Eladio Soriano

Pathogenic significance of methicillin resistance for patients with Staphylococcus aureus bacteremia

To assess whether methicillin resistance is a microbial characteristic associated with deleterious clinical outcome, we performed a cohort study on 908 consecutive episodes of Staphylococcus aureus bacteremia and a case-control study involving 163 pairs of patients matched for preexisting comorbidities, prognosis of the underlying disease, length of hospitalization, and age. Of 908 bacteremic episodes, 225 (24.8%) were due to methicillin-resistant S. aureus (MRSA). Multivariate analysis did not reveal that methicillin resistance was an independent predictor for mortality when shock, source of bacteremia, presence of an ultimately or rapidly fatal underlying disease, acquisition of the infection in an intensive care unit (ICU), inappropriate empirical therapy, female sex, and age were taken into account. Nonetheless, methicillin resistance was an independent predictor for shock. The case-control study could not confirm that shock was linked to MRSA when prior antimicrobial therapy, inappropriate treatment, ICU residence, and female sex were considered. Our data suggest that cohort studies tend to magnify the relationship of MRSA with clinical markers of microbial pathogenicity and that this effect is a shortcoming of these kind of studies that is caused by inadequate control for underlying diseases.

High Incidence of Herpes Zoster in Patients with AIDS Soon After Therapy with Protease Inhibitors

A high incidence of herpes zoster was noticed among patients with AIDS, shortly after addition of a protease inhibitor to their baseline treatment with nucleoside analogue reverse-transcriptase inhibitors. Within a median follow-up of 64 weeks (range, 34-103 weeks), 14 patients (7%) had a first episode or a recurrence of herpes zoster (6.2 episodes per 100 patient-years). No episodes of zoster were diagnosed before week 4. Twelve episodes (86%) occurred between weeks 4 and 16. The risk of zoster was independent of age, sex, type of protease inhibitor, and CD4+ lymphocyte count and viral load at baseline and month 1. A CD8+ lymphocyte proportion at baseline of > 66% (hazard ratio [HR], 10.6; 95% confidence interval [CI], 3.4-33.1) and an increase in CD8+ lymphocyte proportion at month 1 of > 5% (HR, 32; 95% CI, 8.1-126.4) were independently associated with the risk of herpes zoster. These data might be clinically useful for determining transient prophylaxis for those patients at high risk.

Decreased Invasive Capacity of Quinolone-Resistant Escherichia coli in Patients with Urinary Tract Infections

Quinolone-resistant (QR) Escherichia coli may have lower invasive capacity than does quinolone-susceptible E. coli. To evaluate this, we prospectively collected data regarding all cases of E. coli invasive urinary tract infections (IUTI) in 669 adults admitted to the Infectious Diseases Unit of our hospital during a 3-year period, as well as 10,950 patients with cystitis or asymptomatic bacteriuria who presented to the outpatient clinic during a 1-year period. QR E. coli was isolated in 20% of patients with cystitis, compared with 8% of those with IUTI (P<.05). The proportion of E. coli isolates that were quinolone resistant was similar in patients with bacteremic and nonbacteremic IUTI. The factors of urinary manipulation and structural abnormalities were independently associated with the presence of quinolone resistance. Old age was the only variable independently associated with blood invasion. QR E. coli is less likely to produce invasive disease (pyelonephritis and prostatitis) than is quinolone-susceptible E. coli. However, once pyelonephritis or prostatitis have developed, there is no difference in the incidence of bacteremia.

Primary prophylaxis for Pneumocystis carinii pneumonia: a randomized trial comparing cotrimoxazole, aerosolized pentamidine and dapsone plus pyrimethamine.

OBJECTIVE To compare the efficacy and tolerance of monthly aerosolized pentamidine versus cotrimoxazole versus dapsone plus pyrimethamine to prevent the initial episodes of Pneumocystis carinii pneumonia (PCP) in HIV-infected patients. DESIGN An open randomized clinical trial. PATIENTS AND METHODS HIV-infected patients (n = 331) with CD4 cell counts < 200 x 10(6)/l or with AIDS but without a history of PCP or cerebral toxoplasmosis (CT) were randomized to receive pentamidine (300 mg every 4 weeks), cotrimoxazole (160/800 mg 3 days a week) or dapsone plus pyrimethamine (100 and 25 mg weekly). If immunoglobulin G (IgG) antibodies to Toxoplasma were present, patients in the first two groups were randomized further to 25 mg pyrimethamine per week or to no treatment. RESULTS The mean follow-up was 313 days (range, 30-670 days). The three groups were homogeneous for age, sex, risk group for HIV infection, initial CD4 cell count and mean follow-up. PCP developed in 16 patients, with an estimated cumulative probability of 5.3% at 1 year of follow-up. The PCP rate per year of observation, using an intention-to-treat analysis, was 5.6% [95% confidence interval (CI), 0.9-10.3], 3% (95% CI, 0-6.3) and 8.3% (95% CI, 2.8-13.8) in the groups treated with pentamidine, cotrimoxazole and dapsone plus pyrimethamine, respectively (P > 0.05). Moderate or severe side-effects were observed in one patient on pentamidine, 10 on cotrimoxazole and nine on dapsone plus pyrimethamine (P < 0.05); the study drug had to be discontinued in no, 10 and six patients, respectively (P < 0.05). Neither cotrimoxazole alone nor pyrimethamine combined with dapsone or cotrimoxazole prevented initial episodes of toxoplasmosis among patients with IgG antibodies to Toxoplasma gondii. CONCLUSIONS Low-dose thrice-weekly cotrimoxazole or weekly dapsone plus pyrimethamine was not significantly worse (differences > 15% would have been detected with 90% certainty) than monthly aerosolized pentamidine in preventing a first episode of PCP in patients at high risk, but aerosolized pentamidine was better tolerated.

Characteristics of tuberculosis in HIV-infected patients: a case-control study.

To test the hypothesis that HIV infection can modify the clinical characteristics of tuberculosis, 65 consecutive cases of tuberculosis in HIV-seropositive patients diagnosed in Barcelona (Spain) were compared with 65 HIV-seronegative controls matched for age and sex. Thirty of the 65 cases were accepted as AIDS cases (August 1987 Centers for Disease Control criteria) only because of the tuberculosis. Among the cases 54 (83%) were parenteral drug addicts and 88% were males. The tuberculosis was pulmonary or pleural in 62 controls (96%) but in only 25 cases (39%; P less than 0.0001). Lymph nodes were involved in 25 cases (39%) and in none of the controls (P less than 0.0001). Disseminated forms of tuberculosis were present in seven cases (11%) and in no controls (P less than 0.007). Bone, joints and central nervous system involvement were also significantly (P less than 0.05) more frequent in cases. The treatment (isoniazid and rifampin for 6 months plus ethambutol and pyrazinamide during the first 2 months) was always effective. One relapse was detected after a median follow-up of 55 months in cases and none in controls after a median follow-up of 43 months. Twenty-five cases (39%) and 14 controls (22%) developed mild or severe side effects related to the treatment (P less than 0.004). In conclusion, most of the HIV-infected patients with tuberculosis were drug addicts with extrapulmonary or disseminated forms. A short course of treatment (6 or 9 months) may be enough but side effects were frequent.

Pseudomonas aeruginosa bacteremia in patients infected with human immunodeficiency virus type 1

Abstract A prospective analysis of 43 episodes of Pseudomonas aeruginosa bacteremia in HIV-1-infected subjects was performed and the results compared with the incidence and outcome of Pseudomonasaeruginosa bacteremia in other high-risk patients, such as transplant recipients, leukemia patients, or patients hospitalized in the intensive care unit. The incidence of bacteremia/fungemia as a whole and of gram-negative and Pseudomonasaeruginosa bacteremia in particular was greater in HIV-1-infected subjects than in the unselected general population admitted. In contrast, the incidence of Pseudomonasaeruginosa bacteremia in HIV-1-infected patients did not differ from that in patients with other high-risk conditions. In patients with HIV-1 infection, independent risk factors for presenting Pseudomonasaeruginosa bacteremia were nosocomial origin (OR, 2.7; 95% CI, 1.3–5.7), neutropenia (OR, 2.7; 95% CI, 1.07–6.8), previous treatment with cephalosporins (OR, 3.6; 95% CI, 1.1–11.6), and a CD4+ cell count lower than 50 cells/mm3 (OR, 3.1; 95% CI, 1.7–8.6). Primary bacteremia and pneumonia were the most common forms of presentation. Fourteen (33%) patients died as a consequence of the bacteremia. The presence of severe sepsis (OR, 17.5; 95% CI, 3.2–68) and the institution of inappropriate definitive antibiotic therapy (OR, 2.7; 95% CI, 1.1–13) were independently associated with a poor outcome. One year after the development of bacteremia, only eight (19%) patients remained alive.

Central nervous system toxoplasmosis in AIDS patients: efficacy of an intermittent maintenance therapy.

Fifty-five episodes of central nervous system (CNS) toxoplasmosis developing in 43 of the 329 AIDS cases seen at our institution were diagnosed during a 34-month period and were prospectively studied. Acute episodes were treated with a pyrimethamine/sulfadiazine (P/S) combination for a mean of 21 days. Because of a previously known major allergy to sulfonamides, three episodes were treated with clindamycin instead of sulphadiazine. In those patients who accepted maintenance therapy, a combination of P/S or pyrimethamine and clindamycin (P/C) was administered 2 days per week. Thirty-six patients (83.7%) survived the first episode. Four of these 36 were lost to further study. Six of the 12 (50%) who decided not to undergo maintenance therapy relapsed (mean follow-up: 12 months). Fourteen patients were given P/S and none relapsed while they were on maintenance therapy (mean follow-up: 10.3 months). Six patients received an intermittent maintenance treatment with P/C and one relapsed 2 months after starting the maintenance therapy (mean follow-up: 13.7 months). We conclude that an intermittent (2 days per week) maintenance treatment for CNS toxoplasmosis with P/S was effective in preventing relapses, although prospective randomized studies remain to be done.

Detection of Unsuspected Cases of Nosocomial Transmission of Tuberculosis by Use of a Molecular Typing Method

The aim of this study was to use restriction fragment length polymorphism to detect unsuspected cases of nosocomial transmission of tuberculosis (TB) among patients who had been admitted to a university hospital. One hundred fifty-one samples of Mycobacterium tuberculosis isolated from patients with pulmonary TB were studied. The isolates from 37 patients (24.5%) defined 11 clusters. None of the patients infected with these cluster isolates had hospital stays that coincided with one another, and for 5.4% of the patients, the epidemiological link was clearly outside the hospital. Previous incarceration was associated with infection with cluster isolates. In addition, 109 patients without TB (41 of whom were infected with human immunodeficiency virus) who shared a room with patients who had TB were followed for 18-60 months. Among the patients who survived, secondary cases of TB due to nosocomial transmission were not detected.

Risk factors for oxacillin/methicillin resistance in coagulase-negative staphylococci

The clinical variables associated with isolation of oxacillin- and methicillin-resistant, coagulase-negative staphylococci (CNS) from blood cultures of hospitalized patients were studied. One hundred CNS strains (49 oxacillin-susceptible; 51 oxacillin-resistant) isolated consecutively from one of two or more sets of blood cultures were collected. Only two variables were independently associated with recovery of oxacillin/methicillin-resistant strains by a multivariate analysis: length of hospital stay > 10 days (OR 5.2, 95% CI = 1.7-15.7), and administration of antimicrobial agents in the previous 14 days (OR 4.5, 95% CI = 1.7-11.7). Analysis of the antibiotics administered indicated that only beta-lactams were associated with a statistically significant risk of resistance to oxacillin/methicillin (OR of beta-lactams vs no antibiotics = 6.94, 95% CI = 1.9-25.3; OR of non-beta-lactams vs no antibiotics = 2.64, 95% CI = 0.8-8.3). Length of hospital stay (especially > 10 days) and prior administration of antimicrobial agents (mainly beta-lactams) independently predicted the presence of oxacillin/methicillin-resistant CNS in blood cultures.

TUBERCULOSIS AND THE NEW CDC CASE DEFINITION FOR AIDS

In Spain the incidence of tuberculosis is still high in the general population and even higher among human immunodeficiency syndrome (HIV)-infected intravenous drug addicts. Of 138 individuals meeting Centers for Disease Control (CDC) case criteria for acquired immunodeficiency syndrome (AIDS) 48 were male homosexuals 78 were intravenous drug addicts 3 were homosexual intravenous drug addicts and 6 were hemophiliacs; the risk factor in the remaining 3 cases was unknown. 27 (19.6%) were accepted as AIDS cases exclusively because they had a clinical form of tuberculosis infection. As additional 23 (16.7%) patients would have been accepted as AIDS cases from 1 to 7 months earlier had tuberculosis been included in earlier CDC definitions. All but 3 AIDS cases with tuberculosis alone or associated with other opportunistic infections or malignancies were intravenous drug addicts.