Comparative pharmacokinetics of an adalimumab biosimilar SB5 administered via autoinjector or prefilled syringe in healthy subjects.

PURPOSE: The objective of this study was to demonstrate comparable pharmacokinetic (PK), safety, and tolerability parameters of the adalimumab biosimilar SB5 administered via autoinjector (AI) pen or prefilled syringe (PFS). PATIENTS AND METHODS: In this phase 1, randomized, open-label, single-dose, parallel-group study, healthy subjects aged 18-55 years were randomized 1:1 to a single dose of 40 mg SB5 delivered subcutaneously via AI or PFS. PK parameters, safety, and tolerability were assessed for 57 days post-dose. The primary endpoint was area under the curve (AUC) of the concentration-time curve from zero to infinity (AUCinf) and from zero to last quantifiable concentration (AUClast) and maximum serum concentration (Cmax). Equivalence was determined using predefined margins of 0.80-1.25 for the 90% CI for the ratio of SB5 AI to SB5 PFS. RESULTS: Ninety-five subjects were randomized to each group. Mean serum concentration-time profiles were superimposable between groups. Mean values for AUCinf, AUClast, and Cmax were similar between the SB5 AI and SB5 PFS groups. For the primary endpoints, the 90% CIs for the ratio of geometric least squares means for SB5 AI to SB5 PFS ranged between 0.9503 and 1.2240, which were all within the equivalence margin of 0.80-1.25. Incidence of treatment-emergent adverse events and injection site reactions was similar between groups. CONCLUSION: In healthy subjects receiving a single dose of SB5 via AI or PFS, PK parameters and corresponding 90% CIs were within the predefined margins, showing bioequivalence between the two delivery methods. Safety and tolerability assessments were also similar between groups. CLINICALTRIALSGOV IDENTIFIER: NCT02326233. EUDRACT NUMBER: 2014-005178-12.

Bioequivalence, safety and immunogenicity of BI 695501, an adalimumab biosimilar candidate, compared with the reference biologic in a randomized, double-blind, active comparator phase I clinical study (VOLTAIRE®-PK) in healthy subjects.

BACKGROUND: This Phase I study (VOLTAIRE®-PK) aimed to evaluate three-way pharmacokinetic similarity (bioequivalence), safety, and immunogenicity of BI 695501 (a Humira® [adalimumab] biosimilar candidate) compared with US- and EU-approved Humira in healthy male subjects. METHODS: Subjects (N = 327) were randomized 1:1:1 to receive one 40-mg subcutaneous dose of BI 695501, US- or EU-approved Humira; safety was assessed for 70 days. Bioequivalence was evaluated using the average bioequivalence method to test if the 90% confidence intervals (CIs) of the geometric means (BI 695501 vs US- and EU-approved Humira) for the primary end points were within prespecified acceptance ranges (80-125%). Immunogenicity was assessed using a sensitive bridging method. RESULTS: Bioequivalence between BI 695501 and US- and EU-approved Humira was demonstrated with the 90% CIs of the ratios of all primary end points: Cmax, AUC0-inf, pred and AUC0-tz being within the prespecified acceptance ranges of 80-125%. Concentration vs time profiles were similar as were the time course and frequency of immunogenic responses. All study drugs showed similar safety and tolerability results. CONCLUSIONS: Three-way bioequivalence of BI 695501 to US- and EU-approved Humira was demonstrated; safety and immunogenicity results of the three study drugs were also similar. CLINICAL TRIAL REGISTRATION: 2013-003722-84 (EudraCT) and NCT02045979.

Efficacy of a trivalent influenza vaccine against seasonal strains and against 2009 pandemic H1N1: A randomized, placebo-controlled trial.

BACKGROUND: Before pandemic H1N1 vaccines were available, the potential benefit of existing seasonal trivalent inactivated influenza vaccines (IIV3s) against influenza due to the 2009 pandemic H1N1 influenza strain was investigated, with conflicting results. This study assessed the efficacy of seasonal IIV3s against influenza due to 2008 and 2009 seasonal influenza strains and against the 2009 pandemic H1N1 strain. METHODS: This observer-blind, randomized, placebo-controlled study enrolled adults aged 18-64years during 2008 and 2009 in Australia and New Zealand. Participants were randomized 2:1 to receive IIV3 or placebo. The primary objective was to demonstrate the efficacy of IIV3 against laboratory-confirmed influenza. Participants reporting an influenza-like illness during the period from 14days after vaccination until 30 November of each study year were tested for influenza by real-time reverse transcription polymerase chain reaction. RESULTS: Over a study period of 2years, 15,044 participants were enrolled (mean age±standard deviation: 35.5±14.7years; 54.4% female). Vaccine efficacy of the 2008 and 2009 IIV3s against influenza due to any strain was 42% (95% confidence interval [CI]: 30%, 52%), whereas vaccine efficacy against influenza due to the vaccine-matched strains was 60% (95% CI: 44%, 72%). Vaccine efficacy of the 2009 IIV3 against influenza due to the 2009 pandemic H1N1 strain was 38% (95% CI: 19%, 53%). No vaccine-related deaths or serious adverse events were reported. Solicited local and systemic adverse events were more frequent in IIV3 recipients than placebo recipients (local: IIV3 74.6% vs placebo 20.4%, p<0.001; systemic: IIV3 46.6% vs placebo 39.1%, p<0.001). CONCLUSIONS: The 2008 and 2009 IIV3s were efficacious against influenza due to seasonal influenza strains and the 2009 IIV3 demonstrated moderate efficacy against influenza due to the 2009 pandemic H1N1 strain. Funded by CSL Limited, ClinicalTrials.gov identifier NCT00562484.

Late-onset bolus intravenous beta-lactam antibiotic adverse reaction: short-lived symptoms during drug administration and associated laboratory abnormalities.

BACKGROUND: In the 1970s, there were 2 reports of a late-onset adverse reaction during bolus infusions of benzyl penicillin, characterized by short-lived symptoms, most commonly abdominal pain. The mechanism is not known. We set out to further characterize this reaction. METHODS: We conducted a prospective observational study of all adult patients receiving bolus intravenous (IV) beta-lactam antibiotics under the care of our Outpatient IV Antibiotic Service from 1 August 2007 to 31 January 2010, focusing on those who developed infusion-related symptoms. RESULTS: During the 30-month study, 11 of the 163 patients (7%) treated with bolus IV beta-lactam antibiotics developed a late-onset infusion-related adverse reaction. Six of 30 patients (20%) treated with benzyl penicillin developed this adverse reaction compared to 5 of 133 (4%) treated with any other beta-lactam antibiotic (p = 0.006). The median duration of beta-lactam antibiotic before reaction onset was 25 days. Abdominal pain occurred in 9 patients (82%), fever in 3 (27%), and rash in 5 (45%). Seven patients (64%) developed a combination of thrombocytopenia, neutropenia, and/or lymphopenia and 6 (55%), elevated liver enzymes. CONCLUSIONS: This adverse reaction, occurring late during prolonged IV bolus beta-lactam treatment, is most often characterized by short-lived abdominal pain occurring at the time of infusion and is more common in patients receiving benzyl penicillin. It is frequently associated with cytopenias and elevated liver enzymes. It may have both immunological and non-immunological mechanisms.

Comparative pharmacokinetics of subcutaneous trastuzumab administered via handheld syringe or proprietary single-use injection device in healthy males.

PURPOSE: To demonstrate pharmacokinetic (PK) comparability for a single dose of 600 mg subcutaneous (SC) trastuzumab, administered via a novel single-use injection device (SID) or handheld syringe in 119 randomized healthy male subjects. METHODS: The co-primary PK endpoints area under the time-concentration curve from the start of dosing to day 22 (AUC(0-21 days)) and maximum observed trastuzumab serum concentration (C(max)) were dose-normalized and body-weight-adjusted, and compared using geometric mean ratios (GMRs). SID performance, injection site pain, adverse events, and antidrug antibodies (ADAs) were assessed. RESULTS: GMRs and 90 % confidence intervals (CIs) were 1.01 (0.96-1.07) for AUC(0-21 days) and 1.02 (0.96-1.10) for C(max), which fell within the prespecified bioequivalence range (0.80-1.25). No SID quality issues or failures occurred. Adverse events were mostly mild, with no deaths, adverse event-related withdrawals, or life-threatening, cardiac, or serious events reported. The ADA rate was low, and no neutralizing antibodies were detected. CONCLUSIONS: Trastuzumab SC via SID demonstrated comparable PK and safety to handheld syringe administration. SID performance was very satisfactory.

Effects of intravenous zoledronate on bone turnover and bone density persist for at least five years in HIV-infected men.

CONTEXT: In HIV-infected men, the antiresorptive effects of zoledronate persist for at least 2 yr after the second annual dose. OBJECTIVE: Our objective was to determine the duration of action of zoledronate in men. DESIGN AND SETTING: This was 4-yr extension of a 2-yr, double-blind, randomized, placebo-controlled trial at an academic research center. PARTICIPANTS: Participants included 43 HIV-infected men with bone mineral density (BMD) T score below -0.5, 35 of whom entered the extension study. INTERVENTION: Intervention was annual administration of 4 mg iv zoledronate or placebo at baseline and 1 yr and no intervention subsequently. MAIN OUTCOME MEASURES: We evaluated changes in the bone turnover markers, serum osteocalcin and serum C-telopeptide (CTx), and changes in BMD at the lumbar spine, total hip, and total body. RESULTS: There was no time × treatment interaction between 1 and 5 yr after the second zoledronate dose for osteocalcin or CTx (P > 0.4) or any BMD site (P > 0.7). Between 1 and 5 yr after the second dose, on average, osteocalcin was 41% lower (95% confidence interval = 19-62%; P < 0.001), CTx 52% lower (33-71%; P < 0.001), lumbar spine BMD 3.7% greater (0.3-7.0%; P = 0.03), total hip BMD 2.3% greater (0.3-4.3%; P = 0.02), and total body BMD 2.5% greater (0.8-4.1%; P = 0.004) in the zoledronate group than the placebo group. Five years after the second dose, the between-groups differences were 38% (13-62%) for osteocalcin, 49% (20-77%) for CTx, 3.5% (0.7-6.7%) for lumbar spine BMD, 3.4% (1.4-5.4%) for total hip BMD, and 1.6% (0.2-3.1%) for total body BMD. CONCLUSION: The effects of two annual 4-mg doses of zoledronate in men persist for at least 5 yr after the second dose. Larger trials assessing the antifracture efficacy of less frequent dosing of zoledronate are justified.

Stable bone mineral density over 6 years in HIV-infected men treated with highly active antiretroviral therapy (HAART).

OBJECTIVE: Most longitudinal studies of bone mineral density (BMD) in HIV-infected cohorts have been of short duration, typically 1-2 years. Some studies, especially of cohorts treated with highly active antiretroviral therapy (HAART), report short-term stable or increasing BMD, but other studies, often in cohorts initiating HAART, report short-term losses in BMD. We assessed BMD changes over the medium term in HIV-infected men already established on HAART at baseline. DESIGN: Six-year, prospective, longitudinal study. SUBJECTS: Forty-four HIV-infected men treated with HAART and 37 uninfected, healthy controls. MEASUREMENTS: Participants had measurements of BMD at baseline, 2 and 6 years. RESULTS: In the HIV-infected men at baseline, the mean age was 49 years, the mean duration of infection was 8 years, and the mean duration of HAART was 50 months. Over 6 years of follow-up, there was a greater increase in lumbar spine BMD (5·3%, 95% CI 3·8-6·5%) in the HIV-infected men compared with controls (0·3%, 95% CI -1·0 to 1·6%), P < 0·001. There was no difference between the groups in the change in BMD over time at the total hip (HIV group: -0·6%, 95% CI -1·7 to 0·4%, controls -1·0%, 95% CI -2·2 to 0%, P = 0·8) or at the total body (HIV group, 0·3%, 95% CI -0·3 to 1·0%; controls, 0·5%, 95% CI -0·2 to 1·1%, P = 0·15). Lean mass increased in the HIV group, but not in the controls. CONCLUSIONS: There was no evidence of accelerated bone loss over 6 years in middle-aged, HIV-infected men treated with HAART. For such patients, routine monitoring of BMD is not necessary over the short/medium term.

Good outcome with trimethoprim 10 mg/kg/day-sulfamethoxazole 50 mg/kg/day for Pneumocystis jirovecii pneumonia in HIV infected patients.

Pneumocystis jirovecii pneumonia (PCP) in human immunodeficiency virus (HIV)-infected patients is usually treated with trimethoprim (TMP)-sulfamethoxazole (SMX) 1920 mg 3 times daily (approximately equivalent to TMP 15 mg/kg/day-SMX 75 mg/kg/day) for 21 days. Pharmacokinetic data suggest that lower doses would be equally efficacious and might be associated with a lower incidence of adverse effects. We conducted a retrospective review of case notes for the first episode of laboratory-confirmed PCP in HIV-infected patients treated at Auckland City Hospital, from January 1991 through December 2007. Seventy-three of 84 (87%) patients were treated with TMP-SMX 960 mg 4 times daily or 3 times daily (approximately TMP 10 mg/kg/day-SMX 50 mg/kg/day). The overall mortality was 5/73 (7%). The mortality in patients with severe disease (transcutaneous oxygen saturation on admission < or =84%) was 3/16 (19%) and in patients admitted to the intensive care unit was 5/9 (56%). Fifteen of 73 (21%) patients required a change to an alternative treatment regimen because of adverse effects (rash in 10, rash plus fever in 3, neutropenia in 1, fever plus headache in 1). Treatment of PCP in adult HIV-infected patients with TMP-SMX 960 mg QID or TID appears to have comparable efficacy to treatment with higher doses and to be associated with a lower rate of treatment limiting adverse effects.

Evolution of central nervous system multidrug-resistant Mycobacterium tuberculosis and late relapse of cryptic prosthetic hip joint tuberculosis: complications during treatment of disseminated isoniazid-resistant tuberculosis in an immunocompromised host.

We report a case of disseminated isoniazid-resistant tuberculosis in an immunocompromised patient with evolution of rifampin (rifampicin) resistance in the central nervous system. This was cured with intraventricular and oral treatment but was followed by a late relapse of the original infection in a prosthetic hip joint. We provide drug levels in cerebrospinal fluid and serum.

Effects of intravenous zoledronate on bone turnover and BMD persist for at least 24 months.

The duration of the antiresorptive effects of the intravenous bisphosphonate, zoledronate, is not known. Recently, we reported that two annual 4-mg doses of zoledronate suppressed bone turnover and increased BMD in HIV-infected men over 24 mo. We set out to determine the persistence of these effects after two doses of zoledronate. Thirty-three HIV-infected men who completed a randomized trial of 4 mg annual zoledronate (n = 17) or placebo (n = 16) were studied for a further 12 mo, during which time no skeletal therapy was administered. Participants received calcium (400 mg/d) and vitamin D supplements (50,000 IU/mo) for the first 24 mo of the study only. Biochemical markers of bone turnover and BMD were measured every 6 mo. Bone turnover markers were stably suppressed at 24 and 36 mo (12 and 24 mo after the second annual dose of zoledronate, respectively). There were no significant within-group changes in urine N-telopeptide, serum C-telopeptide, and osteocalcin between 24 and 36 mo (p > 0.07), and at each time point, each of the turnover markers was significantly lower in the zoledronate group. There were also no significant between-group differences in the changes in BMD at each site between 24 and 36 mo (p > 0.5), and at each time point, BMD at each site was significantly higher in the zoledronate group. These results suggest that the antiresorptive effects of zoledronate last >12 mo and raise the possibility that zoledronate could be administered less frequently than annually. Randomized trials that address this issue should be performed.

Bone mineral density remains stable in HAART-treated HIV-infected men over 2 years.

OBJECTIVE: Recently we reported that human immunodeficiency virus (HIV)-infected Caucasian men treated with highly active antiretroviral therapy (HAART) have normal weight-adjusted bone mineral density (BMD), in contrast to most other cross-sectional analyses, which have reported low BMD in HIV-infected patients. We have now addressed the question of whether there is accelerated BMD loss over time in HIV-infected men. DESIGN: A 2-year, prospective, longitudinal study. SUBJECTS: Twenty-three HAART-treated, HIV-infected men and 26 healthy controls. MEASUREMENTS: All participants had measurements of BMD and bone-related laboratory parameters at baseline, and a repeat measurement of BMD at 2 years. RESULTS: In the HIV-infected men the mean age was 47 years, the mean duration of infection was 8.2 years, and the mean duration of HAART was 54 months. Over 2 years of follow-up, BMD increased from baseline in the HIV-infected men by 2.6% at the lumbar spine (P = 0.05 vs. baseline), and remained stable at the total hip (mean change 0.1%, P > 0.99) and total body (mean change 0.6%, P = 0.39). Mean changes in BMD in the control group were 1.4% at the lumbar spine, -0.1% at the total hip, and -0.8% at the total body. The HIV-infected men lost less total body BMD than the control group (P = 0.01). In the HIV-infected men, body weight remained stable over 2 years while fat mass decreased and lean mass tended to increase, whereas in the controls, body weight and fat mass increased while lean mass remained stable. CONCLUSIONS: Accelerated bone loss does not occur in HIV-infected men treated with HAART. Monitoring of BMD in HIV-infected men may not be necessary.

Annual zoledronate increases bone density in highly active antiretroviral therapy-treated human immunodeficiency virus-infected men: a randomized controlled trial.

CONTEXT: Recent studies have reported low bone mineral density (BMD) in HIV-infected patients. Annual iv administration of 4 mg zoledronate has been shown to increase BMD and suppress bone turnover in postmenopausal women. OBJECTIVE: The objective of the study was to determine whether annual administration of 4 mg zoledronate will increase BMD in HIV-infected men receiving highly active antiretroviral therapy. DESIGN AND SETTING: A 2-yr randomized placebo-controlled trial was conducted in a clinical research center. PARTICIPANTS: A total of 43 HIV-infected men were treated with highly active antiretroviral therapy for at least 3 months, with BMD T score less than -0.5. INTERVENTION: Participants received annual iv administration of 4 mg zoledronate or placebo. All participants took 400 mg/d calcium and 1.25 mg/month vitamin D. MEASUREMENTS: BMD at the lumbar spine, total hip and total body, and bone turnover markers were measured. RESULTS: At the lumbar spine, BMD increased by 8.9% over 2 yr in the zoledronate group compared with an increase of 2.6% in the control group (P<0.001). At the total hip, BMD increased by 3.8% over 2 yr in the zoledronate group compared with a decrease of 0.8% in the control group (P<0.001). At the total body, BMD increased by 2.3% over 2 yr compared with a decrease of 0.5% in the control group (P<0.001). Urine N-telopeptide decreased by 60% at 3 months in the zoledronate group and thereafter remained stable. CONCLUSIONS: Annual administration of zoledronate is a potent and effective therapy for the prevention or treatment of bone loss in HIV-infected men. The current data provide the first trial evidence of the BMD effects of annual zoledronate beyond 1 yr in any population, as well as being the first reported trial in men.

Bone mineral density is not reduced in HIV-infected Caucasian men treated with highly active antiretroviral therapy.

OBJECTIVE: Recent studies have reported low bone mineral density (BMD) in patients infected with human immunodeficiency virus (HIV). Frequently these findings have been attributed to treatment with highly active antiretroviral therapy (HAART). We sought to determine whether BMD in HIV-infected men treated with HAART for at least 3 months is different from that in healthy controls, and, if so, what HIV-related factors might explain this finding. DESIGN: Cross-sectional analysis. PATIENTS: Fifty-nine HIV-infected Caucasian men treated with HAART, and 118 healthy community-dwelling controls. Each HIV-infected man was age-matched (within 5 years) to two controls. MEASUREMENTS: All participants had measurements of BMD and bone-related laboratory parameters. RESULTS: The mean duration of known HIV infection was 8.5 years, and of treatment with HAART was 52 months. There was no significant difference in mean BMD between groups at the lumbar spine (HIV group: 1.23 g/cm2, controls: 1.25 g/cm2; P = 0.53) or total body (HIV group: 1.18 g/cm2, controls: 1.20 g/cm2; P = 0.09). At the total hip the HIV-infected group had significantly lower BMD than the control group (HIV group: 1.03 g/cm2, controls: 1.09 g/cm2; P = 0.01). The HIV-infected group were, on average, 6.3 kg lighter than the controls. After adjusting for this weight difference, HIV infection was not an independent predictor of BMD at any site (lumbar spine P = 0.79; total hip P = 0.18; total body P = 0.76). CONCLUSIONS: HIV-infected men treated with HAART are lighter than healthy controls. This weight difference is responsible for a small decrement in hip BMD. Overall, BMD is not significantly reduced in HIV-infected Caucasian men treated with HAART.

Hydrocephalus in herpes simplex type 2 meningitis.

A 34-year-old woman presented to hospital with symptoms of meningitis, later confirmed to be due to herpes simplex virus type 2. She developed hydrocephalus on day 2 of her admission. We describe the first case of hydrocephalus associated with herpes simplex type 2 meningitis in an adult.

Leprosy in a backpacker.

Leprosy is the most common cause of peripheral neuropathy in the developing world. It is not expected to be acquired by visitors traveling through these countries. We present a backpacker who contracted leprosy during brief stays in endemic countries.

Outpatient Parenteral Antimicrobial Therapy (OPAT): a review of experience at Auckland Hospital.

AIM: To review the Auckland Hospital Outpatient Parenteral Antimicrobial Therapy (OPAT) Service. METHODS: Patients (>15 years of age) were referred to the Service and assessed for suitability for outpatient therapy by an infectious diseases physician and a specialist nurse. Patient demographics, referring service, site of infection, and infecting organism, antimicrobial agent/s and outcomes of treatment including complications were recorded. RESULTS: Over a 20-month period 100 patients were treated with 107 courses of outpatient parenteral antibiotic therapy. Bone and joint infections accounted for close to two thirds (60%) of the referrals; discitis/osteomyelitis (36%), septic arthritis (14%) and infected metalware/prosthetic joint infections (10%). Staphylococcus aureus was the most frequently isolated organism (42%), and in 21% of cases no organism was identified. In general, antibiotics prescribed were narrow spectrum and all but six patients self-administered up to four times daily. Eighty-eight percent of treatment courses resulted in a cure. Complications related to therapy occurred in 35% of patients. CONCLUSIONS: We have found that parenteral antibiotic therapy can be administered safely and successfully in an outpatient setting despite relatively frequent dosing intervals. The majority of complications were minor, and 88% of patients were cured.

Gram-negative bacillary meningitis after cranial surgery or trauma in adults.

In order to assess the clinical features, aetiology, treatment and outcome of post-neurosurgical and post-traumatic Gram-negative bacillary meningitis (GNBM) we performed a retrospective review of all adult patients admitted to the Department of Neurosurgery who had Gram-negative bacilli cultured from cerebrospinal fluid (CSF) following a neurosurgical procedure or traumatic head/spinal injury. During the 12 y of the review 33 patients had CSF isolates of Gram-negative bacilli that were thought to be significant. The median patient age was 47 y (range 22-77 y) and 21 (64%) were male. Klebsiella pneumoniae, Enterobacter cloacae and Escherichia coli were the most common isolates. Minimal inhibitory concentrations (MIC) measured for half the patients' isolates resulted in 5 regimen changes, including 2 patients with E. cloacae meningitis in whom cephalosporin susceptibility decreased during cephalosporin treatment. Our recommended initial treatment was intravenous ceftriaxone and amikacin, subsequently tailored by susceptibility results; approximately half the patients remained on the antibiotics they started and half were changed to an alternate regimen, most often a carbapenem. Five patients (15%) died, 1 dying after cure of his GNBM. There were no failures in those who received more than 12 d of appropriate treatment: treatment for at least 14 d after the last positive CSF culture guaranteed cure. Initial ceftriaxone and amikacin subsequently changing to susceptibility driven alternatives, often a carbapenem, resulted in cure of 85% of our patients with GNBM.

Three days of intravenous benzyl penicillin treatment of meningococcal disease in adults.

New Zealand has experienced an epidemic of predominantly serogroup B meningococcal disease during the past decade. In a prospective study, we treated adults (age, >15 years) with meningococcal disease with intravenous benzyl penicillin (12 MU [7.2 g] per day) for 3 days. Sixty-one adults with suspected meningococcal disease were consecutively admitted during the 33-month period; 3 patients were excluded. The 58 patients had a mean age (+/- standard deviation [SD]) of 27.9+/-14.5 years (median, 21 years; range, 15-70 years). Forty-four patients had confirmed and 14 patients had probable meningococcal disease. Fifty-seven patients received 12 MU (7.2 g) and 1 received 8 MU (4.8 g) of benzyl penicillin per day. Thirteen patients received additional antibiotics within the first 24 h because of diagnostic uncertainties. Patients received a mean (+/-SD) of 3.0+/-0.5 days of treatment. No patients relapsed. Five patients died. All but 1 death occurred during benzyl penicillin treatment, and the only posttreatment death was not due to meningococcal disease. Three days of intravenous benzyl penicillin is sufficient treatment for adults with meningococcal disease. The usual recommendations for duration of treatment are excessive.