F. Ajana

Procalcitonin as a marker of bacterial sepsis in patients infected with HIV-1

Procalcitonin (ProCT) is a recently described marker of severe sepsis. It was decided to assess the value of proCT as a marker of secondary infection in patients infected with HIV-1. ProCT plasma levels were measured by immunoluminometric assay in a prospective study in 155 HIV-infected individuals: 102 asymptomatic and 53 with lever or suspected secondary infections. The baseline plasma level of ProCT was low (0.5 ng/ml +/- 0.37), even in the latest stages of the disease, and did not differ from the values of healthy subjects (0.54 ng/ml +/- 0.08). EDTA-treated whole blood was collected from patients before starting specific antimicrobial therapy. No elevation of ProCT level was detected in HIV-infected patients with evolving secondary infections including PCP (n = 4), cerebral toxoplasmosis (n = 4), viral infections (n = 9), mycobacterial infections (n = 5), localized bacterial (n = 12) and fungal infections (n = 4), malignancies (n = 3), and in various associated infectious and non-infectious febrile events (n = 13). All these plasma values were lower than 2.1 ng/ml. In contrast, high ProCT plasma levels were detected in one HIV-infected patient with a septicaemic Haemophilus influenzae infection (16.5 ng/ml) and another one with a septicaemic Pseudomonas aeruginosa infection (44.1 ng/ ml), ProCT values decreased rapidly under appropriate therapy. ProCT seems to be a specific marker of bacterial sepsis in HIV-infected patients, as no increase in other secondary infections could be detected in those patients. A rapid determination of ProCT level could be useful to confirm or refute bacterial sepsis for a better management of febrile HIV-infected patients.

Safety and Immunogenicity of a Monovalent 2009 Influenza A/H1N1v Vaccine Adjuvanted With AS03A or Unadjuvanted in HIV-Infected Adults: A Randomized, Controlled Trial

BACKGROUND Human immunodeficiency virus (HIV)-infected patients have decreased immune response to vaccines. Few data are available about pandemic flu vaccination in this population. METHODS We conducted a multicenter, patient-blinded, randomized trial in a cohort of HIV-infected adults. Patients received 2 injections 21 days apart of a AS03(A)-adjuvanted H1N1v vaccine containing 3.75 μg hemagglutinin (HA) or a nonadjuvanted H1N1v vaccine containing 15 μg HA to assess hemagglutination inhibition (HI) response and safety. RESULTS A total of 309 patients were randomized, and 306 were vaccinated. After the first vaccine dose, HI titers ≥1:40 were observed in 93.4% of the patients in the adjuvanted group (A group) (n = 155) and in 75.5% in the nonadjuvanted group (B group) (n = 151) (P < .001); seroconversion rates were 88.8% and 71.2%, and factor increases in geometric mean titers (GMT) of 21.9 and 15.1, respectively. After 2 injections, 98.6% of patients of the A group and 92.1% of the B group demonstrated HI titers ≥1:40 (P = .018); seroconversion rates were 96.5% and 87.1%, respectively, and factor increases in GMT were 45.5 and 21.2, respectively. The majority of adverse events were mild to moderate in severity; no impact on CD4+ cell count or viral load has been detected. CONCLUSIONS In HIV-1-infected adults, the AS03(A)-adjuvanted H1N1v vaccine yielded a higher immune response than did the nonadjuvanted one, with no impact on HIV infection.

Antibodies to tetanus, diphtheria and pertussis among healthy adults vaccinated according to the French vaccination recommendations

In this sero-epidemiological study, we investigated humoral immunity to three vaccine-preventable diseases—tetanus, diphtheria and pertussis—among 331 adults (aged 18–60 years) attending vaccination centres for travellers and who had been vaccinated according to national recommendations in France. Serological results showed that the percentage of subjects with antibodies to diphtheria and tetanus decreases with age. Results also confirmed surveillance data on vaccination in France, with 7.6% of the study population (13.4% of those aged 18–29 years) having recently acquired a pertussis infection. These results confirm the importance of following French recommendations for regular boosters for tetanus and diphtheria among adults. They also indicate the need for better implementation of the current recommendations for pertussis-vaccine boosters in adults.

Tolerance, compliance and psychological consequences of post-exposure prophylaxis in health-care workers

Our objectives were to evaluate tolerance and compliance of postexposure triple therapy in health-care workers (HCWs) by retrospective observational study. Structured telephone interview of HCWs identified through data from antiretroviral prescribing centres. Twenty HCWs who received triple prophylaxis were identified over one year. Sixteen agreed to participate in the study. All but one source patient had documented HIV infection. Half HCWs were not aware of post-exposure therapy. Most HCWs received a zidovudine, lamivudine and indinavir combination. All completed at least 4 weeks of therapy. Only 50% received their first dosage less than 4 h after exposure. Nearly all experienced adverse events, mostly digestive (nausea and abdominal pain n =15) or psychological (anxiety and depression n =15), none resulting in therapy discontinuation. Most events occurred 2 to 7 days after therapy initiation. Most modified their sexual life with abstinence or condom use. Compliance was excellent. Half HCWs did not miss any tablet, 4 forgot one dosing a month and 4 one dosing a week. Follow up is over 6 months in all but one HCW. No HIV seroconversion has been observed to date. In France, post-exposure triple antiretroviral therapy is widely available 24 h a day in every emergency room but further training and development of HCWs is needed to decrease consulting time and increase referral to specialized physicians. Notable moderate adverse events, both physical and psychological are noted, however, compliance is excellent.

High plasma level of soluble tumor necrosis factor receptor type II (sTNFRII) in asymptomatic HIV-1-infected patients

SummaryPlasma concentrations of soluble receptors for tumor necrosis factor type II (sTNFRII) and CD4+ lymphocyte counts were determined in patients with HIV-1 infection grouped according to the 1993 classification of the CDC. Compared with healthy controls (mean ± SD= 2.83±0.70 ng/ml; n=20), higher values of sTNFRII were obtained in most of patients of all groups of HIV-1-infected patients. The levels of sTNFRII were 5.29±1.75 ng/ml (n=23) for stage A1 patients, 5.27±2.25 ng/ml (n=37) for stage A2 patients, 6.03±1.9 ng/ml (n=14) for stage A3 patients, 7.41±3.25 ng/ml (n=21) for stage B and stage C patients. Intra-individual variance in sTNFRII levels in eight clinically stable patients with HIV-1 infection was observed in the course of a short-time follow-up. The increase of sTNFRII plasma levels in five out of ten patients was shown at time lapses of 3 years. In contrast to previous reports no inverse correlation between sTNFRII and CD4+ lymphocyte counts was found in all stages of disease. The increased level of sTNFRII in circulating blood might reflect the activation of the TNFα system. These results support an activation of this system occurring early in the course of HIV infection.ZusammenfassungBei Patienten mit HIV-1-Infektion, eingeteilt nach der CDC-Klassifikation, wurde der Tumornekrosefaktor-Rezeptor Typ II (sTNFRII) und der Anteil zirkulierender CD4+ Lymphozyten bestimmt. Im Vergleich zur gesunden Kontrollgruppe (Mittelwert ± Standardabweichung 2,83±0,70 ng/ml) sind die Werte für sTNFRII bei den meisten Patienten in allen Infektionsstadien höher. Die Konzentrationen für sTNFRII liegen bei 5,29±1,75 ng/ml (n=23) bei Patienten im Stadium A1; bei 5,27±2,25 ng/ml (n=37) bei Patienten im Stadium A2; bei 6,03±1,9 ng/ml (n=14) bei Patienten im Stadium A3 und bei 7,41±3,25 ng/ml (n=21) bei Patienten im Stadium B und im Stadium C. Wir stellten eine intraindividuelle Variabilität des sTNFRII Spiegel bei acht klinisch stabilen HIV-infizierten Patienten im Verlauf eines kurzen Beobachtungszeitraums fest. Wir konnten einen Anstieg des sTNFRII Spiegel in Plasmaproben in einem Zeitintervall von 3 Jahren beobachten. Im Gegensatz zu anderen Ergebnissen fanden wir in den verschiedenen Infektionsstadien keine inverse Korrelation zwischen dem sTNFRII und dem CD4+ Lymphozytenanteil. Der Anstieg der zirkulierenden sTNFRII-Konzentration könnte eine Aktivierung des TNFα-Systems widerspiegeln. Unsere Ergebnisse sprechen für eine Aktivierung dieses Systems zu einem frühen Zeitpunkt der HIV-Infektion.Plasma concentrations of soluble receptors for tumor necrosis factor type II (sTNFRII) and CD4+ lymphocyte counts were determined in patients with HIV-1 infection grouped according to the 1993 classification of the CDC. Compared with healthy controls (mean ± SD= 2.83±0.70 ng/ml; n=20), higher values of sTNFRII were obtained in most of patients of all groups of HIV-1-infected patients. The levels of sTNFRII were 5.29±1.75 ng/ml (n=23) for stage A1 patients, 5.27±2.25 ng/ml (n=37) for stage A2 patients, 6.03±1.9 ng/ml (n=14) for stage A3 patients, 7.41±3.25 ng/ml (n=21) for stage B and stage C patients. Intra-individual variance in sTNFRII levels in eight clinically stable patients with HIV-1 infection was observed in the course of a short-time follow-up. The increase of sTNFRII plasma levels in five out of ten patients was shown at time lapses of 3 years. In contrast to previous reports no inverse correlation between sTNFRII and CD4+ lymphocyte counts was found in all stages of disease. The increased level of sTNFRII in circulating blood might reflect the activation of the TNFα system. These results support an activation of this system occurring early in the course of HIV infection. Bei Patienten mit HIV-1-Infektion, eingeteilt nach der CDC-Klassifikation, wurde der Tumornekrosefaktor-Rezeptor Typ II (sTNFRII) und der Anteil zirkulierender CD4+ Lymphozyten bestimmt. Im Vergleich zur gesunden Kontrollgruppe (Mittelwert ± Standardabweichung 2,83±0,70 ng/ml) sind die Werte für sTNFRII bei den meisten Patienten in allen Infektionsstadien höher. Die Konzentrationen für sTNFRII liegen bei 5,29±1,75 ng/ml (n=23) bei Patienten im Stadium A1; bei 5,27±2,25 ng/ml (n=37) bei Patienten im Stadium A2; bei 6,03±1,9 ng/ml (n=14) bei Patienten im Stadium A3 und bei 7,41±3,25 ng/ml (n=21) bei Patienten im Stadium B und im Stadium C. Wir stellten eine intraindividuelle Variabilität des sTNFRII Spiegel bei acht klinisch stabilen HIV-infizierten Patienten im Verlauf eines kurzen Beobachtungszeitraums fest. Wir konnten einen Anstieg des sTNFRII Spiegel in Plasmaproben in einem Zeitintervall von 3 Jahren beobachten. Im Gegensatz zu anderen Ergebnissen fanden wir in den verschiedenen Infektionsstadien keine inverse Korrelation zwischen dem sTNFRII und dem CD4+ Lymphozytenanteil. Der Anstieg der zirkulierenden sTNFRII-Konzentration könnte eine Aktivierung des TNFα-Systems widerspiegeln. Unsere Ergebnisse sprechen für eine Aktivierung dieses Systems zu einem frühen Zeitpunkt der HIV-Infektion.

Melioidotic Osteomyelitis of the Femur Occurring in a Traveler

Burkholderia pseudomallei is a gram-negative bacillus mainly distributed in South Asia, northern Australia and Iran. 1 However, its incidence is probably greatly underestimated in other regions of the tropical world due to the lack of diagnostic microbiology facilities. Multiple clinical presentations of B. pseudomallei have been reported ranging from localized,benign infection to fulminant septicemia. 2 Relapse of the infection is frequent even among those completing a full course of antibiotic treatment. Septic arthritis and osteomyelitis are an uncommon presentation of the disease; 14 cases have been reported during the last 10 years. 3,4 The optimal treatment remains elusive. We describe a case of melioidotic osteomyelitis treated with an imipenem and doxycycline regimen. A 46-year-old Englishman, who had a 3-week history of traveling in Thailand and jungle tracking at Perhentian Island, Malaysia, presented with a 10-day history of fever, chills, rigors, and right thigh pain and was admitted to Kuala Terengganu Hospital in Malaysia. On examination, he was febrile with temperature of 39.6°C. The right thigh was painful with some limitation of range of movement. A full blood count demonstrated a white cell count of 11.7 � 10 9 /L with predominant neutrophilia and an erythrocyte sedimentation rate (ESR) of 106 mm/h. Blood cultures grew B. pseudomallei and he was started with intravenous ceftazidime and amoxicillinclavulanate. Seven days later he was repatriated to France, where he used to live, and therefore was admitted to our

Failure of intravenous antibiotic therapy of multiple temporal brain abscesses due to Propionibacterium acnes requiring temporal lobectomy.

Propionibacterium acnes is a common skin colonizer. Its involvement in brain abscesses is generally described as a complication of neurosurgical intervention. Propionibacterium acnes is susceptible to antibiotics used as treatment of anaerobic infections, except for the 5-nitroimidazoles. Surgical excision or drainage of a simple abscess combined with a long course of antibiotics is considered the treatment of choice. A case of a patient with multiple brain abscesses located in the right temporal lobe that occurred after the manipulation of an abscess of the right upper maxillary is reported. The patient did not improve despite a prolonged course of high-dose intravenous penicillin plus thiamphenicol and cure was finally obtained after the excision of the right temporal lobe. Culture of the purulent material and the shell of the abscesses yielded P. acnes which was sensitive to all the antibiotics administered to the patient up to the intervention. The temporal lobectomy was followed by a 6-month course of ofloxacin. One year after the intervention, the patient remained apyretic without any other abscess on cranial computed tomography scan.

Natural polymorphisms in HIV‐1 protease: Impact on effectiveness of a first‐line lopinavir‐containing antiretroviral therapy regimen

Mutations on HIV protease lead to resistance to protease inhibitors. However, resistance development may be different according to primary, secondary or polymorphic mutations. The present study was designed to assess the impact of natural protease mutations on the effectiveness of a first‐line antiretroviral therapy (ART), and secondarily, their effect on the initial viral load (VL). The study was conducted in 175 HIV‐1‐infected patients, who initiated a first‐line lopinavir/r‐containing ART regimen and who had an available genotype resistance testing before initiating therapy. We assessed the association between mutations (prevalence ≥10%) and the initial VL. We assessed the association between mutations and ART effectiveness using two surrogate markers: the slope of VL decrease at 1 month and the time to VL undetectability. For the 175 patients, the initial median VL was 4.94 log10 copies/ml [interquartile range: 4.44–5.47] and the initial median CD4 lymphocyte count, 219/µl [129–296]. Eighteen mutations had a prevalence ≥10%. At 1 month, the median VL decrease was 2.35 log10 copies/ml [1.76–2.82]. The median time to VL undetectability was 128 days [91–196]. No mutation was associated significantly with the initial VL, the slope of VL decrease at 1 month or the time to VL undetectability. This study of antiretroviral‐naive patients showed that protease polymorphisms had no impact on the effectiveness of a lopinavir/r‐containing ART regimen. However, polymorphisms may affect ART effectiveness differently in other populations, such as ART‐experienced patients and/or patients treated with protease inhibitors other than the one used here. J. Med. Virol. 80:1871–1879, 2008.

ABCB1 Allele Polymorphism Is Associated with Virological Efficacy in Naïve HIV-Infected Patients on HAART Containing Nonboosted PIs But Not Boosted PIs

Abstract Objective: To assess the effect of the multidrug resistance-1 single nucleotide polymorphism (ABCB1 SNP) C3435T in exon 26 on the virological responses to first-line protease inhibitor (PI)-containing HAART regimens. Method: A cohort of 182 HIV-infected patients with a PI-containing HAART regimen initiated from 1997 to 2004 was enrolled. Time to the first indetectable viral load (VL) was determined in patients with the CC, CT, or TT genotype. Results: There were 37%, 44%, and 19% of patients who had the CC, CT and TT genotypes, respectively. The median estimated times to VL indetectability in the CC, CT, and TT groups were respectively 5.9, 3.9, and 4.8 months (p = .06). In patients on a non-boosted PI regimen, ABCB1 genotype was associated with time to VL indetectability that was shorter in patients with the CT than CC genotype (CT vs. CC, hazard ratio [HR] = 0.62, p = .02; TT vs. CC, HR = 0.72, p = .21). This association was not found in patients with first-generation boosted PI-containing regimens and especially not with second-generation boosted PI-containing regimens. Conclusion: Our results show that the ABCB1 SNP in exon 26 is associated with virological efficacy in HIV-infected patients treated with non-boosted PI-containing regimens but not with those containing boosted PIs, particularly of the second generation.

A multicenter study of lomefloxacin and trimethoprim/sulfamethoxazole in the treatment of uncomplicated acute pyelonephritis

A total of 63 adult patients with uncomplicated acute pyelonephritis were enrolled in a multicenter, randomized comparison of lomefloxacin (400 mg orally once daily for 14 days) and trimethoprim/sulfamethoxazole (TMP/SMX, 160/800 mg orally twice daily for 14 days). Study participants were predominantly female (70% in the lomefloxacin group and 80% in the TMP/SMX group). Escherichia coli was isolated from pretreatment urine cultures in 87.5% of the lomefloxacin group and 80.0% of the TMP/SMX group. Baseline pathogens were eradicated in 100% of evaluable patients in the lomefloxacin group 5-9 days after the end of therapy and in 88.9% of patients in the TMP/SMX group (p = 0.05). The clinical cure rate 5-9 days after therapy with lomefloxacin was 65.0% and for TMP/SMX was 68.4%. At the 4-6 week follow-up in the lomefloxacin group, nine pathogens remained eradicated, one E. coli was isolated, and the results for 14 pathogens were unknown or unevaluable. In the TMP/SMX group, 12 pathogens remained eradicated, three E. coli and one Group D Streptococcus were isolated, and the results for nine pathogens were unknown or unevaluable. Both treatment regimens were well tolerated; adverse events occurred in 12% of patients in the lomefloxacin group and in 17% in the TMP/SMX group. Events considered by the investigators to be probably related to treatment occurred in three patients in each group. In conclusion, once-daily lomefloxacin (400 mg) was a well tolerated and effective alternative to twice-daily TMP/SMX (160/800 mg) for the treatment of adults with uncomplicated acute pyelonephritis.