Genetic relatedness of multidrug-resistant Acinetobacter baumannii endemic to New York City.

Multidrug-resistant isolates of Acinetobacter baumannii from New York City generally belong to one of three ribotypes. To assess the accuracy of ribotyping, the relatedness of representative isolates was further assessed by rep-PCR, pulsed-field gel electrophoresis (PFGE), and DNA sequencing of five genes potentially associated with antimicrobial resistance (ampC, ompA, adeB, adeR, and abeM). The isolates fell into several major groups. The first group shared the same ribotype and had common mutations affecting OmpA, AdeR, and AbeM, but consisted of two subtypes with distinctive rep-PCR and PFGE patterns and ampC mutations. The second and third groups shared common alterations in OmpA, AdeR, and AbeM, but had distinct ribotype, rep-PCR, and PFGE patterns. The resistant isolates were unrelated to the beta-lactam susceptible isolates. Many of the resistant strains shared OmpA and AdeB patterns observed in several European clonal groups. Further development of a multilocus sequencing typing scheme will help determine if multidrug-resistant isolates from diverse geographic areas are indeed ancestrally related.

Evaluation of techniques for detection of carbapenem-resistant Klebsiella pneumoniae in stool surveillance cultures.

Screening for gastrointestinal colonization with multidrug-resistant nosocomial pathogens is an important component of infection control protocols. In the New York City region, carbapenem-resistant Klebsiella pneumoniae strains, which harbor the KPC carbapenem-hydrolyzing beta-lactamase, have rapidly emerged. The potential utility of screening medium, which involved using 10-mug imipenem disks, was investigated. The method of placing a sample from a fecal surveillance culture into broth containing an imipenem disk appeared to have the greatest sensitivity for detecting KPC-producing K. pneumoniae. Gastrointestinal colonization with two other carbapenem-resistant nosocomial pathogens, Pseudomonas aeruginosa and Acinetobacter baumannii, was also detected using this method. Placing fecal surveillance specimens into broth containing an imipenem disk is an easy method for screening samples for carbapenem-resistant nosocomial pathogens.

Multidrug-resistant Pseudomonas aeruginosa in Brooklyn, New York: molecular epidemiology and in vitro activity of polymyxin B.

Multidrug-resistant strains of Pseudomonas aeruginosa have become increasingly problematic in certain hospitals. For a 3-month period in 2001, all unique patient isolates were collected from 15 hospitals in Brooklyn, New York, USA. Of 691 isolates, only 70% were susceptible to imipenem and 56% to ciprofloxacin. These susceptibility rates were lower than those found in a prior surveillance study in 1999 (76% and 71% susceptible to imipenem and ciprofloxacin, respectively; p<0.001). The rate of imipenem resistance was associated with fluoroquinolone usage at each hospital (p=0.04). All isolates were susceptible to polymyxin B and 95% to amikacin. Among 195 imipenem-resistant isolates, 47 unique ribotypes were found. However, four ribotypes accounted for >50% of isolates and were shared by most hospitals. Time-kill studies with 13 unique multiresistant strains revealed that polymyxin B was bactericidal against all strains at 4 mg/l, but only against 3 of 13 (23%) strains at 2 mg/l. Using 2 mg/l, significant bacterial regrowth was evident for 5 of 13 (38%) strains. The addition of azithromycin to polymyxin B (2 mg/l) produced a mean decrease of 1 log cfu/ml greater than polymyxin alone and allowed bacterial regrowth in only 2 of 13 (15%) strains. Multiresistant P. aeruginosa is highly endemic to this city, with a few strains having spread among most hospitals. Polymyxin B remains active against all isolates and produces concentration-dependent killing in vitro. Azithromycin appears to enhance the in vitro activity of polymyxin B. The clinical utility of this combination remains to be established.

Molecular epidemiology of oxacillin-resistant Staphylococcus aureus in Brooklyn, New York.

Although oxacillin-resistant Staphylococcus aureus (ORSA) are well-established pathogens in many hospitals, the impact of infection control measures on the clonal distribution of ORSA is poorly defined. A citywide surveillance study of Staphylococcus aureus in Brooklyn, New York revealed that 36% of isolates were ORSA. Molecular typing showed that one strain (Cluster A) accounted for more than half of the isolates and was present in all 15 hospitals. In one hospital, a distinct strain (Cluster B) accounted for 20% of ORSA isolates. Infection control measures in this hospital significantly decreased the percentage of clinical isolates that belonged to Cluster B, but did not have an effect on the strain endemic to the city (Cluster A). Regional infection control strategies may need to be developed to limit the spread of the ORSA clone endemic to this area.

Comparison of automated ribotyping to pulsed-field gel electrophoresis for genetic fingerprinting of Streptococcus pneumoniae.

Fifty-two isolates of Streptococcus pneumoniae were characterized by pulsed-field gel electrophoresis (PFGE) and automated ribotyping by using HindIII and PvuII. HindIII ribotypes correlated well with PFGE. PvuII produced fewer bands and was less discriminatory. Automated ribotyping with HindIII is an accurate method for genetic fingerprinting of S. pneumoniae and can complement PFGE.

Endemic carbapenem-resistant Acinetobacter species in Brooklyn, New York: citywide prevalence, interinstitutional spread, and relation to antibiotic usage.

Acinetobacter species are problematic nosocomial pathogens. In November 1997, pathogens isolated by microbiology laboratories were collected from 15 hospitals in Brooklyn, New York. Acinetobacter species accounted for 10% of gram-negative isolates. Only half of Acinetobacter species were susceptible to carbapenems; 11 hospitals had at least 1 isolate resistant to carbapenems. Other Acinetobacter susceptibility rates were as follows: polymyxin, 99%; amikacin, 87%; ampicillin/sulbactam, 47%; ceftazidime, 25%; and ciprofloxacin 23%. Overall, 10% were resistant to all commonly used antibiotics. Genetic analysis by use of pulsed-field gel electrophoresis of 12 carbapenem-resistant isolates revealed 4 strains that were recovered from >1 hospital, which suggests interinstitutional spread. Antibiotic usage data from 11 hospitals revealed that the use of third-generation cephalosporins was associated significantly with the percentage of carbapenem-resistant strains (P=.03). Resistant Acinetobacter species have become endemic in Brooklyn, New York. Citywide strategies that involve surveillance, infection-control practices, and the reduction of antibiotic usage may be necessary to control the spread of these pathogens.

Antimicrobial resistance in Enterobacteriaceae in Brooklyn, NY: epidemiology and relation to antibiotic usage patterns.

In November 1997, all Enterobacteriaceae isolated at 15 hospitals in Brooklyn were collected. Extended-spectrum beta-lactamases (ESBLs) were present in 44% of 409 Klebsiella pneumoniae isolates. Six isolates had reduced susceptibility to carbapenems, including two that were not susceptible to any of the antibiotics tested. Pulsed field gel electrophoresis revealed a commonality of resistant isolates within and between hospitals. The occurrence of ESBLcontaining isolates was associated with cephalosporin usage (P = 0.055). ESBLs were present in 4.7% of Escherichia coli and 9.5% of Proteus mirabilis isolates. It is concluded that ESBL-producing Enterobacteriaceae are endemic in Brooklyn, are spread between hospitals, and may be associated with cephalosporin usage.

Reduction in the incidence of methicillin-resistant Staphylococcus aureus and ceftazidime-resistant Klebsiella pneumoniae following changes in a hospital antibiotic formulary.

In 1995, changes in our hospital formulary were made to limit an outbreak of vancomycin-resistant enterococci and resulted in decreased usage of cephalosporins, imipenem, clindamycin, and vancomycin and increased usage of beta-lactam/beta-lactamase-inhibitor antibiotics. In this report, the effect of this formulary change on other resistant pathogens is described. Following the formulary change, there was a reduction in the monthly number (mean +/- SD) of patients with methicillin-resistant Staphylococcus aureus (from 21.9 +/- 8.1 to 17.2 +/- 7.2 patients/1,000 discharges; P = .03) and ceftazidime-resistant Klebsiella pneumoniae (from 8.6 +/- 4.3 to 5.7 +/- 4.0 patients/1,000 discharges; P = .02). However, there was an increase in the number of patients with cultures positive for cefotaxime-resistant Acinetobacter species (from 2.4 +/- 2.2 to 5.4 +/- 4.0 patients/1,000 discharges; P = .02). Altering an antibiotic formulary may be a possible mechanism to contain the spread of selected resistant pathogens. However, close surveillance is needed to detect the emergence of other resistant pathogens.

Deja vu: nosocomial hepatitis B virus transmission and fingerstick monitoring.

PURPOSE: Three patients with acute hepatitis B virus infection were identified who had been hospitalized on the same medical ward during a 19-day period several months earlier. An investigation was undertaken to determine if nosocomial transmission had occurred. SUBJECTS AND METHODS: A cohort study of patients admitted to the medical ward during the 19-day period in 1995 was conducted. In addition, we reviewed medical charts and laboratory records of all patients with acute hepatitis B virus infection who had been admitted to the hospital from 1992 through October 1996 to identify other cases with possible nosocomial acquisition. RESULTS: The 3 patients who had developed acute hepatitis B infection 2 to 5 months after hospitalization on the same medical ward had diabetes mellitus but no identified risk factors for hepatitis B infection. A source patient with diabetes mellitus and hepatitis B "e" antigenemia also was present on the same medical ward at the same time; all 4 patients were infected with the same viral subtype (adw2). Diabetes mellitus and fingerstick monitoring were associated with illness (P <0.001). Through the review of medical charts and laboratory records, 11 additional cases of suspected nosocomial acquisition via fingersticks were identified in 1996, including two clusters involving an unusual subtype of hepatitis B virus (adw4). The fingerstick device employed had a reusable base onto which disposable lancet caps were inserted. There was ample opportunity for cross-contamination among patients because deficiencies in infection control practices, particularly failure to change gloves between patients, were reported by nurses and patients with diabetes mellitus. CONCLUSION: Transmission during fingerstick procedures was the most likely cause of these cases of nosocomial hepatitis B infection. Contamination probably occurred when healthcare workers failed to change gloves between patients undergoing fingerstick monitoring, although other means of contamination cannot be ruled out.

Management of infections due to resistant enterococci: a review of therapeutic options.

The incidence of nosocomial enterococcal infection has increased steadily over the past two decades. The treatment of patients with enterococcal infection has been complicated by the emergence of strains possessing high level resistance to aminoglycosides, penicillins and, most recently, glycopeptides. Several recent studies have evaluated alternative antimicrobial agents for use against strains resistant to some or all standard agents. In this report, we review the therapeutic options for the management of antibiotic-resistant enterococcal infection.

Activity of disinfectants against vancomycin-resistant Enterococcus faecium.

Vancomycin-resistant enterococci (VRE) often contaminate the hospital environment. We examined the activity of commonly used disinfectants against eight strains of VRE, using a quantitative suspension test method. Isopropyl alcohol and sodium hypochlorite were highly effective. Hydrogen peroxide was ineffective for all strains. After 10 minutes of incubation (the manufactures' recommended time of exposure), three phenolic and three quaternary ammonium compounds also were highly effective. After 3 minutes of exposure, however, occasional failures did occur. With the exception of 3% hydrogen peroxide, most disinfectants appear to be active against VRE.

Manipulation of a hospital antimicrobial formulary to control an outbreak of vancomycin-resistant enterococci.

Infection control practices are not uniformly successful in limiting outbreaks of vancomycin-resistant enterococci (VRE). Despite the implementation of barrier precautions for VRE-infected patients, nearly one-half of the inpatients at our center were found to have gastrointestinal colonization by VRE. In an attempt to control the outbreak, we altered the antibiotic formulary by restricting the use of cefotaxime and vancomycin and adding beta-lactamase inhibitors to replace third-generation cephalosporins. The use of clindamycin was also restricted because of a concomitant outbreak of Clostridium difficile colitis. After 6 months, the average monthly use of cefotaxime, ceftazidime, vancomycin, and clindamycin had decreased by 84%, 55%, 34%, and 80%, respectively (P < .02). The point prevalence of fecal colonization with VRE decreased from 47% to 15% (P < .001), and the number of patients whose clinical specimens were culture positive also gradually decreased. A change in antibiotic use appears to have significantly affected our VRE outbreak when previous measures failed.

Experience with a hospital-wide outbreak of vancomycin-resistant enterococci.

BACKGROUND: Vancomycin-resistant enterococci (VRE) were first detected in our institution in 1991. An outbreak was recognized in late 1992 when there was a sudden rise in the number of patients per month with VRE. Little information exists concerning the natural history of infection with these pathogens, and the effect of antimicrobial therapy is unclear. Recent guidelines emphasize prudent use of vancomycin and prompt institution of barrier precautions to limit the spread of vancomycin resistance. METHODS: Data were obtained by review of microbiologic and clinical records. Patients were categorized according to site of infection, and outcome of therapy was assessed. Hospital antibiotic usage was analyzed to determine any correlation with the outbreak. Infection control measures instituted in 1993 included patient isolation, environmental cleaning, and a reemphasis of barrier precautions. Surveillance cultures were performed to assess the extent of the outbreak in January 1995. RESULTS: VRE were detected in clinical cultures from 159 patients from 1991 through 1994. Mortality rate was 48%, but in most cases death could not be attributed to enterococcal infection. Patients with wound infections healed without specific therapy. Many patients with bacteremia had resolution with ampicillin or without specific therapy. Patients were widely scattered throughout the hospital from the beginning of the outbreak. Hospital usage of cefotaxime correlated with the number of cases. Infection control measures were not successful. Surveillance culture results in January 1995 revealed that 53% of all medical and surgical inpatients had fecal colonization with VRE. Genetic analysis of selected isolates revealed that one strain predominated, but at least seven distinct strains were identified. CONCLUSIONS: Our data suggest that many infections with VRE resolve without specific therapy. The infection control measures we used were ineffective, possibly because of the multiple strains present in our hospital. Isolation of all patients with VRE is impractical when there is widespread fecal carriage.

Comparison of five selective media for identifying fecal carriage of vancomycin-resistant enterococci.

There is no uniformly accepted method for detecting colonization with vancomycin-resistant enterococci (VRE). The sensitivities of five culture methods were determined for patients known to harbor VRE. Of 189 inpatients, 101 were found to harbor VRE by at least one method. Three methods detected fewer than half of the cultures. Campylobacter agar identified 70% of patients. Enterococcosel broth (containing vancomycin and aztreonam) identified 88% and may be preferred over other media for routine surveillance.

Treatment of experimental endocarditis caused by multidrug resistant Enterococcus faecium with ramoplanin and penicillin.

Antibiotic resistant strains of enterococci are being isolated with increasing frequency. Effective treatment of infections caused by Enterococcus faecium resistant to ampicillin, vancomycin and aminoglycosides has not been established. We studied the activity of ramoplanin, a new lipoglycopeptide antibiotic, against two strains of multidrug resistant E. faecium. In time kill studies, ramoplanin was bactericidal against both strains, but not in the presence of 50% serum. The combination of ramoplanin and penicillin was bactericidal even in the presence of serum. In rabbits with experimental endocarditis neither penicillin nor ramoplanin significantly reduced vegetation colony counts when given alone, although ramoplanin significantly reduced spleen and kidney bacterial counts of both strains. The combination of ramoplanin plus penicillin resulted in a significant reduction of vegetation bacterial counts (-3.2 and -3.7 log10 cfu/g for strains VA3 and MMC3, respectively, P < 0.01). All spleen cultures and 9 out of 10 kidney cultures from each strain were sterile following combination therapy. While ramoplanin will not be available for parenteral therapy, further research into the development of other lipoglycopeptide antibiotics is warranted.

In vitro activity of Cinnamomum zeylanicum against azole resistant and sensitive Candida species and a pilot study of cinnamon for oral candidiasis.

Fluconazole-resistant Candida species are an emerging problem. In this report, the in vitro activity of C. zeylanicum against fluconazole-resistant and-susceptible Candida isolates is described. The MICs of the bark of C. zeylanicum ranged from < 0.05-30 mg/ml, and were slightly better than commercially available cinnamon powder. Trans-cinnamaldehyde and O-methoxycinnamaldehyde had MICs of 0.03-0.5 mg/ml. The MICs of selected cinnamon candies and gums generally ranged from 25-100 mg/ml. Five patients with HIV infection and oral candidiasis received a commercially available cinnamon preparation for one week. There of the five patients had improvement of their oral candidiasis. Clinical trials will be necessary to determine the usefulness of cinnamon for the treatment of mucosal candidiasis.

Treatment of experimental endocarditis due to multidrug-resistant Enterococcus faecium with clinafloxacin and penicillin.

Clinafloxacin, a new quinolone antibiotic with enhanced activity against Gram-positive bacteria, has demonstrated in-vitro activity against multidrug-resistant Enterococcus faecium, particularly when combined with penicillin. Rabbits with experimental endocarditis due to a multidrug-resistant strain of E. faecium were treated with clinafloxacin and/or penicillin. After three days of therapy, significant reduction of bacterial concentrations were found in vegetations, kidneys, and spleens of animals treated with clinafloxacin. The combination of clinafloxacin and penicillin was significantly better in reducing vegetation bacterial concentrations compared to the other groups (-4.4 log10 cfu/g compared with control). Serum levels of clinafloxacin consistently exceeded the MIC of the strain, and clinafloxacin-resistant isolates could not be detected. Clinafloxacin demonstrated promising activity in vivo against multidrug-resistant E. faecium, and further studies are warranted.