Paromomycin: no more effective than placebo for treatment of cryptosporidiosis in patients with advanced human immunodeficiency virus infection. AIDS Clinical Trial Group.

To evaluate the efficacy of paromomycin for the treatment of symptomatic cryptosporidial enteritis in human immunodeficiency virus-infected adults, we conducted a prospective, randomized, double-blind, placebo-controlled trial before the widespread introduction of highly active antiretroviral therapy (HAART). Seven units under the auspices of the AIDS Clinical Trials Group enrolled 35 adults with CD4 cell counts of < or = 150/mm(3). Initially, 17 patients received paromomycin (500 mg 4 times daily) and 18 received matching placebo for 21 days. Then all patients received paromomycin (500 mg q.i.d.) for an additional 21 days. Clinical definitions of response were measured by an average number of bowel movements per day in association with concurrent need for antidiarrheal agents that was lower than that before study entry. There was no treatment response during the placebo-controlled phase of the study according to protocol-defined criteria (P=.88). Three paromomycin recipients (17.6%) versus 2 placebo recipients (14.3%) responded completely. Rates of combined partial and complete responses in the paromomycin arm (8 out of 17, 47.1%) and the placebo arm (5 out of 14, 35.7%) of the study were also similar (P=.72). The clinical course of cryptosporidiosis was quite variable. Paromomycin was not shown to be more effective than placebo for the treatment of symptomatic cryptosporidial enteritis. However, inadequate statistical power prevents definitive rejection of the usefulness of paromomycin as therapy for this infection.

Tuberculosis in physicians. Compliance with preventive measures.

Compliance with public health recommendations for tuberculosis control was evaluated by a survey of 4,417 physicians who had not contracted tuberculosis during medical school nor during the 4 decades after graduation through 1981. Thirty-one percent of the cohort had been vaccinated with bacille Calmette-Guérin (BCG) and 47% considered themselves tuberculin-positive. Thirty-two percent of 1,088 physicians who graduated after 1974 had been exposed to 3 or more patients with infectious tuberculosis in the previous year. Fifty-eight percent of 738 unimmunized, tuberculin-negative physicians who had been exposed to one or more patients with infectious tuberculosis in the previous year had tuberculin tests every 1 to 2 yr. Forty-nine percent of 597 unimmunized tuberculin reactors with similar occupational exposure had chest roentgenograms every 1 to 2 yr. The BCG-vaccinated physicians were less likely to have frequent tuberculin tests but no different frequency of chest roentgenograms. Eight percent of 1,460 unimmunized tuberculin reactors received isoniazid chemoprophylaxis, including 39% of 128 tuberculin reactors who graduated after 1974 (the majority of the latter were younger than 35 yr of age). Of 66 physicians who had active tuberculosis during medical school or after graduation, 20 (30%) had not received any antituberculosis chemotherapy, whereas 2 of 46 who did, received chemotherapy only after a second episode of tuberculosis. In summary, our study documents poor compliance by physicians with recommended policies for the prevention of tuberculosis in health care workers.

Efficacy of pneumococcal vaccine in high-risk patients. Results of a Veterans Administration Cooperative Study.

We conducted a randomized, double-blind, placebo-controlled trial to test the efficacy of the 14-valent pneumococcal capsular polysaccharide vaccine in 2295 high-risk patients (patients with one or more of the following: age above 55 years and the presence of chronic cardiac, pulmonary, renal, or hepatic disease, alcoholism, or diabetes mellitus). Seventy-one episodes of proved or probable pneumococcal pneumonia or bronchitis occurred among 63 of the patients (27 placebo recipients and 36 vaccine recipients). Vaccine-serotype Streptococcus pneumoniae strains were recovered in association with 11 infections in the placebo group and 14 infections in the vaccine group. Pneumococcal infections occurred most frequently among patients with chronic pulmonary, cardiac, or renal diseases. Among vaccine recipients who subsequently had vaccine-type pneumonia or bronchitis, the majority did not make or sustain serum antibodies against their infecting organism in concentrations that were twice as high as the base-line values, or more than 400 ng of antibody nitrogen per milliliter, although their base-line levels were higher than those in subjects in whom infection did not develop. We were unable to demonstrate any efficacy of the pneumococcal vaccine in preventing pneumonia or bronchitis in this population. Our data suggest that chronically ill patients, who are most susceptible to infection, may have an impaired immune response to the pneumococcal vaccine.

Tuberculosis in physicians: a continuing problem.

We evaluated the occurrence of active tuberculosis in 4,575 physicians who graduated between 1938 and 1981 from the same medical school. There were 66 cases. Fifteen (23%) cases were detected after 1970 including 4 diagnosed in 1981. For most years, the incidence of tuberculosis was higher in physicians than in the general population. Forty-eight (73%) patients were between 25 and 34 yr of age at the time of diagnosis. Two thirds of all cases occurred within 6 yr of graduation, even in graduates since 1970. The risk of tuberculosis was 140 per 100,000 persons-years within 6 yr of graduation. Sixty-three percent of initially tuberculin-negative medical students who subsequently had active tuberculosis converted their tuberculin reaction during medical school or clinical training. Recipients of BCG vaccine had 40% less tuberculosis than unimmunized, initially tuberculin-negative, physicians. Health authorities should be cognizant of the continuing risk of tuberculosis in medical students and physicians.

Antibiotic-resistant isolates of Streptococcus pneumoniae from clinical specimens: a cluster of serotype 19A organisms in Brooklyn, New York.

Ten of 294 isolates of Streptococcus pneumoniae from patients enrolled in a Veterans Administration Cooperative Studies Program trial of pneumococcal vaccine efficacy were moderately resistant or resistant to penicillin. Nine of these organisms were serotype 19A isolated from patients at the Brooklyn (New York) V.A. Medical Center over an 18-month period (March 1983-November 1984). The minimal inhibitory concentration of penicillin for these pneumococci ranged from 1.0 to 2.0 micrograms/ml by the agar dilution technique and from 4.0 to 8.0 micrograms/ml by tube dilution. These organisms were resistant also to other beta-lactam antibiotics and to tetracycline, chloramphenicol, and trimethoprim-sulfamethoxazole. They were sensitive to erythromycin, clindamycin, vancomycin, and rifampin. The epidemiological source of these isolates was not discovered. However, it is possible that a focus of multiple antibiotic-resistant serotype 19A S. pneumoniae is present in Brooklyn.

Dosage of antituberculous drugs in obese patients.

There are no published data defining efficacious drug therapy for obese patients with active tuberculosis. Current dosage recommendations are based on total body weight (TBW); drug toxicity might result in obese patients receiving TBW doses. Peak and trough serum levels were measured for rifampin, streptomycin, ethambutol, and pyrazinamide in an obese patient (166 kg TBW, 87 kg ideal body weight (IBW] with miliary and meningeal tuberculosis. The observed drug levels and the calculated serum half-lives of these drugs were compared with the expected serum levels and serum half-lives in lean patients treated with literature-recommended doses. The observed serum levels in our obese patients were within the expected range for lean patients when dosage was based on IBW rather than on TBW. The observed cerebrospinal fluid penetrations of the drugs studied in our obese patient were similar to those reported in lean patients.

Evaluation of Gonozyme, an enzyme immunoassay for the rapid diagnosis of gonorrhea.

A new indirect enzyme immunoassay (EIA), Gonozyme (Abbott Laboratories), was assessed for rapid detection of gonococcal antigens. A correlation of optic density (OD) readings by EIA with colony counts of serial dilutions of Neisseria gonorrhoeae ATCC 19424 disclosed that EIA detected 10(3) CFU/ml at OD readings of 0.1 to 0.3, that EIA consistently detected greater than or equal to 10(4) CFU/ml at OD readings of 0.6 to 1.3, and that concentrations of greater than or equal to 10(5) CFU/ml were associated with OD readings of greater than or equal to 2.0. The clinical usefulness of Gonozyme was evaluated by comparing results of EIA with those of Gram stain (GS) and culture for N. gonorrhoeae from urethral and endocervical swabs obtained prospectively in 886 randomly selected patients attending a clinic for sexually transmitted diseases. The patients evaluated included 83 female contacts of men with gonorrhea and 56 patients seen at the clinic for test of cure. In tests with 295 males, the sensitivities of GS and EIA were 91.3 and 97.1%, respectively, and both tests had specificities of greater than 96%. In tests with 591 females, the sensitivities of GS and EIA were 51.4 and 96.4%, respectively (P less than 0.0001, Z proportionality test), and the specificities were 98.7 and 86.5%, respectively (P less than 0.0001). In tests with 61 females and 3 males, EIA was positive, whereas GS and cultures were negative for N. gonorrhoeae. Gonozyme is a highly sensitive method for rapid detection of gonococcal antigens. EIA is comparable to GS for males and more sensitive though less specific than GS for females. Possible reasons for the lower specificity of EIA for females are discussed. Due to its high negative predictive value for female contacts, EIA offers an alternative to epidemiological treatment of contacts before culture results.

Failure of medical therapy in tricuspid endocarditis due to Staphylococcus aureus.

A patient with isolated tricuspid endocarditis due to Staphylococcus aureus had persistent bacteremia despite antibiotic therapy for 47 days until surgery. Cultures of the resected valve disclosed 1.4 X 10(8) colony forming units per gram of valve. Time-kill studies done with the strain of S. aureus and the antibiotics used in the therapy of this patient disclosed decreased bactericidal activity of these antibiotics with increasing inocula concentrations. At 10(8) inoculum, only the combination of vancomycin and tobramycin was bactericidal. The inoculum dependence of bactericidal activity might explain the lack of correlation between in vitro susceptibility tests with clinical outcome of some endocarditis patients.

Coagglutination for detection and serotyping of bacterial antigens: usefulness in acute pneumonias.

Staphylococcal coagglutination was evaluated for detection of Streptococcus pneumoniae and Haemophilus influenzae antigens in vitro and in the clinical setting of acute pneumonia. Coagglutination testing was performed with Phadebact reagents and with polyvalent and type-specific reagents for pneumococci prepared in the laboratory. Purified capsular antigens of 10 of 14 pneumococcal serotypes (included in the current pneumococcal vaccine formulation) were detected by coagglutination in the range of 0.5-62 ng/ml; serotype 6 was detected at 125 ng/ml, and serotypes 12, 23, and 25 were detected only at 500 ng/ml or more. Haemophilus influenzae type b antigen was detected at 100 ng/ml. Sputum, blood, and urine specimens of 36 consecutive patients admitted with pneumonia were evaluated prospectively by coagglutination. Nonspecific reactions were eliminated by pretreatment with ethylenediaminetetra-acetic acid and heating and with staphylococcal protein A. Eight of nine patients with sputum cultures positive for pneumococci had positive sputum coagglutination (sensitivity of 89%); 24 of 27 patients with cultures negative for pneumococci had negative sputum coagglutination (specificity of 89%). Serum or urine coagglutination was positive in five patients with pneumococcal pneumonia, including the only bacteremic case, the only fatality, and another patient who had a protracted clinical course. In conclusion, coagglutination is a simple, rapid, sensitive, and specific test for antigen detection in patients with acute pneumonia.

Rapid diagnosis of septic arthritis by coagglutination.

Pneumococcal capsular antigens were detected and serotyped by coagglutination in joint fluids and serum of a patient with septic arthritis within 1 h of obtaining the specimens. Pneumococcal antigens continued to be detected by coagglutination for 3 days, whereas cultures and Gram stains were negative after 1 day of antibiotic therapy.

Nosocomial outbreak of nitrate-negative Serratia marcescens infections.

Bacteremia due to multiply-antibiotic-resistant Serratia marcescens occurred within 1 week in four patients who were in adjacent beds in an intensive care unit. The strains were serotyped as O14:H12 and were nitrate negative. This unusual biochemical marker was useful in the investigation of the outbreak.

Bacterial meningitis without clinical signs of meningeal irritation.

A clinical diagnosis of meningitis in neonates is difficult because of paucity of physical findings. In older infants and children, nuchal rigidity, Kernig's or Brudzinski's sign, or bulging fontanelles are sought. A review of 1,064 cases of bacterial meningitis beyond the neonatal period revealed that 16 (1.5%) patients had none of those meningeal signs during the entire hospitalization, despite CSF pleocytosis. Eight patients (50%) were 2 years old or older. Lumbar punctures were done because of unexplained fever, changes in behavior or mental status,, seizures, or occurrence of skin petechiae in febrile patients. These patients frequently had moderate pleocytosis and all survived. The meningitis was caused by Neisseria meningitidis in seven patients, Haemophilus influenzae in six, Streptococcus pneumoniae in two, and Salmonella enteritidis in one patient. CSF should be examined in a patient of any age whenever meningitis is a consideration, even if patients lack meningeal signs.

Community-acquired purulent meningitis of unknown etiology. A continuing problem.

The clinical features and hospital course of 132 patients with purulent meningitis of unknown etiology (PMU) were compared with those of 1,032 patients with proven bacterial meningitis; all patients were admitted to a major referral center for meningitis treatment between 1954 and 1976. Most patients had no major underlying illnesses. Patients with PMU were more frequently older, "pretreated" with antibiotics, had longer duration of symptoms, evidenced less marked alterations of mental status, and died later in the hospitalization; however, the mortality and frequency of neurologic complications were similar to those in patients with bacterial meningitis. Patients with PMU who also had hemorrhagic rashes had fewer neurologic complications and none died; these patients comprised a distinct group in terms of better prognosis. New methods for rapid diagnosis of bacterial meningitis have only partially resolved the diagnostic dilemma of PMU.

Unusual aspects of Salmonella meningitis.

Two cases of salmonella meningitis that demonstrate unusual clinical and epidemiologic features are reported. The first case was a two-month-old infant with relapsing salmonella meningitis in whom ECHO 2 virus and S. enteritidis grew in mixed culture from cerebrospinal fluid. The second case was a five-month-old with typhoid meningitis. Although this patient eventually responded to chloramphenical, repeated CSF cultures grew S. typhi despite his receiving high dose parenteral therapy with ampicillin and chloramphenicol. Stool cultures disclosed that the patient's mother was an asymptomatic carrier of S. typhi. Nine days after the positive stool culture, the mother developed S. typhi bacteremia.

Community-acquired purulent meningitis: a review of 1,316 cases during the antibiotic era, 1954-1976.

This review of 1,316 cases of purulent meningitis assessed changes in the etiology, clinical features, and fatality rate during the antibiotic era. Hemophilus influenzae was the most frequent cause of purulent meningitis (458 cases), Neisseria meningitidis the second most frequent (396 cases), and Streptococcus pneumoniae the third most frequent (178 cases). No bacterial etiology was found for 148 patients with purulent meningitis, the fourth major category of meningitis throughout the 23 years surveyed. Few patients had notable underlying diseases or predisposing conditions; 77.4% were less than 10 years old, but only 13 patients were less than one month old. Patients with meningitis caused by Staphylococcus aureus or various streptococci commonly had associated suppurative foci and the highest fatality rate. There were 103 deaths, of which 70.8% occurred during the first 48 hr of hospitalization. Antibiotics had been given to 54.6% of patients before admission to the hospital. Bacteriologic and cerebrospinal fluid (CSF) findings for patients who received antibiotics prior to admission ("pretreated") were compared with these findings for those who had not had antibiotics in 1,032 cases of meningitis caused by H. influenzae, N. meningitidis, or S. pneumoniae. No significant differences in white blood cell counts or in glucose or protein concentrations in CSF were noted among patients infected with any of the three organisms; positive cultures of blood and CSF were significantly less frequent in "pretreated" patients whose disease was caused by any of the three organisms, and particularly in those with meningitis due to N. meningitidis. Nasopharyngeal, throat, and rectal swabs and CSF specimens from 141 patients were cultured for virus. Enteroviruses were isolated from rectal swabs of two patients with bacterial meningitis and from the CSF of two patients (in mixed culture with Salmonella enteritidis in one case).