的抗菌活性.     

Geographic variations in activity of broad-spectrum beta-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.     

Potency and antimicrobial spectrum update for piperacillin/tazobactam (2000): emphasis on its activity against resistant organism populations and generally untested species causing community-acquired respiratory tract infections

The in vitro activity of piperacillin/tazobactam and several comparison broad-spectrum compounds was assessed against recent clinical isolates of Gram-positive and -negative bacteria from geographically diverse medical centers in Europe, North and Latin America participating in various surveillance programs in 2000. Several organisms were characterized for phenotypic expression of various resistant determinants such as extended-spectrum beta-lactamase (ESBL) or amp C cephalosporinase hyperproduction, and vancomycin resistance in enterococci (VRE). Piperacillin/tazobactam retained activity (MIC50) against oxacillin-susceptible Staphylococcus spp. (0.12-0.5 microg/ml), Bacillus spp. (0.5 microg/ml), vancomycin-susceptible enterococci (>4 microg/ml), and Corynebacterium spp. (2 microg/ml; not including C. jeikeium) with susceptibility rates of 100.0, 91.7, 85.7 and 81.8%, respectively. Piperacillin/tazobactam inhibited all Streptococcus spp. strains at < or = 16 microg/ml, including penicillin-resistant strains many of which were co-resistant to erythromycin (90%) and other beta-lactams. A specific breakpoint for these streptococci when testing piperacillin/tazobactam appears needed to prevent false-resistant reports using penicillin as a class representative. The carbapenems among beta-lactams were the most active agents against the ESBL-producing species of Escherichia coli and Klebsiella pneumoniae and those strains which hyper-express amp C enzymes including Citrobacter spp. and Enterobacter spp. Piperacillin/tazobactam only exhibited modest activity against the "amp C resistance group" strains (68.8% susceptible or intermediate, MIC < or = 64 microg/ml). Piperacillin/tazobactam (MIC50, 8 microg/ml; 79.5% susceptible) was the most active agent tested against multi-drug resistant isolates of Pseudomonas aeruginosa. Against sampled Haemophilus influenzae (39.2% ampicillin-resistant), piperacillin/tazobactam (MIC(90,) < or = 0.06 microg/ml), ceftriaxone and ceftazidime inhibited 100.0% of the isolates at < or = 0.25 microg/ml. These in vitro surveillance results from the year 2000 on three continents, demonstrated a sustained potent activity of piperacillin/tazobactam against selected problematic nosocomial and community-acquired pathogens. The potential importance of these findings is that this beta-lactamase inhibitor combination can be used an empiric treatment of serious infections in hospital environments where resistance has emerged, as well as covering nearly all isolates of fastidious respiratory tract pathogens acquired in the community setting.     

Relationship between the usage of carbapenem antibiotics and the incidence of imipenem-resistant Pseudomonas aeruginosa

Metallo-β-lactamase (MBL)-producing Pseudomonas aeruginosa isolates are resistant to almost all broadspectrum β-lactams and carbapenems. We investigated 389 P. aeruginosa isolates, collected from 29 hospitals in the Tohoku area of Japan, to determine their susceptibilities to ten antimicrobial drugs, and the rates of MBL-producing P. aeruginosa among them. Two hundred and one P. aeruginosa strains were isolated from small (group S)hospitals that had adopted imipenem as a carbapenem antibiotic, and 188 were isolated from general (group G) hospitals, which employed three or four carbapenems. MBL genes were analyzed by polymerase chain reaction (PCR) in all isolates for which the sodium mercaptoacetic acid (SMA) disk method gave positive results. The antimicrobial agents tested were imipenem, meropenem, biapenem, panipenem, piperacillin, ceftazidime, sulbactam/cefoperazone, amikacin, arbekacin, and ciprofloxacin. Sixteen (8.0%) of the 201 isolates from group S hospitals and three (1.6%) of the 188 isolates from group G hospitals were MBL-producing P. aeruginosa. In this study, the proportion of MBL-producing P. aeruginosa in group S was significantly higher than that found in group G (P < 0.01). The use of only one agent as a carbapenem antibiotic may have been one of the factors contributing to the high detection rate of MBL-producing P. aeruginosa observed in group S hospitals.     

Unit differences in pathogen occurrence arising from the MYSTIC program European database (1997-2000).

The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program is a longitudinal global antimicrobial surveillance study that compares the activity of meropenem and comparator antimicrobial agents against pathogens isolated from intensive care, neutropenic or cystic fibrosis patients, and general wards. Data from the different European MYSTIC Program units (1997-2000) showed that the most prevalent isolates tested overall were methicillin-susceptible Staphylococcus aureus (MSSA; in accordance with study design methicillin-resistant S. aureus was not tested), Pseudomonas aeruginosa and Escherichia coli. In all the unit types, E. coli (approximately 20% having an extended spectrum beta-lactamase phenotype) and MSSA were highly susceptible to meropenem (97-99% susceptibility). Isolates of MSSA showed lower levels of susceptibility to ciprofloxacin (61-77% susceptibility) in both cystic fibrosis and neutropenia patients, and particularly high levels of resistance to ceftazidime (38% susceptibility) in cystic fibrosis units. Ciprofloxacin (54% susceptibility) and gentamicin (46% susceptibility) demonstrated low levels of activity against P. aeruginosa (frequently encountered in cystic fibrosis units). Meropenem and piperacillin/tazobactam were the most active agents against P. aeruginosa in all the unit types. Carbapenems and piperacillin/tazobactam have sustained > 90% susceptibility rates overall against the most frequently isolated pathogens. The analysis of specific units that house patients with a high-risk of contracting antimicrobial-resistant pathogens remains very important for the optimal selection of empiric regimens.