Charles M. Nolan

Staphylococcus aureus bacteremia: Current clinical patterns☆

One hundred and five cases of bacteremia due to Staphylococcus aureus were reviewed to assess the current clinical spectrum of serious staphylococcal disease. Mortality was 21 percent, lower than previously reported. Patients could be separated into two groups according to the presence of identifiable primary staphylococcal infections; 63 bacteremic patients had such lesions, the remaining 42 lacked them. The latter group contained 24 of 26 cases of endocarditis. Illnesses in that group were marked by the presence (in 38 of 42 patients) of staphylococcal foci occurring secondary to bacteremia. Such foci were responsible for five of seven instances of relapse or treatment failure encountered in that group. Secondary staphylococcal foci occurred in only five of 63 patients with primary infections, and the response of this group to conventional therapy for bacteremia was satisfactory. This study suggests that endocarditis has become an unusual complication of identifiable primary staphylococcal infection. A clinical classification based on the presence of such lesions therefore separates bacteremic patients likely to be cured by conventional antibiotic therapy (those with primary infections but no secondary foci) from others (those with secondary foci, suggesting endocarditis) who should receive a more prolonged course of antibiotics.

Diphtheria among Alcoholic Urban Adults: A Decade of Experience in Seattle

Three outbreaks of Corynebacterium diphtheriae infection occurred in Seattles Skid Road from 1972 through 1982. The first involved a single toxigenic, intermedius biotype clone, whereas the second and third outbreaks involved nontoxigenic mitis and gravis strains. Of 1100 total infections, 947 (86%) were cutaneous. The incidence was highest in winter and spring. In Skid Road, the estimated attack rate during 17 months in 1974 to 1975 was 5% for whites and 27% for native Americans. Streptococcus pyogenes was isolated from 73% of diphtheritic and 41% of nondiphtheritic skin lesions (P less than 0.001). Skin infection and environmental contamination by C. diphtheriae were correlated. Complications occurred in 21% of symptomatic nasopharyngeal and 3% of cutaneous toxigenic intermedius infections (P less than 0.001), and were significantly correlated with ages 60 years or more. Preferential use of erythromycin for diphtheria and pyodermas preceded plasmid-mediated resistance to erythromycin in C. diphtheriae. Diphtheria outbreaks in urban alcoholic persons are associated with poor hygiene, crowding, season, contaminated fomites, underlying skin disease, hyperendemic streptococcal pyoderma, and introduction of new strains from exogenous reservoirs.

Multidrug-resistant Mycobacterium tuberculosis in HIV-Infected Persons, Peru

During 1999 to 2000, we identified HIV-infected persons with new episodes of tuberculosis (TB) at 10 hospitals in Lima-Peru and a random sample of other Lima residents with TB. Multidrug-resistant (MDR)-TB was documented in 35 (43%) of 81 HIV-positive patients and 38 (3.9%)of 965 patients who were HIV-negative or of unknown HIV status (p < 0.001). HIV-positive patients with MDR-TB were concentrated at three hospitals that treat the greatest numbers of HIV-infected persons with TB. Of patients with TB, those with HIV infection differed from those without known HIV infection in having more frequent prior exposure to clinical services and more frequent previous TB therapy or prophylaxis. However, MDR-TB in HIV-infected patients was not associated with previous TB therapy or prophylaxis. MDR-TB is an ongoing problem in HIV-infected persons receiving care in public hospitals in Lima and Callao; they represent sentinel cases for a potentially larger epidemic of nosocomial MDR-TB.

Persistent Campylobacter jejuni Infection in an Immunocompromised Patient

Recurrent bacteremia and enteritis due to a specific serotype of Campylobacter jejuni occurred over a 12-month period in a patient on hemodialysis with systemic lupus erythematosus who was also deficient in serum IgA and IgM. A bactericidal defect in the patients sera for C. jejuni was shown. A role for immunoglobulins in the host response to C. jejuni is suggested, in that the IgA deficiency may have predisposed the patient to chronic gastrointestinal carriage and because the resolution of the bacteremia corresponded with the delayed appearance in the blood of IgG specific for the infecting strain.

Persistent Neuropsychological Sequelae of Toxic Shock Syndrome

Twelve women, aged 16 to 29 years, were interviewed and examined for possible neuropsychological sequelae 2 to 12 months after they recovered from toxic shock syndrome. Six of the 12 women had symptoms such as difficulty concentrating, headache, recent memory lapses, inability to compute, and loss of other higher integrative functions. Eight patients were found to have electroencephalographic abnormalities. All six symptomatic patients but no asymptomatic patients had abnormal neurologic findings. Abnormalities such as impaired memory and calculation and poorly sustained concentration were found in five of six symptomatic patients but in no asymptomatic patient. Six control subjects, all asymptomatic women aged 17 to 29 years, were interviewed and examined 2 to 12 months after they recovered from postpartum endometritis; these subjects were normal in all parameters tested. A direct effect of the staphylococcal toxin on the central nervous system may be the cause of these sequelae.

Influence of polymorphic N-acetyltransferase phenotype on the inhibition and induction of acetaminophen bioactivation with long-term isoniazid

To determine in patients receiving isoniazid prophylaxis whether an increase in the CYP2E1‐dependent formation clearance of acetaminophen (paracetamol) to N‐acetyl‐p‐benzoquinone imine (NAPQI) occurs during a normal 24‐hour isoniazid dose interval and whether the interaction is dependent on acetylation status.

Expanded Geographical Distribution of the N Family of Mycobacterium tuberculosis Strains within the United States

ABSTRACT The N and W-Beijing families of Mycobacterium tuberculosis are phylogenetically closely related. The ability of the W-Beijing family to rapidly cause widespread disease is well described; however, few outbreaks involving the N family have been reported outside the New York City, N.Y., area. During 2002 to 2003, Seattle, Wash., experienced a rapidly expanding tuberculosis outbreak involving 38 persons in a 23-month period. The outbreak strain, SBRI9, exhibited the genotypic properties of the N family. Its IS6110 restriction fragment length polymorphism pattern was identical or nearly identical to those of two N family strains that were responsible for clusters of tuberculosis cases, including a large nosocomial outbreak, in New York City and New Jersey from 1989 to 1990. It was also identical to strains involved in late 1990s tuberculosis cases in Michigan, Maryland, and Arkansas. Further monitoring of the N family may show that it shares with the W-Beijing family the propensity to spread rapidly, suggesting that this characteristic evolved prior to the divergence of the two genetic lineages.

Community-Wide Implementation of Targeted Testing for and Treatment of Latent Tuberculosis Infection

Treatment of latent infection due to Mycobacterium tuberculosis will likely increase in importance as a strategy to prevent tuberculosis in the United States. This review was undertaken to assess how targeted testing and treatment of latent tuberculosis infection are currently organized, with a focus on the extension of those services from public health clinics to other community sites. Targeted testing programs are now being implemented in primary care neighborhood clinics, syringe-exchange programs, jails, and teen health clinics. Organizational issues at those new sites include the need for a tracking system for clinical follow-up and for incentives to promote adherence. There is increasing experience with directly observed treatment of latent tuberculosis infection. Communities that receive large numbers of immigrants and refugees should prioritize the evaluation of those whose chest radiographs are suggestive of tuberculosis. Current studies continue to point out imperfections in the current tools, such as the tuberculin skin test and isoniazid. Finally, the advent of managed care, especially for Medicaid recipients, presents both opportunities and challenges for expansion of population-based preventive health services.

Experimental pneumococcal meningitis: III. Chemotactic activity in cerebrospinal fluid

Summary Chemotactic activity was assayed in CSF of rabbits with pneumococcal meningitis to further characterize the inflammatory response in this infection. CSF chemotactic activity was detected in increasing levels for 72 hr after infection. Activity was stable at 56° and was inactivated by agents which denature proteins. Gel filtration demonstrated two chemotactically active fractions in infected CSF with mol wts of approximately 3000 and 11,000. Bacterial products appear to account for a portion of the observed CSF chemotactic activity, but the role of host factors remains to be clarified.

Use of Rapid Genomic Deletion Typing To Monitor a Tuberculosis Outbreak within an Urban Homeless Population

ABSTRACT Beginning in mid-2002, a large tuberculosis outbreak occurred among homeless persons in King County, Washington. In order to further monitor the outbreak following its peak in 2003, Mycobacterium tuberculosis isolates from all new King County tuberculosis (TB) patients in 2004 and the first half of 2005 (n = 220) were genotyped by using a rapid comparative genomics-based (genomic deletion-typing) approach, with confirmation by mycobacterial interspersed repetitive units and repetitive-sequence-based PCR (rep-PCR). Results were compared to retrospective genotypic data from 1995 to 2003. The outbreak strain SBRI9, which was not seen among King County homeless persons prior to 2002, accounted for 16 out of 30 TB cases (53%) within this population in 2002. This trend continued with 27 out of 35 cases (77%) caused by the outbreak strain in 2003, 11 out of 13 cases (85%) caused by the outbreak strain in 2004, and 4 out of 10 cases (40%) caused by the outbreak strain in the first 5 months of 2005. Thus, the outbreak strain remained well established within this homeless population throughout the study period. At least four SBRI9 cases were in people who had previously been infected by other strains. The novel PCR-based strain-typing approach used in this investigation proved to be cost-effective and very rapid. In most cases, it was possible to analyze DNA extracted directly from primary isolation (Mycobacterium growth indicator tube) cultures submitted by clinical laboratories, a feature that markedly reduced the delay between diagnosis and strain typing results. This rapid turnaround facilitated public health efforts to prevent new outbreaks involving this strain.