Tracking resistance among bacterial respiratory tract pathogens: summary of findings of the TRUST Surveillance Initiative, 2001-2005.

Antimicrobial resistance observed among common respiratory tract pathogens--Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis--may complicate empiric therapeutic selection to treat community-acquired respiratory tract infections. The Tracking Resistance in the United States Today (TRUST) study determined the in vitro activities of frequently prescribed antimicrobial agents against isolates collected from all 50 states from 2001 to 2005. For S pneumoniae (N = 27,781), susceptibility of selected agents in ascending order were penicillin (oral) (65.4%), trimethoprim-sulfamethoxazole (TMP-SMX) (69.5%), erythromycin (72.0%), cefuroxime (oral) (75.9%), tetracycline (85.3%), amoxicillinclavulanate (92.6%), ceftriaxone (nonmeningitis) (96.6%), and levofloxacin (99.0%). Susceptibility to levofloxacin, which was used as a representative of the respiratory fluoroquinolones, was near 99% from 2001 to 2005, and the minimum inhibitory concentration (90%) (MIC(90)) remained unchanged at 1 microg/mL. Levofloxacin and the other respiratory fluoroquinolones remained highly effective against penicillin-resistant S pneumoniae(PRSP) (98%-99% susceptible). However, susceptibility of PRSP to amoxicillin-clavulanate decreased from 62%S in 2003 to 48%S in 2005. Haemophilus influenzae susceptibility to ampicillin averaged near 70%, and near 75% to TMP-SMX. Susceptibility rates to levofloxacin and the other respiratory fluoroquinolones for H influenzae and M catarrhalis remained at or near 100%. Although resistance rates among S pneumoniae have stabilized for penicillin (oral) at elevated levels and increased for macrolides, susceptibility to the respiratory fluoroquinolones has consistently remained high, as they have for H influenzae and M catarrhalis.

Sporadic occurrences of fluoroquinolone-resistant Streptococcus pneumoniae in the United States: longitudinal analysis of institutions from the New England and West South Central regions during the TRUST 4-9 (2000-2005) Surveillance Studies.

Twenty-six institutions in New England and 24 institutions in West South Central regions participating in the Tracking Resistance in the United States Today (TRUST) 4-9 surveillance studies (2000-2005) were monitored for levofloxacin-resistant Streptococcus pneumoniae to determine if resistance was sporadic or persistent. Levofloxacin was used as a representative of the respiratory fluoroquinolones. Levofloxacin-resistant isolates were identified in 8 of the 26 New England institutions and in 11 of the 24 West South Central institutions during the surveillance period. Resistant isolates were recovered in consecutive years from 3 institutions: 1 each in Massachusetts, Oklahoma, and Texas. In total, 34 levofloxacin-resistant isolates (14 from New England, 20 from the West South Central region) were identified over the 6-year period. Two of these isolates from an institution in Connecticut and 2 from an institution in Oklahoma had the same serotype, pulsed-field gel electrophoresis pattern, and quinolone resistance-determining region (QRDR) mutations. States with elevated pneumococcal levofloxacin resistance rates, compared with the national average, did not maintain this status in consecutive years. Based on data from the same institutions over 6 years, levofloxacin resistance among US pneumococci has been sporadic, nonclonal, and rare.

Antimicrobial activity among multidrug-resistant Streptococcus pneumoniae isolated in the United States, 2001-2005.

Infections caused by multidrug-resistant (MDR) Streptococcus pneumoniae remain a major concern when selecting an appropriate antimicrobial agent. In this analysis, 27 781 isolates of S pneumoniae collected from 2001 to 2005 in the United States were tested for MDR phenotypes. About 25% of all isolates were MDR, defined as resistant to 2 or more of the following agents: cefuroxime, a macrolide, penicillin, tetracycline (if available), and trimethoprim-sulfamethoxazole (TMP-SMX). There was a slight decreasing trend over time in multidrug resistance prevalence with erythromycin. Among MDR strains, the most common coresistance pair was erythromycin and TMP-SMX (74% of isolates, irrespective of resistance to other agents), although penicillin-erythromycin and penicillin-TMP-SMX coresistance patterns were also found in more than 56% of MDR strains. Resistance to 4 antimicrobial agents tested was observed in 33% of all antimicrobial-resistant isolates. Levofloxacin, which was used as a representative of the fluoroquinolone class, was active against at least 98% of all MDR isolates, and the minimum inhibitory concentration (90%) (MIC(90)) for this population was 1 microg/mL (identical to the total S pneumoniae, population). Multidrug-resistant isolates from 2003 to 2005 were found to be equally susceptible (98%) to other respiratory fluoroquinolones (gatifloxacin and moxifloxacin; data not shown), although only 88% of MDR isolates (from 2001-2005) were susceptible to ciprofloxacin. Careful monitoring of multidrug resistance patterns will help guide appropriate therapeutic selection and may provide early detection of changes in resistance to more potent agents.

Decline in the prevalence of pandemic clones Spain23F-1 and Spain9V-3 among US fluoroquinolone-resistant Streptococcus pneumoniae TRUST Surveillance isolates since 2001.

Fluoroquinolone-resistant variants of pandemic clones Spain(23F)-1, Spain(6B)-2, Spain(9V)-3, and Spain(14)-5 have been seen in various regions of the United States and the world, leading to the speculation that fluoroquinolone resistance among US Streptococcus pneumoniae may increase because of clonal spread. Using levofloxacin as a representative of the fluoroquinolone class, all 196 levofloxacin-resistant pneumococci from a total of 22 794 isolates in the Tracking Resistance in the United States Today (TRUST) 5-8 studies (2001-2004) were subjected to pulsed-field gel electrophoresis (PFGE), serotyping, and sequencing of parC/E and gyrA/B quinolone resistance-determining regions (QRDR) to measure the extent of clonality. In addition, susceptibility testing of these isolates to ciprofloxacin, gatifloxacin, levofloxacin, and moxifloxacin was performed. ATCC type strains of Spain(23F)-1, Spain(6B)-2, Spain(9V)-3, and Spain(14)-5 clones were included as comparators. Levofloxacin-resistant isolates with Spain(23F)-1-related PFGE patterns decreased from 28% of the resistant isolates in 2001 to 6% in 2004. These isolates, with serotypes 23F (n = 17), 19F (n = 17), or 19A (n = 1), had 15 different QRDR profiles and were all ciprofloxacin- and gatifloxacin-resistant. Levofloxacin-resistant isolates with Spain(9V)-3-related PFGE patterns decreased from 13% of the resistant isolates in 2001 to 2% in 2004. The Spain(9V)-3-related isolates were serotype 9V (n = 9), 9A (n = 2), and 9N (n = 1) and exhibited 6 different QRDR profiles. All were resistant to all fluoroquinolones tested. None of the levofloxacin-resistant isolates had PFGE patterns related to Spain(6B)-2 or Spain(14)-5. Resistance to respiratory fluoroquinolones among pneumococci has remained constant at about 1% (0.8%-1.1%) since 2001, and there has been a decrease in the prevalence of levofloxacin-resistant isolates similar to Spain(23F)-1 or Spain(9V)-3. Considerable QRDR variability among these strains appears to be the result of sporadic independent mutational events as opposed to clonal expansion.

Stratified analysis of multidrug-resistant Escherichia coli in US health care institutions.

Surveillance studies typically fail to provide sufficient information on how susceptibility rates differ among institutions and within patient age groups. Furthermore, antimicrobial resistance in context with resistance to other antimicrobial classes may help to understand resistance trends and may be useful for implementing control initiatives. This study used The Surveillance Network-USA (TSN-USA) and the Tracking Resistance in the United States Today (TRUST) surveillance data (2003-2005) to analyze multidrug-resistant (MDR) Escherichia coli at 229 institutions across the United States. Institutions with a higher prevalence of E coli resistant to multiple nonfluoroquinolone agents were associated with lower fluoroquinolone susceptibility. The prevalence of fluoroquinolone and multidrug resistance was also associated with increased patient age and locations such as long-term care facilities. Institutions attempting to understand and control E coli resistance to fluoroquinolones should carefully examine the patient population and prevalence of resistance to other agents.

Effects of the 7-valent pneumococcal conjugate vaccine on U.S. levofloxacin-resistant Streptococcus pneumoniae.

BACKGROUND: Seven-valent pneumococcal conjugate vaccine (PCV7) provides protection against invasive pneumococcal disease that extends to unvaccinated populations, such as elderly or immunocompromised adults. PCV7 also reduces incidence of pneumococcal penicillin resistance. In this study, the potential impact of PCV7 on pneumococcal fluoroquinolone resistance was examined. METHODS: U.S. levofloxacin-resistant isolates (264) from TRUST surveillance studies (1999-2004) were serotyped and quinolone resistance-determining region of parC/E and gyrA/B sequenced. Changes in prevalence of vaccine/nonvaccine serotypes during 2000-2004 and 1999-2004 were analyzed by regression analyses and chi-square trend test. RESULTS: The introduction of PCV7 (2000-2004) did not affect fluoroquinolone resistance prevalence, but mutants with vaccine serotypes declined linearly at -6.6 +/- 0.8% per year (p = 0.003), with concomitant replacement by nonvaccine serotypes; vaccine-related serotypes (6A, 9N, 19A, and 23N) increased (p = 0.04). Differential selection between vaccine and nonvaccine serotypes occurred for mutants containing amino acid substitutions at either ParC Ser79 (p = 0.01) or both ParC Ser79 and GyrA Ser81 (p = 0.04). Among mutants with ParC Ser79 substitutions, vaccine serotypes declined linearly (p = 0.02), whereas nonvaccine serotypes increased (p = 0.04). Additionally, a vaccine-independent effect became apparent during 1999-2004, as the incidence of ParC Ser79 and Asp83 mutations declined in fluoroquinolone-resistant strains, suggesting that these substitutions conferred decreased fitness. CONCLUSIONS: PCV7 has led to extensive replacement of vaccine serotypes by nonvaccine serotypes among levofloxacin-resistant pneumococci.

Antimicrobial resistance trends among sinus isolates of Streptococcus pneumoniae in the United States (2001-2005).

OBJECTIVE: To test the susceptibility of Streptococcus pneumoniae sinus isolates collected across the United States against commonly used antimicrobial agents. STUDY DESIGN AND SETTING: S. pneumoniae sinus isolates (N = 847) collected as part of the Tracking Resistance in the US Today Surveillance Program from 2001 to 2005 were tested against 8 antimicrobial agents. RESULTS: In ascending order, the relative activities (% susceptible) were penicillin (51.8%), trimethoprim/sulfamethoxazole (TMP/SMX) (57.6%), erythromycin (59.5%), cefuroxime (62.0%), amoxicillin/clavulanate (85.5%), clindamycin (86.1%), levofloxacin (99.4%), and linezolid (100%; for 2004 and 2005 respiratory seasons, only). Resistance rates over the 5 years remained generally stable, although resistance to amoxicillin/clavulanate nearly doubled (from 6.5% to 12.9%). Forty percent of isolates were resistant to >or=2 agents tested. CONCLUSIONS AND SIGNIFICANCE: Susceptibility trends among sinus S. pneumoniae isolates appear to have stabilized over the past 5 years. Resistance rates remain elevated for penicillin and macrolides, whereas the high prevalence of multidrug resistance remains a concern.

Infrequent occurrence of single mutations in topoisomerase IV and DNA gyrase genes among US levofloxacin-susceptible clinical isolates of Streptococcus pneumoniae from nine institutions (1999-2003).

OBJECTIVES: Prevalence of single quinolone-resistance determining region (QRDR) mutations in Streptococcus pneumoniae was studied from nine institutions over 5 years to track the incidence of single QRDR mutations. METHODS: All 1106 levofloxacin-susceptible pneumococci (MICs < or = 2.0 mg/L) identified from 1112 total isolates (99.5% susceptibility) in TRUST 3 (1999), TRUST 5 (2001) and TRUST 7 (2003) surveillance studies from the same nine hospitals in nine states were screened for QRDR mutations. Using pyrosequencing, the strains were screened for mutations corresponding to hot spots Asp-78, Ser-79 and Asp-83 in ParC; Asp-80, Ser-81 and Glu-85 in GyrA; Asp-435 in ParE and Asp-435 in GyrB. DNA sequencing of QRDRs was performed to confirm mutations. RESULTS: No QRDR mutations were found in any of the isolates with levofloxacin MICs < or = 0.5 mg/L and no gyrA or gyrB QRDR mutations were found in any of the screened isolates (MICs < or = 2 mg/L). Four single-step QRDR mutants with the following amino acid substitutions were found: ParE Asp-435 to Asn (isolated in 1999 in Colorado); ParC Asp-83 to Asn (isolated in 2001 in Kentucky); ParC Ser-79 to Phe (isolated in 2003 in Indiana) and ParC Ser-79 to Tyr (isolated in 2003 in California). These non-clonal strains had levofloxacin MICs of 1 mg/L and were non-susceptible to ciprofloxacin (MIC 2-4 mg/L). CONCLUSIONS: Overall prevalence of single QRDR mutations in levofloxacin-susceptible S. pneumoniae with MICs of < or = 2 mg/L was 0.4% (4/1106) and has remained <1% within nine institutions over 5 years (1999-2003).

Stable antimicrobial susceptibility rates for clinical isolates of Pseudomonas aeruginosa from the 2001-2003 tracking resistance in the United States today surveillance studies.

From 2001 to 2003, rates of susceptibility to piperacillin-tazobactam (86%), ceftazidime (80%), ciprofloxacin (68%), and levofloxacin (67%) did not decrease or decreased by <1.5%, whereas the rate of susceptibility to gentamicin decreased by 3.2% (from 75.5% to 72.3%) and the rate of susceptibility to imipenem decreased by 5.6% (from 84.4% to 78.8%), for 2394 clinical isolates of Pseudomonas aeruginosa collected in the Tracking Resistance in the United States Today surveillance studies. Rates of multidrug resistance (i.e., resistance to > or =3 antimicrobial agents) increased from 7.2% in 2001 to 9.9% in 2003 and were significantly higher for isolates from the East North Central and Mid-Atlantic regions of the United States than for isolates from other regions. Analysis of minimum inhibitory concentrations (MICs) suggested that combining an antipseudomonal beta -lactam with ciprofloxacin or levofloxacin would yield a 3.4%-7.1% increase in the percentage of isolates susceptible to the combination, compared with the beta -lactam alone. Ratios of the area under the serum concentration-time curve values for free drug to modal MICs for ciprofloxacin and levofloxacin were similar and were >125 (target ratio), whereas those ratios for gatifloxacin and moxifloxacin were significantly lower. Ongoing surveillance of P. aeruginosa is essential.