Meridith E. Erwin

Nosocomial enterococcal blood stream infections in the SCOPE program: Antimicrobial resistance, species occurrence, molecular testing results, and laboratory testing accuracy☆

Characteristics of nosocomial enterococcal blood stream infection (NEBSI) isolates obtained from patients at 41 U.S. hospitals participating in the SCOPE Program were studied. Isolates from 480 episodes of NEBSI were characterized according to species and antimicrobial susceptibility profile. Selected isolates were also identified to species and vancomycin resistance genotype using polymerase chain reaction based methods. Polymerase chain reaction genotyping and ribotyping were used as genetic markers for molecular epidemiologic typing. Enterococci were the third most common cause of nosocomial blood stream infection in this study, accounting for 11.7% of all isolates reported. Enterococcus faecalis was the most common species (59.6%), followed by E. faecium (19.4%). Species identification errors involving E. faecium, E. durans, E. avium, and E. raffinosus were observed. Vancomycin resistance was observed in 36.4% of all participating medical centers and varied from 11.1% of medical centers in the Northwest to 60.9% of medical centers in the Southwest. Vancomycin-resistant enterococci accounted for 20.6% of NEBSI in the Northeast, 11.4% in the Southeast, 11.1% in the Southwest, and 9.5% in the Northwest regions. VanA genotypes predominated in the Northeast and Southwest, whereas vanA and vanB genotypes were equally prevalent in the Northwest and Southeast. Molecular typing studies identified strains that were unique to individual hospitals as well as strains that were prevalent in several different hospitals. NEBSI with vancomycin-resistant enterococci continues to escalate among hospitalized patients in all geographic areas of the USA.

Prevalence of important pathogens and antimicrobial activity of parenteral drugs at numerous medical centers in the United States. I: Study on the threat of emerging resistances : real or perceived ?

Forty-three medical centers participated in a national (United States) surveillance study of parenteral antimicrobial agents as empiric therapy of pathogens isolated from blood, skin wounds, respiratory tract, and urine (> 8500 strains, 200 per laboratory). All laboratories tested each organism by the same reagent disks and/or Etest (AB Biodisk, Solna, Sweden) strips. Quality control results validated all laboratories for analyses. The most common isolates were Escherichia coli (1648), Staphylococcus aureus (1408), Pseudomonas aeruginosa (1003), Klebsiella species (792), and the enterococci (684). Among the tested drugs the percent susceptible rates observed were ofloxacin (83.4%), ciprofloxacin (82.0%), and cefuroxime (62.9%) tested against all organisms; cefazolin (54.7%) and ceftazidime (76.7%) tested against all nonfastidious aerobes; gentamicin (91.2%), imipenem (95.3%), ticarcillin-clavulanate (78.2%), and ceftriaxone (66.2%) tested against Gram-negative organisms only; and vancomycin (97.9%) and erythromycin (49.2%) tested against Gram-positive aerobes. Several drug-resistant species appear to be emerging or increasing in the United States: (a) vancomycin-resistant enterococci (7.9%, mostly Enterococcus faecium); (b) oxacillin-resistant S. aureus (21.0%); (c) third-generation cephalosporin-resistant Enterobacteriaceae, including E. coli and Klebsiella species with extended-spectrum beta-lactamases (approximately 1.3%-8.6%); (d) penicillin-resistant Streptococcus pneumoniae (17.8%); and (e) ciprofloxacin-resistant P. aeruginosa (14.9%). Fluoroquinolone resistance among the enteric bacilli was confirmed in 60 of 66 referred strains (0.8% of total strains), and cross-resistance was high among ciprofloxacin, ofloxacin, lomefloxacin, fleroxacin, and norfloxacin (98.3%-100%). Seventeen strains of fluoroquinolone-resistant enteric bacilli (0.2% of total) also harbored an ESBL and resistance to aminoglycosides. Clonal spread within medical centers was observed with the ESBL-producing Klebsiella pneumoniae. This national clinical isolate data base continues to demonstrate broad fluoroquinolone efficacy (ofloxacin > ciprofloxacin) against hospital-based pathogens and many strains of emerging resistant bacteria. Continued US surveillance studies are urged to monitor emerging antimicrobial resistance and to guide interventions to minimize its occurrence.

Emerging multiply resistant enterococci among clinical isolates I. Prevalence data from 97 medical center surveillance study in the United States

To assess the evolving problem of therapeutic drug resistances among enterococci, we organized a comprehensive national (United States) surveillance trial using 99 recruited microbiology laboratories in 48 of the 49 contiguous states or districts. All but two sites completed the protocol that generated information from nearly 2000 enterococci, usually isolated from blood cultures. All strains were speciated by the same method (API 20S) and were susceptibility tested by three methods (broth microdilution, disk diffusion, and Etest) against ampicillin, penicillin, vancomycin, teicoplanin, gentamicin, and streptomycin. Strains resistant to a glycopeptide or penicillin, or possessing high-level aminoglycoside resistance were referred to the monitors laboratory for validation and additional susceptibility testing against other alternative antimicrobial agents. The most common species were Enterococcus faecalis and Enterococcus faecium. However, antimicrobial resistance occurred most often among the E. faecium isolates. Twenty-three percent of participant centers (22 sites) reported 87 vancomycin-resistant isolates, which accounts for 4.4% of the isolates evaluated. A recent audit (March 1994) of the laboratories not reporting vancomycin resistance during the study interval (October-December 1992) revealed that 61% of sites have now recognized these strains, a threefold increase in 12-15 months. Teicoplanin remained active against 28% (Van B phenotype) of vancomycin-resistant enterococci (10 E. faecalis, 13 E. faecium, and one Enterococcus spp.). Ampicillin-resistant beta-lactamase-positive strains were found only at one medical center (two strains, 0.2% of referred or validated strains); however, ampicillin-resistant strains represented 12% of all enterococcal, but nearly 60% of E. faecium strains.(ABSTRACT TRUNCATED AT 250 WORDS)

Antimicrobial Activity and Spectrum Investigation of Eight Broad-Spectrum β-Lactam Drugs: A 1997 Surveillance Trial in 102 Medical Centers in the United States

Abstract Because antimicrobial agents become less effective after the emergence of resistance mechanisms in clinically prevalent pathogens, physicians must utilize local, regional, and national antimicrobial susceptibility surveillance data to assist in choices of appropriate agents. An investigation of the spectrum and potency of eight broad-spectrum β-lactam drugs (cefepime, cefotaxime, ceftazidime, ceftriaxone, imipenem, piperacillin with or without tazobactam, and ticarcillin/clavulanic acid) was performed using a common protocol and method (Etest; AB BIODISK, Solna, Sweden) in 102 clinical microbiology laboratories in the United States. A total of 9777 strains of Gram-negative bacilli were tested from late 1996 through April 1997. Quality assurance measures using three control strains observed quality control failures in 13 laboratories (usually ticarcillin/clavulanic acid or piperacillin), but only 2% of results required deletion. A total of 33.4% of Enterobacter spp. (1977 strains) were either resistant or intermediately susceptible to ceftazidime. Only imipenem (99.6% susceptible) and cefepime (99.1%) remained highly active against strains of Enterobacter , as well as Citrobacter freundii , indole-positive Proteae , and Serratia spp. Ceftazidime-resistant Escherichia coli and Klebsiella pneumoniae were detected at rates of 10.3% and 23.8%, respectively. Although these were participant-selected strains, only imipenem and cefepime had broad-spectrum coverage (≥97.1%) against these extended-spectrum β-lactamase phenotypes. A dominant number of these extended-spectrum β-lactamase phenotypes were reported from medical centers in the Northeast, but a nationwide distribution was observed. Among the nonenteric Gram-negative bacilli (4057 strains), the rank order of susceptibility (percent inhibited at published breakpoint concentrations) was: imipenem (86.1%) > piperacillin/tazobactam (80.1%) > cefepime (77.1%) > ceftazidime=piperacillin (74.9%) > ticarcillin/clavulanic acid (61.6%) > cefotaxime (18.2%) > ceftriaxone (12.9%). The cephalosporins, cefepime and ceftazidime, had rates of resistance for the 3005 Pseudomonas aeruginosa isolates of 10.1% and 14.4%, respectively. For all Gram-negative strains tested, only two contemporary β-lactam antimicrobials exhibited >90% inhibition of strains, imipenem at 93.6% and cefepime at 90.2%. These drugs were superior to the other tested compounds (48.8–84.3%). Ticarcillin/clavulanic acid had the narrowest spectrum of activity (48.8% of isolates susceptible). These results indicate that carbapenems and a new fourth-generation cephalosporin, cefepime, possess usable in vitro potencies against current clinical strains of Gram-negative bacilli, many of which harbored resistance to other antimicrobial agents.

In vitro activity evaluations of cefdinir (FK482, CI-983, and PD134393): A novel orally administered cephalosporin

Cefdinir, a so-called third-generation oral cephalosporin was tested in vitro against over 700 pathogens from patients with bacteremia. Cefdinir was very active against the Enterobacteriaceae with a 50% minimum inhibitory concentration (MIC50) value range of less than or equal to 0.03-8 micrograms/ml. The enteric species having the highest MIC90S (greater than or equal to 16 micrograms/ml) were Citrobacter freundii, and the enterobacters, Morganella morganii, Proteus vulgaris, and Serratia marcescens. Cefdinir was generally two- to fourfold less active than cefixime, but markedly more potent with a wider spectrum compared with older oral cephalosporins, cefaclor or cefuroxime. In contrast to cefixime, cefdinir inhibited Staphylococcus aureus (MIC90, 1 micrograms/ml) and other staphylococci. Pneumococci, beta-hemolytic streptococci, Haemophilus influenzae, Moraxella catarrhalis, and pathogenic Neisseria spp. (MIC90S, 0.12-0.5 micrograms/ml) were cefdinir susceptible, but Pseudomonas aeruginosa, oxacillin-resistant staphylococci and Bacteroides fragilis gr. strains were resistant. Cefdinir was generally bactericidal with a minimal inoculum effect at 10(6) colony-forming units per spot. Cefdinir beta-lactamase hydrolysis by some recently described extended broad spectrum beta-lactamases was suspected. Cefdinir exhibited a wide, balanced spectrum for an oral cephalosporin indicating possible clinical use against susceptible pathogens in respiratory tract, urinary tract, genital and cutaneous infections.

Antimicrobial activity evaluations of two new quinolones, PD127391 (CI-960 and AM-1091) and PD131628

The in vitro activities of PD127391 and the new fluorinated-4-quinolone, PD131628, were compared with each other and with five similar fluoroquinolones (ciprofloxacin, enoxacin, fleroxacin, norfloxacin, and ofloxacin). A total of 844 isolates mainly from recent clinical bacteremias and additional stock strains with well-characterized resistance mechanisms were tested. PD127391 had slightly more activity than PD131628 (90% minimum inhibitory concentration (MIC90)] 0.008-0.12) against the Enterobacteriaceae, but both were two- to fourfold more potent than ciprofloxacin. PD131628 activity was equal to or greater than PD127391 when tested against Pseudomonas aeruginosa. PD127391 showed greatest activity against Bacteroides fragilis group strains (MIC90, 2 micrograms/ml) when compared with PD131628 (MIC90 greater than 8 micrograms/ml). Both PD127391 (MIC90s, 0.015-1.0 micrograms/ml) and PD131628 (MIC90s, 0.03 - greater than 8 micrograms/ml) were more active than ciprofloxacin against Gram-positive organisms. Altering the medium pH, adding divalent cations (magnesium), and increasing the inoculum concentration to 10(6) colony-forming units per spot adversely effected the activity of both PD127391 and PD131628. Resistance selection and mutational rates to resistance were identical to previously studied drugs in their class.

Emerging multiply resistant enterococci among clinical isolates. II: Validation of the etest to recognize glycopeptide-resistant strains

Accurate, quantitative susceptibility testing of the enterococci for glycopeptide (vancomycin and teicoplanin) activity has become very important to guide chemotherapy as a result of emerging resistance. Reference dilution tests using broth and agar are generally difficult to perform, or in some commercial forms have demonstrated interpretive error. An alternative method, the Etest has promise as a system with qualitative and quantitative accuracy. Nearly 2000 enterococci from 97 laboratories in the United States were tested using broth microdilution, disk diffusion, and Etest methods. The Etest quantitative accuracy (+/- 1 log2 dilution) compared to the broth microdilution minimum inhibitory concentration was 90.1% (teicoplanin) to 94.1% (vancomycin). The qualitative interpretive accuracy of the Etest ranged from 98.7% for vancomycin to 99.9% for teicoplanin (no false-susceptible errors). All three tests were in remarkable agreement, with < or = 0.8% maximal discord by interpretive category. The Etest appears to be an excellent alternative to reference and standardized methods for producing quantitative activity measurements of glycopeptide susceptibility or resistance.

Etest for routine clinical antimicrobial susceptibility testing of rapid-growing mycobacteria isolates

The Etest has become a widely accepted alternative susceptibility-testing method for difficult-to-assess organisms, including rapid-growing Mycobacterium spp. Following an internal validation and literature reviews, the Etest was applied as the routine method for testing Mycobacterium chelonae and Mycobacterium fortuitum isolates. Results from testing 31 strains confirmed the utility of the Etest and the simplicity of the procedure. Mycobacterium chelonae were generally more resistant to all drugs except amikacin (MIC90, 32 micrograms/ml), compared with M. fortuitum strains that were inhibited (MIC50 in the susceptible range) by amikacin (1 microgram/ml), ciprofloxacin (0.032 microgram/ml), doxycycline (0.125 microgram/ml), and trimethoprim-sulfamethoxazole (0.032 microgram/ml). The polymyxin-B disk used as an identification method was confirmed (> or = 10 mm = M. fortuitum). The Etest provides a simple and accurate method for selecting appropriate therapy for infections caused by rapid-growing mycobacteria (a typical case report is presented).

Ofloxacin, a new broad-spectrum fluoroquinolone results from a multicenter, national comparative activity surveillance study

Ofloxacin, a newer broad-spectrum fluoroquinolone, was evaluated against 6967 clinical isolates in a multicenter surveillance trial using a standardized disk diffusion method. Thirty-five geographically diverse laboratories contributed zone diameter results for two (ofloxacin and ciprofloxacin) to five (ofloxacin, ciprofloxacin, ampicillin, cefaclor, and cefixime) antimicrobial agents, depending on the site of infection. Ofloxacin was determined to have the widest spectrum of activity and potential empiric use (90.6%, range 87.1%-92.2%) for respiratory tract, urinary tract, and cutaneous infections. The spectrum was superior to ciprofloxacin (average 85.3% versus three sites), ampicillin (35.5%, respiratory tract), cefaclor (60.5%, respiratory tract), cefixime (60.9%, respiratory tract), and norfloxacin (87.3%, urinary tract). Strains resistant to ofloxacin (35 isolates, 0.5%) were confirmed by reference laboratory tests and cross resistance was observed among several current and investigational fluoroquinolone agents. The species most often found to be fluoroquinolone resistant among the Enterobacteriaceae were Klebsiella pneumoniae, Serratia marcescens, and Providencia spp. Monitoring for increasing fluoroquinolone resistance should be considered as greater use of drugs in this class develops. By these cited statistics, ofloxacin appears to have a broad and balanced spectrum of potential use, particularly against Gram-positive pathogens.

Cefdinir (FK482), an orally administered cephalosporin in vitro activity comparison against recent clinical isolates from five medical centers and determination of MIC quality control guidelines

Cefdinir, a new oral cephalosporin, was compared to cefaclor, cefadroxil, cefixime, and cefuroxime against greater than 5000 recent aerobic clinical isolates. This multicenter study revealed broad-spectrum cefdinir activity against all Enterobacteriaceae (MIC50s, 0.06-2 micrograms/ml) except Enterobacter cloacae, Morganella morganii, Proteus vulgaris, and Serratia marcescens (MIC50s, greater than or equal to 4 micrograms/ml). Oxacillin-susceptible staphylococci (MIC90s, 0.5-2 micrograms/ml), beta-hemolytic Streptococcus group B (MIC90, 0.06 micrograms/ml), and Acinetobacter lwoffii were also susceptible to cefdinir. The activity of cefdinir was similar to that of cefixime and cefuroxime against Gram-negative organisms and superior to all tested oral cephems when tested against Gram-positive cocci. None of the cephalosporins were active against oxacillin-resistant Staphylococcus spp., enterococci, Pseudomonas spp., or Xanthomonas maltophilia. MIC quality control range guidelines were established for the strains recommended by the National Committee for Clinical Laboratory Standards documents.