Susan E. Beekmann

Antimicrobial Resistance among Gram-Negative Bacilli Causing Infections in Intensive Care Unit Patients in the United States between 1993 and 2004

ABSTRACT During the 12-year period from 1993 to 2004, antimicrobial susceptibility profiles of 74,394 gram-negative bacillus isolates recovered from intensive care unit (ICU) patients in United States hospitals were determined by participating hospitals and collected in a central location. MICs for 12 different agents were determined using a standardized broth microdilution method. The 11 organisms most frequently isolated were Pseudomonas aeruginosa (22.2%), Escherichia coli (18.8%), Klebsiella pneumoniae (14.2%), Enterobacter cloacae (9.1%), Acinetobacter spp. (6.2%), Serratia marcescens (5.5%), Enterobacter aerogenes (4.4%), Stenotrophomonas maltophilia (4.3%), Proteus mirabilis (4.0%), Klebsiella oxytoca (2.7%), and Citrobacter freundii (2.0%). Specimen sources included the lower respiratory tract (52.1%), urine (17.3%), and blood (14.2%). Rates of resistance to many of the antibiotics tested remained stable during the 12-year study period. Carbapenems were the most active drugs tested against most of the bacterial species. E. coli and P. mirabilis remained susceptible to most of the drugs tested. Mean rates of resistance to 9 of the 12 drugs tested increased with Acinetobacter spp. Rates of resistance to ciprofloxacin increased over the study period for most species. Ceftazidime was the only agent to which a number of species (Acinetobacter spp., C. freundii, E. aerogenes, K. pneumoniae, P. aeruginosa, and S. marcescens) became more susceptible. The prevalence of multidrug resistance, defined as resistance to at least one extended-spectrum cephalosporin, one aminoglycoside, and ciprofloxacin, increased substantially among ICU isolates of Acinetobacter spp., P. aeruginosa, K. pneumoniae, and E. cloacae.

Epidemiology and Outcome of Nosocomial and Community-Onset Bloodstream Infection

ABSTRACT We performed a prospective study of bloodstream infection to determine factors independently associated with mortality. Between February 1999 and July 2000, 929 consecutive episodes of bloodstream infection at two tertiary care centers were studied. An ICD-9-based Charlson Index was used to adjust for underlying illness. Crude mortality was 24% (14% for community-onset versus 34% for nosocomial bloodstream infections). Mortality attributed to the bloodstream infection was 17% overall (10% for community-onset versus 23% for nosocomial bloodstream infections). Multivariate logistic regression revealed the independent associations with in-hospital mortality to be as follows: nosocomial acquisition (odds ratio [OR] 2.6, P < 0.0001), hypotension (OR 2.6, P < 0.0001), absence of a febrile response (P = 0.003), tachypnea (OR 1.9, P = 0.001), leukopenia or leukocytosis (total white blood cell count of <4,500 or >20,000, P = 0.003), presence of a central venous catheter (OR 2.0, P = 0.0002), and presence of anaerobic organism (OR 2.5, P = 0.04). Even after adjustments were made for underlying illness and length of stay, nosocomial status of bloodstream infection was strongly associated with increased total hospital charges (P < 0.0001). Although accounting for about half of all bloodstream infections, nosocomial bloodstream infections account for most of the mortality and costs associated with bloodstream infection.

Antimicrobial Resistance among Streptococcus pneumoniae in the United States: Have We Begun to Turn the Corner on Resistance to Certain Antimicrobial Classes?

BACKGROUND Antimicrobial resistance has emerged as a major problem in Streptococcus pneumoniae in the United States during the past 15 years. This study was undertaken to elucidate the current scope and magnitude of this problem in the United States and to assess resistance trends since 1994-1995. METHODS A total of 1817 S. pneumoniae isolates obtained from patients with community-acquired respiratory tract infections in 44 US medical centers were characterized during the winter of 2002-2003. The activity of 27 antimicrobial agents was assessed. In addition, selected isolates were examined for the presence of mutations in the quinolone-resistance determining regions (QRDRs) of parC and gyrA that resulted in diminished fluoroquinolone activity. The results of this survey were compared with the results of 4 previous surveys conducted in a similar manner since 1994-1995. RESULTS Overall rates of resistance (defined as the rate of intermediate resistance plus the rate of resistance) were as follows: penicillin, 34.2%; ceftriaxone, 6.9%; erythromycin, 29.5%; clindamycin, 9.4%; tetracycline, 16.2%; and trimethoprim-sulfamethoxazole (TMP-SMX), 31.9%. No resistance was observed with vancomycin, linezolid, or telithromycin; 22.2% of isolates were multidrug resistant; 2.3% of isolates had ciprofloxacin MICs of >or=4.0 microg/mL. It was estimated that 21.9% of the isolates in this national collection had mutations in the QRDRs of parC and/or gyrA, with parC only mutations occurring most often (in 21% of all isolates). Trend analysis since 1994-1995 indicated that rates of resistance to beta -lactams, macrolides, tetracyclines, TMP-SMX, and multiple drugs have either plateaued or have begun to decrease. Conversely, fluoroquinolone resistance among S. pneumoniae is becoming more prevalent. CONCLUSION It appears that, as fluoroquinolone resistance emerges among S. pneumoniae in the United States, resistance to other antimicrobial classes is becoming less common.

Effects of Rapid Detection of Bloodstream Infections on Length of Hospitalization and Hospital Charges

ABSTRACT Current automated continuous-monitoring blood culture systems afford more rapid detection of bacteremia and fungemia than is possible with non-instrument-based manual methods. Use of these systems has not been studied objectively with respect to impact on patient outcomes, including hospital charges and length of hospitalization. We conducted a prospective, two-center study in which the time from the obtainment of the initial positive blood culture until the Gram stain was called was evaluated for 917 cases of bloodstream infection. Factors showing univariate associations with a shorter time to notification included higher body temperature and respiratory rate and higher percentage of immature neutrophils. Multiple linear regression models determined that the primary predictors of both increased microbiology laboratory and total hospital charges for patients with bloodstream infection were nonmicrobiologic and included length of stay and host factors such as the admitting service and underlying illness score. Significant microbiologic predictors of increased charges included the number of blood cultures obtained, nosocomial acquisition, and polymicrobial bloodstream infections. Accelerated failure time regression analysis demonstrated that microbiologic factors, including time until notification, organism group, and nosocomial acquisition, were independently associated with length of hospitalization after bacteremia, as were the factors of admitting service, gender, and age. Our data suggest that an increased time to notification of bloodstream infection is independently associated with increased length of stay. We conclude that the time to notification is an obvious target for efforts to shorten length of stay. The newest generation of automated continuous-monitoring blood culture systems, which shorten the time required to obtain a positive result, should impact length of hospitalization.

Detection and Treatment of Bloodstream Infection: Laboratory Reporting and Antimicrobial Management

ABSTRACT We analyzed antimicrobial use in 509 episodes of clinically significant bloodstream infection to assess the impact that microbiology laboratory reporting had on antimicrobial management. Most therapy interventions occurred at the time of phlebotomy and after notification of Gram stain results by telephone. Release of antimicrobial susceptibility data had the least impact on antimicrobial management.

Percutaneous Injury, Blood Exposure, and Adherence to Standard Precautions: Are Hospital-Based Health Care Providers Still at Risk?

To examine factors associated with blood exposure and percutaneous injury among health care workers, we assessed occupational risk factors, compliance with standard precautions, frequency of exposure, and reporting in a stratified random sample of 5123 physicians, nurses, and medical technologists working in Iowa community hospitals. Of these, 3223 (63%) participated. Mean rates of hand washing (32%-54%), avoiding needle recapping (29%-70%), and underreporting sharps injuries (22%-62%; overall, 32%) varied by occupation (P<.01). Logistic regression was used to estimate the adjusted odds of percutaneous injury (aOR(injury)), which increased 2%-3% for each sharp handled in a typical week. The overall aOR(injury) for never recapping needles was 0.74 (95% CI, 0.60-0.91). Any recent blood contact, a measure of consistent use of barrier precautions, had an overall aOR(injury) of 1.57 (95% CI, 1.32-1.86); among physicians, the aOR(injury) was 2.18 (95% CI, 1.34-3.54). Adherence to standard precautions was found to be suboptimal. Underreporting was found to be common. Percutaneous injury and mucocutaneous blood exposure are related to frequency of sharps handling and inversely related to routine standard-precaution compliance. New strategies for preventing exposures, training, and monitoring adherence are needed.

Mycobacterial and Other Serious Infections in Patients Receiving Anti-Tumor Necrosis Factor and Other Newly Approved Biologic Therapies: Case Finding through the Emerging Infections Network

We present the results of a nationwide survey of infectious disease consultants to identify mycobacterial and other serious infections in patients receiving anti-tumor necrosis factor compounds and other novel targeted therapies. Nontuberculous mycobacterial infections, histoplasmosis, and invasive Staphylococcus aureus infection were all reported more frequently than was tuberculosis disease in this context.

Changing Epidemiology of Antimicrobial-Resistant Streptococcus pneumoniae in the United States, 2004–2005

BACKGROUND The impact of pediatric 7-valent pneumococcal conjugate vaccination (PCV-7) on the population of Streptococcus pneumoniae in the United States was examined by determining the serotypes, antimicrobial resistance profiles, and genetic relatedness of isolates from patients with invasive and noninvasive infections during the 2004-2005 respiratory illness season. METHODS Susceptibility testing, serotyping, and pulsed-field gel electrophoresis analysis were performed on 1647 S. pneumoniae isolates obtained from 41 US medical centers in 2004-2005 as part of a longitudinal antimicrobial resistance surveillance program. The results were compared with surveillance data from earlier periods. RESULTS From the 1999-2000 to the 2004-2005 respiratory illness season, the prevalence of isolates with intermediate penicillin resistance (minimum inhibitory concentration, 0.1-1 microg/mL) increased from 12.7% to 17.9%, prevalence of penicillin-resistant isolates (minimum inhibitory concentration, >or=2 microg/mL) decreased from 21.5% to 14.6%, and prevalence of isolates resistant to erythromycin increased from 25.7% to 29.1% among S. pneumoniae isolates. The prevalence of multidrug resistance among isolates did not change (22.4% in 1999-2000 and 20.0% in 2004-2005). Sixty different serotypes were recognized among the isolates from 2004-2005; predominant serotypes were 19A (14.5%), 3 (11.2%), 6A (7.1%), 19F (7%), and 11A (6%). Serotypes that were included in PCV-7 accounted for 16.3% of isolates; 28.4% of strains isolated had PCV-7-related serotypes, and the remaining 55.3% of isolates had serotypes that were unrelated to PCV-7. The serotype distribution of the penicillin-resistant S. pneumoniae population changed from 1999-2000 to 2004-2005, with an increase in the prevalence of serotype 19A (1.5% to 35.4%) and serotype 35B (1.2% to 12.5%) and a decrease in the prevalence of most PCV-7 serotypes, including 23F (16.1% to 5%), 9V (16.1% to 4.2%), 6B (13.7% to 3.8%), and 14 (18.5% to 2.9%). CONCLUSIONS The penicillin-resistant S. pneumoniae population has changed; most isolates are now closely related to 2 Pneumococcal Molecular Epidemiology Network clones that increased in prevalence from 1999-2000 to 2004-2005 (Taiwan(19F)-14 [14.6% to 36.7%; 60% were serotype 19A] and Utah(35B)-24 [0.9% to 16.3%]).

Macrolide-Resistant Streptococcus pyogenes in the United States, 2002–2003

BACKGROUND Increased levels of macrolide-resistant Streptococcus pyogenes in focal regions of the United States have been reported. The purpose of this study was to determine the antimicrobial susceptibility of a large collection of S. pyogenes isolates from throughout the United States and to elucidate the mechanisms of resistance and genetic relatedness of macrolide-resistant isolates. METHODS During 2002-2003, a total of 1885 S. pyogenes clinical isolates were obtained from 45 US medical centers. Susceptibility to penicillin, cefdinir, erythromycin, azithromycin, clarithromycin, clindamycin, telithromycin, and levofloxacin was determined. Macrolide resistance phenotypes were determined by double-disk diffusion, and macrolide resistance genotypes were determined by polymerase chain reaction and sequencing. All macrolide-resistant isolates and all isolates recovered from sterile sites were further characterized by pulsed-field gel electrophoresis (PFGE) and emm typing. RESULTS The majority (85%) of isolates were pharyngeal. Resistance was detected to erythromycin (6.8% of isolates), azithromycin (6.9%), clarithromycin (6.6%), clindamycin (0.5%), telithromycin (0.2%), and levofloxacin (0.05%). The macrolide-resistance phenotype distribution was as follows: macrolide-lincosamide-streptogramin B (MLSB), 56% of isolates (inducible, 47%; constitutive, 9%); and M, 44%. The genotypes detected were as follows: ermA, 46% of isolates (95% with inducible MLSB phenotype); mefA, 43% (all with M phenotype); and ermB, 8.5% (45% with inducible MLSB and 45% with constitutive MLSB). Three isolates with constitutive MLSB phenotypes had 23S ribosomal RNA mutations. The 129 erythromycin-resistant isolates belonged to 28 emm types and 44 PFGE patterns, with 51% of the isolates in 4 major PFGE clones each associated with a predominant emm type (emm75, emm58, emm12, and emm114) and resistance genotype (mefA or ermA)). CONCLUSIONS The population of macrolide-resistant S. pyogenes isolates in the United States is small, but it includes several large clones with potential for expansion.

Minimizing the Workup of Blood Culture Contaminants: Implementation and Evaluation of a Laboratory-Based Algorithm

ABSTRACT An algorithm was implemented in the clinical microbiology laboratory to assess the clinical significance of organisms that are often considered contaminants (coagulase-negative staphylococci, aerobic and anaerobic diphtheroids, Micrococcus spp., Bacillus spp., and viridans group streptococci) when isolated from blood cultures. From 25 August 1999 through 30 April 2000, 12,374 blood cultures were submitted to the University of Iowa Clinical Microbiology Laboratory. Potential contaminants were recovered from 495 of 1,040 positive blood cultures. If one or more additional blood cultures were obtained within ±48 h and all were negative, the isolate was considered a contaminant. Antimicrobial susceptibility testing (AST) of these probable contaminants was not performed unless requested. If no additional blood cultures were submitted or there were additional positive blood cultures (within ±48 h), a pathology resident gathered patient clinical information and made a judgment regarding the isolates significance. To evaluate the accuracy of these algorithm-based assignments, a nurse epidemiologist in approximately 60% of the cases performed a retrospective chart review. Agreement between the findings of the retrospective chart review and the automatic classification of the isolates with additional negative blood cultures as probable contaminants occurred among 85.8% of 225 isolates. In response to physician requests, AST had been performed on 15 of the 32 isolates with additional negative cultures considered significant by retrospective chart review. Agreement of pathology resident assignment with the retrospective chart review occurred among 74.6% of 71 isolates. The laboratory-based algorithm provided an acceptably accurate means for assessing the clinical significance of potential contaminants recovered from blood cultures.