Ellis-Pegler Rb

Prospective study of 424 cases of Staphylococcus aureus bacteraemia: determination of factors affecting incidence and mortality

Background: Staphylococcus aureus bacteraemia (SAB) is a common complication of S. aureus infection and is associated with a high mortality.

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.

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.

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 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.

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.

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.

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 ≤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.

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.

Short course intravenous benzylpenicillin treatment of adults with meningococcal disease

Abstract