Discontinuation of chemoprophylaxis against Pneumocystis carinii pneumonia in patients with HIV infection. HIV Outpatient Study (HOPS) Investigators.

BACKGROUND: HIV-infected patients with sustained immunologic improvement from antiretroviral therapy may be able to discontinue chemoprophylaxis against Pneumocystis carinii pneumonia (PCP). OBJECTIVE: To compare PCP incidence in HIV-infected patients who had sustained CD4+ lymphocyte counts greater than 200 cells/mm3 and who either discontinued or continued PCP prophylaxis. DESIGN: Nonrandomized prospective cohort study. SETTING: 10 HIV clinics in eight U.S. cities. PATIENTS: 146 patients had follow-up visits for a mean of 18.2 months after discontinuation of PCP prophylaxis, and 345 patients who continued PCP prophylaxis had follow-up visits for a mean of 14.0 months. MEASUREMENTS: Incidence of PCP. RESULTS: Patients who discontinued PCP prophylaxis had higher maximum and minimum CD4+ cell counts and lower vira loads than patients who continued PCP prophylaxis. Pneumocystis carinii pneumonia did not develop in either group (upper 95% exact binomial confidence limit of incidence for those who discontinued PCP prophylaxis, 2.3/100 person-years). CONCLUSIONS: Discontinuation of PCP chemoprophylaxis may be appropriate for some HIV-infected ambulatory patients.

Changing conditions and treatments in a dynamic cohort of ambulatory HIV patients: the HIV outpatient study (HOPS).

PURPOSE: Most HIV-infected persons are now treated as ambulatory patients. Obtaining continually updated data about these patients' changing conditions, therapies, and reimbursement is essential to health care provision and planning. The systematic tracking of patient medical and laboratory information in an ongoing commercial data collection program (The Health Research Network) allows clinicians to better understand health outcomes, practice patterns, and epidemiologic trends for their patients. METHODS: To evaluate trends in conditions and therapies of ambulatory HIV-infected patients, we analyzed such data electronically and prospectively collected in the HIV Outpatient Study (HOPS) from 1992 through 1996 from 1876 patients seen in 11,755 clinic visits to ten HIV clinical practices. RESULTS: Patients were as likely to be diagnosed with Mycobacterium avium complex ([MAC] 5.4 cases per 100 person-years) or wasting syndrome (7.8 cases per 100 person-years), as Pneumocystis carinii pneumonia ([PCP]; 7.6 cases per 100 person-years) or Kaposi sarcoma ([KS]; 6.9 cases per 100 person-years). A nested analysis showed that HIV-infected cigarette smokers were at substantially greater risk of pneumonia (relative hazard [RH] = 2.3), bronchitis (RH = 1.7) and hairy leukoplakia (RH = 1.9) than nonsmokers. By 1996, 35 (56%) of 62 patients with PCP, 9 (30%) of 30 patients with other pneumonias, 28 (90%) of 31 patients with KS, 35 (73%) of 48 patients with MAC, and 24 (63%) of 38 patients with cytomegalovirus retinitis were treated without hospitalization. CONCLUSIONS: The HOPS provides continually updated information on the changing characteristics, conditions, and therapy of ambulatory HIV-infected patients.

Rapidly progressive herpetic retinal necrosis: a blinding disease characteristic of advanced AIDS.

Eleven patients with rapidly progressive herpetic retinal necrosis (RPHRN) complicating AIDS were investigated retrospectively to study the disease spectrum, systemic involvement, and therapy. The mean CD4 cell count was 24/microL. There was a characteristic disease pattern with rapid progression, 82% bilaterality, relative resistance to intravenous antiviral therapy, and 70% retinal detachment. Varicella-zoster virus was the probable cause in 10 patients (detected by polymerase chain reaction in two eyes investigated), and herpes simplex virus was the probable cause in one. Cutaneous zoster occurred previously in 73% but was not concurrent. Seventy-three percent had central nervous system disease, possibly virus-related. RPHRN may be a local herpetic recrudescence in an immune-privileged site with transneural spread. Only four of 20 affected eyes retained useful vision. Poor ocular bioavailability, retinal ischemia, acquired drug resistance, and strain pathogenicity may underlie treatment failure. Acyclovir therapy appears relatively ineffective. Combined intravenous and intravitreal therapy with foscarnet and ganciclovir may be the best current management. Research advances are needed urgently.

Randomised trial of MNrgp120 HIV-1 vaccine in symptomless HIV-1 infection.

BACKGROUND: Most individuals infected with HIV-1 show disease progression despite both cellular and humoral immune responses. We investigated whether immunisation of patients who had symptomless HIV-1 infection with an envelope subcomponent vaccine (MNrgp120) to augment immune response can slow progression of HIV-1 disease. METHODS: In a randomised, double-blind, placebo-controlled trial, carried out in university infectious disease clinics and community infectious disease practices, we enrolled 573 HIV-infected patients with CD4 counts above 600 cells/microL (0.6 x 10(9)/L). Patients received 600 micrograms vaccine or placebo by intramuscular injection monthly for 6 months then every alternate month throughout the study. The primary endpoint was the rate of decline in CD4 count; secondary endpoints were HIV-1 RNA concentrations in plasma and minor clinical events associated with HIV. Analysis was by intention to treat. FINDINGS: At baseline, the study participants had a mean CD4 count of 775 cells/microL (SD 172) and 89% of participants had detectable HIV RNA (> 200 copies/mL). These RNA-positive individuals had a median viral load of 9250 copies/mL (IQR 2670-26960). Analysis after 15 months of follow-up of the 568 subjects who had at least one CD4 count done after randomisation showed no difference between the 287 vaccine recipients and 281 placebo recipients in rate of decline of CD4 count (yearly decrease 53.8 [SE 7.6] vs 42.3 [7.6] cells/microL; ratio of mean gradients 1.27 [95% CI 0.63-2.55]) or in plasma HIV-1 RNA concentrations (p > or = 0.63). The study was designed with power to detect a vaccine-induced reduction in rate of decline in CD4 count of 60%; these results exclude with 95% confidence a reduction of 40% or more. More vaccine-treated patients than placebo recipients showed a 50% decrease in CD4 count (11 vs 5; relative risk 2.15 [95% CI 0.76-6.12], p = 0.13). The frequencies of HIV-related minor clinical events were similar in the two groups. Pain at the injection site was the only adverse event that occurred more frequently in vaccine-treated group. INTERPRETATION: Postinfection immunisation of symptom-free HIV-infected patients with MNrgp120 vaccine did not alter HIV-1 disease progression as measured by immunological, virological, and clinical endpoints over a 15-month period.

A randomized trial of clarithromycin as prophylaxis against disseminated Mycobacterium avium complex infection in patients with advanced acquired immunodeficiency syndrome.

BACKGROUND: Disseminated infection with Mycobacterium avium complex is the most common opportunistic infection in patients with advanced stages of the acquired immunodeficiency syndrome (AIDS). We studied the efficacy and safety of prophylactic treatment with clarithromycin, a macrolide antibiotic. METHODS: We conducted a randomized, placebo-controlled, double-blind study of clarithromycin in patients with AIDS in the United States and Europe. Entry criteria included blood cultures that were negative for M. avium complex, a Karnofsky performance score of 50 or higher, a CD4 cell count of 100 or less per cubic millimeter, and a life expectancy of at least six months. RESULTS: After the first interim analysis, the study was stopped. M. avium complex infection developed in 19 of the 333 patients (6 percent) assigned to clarithromycin and in 53 of the 334 (16 percent) assigned to placebo (adjusted hazard ratio, 0.31; 95 percent confidence interval, 0.18 to 0.53; P<0.001). During the follow-up period of about 10 months, 32 percent of the patients in the clarithromycin group died and 41 percent of those in the placebo group died (hazard ratio, 0.75; P=0.026). In the clarithromycin group, isolates from 11 of the 19 patients with M. avium complex infection were resistant to clarithromycin. Prophylaxis with clarithromycin was associated with an increased incidence of taste perversion (11 percent in the clarithromycin group vs. 2 percent in the placebo group, P<0.001) and rectal disorders (8 percent vs. 3 percent, P = 0.007); however, the frequency of more severe adverse events was similar in the two groups (7 percent and 6 percent, respectively). CONCLUSIONS: In patients with advanced AIDS, the prophylactic administration of clarithromycin is well tolerated, prevents M. avium complex infection, and reduces mortality.

Elimination of Staphylococcus aureus nasal carriage in health care workers: analysis of six clinical trials with calcium mupirocin ointment. The Mupirocin Collaborative Study Group.

Six double-blind, independently randomized studies evaluated the efficacy and safety of calcium mupirocin ointment in eliminating nasal carriage of Staphylococcus aureus among health care workers. Healthy volunteers with stable nasal carriage of S. aureus (n = 339) received either calcium mupirocin ointment (n = 170) or an identical placebo ointment (n = 169) intranasally for 5 days. Nasal carriage was eliminated 48-96 hours after completion of treatment in 130 (91%) of 143 evaluable volunteers receiving mupirocin but in only 8 (6%) of 142 evaluable volunteers receiving placebo. The 85% crude difference represents a 90% pooled (adjusted) estimate of the risk difference (95% confidence interval, 0.86-0.95) and a risk ratio of 16 (P < .0001). This effect of treatment with mupirocin was observed consistently (risk ratio, 8-32) in all six centers. In addition, 96 of the 130 mupirocin-treated volunteers and 1 of the 8 placebo-treated volunteers who were culture-negative at the end of therapy remained free of S. aureus 4 weeks after treatment. Adverse events in each treatment arm were mild and equally frequent. These data, consistent across six institutions, demonstrate that calcium mupirocin ointment administered intranasally for 5 days is safe and effective in eliminating stable nasal carriage of S. aureus.

Epidemiology and infectious complications of human immunodeficiency virus antibody positive patients.

From July 1, 1991 to March 31, 1992, 156 patients (pts) with positive antibody titers to the human immunodeficiency virus (HIV) were seen in our clinic. A retrospective review of the epidemiology and infectious complications of these patients is presented. There were 129 males and 27 females (4.8:1, ratio). Only 10/156 (12.8%) were non-whites (13 blacks and 7 hispanics). The majority, 126 (80.7%), were 25 to 44 years old. The most common risk factor was homosexuality or bisexuality 100 (64.1%), followed by heterosexual acquisition 25 (16%), intravenous drug abuse 23 (13.7%), unknown 6 (3.8%) and transfusion-related 3 (1.9%). Sixty-five pts had no infections. In the remaining 91 pts, the infections noted were: candidiasis (54 pts); Pneumocystis carinii pneumonia (25 pts); Herpes simplex (13 pts); cytomegalovirus (CMV) retinitis (11 pts) and CMV esophagitis (1 pt), central nervous system toxoplasmosis (8); Herpes zoster (6 pts); cryptococcal meningitis (5 pts); Mycobacterium avium complex bacteremia (4 pts); Molluscum contagiosum, hepatitis-B, staphylococcal infection, perirectal abscess and oral hairy leukoplakia (2 pts each); syphilis, cryptosporidiosis, nocardiosis, histoplasmosis and laryngeal papillomatosis (1 pt each). Infections were multiple in 57/91 (62%) pts and tend to occur more often when the helper cells are < 200 47/57 (82%) pts. Appropriate antimicrobials for prophylaxis and maintenance therapy appeared to decrease the occurrence or relapse of infections such as pneumocystosis, candidiasis, cryptococcosis, tuberculosis and toxoplasmosis.

Twice daily intramuscular imipenem/cilastatin in the treatment of skin and soft tissue infections.

One hundred and two patients were enrolled in an open-label evaluation of intramuscular imipenem/cilastatin using doses of either 500 or 750 mg every 12 h in the treatment of mild to moderately severe skin and soft tissue infections. Seventy-four of 102 patients were clinically evaluable. Thirty-one patients had abscesses, 20 had cellulitis and 23 had wound infections. One hundred seventy-eight isolates were recovered from these 74 patients (average 2.4 isolates/patient). Sixty of 74 evaluable patients (82%) were cured; 12 of 74 (16%) were improved. Two patients failed to improve. Therapy was well tolerated. Adverse effects occurred in 8 patients. All of these effects were minor, and none required discontinuation of therapy. Eighty-two percent of patients reported no pain with injections. Therapy did not need to be interrupted or discontinued in the remaining 18% of patients reporting moderate local pain with injections. Peak and trough serum imipenem levels were measured in 15 patients receiving a 500-mg intramuscular dose of imipenem/cilastatin. The mean peak imipenem concentration in 15 patients was 10.7 micrograms/ml (range 3.3-17.8); the mean trough concentration was 2.1 micrograms/ml (range 0.8-4.9). The trough levels were higher than those found in healthy volunteers and may reflect the age and mild renal dysfunction in this group of treated patients. Imipenem/cilastatin used for mild or moderate skin and soft tissue infections was both efficacious and well tolerated. Intramuscular therapy with this agent offers advantages over intravenous therapy because of its long apparent half-life and pharmacokinetics.

A multicenter trial comparing the efficacy and safety of cefuroxime axetil and cefaclor in pneumonia of adults.

The 185 hospitalized patients (aged 19 to 95 years) with pneumonia were randomly assigned to receive 500 mg of cefuroxime axetil orally (250 mg q12h), 1,000 mg of cefuroxime axetil orally (500 mg q12h), or 1,500 mg of cefaclor orally (500 mg q8h), daily, for a mean of nine days. Among the 151 evaluable patients, clinical cure was noted in 58% of the 500-mg cefuroxime axetil group, 94% of the 1,000-mg cefuroxime axetil group, and 88% of the cefaclor group, and clinical improvement in 32%, 4%, and 9%. Bacteriologic outcome was similar in the three groups. Adverse events were minor and comparable among the treatment groups. Cefuroxime axetil is a safe and effective oral antimicrobial for the treatment of pneumonia in adults.

Chromomycosis in a steroid-dependent patient with chronic obstructive pulmonary disease.

Cutaneous chromomycosis developed in an elderly man with steroid-dependent chronic obstructive pulmonary disease. This patient had no history of foreign travel. Chromomycosis acquired in the United States is rare and may be seen in immunosuppressed patients, as exemplified by this case. Satisfactory response was observed in this patient with surgical debridement and continuing oral ketoconazole therapy.

What is leaky can be risky: a study of the integrity of hospital gloves.

One thousand six-hundred and eighteen medical gloves were tested to determine whether, with current increased demands, these gloves are of high quality, i.e., free of leaks. The risk of exposure to potentially infected fluids when using leaky gloves was also estimated. Using a four-stage leak test, no significant difference was found between 64 of 790 (8.1%, range 0% to 44.4%) unsterile latex gloves and 11 of 210 (5.2%, range 1.7% to 21.7%) unsterile vinyl gloves (p = .21). Sterile surgical gloves (7 of 618, 1.13% [range 0% to 3%]) had fewer leaks compared to unsterile latex and vinyl gloves combined (p less than .0001). The safranin test was positive in 27 of 28 (96.4%) leaky gloves tested, indicating a high risk of exposure to potentially infected fluids when leaky gloves are used. Because of these findings, elements of "universal precautions" such as changing gloves after each patient contact and good handwashing after using gloves should be carefully observed. There is a need for the Food and Drug Administration to establish more stringent guidelines for manufacturing gloves and to verify compliance with these guidelines.

Seizure propensity with imipenem.

Five patients with seizures related to imipenem administration are described. The potential of imipenem therapy to cause seizure was further studied in a mouse model and compared with the potential for seizure with penicillin and cefotaxime therapy. Penicillin caused ataxia and seizure at a mean mouse serum level of 5800 microns/mL, cefotaxime at 3400 microns/mL, and imipenem at a much lower serum concentration of 1900 microns/mL. The potent activity of imipenem therapy against bacteria, allowing for a clinical dose of only 2 g/d, is unfortunately offset by its higher propensity to induce neurologic symptoms in humans and mice at much smaller doses than would therapy with penicillin G or the cephalosporins, such as cefotaxime.

Oral ciprofloxacin treatment of infections in geriatric patients.

The efficacy and safety of oral ciprofloxacin (750 mg every 12 hours) in the treatment of infections was evaluated in 84 geriatric patients. Duration of treatment ranged from three to 42 days (for a mean of 10.45 days). Satisfactory responses (cured or improved) were noted in 33 of 34 cases of urinary tract infections (97%); in 11 of 13 cases of lower respiratory tract infections (85%); in four of nine cases of skin and skin structure infections (44%); and in both cases of bone infection and bacteremia. Bacteriological cure rates were 91% of 33 urinary tract infections; 83% of 12 lower respiratory tract infections; 62% of eight skin and skin structure infections; and in both cases of bone infection and bacteremia. Three patients evaluable for clinical purposes were bacteriologically unevaluable. Overall clinical efficacy and bacteriological cure rates were 86% and 85%, respectively. Of the 78 evaluable pathogens isolated, 70 (90%) were eradicated. Adverse reactions occurred in 24 patients (29%) and included candida colonization in eight, gastrointestinal upset in six, dermatologic symptoms in five, and vaginal candidiasis, chest pain, renal failure, tremors, monocytosis, thrombocytosis, and increased serum theophylline level in one patient each. Ciprofloxacin appears to be a safe and effective treatment for infections in geriatric patients. Advantages of the oral form include cost effectiveness and decreased length of hospitalization.

Comparative evaluation of safety and efficacy of cefmetazole and cefoxitin in lower respiratory tract infections.

The efficacy and safety of cefmetazole and cefoxitin were compared in a randomized open-label parallel trial in 68 hospitalized adult patients with lower respiratory tract infections. Of 40 patients evaluable for efficacy, 23/25 (92%) in the cefmetazole group and 13/15 (87%) in the cefoxitin group demonstrated a favourable clinical response. The causative bacteria were eradicated in 30/32 (94%) and 13/14 (93%) of isolates in the cefmetazole and cefoxitin groups, respectively. A total of 51 adverse events was noted in 68 patients: 36 in 26 patients (55%) in the cefmetazole group and 15 in 12 patients (57%) in the cefoxitin group. These events were reversible, and except in one patient who was treated for oral candidiasis, did not require any therapeutic intervention or prolonged hospitalization. Cefmetazole appears to be as safe and effective as cefoxitin in the treatment of lower respiratory tract infections of hospitalized patients.

The hamster model of chronic Mycobacterium avium complex infection.

Male golden Syrian hamsters were evaluated as a model for the pathogenesis of human infection with Mycobacterium avium complex. Intratracheal inoculation produced a chronic, nonfatal, pulmonary and disseminated infection (overall rate, 86%). The frequency of infection in hamsters that received 5 x 10(8) versus 1 x 10(8) colony forming units (cfu) was not significantly different (87% and 92%, respectively), but 1 x 10(7) cfu produced infection in only 78% of inoculated animals (P = .034). The percentage of animals developing pulmonary infection with M. avium complex did not differ between inoculum groups (77%-80%). Disseminated infection occurred significantly less frequently in the 1 x 10(7) group (46%) compared with the 5 x 10(8) (79%) and 1 x 10(8) (68%) groups (P = .001 and .056, respectively). After seven weeks, partial clearance of M. avium complex from the lungs coincided with an increased number of animals with splenic involvement. The hamster may be a useful model for human infection with M. avium complex.

Comparative efficacy and safety of ceftizoxime, cefotaxime and latamoxef in the treatment of bacterial pneumonia in high risk patients.

One hundred and thirty-five patients with bacterial pneumonia who had risk factors (alcoholism, chronic obstructive pulmonary disease, corticosteroid therapy diabetes mellitus, advanced age, solid tumours) were randomly allocated in a double-blind fashion to receive either ceftizoxime (2-4 g every 8 h), cefotaxime (1-2 g every 4 h), or latamoxef (2-4 g every 8 h). Of the 84 patients evaluable for efficacy, clinical cure was achieved in 91%, 85%, and 89% of ceftizoxime- (20/22), cefotaxime-(23/27), and latamoxef-treated (31/35) patients, respectively. Adverse reactions occurred in one of 45 ceftizoxime-treated patients, one of 43 cefotaxime-treated patients, and seven of 47 latamoxef-treated patients. Abnormal laboratory values during therapy were seen in 50% of latamoxef-treated and 43% of cefotaxime-treated patients and in 29% of ceftizoxime-treated patients. Hypoprothrombinaemia occurred in five latamoxef-treated patients and one of these patients experienced an episode of haematemesis. In this study, ceftizoxime, cefotaxime, and latamoxef were similarly effective; however, the incidence of side effects was most frequent with latamoxef.

Clinical study evaluating efficacy of praziquantel in clonorchiasis.

In 74 patients with clonorchiasis, the efficacy and safety of praziquantel was evaluated in a two-phase study: a double-blind, randomized controlled trial of praziquantel versus placebo (42 patients) and an open study (32 patients). All but one of the patients were Laotians. The intensity of clonorchiasis was light in 85% (63 of 74) and moderate in 15% (11 of 74) of the patients. Cure based on our established criteria was noted in 67 of 67 patients (100%) treated with praziquantel at a dose of 75 mg/kg per day. In contrast, four patients (20%) in the placebo group, each with light infection, ceased passing eggs and were, according to our established protocol, considered spontaneous cures (P less than 0.0001). Adverse effects of praziquantel were transient and included nausea and vomiting (15%), vertigo (12%), hepatomegaly (4.5%), headache (1.5%), rash (1.5%), and hypotension (1.5%). Of 20 patients who received placebo, 1 (5%) developed transient skin rash, fever, and chills. Clinically minor and transient, but statistically significant, changes in hemoglobin, total protein in serum, and levels of uric acid, cholesterol, and bilirubin in serum were noted. Results of this study showed that praziquantel is safe, well tolerated, and effective and should be considered as the drug of choice for treatment of clonorchiasis. In moderate infections, a second course of praziquantel therapy may be necessary to eliminate infection.

Comparative multicentre evaluation of the safety and efficacy of ceftazidime versus cefamandole for pneumonia.

Ceftazidime and cefamandole were compared in a randomized multicentre trial in hospitalized patients with pneumonia. Of 290 patients enrolled, 92 patients in the ceftazidime group and 71 patients in the cefamandole group were evaluable. Geometric mean MICs of organisms isolated and tested to ceftazidime were within achievable therapeutic serum concentrations of ceftazidime. Satisfactory clinical responses were observed in 91% (84/92) of ceftazidime-treated patients and 83% (59/71) of cefamandole-treated patients (P greater than 0.05). Superinfection occurred in one (1%) ceftazidime-treated patient and in five (7%) cefamandole-treated patients. Side effects were infrequent with either treatment. Ceftazidime is as safe and effective as cefamandole for the treatment of pneumonia due to a variety of Gram-positive and Gram-negative pathogens.

Comparative antigenic studies of species of Basidiobolus and other medically important fungi.

An immunodiffusion technique was used to evaluate the antigenic relationship of various pathogenic and saprobic Basidiobolus spp., Conidiobolus spp., isolates of the order Mucorales, and several other medically important nonzygomycetous fungi. The antiserum to Basidiobolus haptosporus shared two lines of identity, designated inner (N) and outer (Y), when tested against exoantigens of known strains of B. haptosporus and Basidiobolus ranarum as well as exoantigens of a human Nigerian isolate and several wild isolates tentatively identified in B. ranarum. Both bands were heat stable at 56 degrees C for 30 min. Exoantigens of strains of Basidiobolus meristosporus, Basidiobolus microsporus, Conidiobolus incongruus, Conidiobolus coronatus, and other wild isolates of Basidiobolus spp. tested formed only the N immunoprecipitin band. Exoantigens of 10 isolates from other taxa did not produce any cross-reactive precipitin line. B. meristosporus antiserum that was tested against exoantigens of Basidiobolus spp. and of Conidiobolus spp. developed only an N band without a Y band. These data suggest that B. haptosporus and B. ranarum are antigenically similar to each other and distinct from B. meristosporus. Basidiobolus spp. and Conidiobolus spp. share a common N immunoprecipitin band, which implies a taxonomic relationship between these two genera. The absence of lines of identity between Basidiobolus spp. and other fungi tested suggests that, antigenically, Basidiobolus is a distinct genus.