Prevalence of antimicrobial resistance in bacteria isolated from central nervous system specimens as reported by U.S. hospital laboratories from 2000 to 2002

BACKGROUND: Bacterial infections of the central nervous system, especially acute infections such as bacterial meningitis require immediate, invariably empiric antibiotic therapy. The widespread emergence of resistance among bacterial species is a cause for concern. Current antibacterial susceptibility data among central nervous system (CNS) pathogens is important to define current prevalence of resistance. METHODS: Antimicrobial susceptibility of pathogens isolated from CNS specimens was analyzed using The Surveillance Database (TSN(®)) USA Database which gathers routine antibiotic susceptibility data from >300 US hospital laboratories. A total of 6029 organisms derived from CNS specimen sources during 2000–2002, were isolated and susceptibility tested. RESULTS: Staphylococcus aureus (23.7%) and Streptococcus pneumoniae (11.0%) were the most common gram-positive pathogens. Gram-negative species comprised approximately 25% of isolates. The modal patient age was 1 or <1 year for most organisms. Prevalence of MRSA among S. aureus from cerebrospinal fluid (CSF) and brain abscesses were 29.9–32.9%. Penicillin resistance rates were 16.6% for S. pneumoniae, 5.3% for viridans group streptococci, and 0% for S. agalactiae. For CSF isolates, ceftriaxone resistance was S. pneumoniae (3.5%), E. coli (0.6%), Klebsiella pneumoniae (2.8%), Serratia marcescens (5.6%), Enterobacter cloacae (25.0%), Haemophilus influenzae (0%). Listeria monocytogenes and N. meningitidis are not routinely susceptibility tested. CONCLUSIONS: Resistance is commonly detected, albeit still at relatively low levels for key drugs classes such as third-generation cephalosporins. This data demonstrates the need to consider predominant resistance phenotypes when choosing empiric therapies to treat CNS infections

Emerging resistance among bacterial pathogens in the intensive care unit – a European and North American Surveillance study (2000–2002)

Background Globally ICUs are encountering emergence and spread of antibiotic-resistant pathogens and for some pathogens there are few therapeutic options available. Methods Antibiotic in vitro susceptibility data of predominant ICU pathogens during 2000–2 were analyzed using data from The Surveillance Network (TSN) Databases in Europe (France, Germany and Italy), Canada, and the United States (US). Results Oxacillin resistance rates among Staphylococcus aureus isolates ranged from 19.7% to 59.4%. Penicillin resistance rates among Streptococcus pneumoniae varied from 2.0% in Germany to as high as 20.2% in the US; however, ceftriaxone resistance rates were comparably lower, ranging from 0% in Germany to 3.4% in Italy. Vancomycin resistance rates among Enterococcus faecalis were ≤ 4.5%; however, among Enterococcus faecium vancomycin resistance rates were more frequent ranging from 0.8% in France to 76.3% in the United States. Putative rates of extended-spectrum β-lactamase (ESBL) production among Enterobacteriaceae were low, \u3c6% among Escherichia coli in the five countries studied. Ceftriaxone resistance rates were generally lower than or similar to piperacillin-tazobactam for most of the Enterobacteriaceae species examined. Fluoroquinolone resistance rates were generally higher for E. coli (6.5% – 13.9%), Proteus mirabilis (0–34.7%), and Morganella morganii (1.6–20.7%) than other Enterobacteriaceae spp (1.5–21.3%). P. aeruginosa demonstrated marked variation in β-lactam resistance rates among countries. Imipenem was the most active compound tested against Acinetobacter spp., based on resistance rates. Conclusion There was a wide distribution in resistance patterns among the five countries. Compared with other countries, Italy showed the highest resistance rates to all the organisms with the exception of Enterococcus spp., which were highest in the US. This data highlights the differences in resistance encountered in intensive care units in Europe and North America and the need to determine current local resistance patterns by which to guide empiric antimicrobial therapy for intensive care infections

Prevalence and antimicrobial susceptibilities of bacteria isolated from blood cultures of hospitalized patients in the United States in 2002

BACKGROUND: Bloodstream infections are associated with significant patient morbidity and mortality. Antimicrobial susceptibility patterns should guide the choice of empiric antimicrobial regimens for patients with bacteremia. METHODS: From January to December of 2002, 82,569 bacterial blood culture isolates were reported to The Surveillance Network (TSN) Database-USA by 268 laboratories. Susceptibility to relevant antibiotic compounds was analyzed using National Committee for Clinical Laboratory Standards guidelines. RESULTS: Coagulase-negative staphylococci (42.0%), Staphylococcus aureus (16.5%), Enterococcus faecalis (8.3%), Escherichia coli (7.2%), Klebsiella pneumoniae (3.6%), and Enterococcus faecium (3.5%) were the most frequently isolated bacteria from blood cultures, collectively accounting for >80% of isolates. In vitro susceptibility to expanded-spectrum β-lactams such as ceftriaxone were high for oxacillin-susceptible coagulase-negative staphylococci (98.7%), oxacillin-susceptible S. aureus (99.8%), E. coli (97.3%), K. pneumoniae (93.3%), and Streptococcus pneumoniae (97.2%). Susceptibilities to fluoroquinolones were variable for K. pneumoniae (90.3–91.4%), E. coli (86.0–86.7%), oxacillin-susceptible S. aureus (84.0–89.4%), oxacillin-susceptible coagulase-negative staphylococci (72.7–82.7%), E. faecalis (52.1%), and E. faecium (11.3%). Combinations of antimicrobials are often prescribed as empiric therapy for bacteremia. Susceptibilities of all blood culture isolates to one or both agents in combinations of ceftriaxone, ceftazdime, cefepime, piperacillin-tazobactam or ciprofloxacin plus gentamicin were consistent (range, 74.8–76.3%) but lower than similar β-lactam or ciprofloxacin combinations with vancomycin (range, 93.5–96.6%). CONCLUSION: Ongoing surveillance for antimicrobial susceptibility remains essential, and will enhance efforts to identify resistance and attempt to limit its spread

Tracking the implementation of NCCLS M100-S12 expanded-spectrum cephalosporin MIC breakpoints for nonmeningeal isolates of Streptococcus pneumoniae by clinical laboratories in the United States during 2002 and 2003

BACKGROUND: The Performance Standards for Antimicrobial Susceptibility Testing, Twelfth Informational Supplement, M100-S12, published by the National Committee for Clinical Laboratory Standards (NCCLS) in January 2002 introduced distinct minimum inhibitory concentration (MIC) interpretative breakpoints for ceftriaxone, cefotaxime, and cefepime for nonmeningeal isolates of Streptococcus pneumoniae. Previously, a single set of interpretative breakpoints was used for both meningeal and nonmeningeal isolates. METHODS: To estimate the rate of adoption of the M100-S12 interpretive breakpoints by clinical laboratories, antimicrobial susceptibility test results for ceftriaxone and cefotaxime from nonmeningeal S. pneumoniae isolates were studied using data collected from January 2002 to June 2003 by The Surveillance Network(® )Database – USA (TSN(®)), an electronic surveillance database. RESULTS: Of the 262 laboratories that provided data that could be evaluated, 67.6% had adopted the M100-S12 breakpoints one and one-half years after they were published. CONCLUSIONS: The NCCLS M100-S12 recommendation to interpret MICs to expanded-spectrum cephalosporins using two distinct sets of breakpoints for meningeal and nonmeningeal isolates of S. pneumoniae was steadily implemented by clinical microbiology laboratories in the United States following their initial publication in January 2002. The use of these new breakpoints more accurately reflects the clinical activities of expanded-spectrum cephalosporins than did the single set of interpretative breakpoints previously used for both meningeal and nonmeningeal isolates

In Vitro Activity of Linezolid against Key Gram-Positive Organisms Isolated in the United States: Results of the LEADER 2004 Surveillance Program

Since the approval of linezolid in 2000, sporadic reports of resistance have been given and a greater understanding of the underlying mechanisms of resistance has been gained. However, since these developments, an updated status of the in vitro activity of linezolid against gram-positive organisms from the United States has not been reported. The LEADER 2004 surveillance initiative was undertaken to obtain current and representative data on the activity of linezolid against key species, including isolates with significant resistance phenotypes. Organisms were isolated during 2004 and included 2,872 Staphylococcus aureus, 496 coagulase-negative staphylococcus (CNS), 428 Enterococcus faecalis, 196 Enterococcus faecium, and 422 Streptococcus pneumoniae isolates. All S. aureus isolates (54.2% oxacillin resistant) were susceptible to linezolid (MIC(90) = 2 μg/ml); MIC distributions were consistent, regardless of oxacillin or multidrug resistance status. For CNS, one nonsusceptible isolate was encountered (Staphylococcus epidermidis; MIC = 32 μg/ml), but overall, the MIC(90) (1 μg/ml) was lower than that obtained with S. aureus. For E. faecalis and E. faecium, 99.5% and 96.4% of isolates, respectively, were linezolid susceptible. Both species had an MIC(90) of 2 μg/ml, and MIC distributions did not vary with the vancomycin susceptibility status of the populations analyzed. Linezolid nonsusceptibility was not encountered among the S. pneumoniae isolates. These findings indicate that linezolid nonsusceptibility has remained rare among staphylococci and uncommon and sporadic among enterococci. Nonetheless, careful and ongoing monitoring of the in vitro effectiveness of linezolid will be needed so that any changes to the current status may be detected as soon as possible

In Vitro Activity of Tigecycline against Gram-Positive and Gram-Negative Pathogens as Evaluated by Broth Microdilution and Etest▿

The current surveillance establishes the activity profile of tigecycline against recent clinical U.S. isolates of target pathogens. Findings from a distributed surveillance that utilized Etest yielded a tigecycline activity profile that varied from that observed in a separate centralized broth microdilution (BMD) surveillance (D. C. Draghi et al., Poster D-0701, 46th Intersci. Conf. Antimicrob. Agents Chemother., San Francisco, CA). Differences were noted among Acinetobacter spp. and Serratia marcescens and, to a lesser extent, with Streptococcus pyogenes. To address whether these differences were due to discordance in testing methodology or to variations among the analyzed populations, isolates from the current surveillance were concurrently tested by BMD and Etest. In all, 1,800 Staphylococcus aureus, 259 S. pyogenes, 226 Streptococcus pneumoniae, 93 Enterococcus faecalis, 1,356 Enterobacteriaceae, and 227 Acinetobacter baumannii strains were evaluated. Tigecycline had potent activity by BMD, with >99.6% susceptibility (%S) observed for all pathogens with interpretive criteria, excluding Enterobacter cloacae (98.3% S) and E. faecalis (86.0% S), and MIC90s ranged from 0.03 μg/ml (S. pyogenes/S. pneumoniae) to 1 μg/ml (Enterobacteriaceae/A. baumannii). Similar profiles were observed by Etest, with the exception of A. baumannii, although for most evaluated pathogens Etest MICs trended one doubling-dilution higher than BMD MICs. Major or very major errors were infrequent, and a high degree of essential agreement was observed, excluding A. baumannii, S. marcescens, and S. pneumoniae, for which ≥4-fold differences in MICs were observed for 29, 27.1, and 34% of the isolates, respectively. Further analysis regarding the suitability of the tigecycline Etest for testing S. marcescens, Acinetobacter spp., and S. pneumoniae is warranted

Bactericidal Activity and Resistance Development Profiling of Dalbavancin

Dalbavancin, a semisynthetic lipoglycopeptide being developed for the treatment of skin and skin structure infections (SSSIs), has a half-life of 5 to 7 days in humans and offers promise for a convenient weekly dosing regimen. We studied the in vitro bactericidal activity of dalbavancin against target organisms, using the concentrations that are maintained in human blood with the proposed dosage regimen. Dalbavancin minimal bactericidal concentrations (MBCs) were ≤0.5 μg/ml for eight staphylococcal isolates; and for six of these strains, including one vancomycin-intermediate Staphylococcus aureus (VISA) isolate, the MBCs were equal to or within 1 doubling dilution of the MIC. Dalbavancin MICs for all three Streptococcus pyogenes strains were 0.008 μg/ml, as were the MBCs for two of the isolates. In time-kill studies conducted with a different set of seven strains (two methicillin-susceptible S. aureus isolates, three methicillin-resistant S. aureus isolates, one VISA isolate, and one S. pyogenes isolate), all strains exhibited a ≥3-log(10) decrease in their viable counts when they were exposed to ≥1 μg/ml of dalbavancin for 24 h. Resistance development studies by both direct selection (resistance frequency, <10(−10)) and serial passage failed to produce stable mutants with decreased susceptibility to dalbavancin. These observations suggest that dalbavancin will be an effective choice for the management of patients with SSSIs

Surveillance for Antimicrobial Susceptibility among Clinical Isolates of Pseudomonas aeruginosa and Acinetobacter baumannii from Hospitalized Patients in the United States, 1998 to 2001

Pseudomonas aeruginosa and Acinetobacter baumannii are the most prevalent nonfermentative bacterial species isolated from clinical specimens of hospitalized patients. A surveillance study of 65 laboratories in the United States from 1998 to 2001 found >90% of isolates of P. aeruginosa from hospitalized patients to be susceptible to amikacin and piperacillin-tazobactam; 80 to 90% of isolates to be susceptible to cefepime, ceftazidime, imipenem, and meropenem; and 70 to 80% of isolates to be susceptible to ciprofloxacin, gentamicin, levofloxacin, and ticarcillin-clavulanate. From 1998 to 2001, decreases in antimicrobial susceptibility (percents) among non-intensive-care-unit (non-ICU) inpatients and ICU patients, respectively, were greatest for ciprofloxacin (6.1 and 6.5), levofloxacin (6.6 and 3.5), and ceftazidime (4.8 and 3.3). Combined 1998 to 2001 results for A. baumannii isolated from non-ICU inpatients and ICU patients, respectively, demonstrated that >90% of isolates tested were susceptible to imipenem (96.5 and 96.6%) and meropenem (91.6 and 91.7%); fewer isolates from both non-ICU inpatients and ICU patients were susceptible to amikacin and ticarcillin-clavulanate (70 to 80% susceptible); and <60% of isolates were susceptible to ceftazidime, ciprofloxacin, gentamicin, or levofloxacin. From 1998 to 2001, rates of multidrug resistance (resistance to at least three of the drugs ceftazidime, ciprofloxacin, gentamicin, and imipenem) showed small increases among P. aeruginosa strains isolated from non-ICU inpatients (5.5 to 7.0%) and ICU patients (7.4 to 9.1%). From 1998 to 2001, rates of multidrug resistance among A. baumannii strains isolated from non-ICU inpatients (27.6 to 32.5%) and ICU patients (11.6 to 24.2%) were higher and more variable than those observed for P. aeruginosa. Isolates concurrently susceptible, intermediate, or resistant to both imipenem and meropenem accounted for 89.8 and 91.2% of P. aeruginosa and A. baumannii isolates, respectively, studied from 1998 to 2001. In conclusion, for aminoglycosides and most β-lactams susceptibility rates for P. aeruginosa and A. baumannii were constant or decreased only marginally (≤3%) from 1998 to 2001. Greater decreases in susceptibility rates were, however, observed for fluoroquinolones and ceftazidime among P. aeruginosa isolates

In Vitro Susceptibilities of Gram-Negative Bacteria Isolated from Hospitalized Patients in Four European Countries, Canada, and the United States in 2000-2001 to Expanded-Spectrum Cephalosporins and Comparator Antimicrobials: Implications for Therapy

Access to current antimicrobial agent surveillance data is an important prerequisite for the optimal management of patients with hospital-acquired infections. The present study used data collected in 2000 to 2001 from 670 laboratories in Europe (France, Germany, Italy, and Spain), Canada, and the United States to report on the in vitro activities of ceftriaxone, cefotaxime, and comparative agents against >125,000 isolates of gram-negative bacteria from hospitalized patients. All but two isolates of Enterobacteriaceae (one isolate of Proteus mirabilis from France and one isolate of Morganella morganii from Canada) were susceptible to imipenem. The susceptibility of Escherichia coli to ceftriaxone or cefotaxime was ≥97% in each country, and for P. mirabilis, susceptibility was 99% in each country except Italy. In contrast, susceptibility of E. coli to ciprofloxacin varied from 80.5% (Spain) to 94.0% (France); levofloxacin susceptibility ranged from 75.2% (Spain) to 91.6% (United States). Among Klebsiella pneumoniae and Klebsiella oxytoca isolates, ceftriaxone and cefotaxime susceptibilities ranged from 86.6 to 98.7% and 83.5 to 99.7%, respectively, depending upon the country. Considerable geographic variation in the susceptibilities (generally 85 to 95% susceptible) of Serratia marcescens and M. morganii to ceftriaxone and cefotaxime were observed. For S. marcescens, susceptibility to piperacillin-tazobactam varied from 81.5% (France) to 94.1% (Italy) and susceptibility to ciprofloxacin ranged from 66.2% (Germany) to 90.7% (Spain). Enterobacter cloacae and Enterobacter aerogenes were less susceptible to ceftriaxone and cefotaxime than were the other species of Enterobacteriaceae studied. The present study demonstrated that established parenteral expanded-spectrum cephalosporin antimicrobial agents retain significant in vitro activity against many clinically important gram-negative pathogens