Pablo San Gabriel

Outbreak of Extended-Spectrum Beta-Lactamase–Producing Klebsiella Pneumoniae in a Neonatal Intensive Care Unit Linked to Artificial Nails

BACKGROUND From April to June 2001, an outbreak of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae infections was investigated in our neonatal intensive care unit. METHODS Cultures of the gastrointestinal tracts of patients, the hands of healthcare workers (HCWs), and the environment were performed to detect potential reservoirs for ESBL-producing K. pneumoniae. Strains of K. pneumoniae were typed by pulsed-field gel electrophoresis using XbaI. A case-control study was performed to determine risk factors for acquisition of the outbreak clone (clone A); cases were infants infected or colonized with clone A and controls (3 per case) were infants with negative surveillance cultures. RESULTS During the study period, 19 case-infants, of whom 13 were detected by surveillance cultures, harbored clone A. The overall attack rate for the outbreak strain was 45%; 9 of 19 infants presented with invasive disease (n = 6) or developed invasive disease (n = 3) after colonization was detected. Clone A was found on the hands of 2 HCWs, 1 of whom wore artificial nails, and on the designated stethoscope of a case-infant. Multiple logistic regression analysis revealed that length of stay per day (odds ratio [OR], 1.05; 95% confidence interval [CI95], 1.02 to 1.09) and exposure to the HCW wearing artificial fingernails (OR, 7.87; CI95, 1.75 to 35.36) were associated with infection or colonization with clone A. CONCLUSION Short, well-groomed, natural nails should be mandatory for HCWs with direct patient contact

Cathelicidin Peptides Inhibit Multiply Antibiotic-Resistant Pathogens from Patients with Cystic Fibrosis

ABSTRACT Endogenous peptide antibiotics are under investigation as inhaled therapeutic agents for cystic fibrosis (CF) lung disease. The bactericidal activities of five cathelicidin peptides (LL37 [human], CAP18 [rabbit], mCRAMP [mouse], rCRAMP [rat], and SMAP29 [sheep]), three novel alpha-helical peptides derived from SMAP29 and termed ovispirins (OV-1, OV-2, and OV-3), and two derivatives of CAP18 were tested by broth microdilution assays. Their MICs were determined for multiply antibiotic-resistant Pseudomonas aeruginosa(n = 24), Burkholderia cepacia(n = 5), Achromobacter xylosoxidans(n = 5), and Stenotrophomonas maltophilia (n = 5) strains isolated from CF patients. SMAP29 was most active and inhibited mucoid and nonmucoidP. aeruginosa strains (MIC, 0.06 to 8 μg/ml). OV-1, OV-2, and OV-3 were nearly as active (MIC, 0.03 to 16 μg/ml), but CAP18 (MIC, 1.0 to 32 μg/ml), CAP18-18 (MIC, 1.0 to >32 μg/ml), and CAP18-22 (MIC, 0.5 to 32 μg/ml) had variable activities. LL37, mCRAMP, and rCRAMP were least active against the clinical isolates studied (MIC, 1.0 to >32 μg/ml). Peptides had modest activities against S. maltophilia and A. xylosoxidans (MIC range, 1.0 to > 32 μg/ml), but none inhibited B. cepacia. However, CF sputum inhibited the activity of SMAP29 substantially. The effects of peptides on bacterial cell membranes and eukaryotic cells were examined by scanning electron microscopy and by measuring transepithelial cell resistance, respectively. SMAP29 caused the appearance of bacterial membrane blebs within 1 min, killed P. aeruginosa within 1 h, and caused a dose-dependent, reversible decrease in transepithelial resistance within 5 h. The tested cathelicidin-derived peptides represent a novel class of antimicrobial agents and warrant further development as prophylactic or therapeutic agents for CF lung disease.

Synergistic Activities of Macrolide Antibiotics against Pseudomonas aeruginosa, Burkholderia cepacia, Stenotrophomonas maltophilia, and Alcaligenes xylosoxidans Isolated from Patients with Cystic Fibrosis

ABSTRACT Azithromycin and clarithromycin were paired with other antibiotics to test synergistic activity against 300 multidrug-resistant pathogens isolated from cystic fibrosis (CF) patients. Clarithromycin-tobramycin was most active against Pseudomonas aeruginosa and inhibited 58% of strains. Azithromycin-trimethoprim-sulfamethoxazole, azithromycin-ceftazidime, and azithromycin-doxycycline or azithromycin-trimethoprim-sulfamethoxazole inhibited 40, 20, and 22% of Stenotrophomonas maltophilia, Burkholderia cepacia complex, and Achromobacter (Alcaligenes) xylosoxidans strains, respectively.

Identification and Antimicrobial Susceptibility of Alcaligenes xylosoxidans Isolated from Patients with Cystic Fibrosis

ABSTRACT In the past decade, potential pathogens, includingAlcaligenes species, have been increasingly recovered from cystic fibrosis (CF) patients. Accurate identification of multiply antibiotic-resistant gram-negative bacilli is critical to understanding the epidemiology and clinical implications of emerging pathogens in CF. We examined the frequency of correct identification ofAlcaligenes spp. by microbiology laboratories affiliated with American CF patient care centers. Selective media, anexotoxin A probe for Pseudomonas aeruginosa, and a commercial identification assay, API 20 NE, were used for identification. The activity of antimicrobial agents against these clinical isolates was determined. A total of 106 strains from 78 patients from 49 CF centers in 22 states were studied. Most (89%) were correctly identified by the referring laboratories as Alcaligenes xylosoxidans. However, 12 (11%) strains were misidentified; these were found to be P. aeruginosa(n = 10), Stenotrophomonas maltophilia(n = 1), and Burkholderia cepacia(n = 1). Minocycline, imipenem, meropenem, piperacillin, and piperacillin-tazobactam were the most active since 51, 59, 51, 50, and 55% of strains, respectively, were inhibited. High concentrations of colistin (100 and 200 μg/ml) inhibited 92% of strains. Chloramphenicol paired with minocycline and ciprofloxacin paired with either imipenem or meropenem were the most active combinations and inhibited 40 and 32%, respectively, of strains. Selective media and biochemical identification proved to be useful strategies for distinguishing A. xylosoxidans from other CF pathogens. Standards for processing CF specimens should be developed, and the optimal method for antimicrobial susceptibility testing ofA. xylosoxidans should be determined.

Antimicrobial Susceptibility and Synergy Studies of Stenotrophomonas maltophilia Isolates from Patients with Cystic Fibrosis

ABSTRACT Stenotrophomonas maltophilia is a newly emerging pathogen being detected with increasing frequency in patients with cystic fibrosis (CF). The impact of this multidrug-resistant organism on lung function is uncertain. The optimal treatment for S. maltophilia in CF patients is unknown. We studied the in vitro activity of ten antimicrobial agents, and conducted synergy studies by using checkerboard dilutions of eight pairs of antimicrobial agents against strains isolated from 673 CF patients from 1996 to 2001. This represents approximately 7 to 23% of the CF patients in the United States who harbor S. maltophilia annually. Doxycycline was the most active agent and inhibited 80% of 673 initial patient isolates, while trimethoprim-sulfamethoxazole inhibited only 16%. High concentrations of colistin proved more active than high concentrations of tobramycin and gentamicin. Serial isolates (n = 151) from individual patients over time (median, 290 days) showed minimal changes in resistance. Synergistic or additive activity was demonstrated by trimethoprim-sulfamethoxazole paired with ticarcillin-clavulanate (65% of strains), ciprofloxacin paired with ticarcillin-clavulanate (64% of strains), ciprofloxacin paired with piperacillin-tazobactam (59% of strains), trimethoprim-sulfamethoxazole paired with piperacillin-tazobactam (55% of strains), and doxycycline paired with ticarcillin-clavulanate (49% of strains). In all, 522 (78%) isolates were multidrug resistant (i.e., resistant to all agents in two or more antimicrobial classes) but 473 (91%) of these were inhibited by at least one antimicrobial combination (median, four; range, one to eight). To determine appropriate treatment for patients with CF, it is important to monitor the prevalence, antimicrobial susceptibility, and clinical impact of S. maltophilia in this patient population.

A survey of latent tuberculosis infection among laboratory healthcare workers in New York City

OBJECTIVE To determine the prevalence of positive tuberculin skin tests (TSTs), incidence of TST conversion, risk factors for positive TSTs, and history of active TB among HCWs in microbiology laboratories in New York City. DESIGN Two-year survey from May 1999 to June 2001. SETTING Nineteen microbiology laboratories. RESULTS During the first year, interviews were conducted with 345 laboratory HCWs (mean, 18 HCWs per site; range, 2 to 51) to assess the prevalence of positive TSTs, but 3 (1%) could not recall their result and were excluded from further analyses. The mean age of the remaining 342 HCWs was 48 years; 68% (n = 233) were female, 54% (n = 183) received bacille Calmette-Guerin (BCG) vaccination, and 71% (n = 244) were foreign born. The prevalence of a positive TST was 57% (n = 196), but only 20% (n = 39) of the HCWs received isoniazid. The incidence of TST conversion in the second year of the study was 1% (1 of 108). Multivariate analysis identified age (odds ratio [OR] per year, 1.05; 95% confidence interval [CI95], 1.02-1.08), foreign birth (OR, 3.80; CI95, 1.98-7.28), BCG immunization (OR, 4.89; CI95, 2.72-8.80), and employment in a mycobacteriology laboratory (OR, 2.14; CI95, 1.25-3.68) as risk factors for a positive TST. Only one HCW had been treated for active TB. CONCLUSIONS The prevalence of positive TSTs was high among laboratory HCWs, but the TST conversion rate was low. Higher rates of treatment for latent TB infection are desirable.

Observational study of the use of infection control interventions for Mycobacterium tuberculosis in pediatric facilities

Introduction. Hospital transmission of Mycobacterium tuberculosis (TB) is a problem in US facilities where adults are treated. However, specific guidelines for facilities in which pediatric patients are cared for have never been defined, nor has any study attempted to assess pediatric health care worker (HCW) compliance with TB infection control (IC) guidelines. Methods. An observational study was performed in two pediatric inpatient hospitals from May, 1996, to December, 1997. A trained observer tallied persons (i.e. professional HCWs, ancillary HCWs and non-HCWs) entering and leaving occupied TB isolation rooms and recorded adherence with IC practices (e.g. proper use of respirators, prompt door closures, door signage). Results. Thirty children with confirmed or suspected TB were admitted during the study period and observed for a total of 242 h during which 656 visits by professional (n = 391) and ancillary (n = 131) HCWs and by family members (n = 134) were recorded. During 30% of visits doors remained open an average of 10 min, and during 20% of visits no respiratory protection was worn. In all, visitors wore the correct respiratory protection appropriately only 55% of the time. HCWs were more likely to wear respiratory protection when caring for children with a positive acid-fast bacillus smear than family members, but professional staff were no more likely than ancillary staff to do so. Conclusions. This is the first study to quantify compliance with IC practices for TB in pediatric hospitals. The majority of visitors entering TB isolation rooms occupied by children with confirmed or suspected TB complied with IC guidelines, but discrepancies were seen. Rather than relying on TB IC guidelines designed for adult facilities, guidelines specific for pediatric facilities that consider the local epidemiology of TB should be developed.