Timothy Cleary

An outbreak of tuberculosis caused by multiple-drug-resistant tubercle bacilli among patients with HIV infection

OBJECTIVE To evaluate a nosocomial outbreak of tuberculosis caused by multiple-drug-resistant bacilli among patients with tuberculosis and HIV infection. DESIGN A case-control study. PATIENTS Patients with HIV infection and culture-proven tuberculosis. MEASUREMENTS Patient characteristics, date of diagnoses of HIV infection and disease, date of diagnosis of tuberculosis, Mycobacterium tuberculosis susceptibility results, and medical center contact. RESULTS Sixty-two patients who had tuberculosis caused by multiple-drug-resistant bacilli (cases) and 55 patients who had tuberculosis caused by susceptible or single-drug-resistant bacilli (controls) were identified. Controls were more likely to be black (odds ratio, 0.4; 95% CI, 0.2 to 0.9) or Haitian (odds ratio, 0.2; CI, 0.1 to 0.6) compared with cases, who were more likely to be homosexual men (odds ratio, 2.9; CI, 1.3 to 6.4). Forty-four cases (71%) had previous contact with an HIV clinic compared with 15 controls (27%) (P less than 0.0001). Cases were more likely to have had AIDS (odds ratio, 7.7; CI, 1.5 to 53.7), to have been hospitalized on an HIV ward (odds ratio, 8.3; CI, 2.3 to 29.7), to have been seen in an HIV clinic (odds ratio, 7.8; CI, 3.4 to 18.1), to have received intravenous therapy in an HIV clinic (odds ratio, 13.0; CI, 4.6 to 37.0), or to have received inhalation pentamidine in an HIV clinic before a diagnosis of tuberculosis was made. Multiple logistic regression analysis showed that a diagnosis of AIDS (odds ratio, 11.2; CI, 3.1 to 40.6) and HIV clinic visits (odds ratio, 13.0; CI, 2.7 to 63.7) before a diagnosis of tuberculosis were significantly associated with tuberculosis caused by multiple-drug-resistant bacilli. Using susceptibility patterns and appointment dates, we found that 22 cases had previous contact with a person who had tuberculosis caused by multiple-drug-resistant bacilli in the HIV clinic. CONCLUSIONS Nosocomial transmission of M. tuberculosis from other HIV-infected patients with tuberculosis caused by multiple-drug-resistant bacilli can occur. These findings have serious public health implications and demand strict adherence to acid-fast bacilli isolation precautions.

Clinical Presentation and Outcome of Patients with HIV Infection and Tuberculosis Caused by Multiple-Drug-resistant Bacilli

OBJECTIVE To determine the clinical manifestations of patients with human immunodeficiency virus (HIV) infection and tuberculosis caused by multiple-drug-resistant bacilli compared with those with single-drug-resistant or susceptible bacilli. DESIGN Descriptive, case-control, and cohort studies. SETTING A large urban teaching hospital. PATIENTS Sixty-two patients with tuberculosis caused by multiple-drug-resistant bacilli (cases) and 55 patients with tuberculosis caused by single-drug-resistant or susceptible bacilli (controls). MEASUREMENTS Characteristics of clinical presentation, radiographs, pathologic abnormalities, antituberculosis treatment, and clinical course. RESULTS Twenty cases (32%) had concomitant pulmonary and extrapulmonary disease at presentation compared with 9 controls (16%; odds ratio, 2.4; 95% CI, 1.0 to 5.9). More cases had alveolar infiltrates (76%; odds ratio, 3.6; CI, 1.2 to 11.4), interstitial infiltrates with a reticular pattern (67%; odds ratio, 7.8; CI, 1.0 to 83.5), and cavitations (18%; odds ratio, 6.6; CI, 0.8 to 315.3) on initial chest radiographs compared with controls (49%, 19%, and 3%, respectively). Pathologic specimens from cases showed extensive necrosis, poor granuloma formation, marked inflammatory changes with a predominance of neutrophils, and abundant acid-fast bacilli. Twenty-five cases received two or more effective antituberculosis drugs for more than 2 months. Only 2 cases had three consecutive negative cultures for Mycobacterium tuberculosis; one patient died within 1 day of the last negative culture, and the other had positive cultures 496 days later. The remaining 23 cases had persistently or intermittently positive cultures despite therapy. The clinical course of these cases suggested overwhelming miliary tuberculosis with involvement of the lungs (77%), pleura (15%), stool (34%), meninges (13%), bone marrow (16%), blood (10%), lymph nodes (10%), and skin (8%). The median survival time was 2.1 months for cases compared with 14.6 months for controls (P = 0.001, log-rank test). CONCLUSIONS Tuberculosis caused by multiple-drug-resistant bacilli in patients with HIV infection is associated with widely disseminated disease, poor treatment response with an inability to eradicate the organism, and substantial mortality.

Molecular epidemiological analysis of Escherichia coli sequence type ST131 (O25:H4) and bla CTX-M-15among extended-spectrum-β- lactamase-producing E. coli from the United States, 2000 to 2009

ABSTRACT Escherichia coli sequence type ST131 (from phylogenetic group B2), often carrying the extended-spectrum-β-lactamase (ESBL) gene blaCTX-M-15, is an emerging globally disseminated pathogen that has received comparatively little attention in the United States. Accordingly, a convenience sample of 351 ESBL-producing E. coli isolates from 15 U.S. centers (collected in 2000 to 2009) underwent PCR-based phylotyping and detection of ST131 and blaCTX-M-15. A total of 200 isolates, comprising 4 groups of 50 isolates each that were (i) blaCTX-M-15 negative non-ST131, (ii) blaCTX-M-15 positive non-ST131, (iii) blaCTX-M-15 negative ST131, or (iv) blaCTX-M-15 positive ST131, also underwent virulence genotyping, antimicrobial susceptibility testing, and pulsed-field gel electrophoresis (PFGE). Overall, 201 (57%) isolates exhibited blaCTX-M-15, whereas 165 (47%) were ST131. ST131 accounted for 56% of blaCTX-M-15-positive- versus 35% of blaCTX-M-15-negative isolates (P < 0.001). Whereas ST131 accounted for 94% of the 175 total group B2 isolates, non-ST131 isolates were phylogenetically distributed by blaCTX-M-15 status, with groups A (blaCTX-M-15-positive isolates) and D (blaCTX-M-15-negative isolates) predominating. Both blaCTX-M-15 and ST131 occurred at all participating centers, were recovered from children and adults, increased significantly in prevalence post-2003, and were associated with molecularly inferred virulence. Compared with non-ST131 isolates, ST131 isolates had higher virulence scores, distinctive virulence profiles, and more-homogeneous PFGE profiles. blaCTX-M-15 was associated with extensive antimicrobial resistance and ST131 with fluoroquinolone resistance. Thus, E. coli ST131 and blaCTX-M-15 are emergent, widely distributed, and predominant among ESBL-positive E. coli strains in the United States, among children and adults alike. Enhanced virulence and antimicrobial resistance have likely promoted the epidemiological success of these emerging public health threats.

The Prevalence of Tuberculosis and Drug Resistance among Haitians

TUBERCULOSIS is a major health problem among Haitians who have recently entered southern Florida. Among those medically screened on arrival, we found that the prevalence of tuberculosis was 650 cas...

Emergence of KPC-Producing Pseudomonas aeruginosa in the United States

Recent years have shown the emergence and dissemination of isolates of Enterobacteriaceae producing carbapenemases in different parts of the world (3). In many cases, those carbapenemases were KPC -lactamases (5). Those enzymes hydrolyze all -lactams, including carbapenems at a significant level, with the exception of cephamycins. The blaKPC-like genes have been reported most often from enterobacterial species (mostly Klebsiella pneumoniae species) recovered from several states in the United States (5). Besides the United States, KPC-producing K. pneumoniae isolates are found to be endemic in Greece and Israel, and there are, in addition, scattered reports from all over the world, including Western Europe, China, and South and Central America (5). In Colombia, the first identification of KPC-2-positive Pseudomonas aeruginosa isolates has been reported (6). We describe here the first identification of a KPC-producing P. aeruginosa isolate now in the United States. In October 2009, a 68-year-old African-American man with history of diabetes and hypertension was admitted with a myocardial infarction to a 1,500-bed teaching hospital in south Florida. Mechanical ventilation was required upon admission to the medical intensive care unit. He did not report any recent history of hospitalization or travel. The patient received an empirical antibiotic therapy consisting of ceftriaxone and vancomycin. Four weeks after admission, he developed hypothermia and blood and urine cultures grew P. aeruginosa. The patient subsequently received an empirical therapy based on meropenem. MICs of the P. aeruginosa P13 isolate measured by the Etest method (AB Biodisk, Solna, Sweden) and interpreted according to CLSI standards showed multidrug resistance including resistance to all carbapenems (carbapenem MICs of 256 g/ml) (2). That isolate remained susceptible only to amikacin, gentamicin, and colistin. Consequently, the therapy was based on colistin and amikacin, and his subsequent blood cultures remained negative. Molecular investigations were then performed on this isolate. PCR primers were used for the detection of Ambler class A and class B -lactamase genes, followed by sequencing, which identified the blaKPC-2 -lactamase gene coding for carbapenemase KPC-2 (8). Analysis of the plasmid content of P. aeruginosa isolate 13 identified a single plasmid of ca. 66 kb that was successfully transferred to Escherichia coli by electroporation, with a selection performed on amoxicillin (100 g/ml)containing agar plates. The E. coli transformants expressing KPC-2 showed a 3-fold increase of MICs for imipenem, meropenem, and ertapenem, but they did not show any additional non--lactam resistance. PCR mapping performed as described previously (3) showed that the blaKPC-2 gene was part of the Tn4401b transposon originally identified from a K. pneumoniae isolate from New York (4) and also identified from the clonally related Colombian P. aeruginosa isolates (6). Pulsed-field gel electrophoresis (PFGE) performed as described previously, however, indicated that P. aeruginosa isolate P13 was clonally unrelated to P. aeruginosa PA2404 from Colombia (data not shown). This is the first identification of a KPC-producing P. aeruginosa isolate in the United States. It is noteworthy that it did not correspond to an imported case. It therefore remains to be evaluated to what extent KPC-type enzymes have spread in P. aeruginosa in the United States, since the phenotypic detection of production of that carbapenemase remains impossible. Use

Decreasing operating room environmental pathogen contamination through improved cleaning practice

OBJECTIVE Potential transmission of organisms from the environment to patients is a concern, especially in enclosed settings, such as operating rooms, in which there are multiple and frequent contacts between patients, providers hands, and environmental surfaces. Therefore, adequate disinfection of operating rooms is essential. We aimed to determine the change in both the thoroughness of environmental cleaning and the proportion of environmental surfaces within operating rooms from which pathogenic organisms were recovered. DESIGN Prospective environmental study using feedback with UV markers and environmental cultures. SETTING A 1,500-bed county teaching hospital. PARTICIPANTS Environmental service personnel, hospital administration, and medical and nursing leadership. RESULTS The proportion of UV markers removed (cleaned) increased from 0.47 (284 of 600 markers; 95% confidence interval [CI], 0.42-0.53) at baseline to 0.82 (634 of 777 markers; 95% CI, 0.77-0.85) during the last month of observations ([Formula: see text]). Nevertheless, the percentage of samples from which pathogenic organisms (gram-negative bacilli, Staphylococcus aureus, and Enterococcus species) were recovered did not change throughout our study. Pathogens were identified on 16.6% of surfaces at baseline and 12.5% of surfaces during the follow-up period ([Formula: see text]). However, the percentage of surfaces from which gram-negative bacilli were recovered decreased from 10.7% at baseline to 2.3% during the follow-up period ([Formula: see text]). CONCLUSIONS Feedback using Gram staining of environmental cultures and UV markers was successful at improving the degree of cleaning in our operating rooms.

Successful Eradication of a Monoclonal Strain of Klebsiella pneumoniae during a K. pneumoniae Carbapenemase- Producing K. pneumoniae Outbreak in a Surgical Intensive Care Unit in Miami, Florida

We describe the investigation and control of a Klebsiella pneumoniae carbapenemase-producing K. pneumoniae outbreak in a 20-bed surgical intensive care unit during the period from January 1, 2009 through January 1, 2010. Nine patients were either colonized or infected with a monoclonal strain of K. pneumoniae. The implementation of a bundle of interventions on July 2009 successfully controlled the further horizontal spread of this organism.

Detection of herpes viral genomes in normal and diseased corneal epithelium

Herpetic ocular disease is one of the major causes of corneal blindness. Clinical diagnosis of corneal disease is based principally on corneal appearance. However, abnormal morphology of the corneal epithelium (CE) is not an indicator for the presence of a herpes virus. Further, it has not been established if herpes viruses are present in normal corneal epithelial tissue. In these studies, the polymerase chain reaction was used to evaluate normal and diseased corneal epithelium for the presence of herpes simplex virus type 1 (HSV-1), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) genomic sequences. Thirty-two normal corneal epithelium specimens obtained from cadavers shortly after death were analyzed for HSV-1, EBV and CMV genomic sequences. Three of the 32 normal CE specimens were positive for amplified EBV DNA, 1 was positive for HSV-1 DNA, and none was positive for CMV DNA. We also tested eight herpetic dendritic lesions of which 3 were HSV-1 culture and PCR positive. The remaining five dendritic lesions were HSV-1 culture and PCR negative. Since these lesions were not evaluated for other herpesviruses, the etiology of these dendritic lesions is unknown. Six corneal epithelium samples from HIV-infected donors were negative for EBV, CMV and HSV-1 amplified sequences. Positive EBV, CMV and HSV-1 serology on all normal donors and on donors with clinically apparent disease did not correlate with positive PCR results. The results of these studies suggest that EBV and HSV-1 DNA can be amplified from a small percentage of apparently normal corneal epithelium.

Rapid and Specific Detection of Mycobacterium tuberculosis by Using the Smart Cycler Instrument and a Specific Fluorogenic Probe

ABSTRACT A procedure using the Smart Cycler instrument and a fluorescence quencher (FQ) probe for the specific identification of Mycobacterium tuberculosis complex (MTB) was used to detect organisms in 366 acid-fast bacillus smear-positive respiratory specimens. It was compared to culture and the AMPLICOR M. tuberculosis PCR test. MTB was isolated from 198 of these samples. The FQ PCR assay was sensitive (197 of 198, 99.5%) and specific (165 of 168, 98.2%); no significant difference was observed between the two PCR protocols. After DNA extraction, a final result was available within 1.5 h with the real-time PCR protocol.

Fungal cerebritis from intravenous drug abuse.

Three intravenous drug abusers (predominantly cocaine) developed a fulminant fungal cerebritis without any other identifiable predisposing factor. Two died and one survived with a severe neurologic deficit. Zygomycetes (nonseptated fungi) were identified in the brain tissue of two victims and Acremonium alabamensis was cultured from the brain tissue of the third. Fulminant fungal cerebritis in intravenous drug abusers (in the absence of any predisposing illness) may represent a unique variant of the acquired immunodeficiency syndrome (AIDS). Future surviving patients should be evaluated for the possibility of a cellular immune deficiency state in order to confirm this impression.