Outcome of treatment of MDR-TB or drug-resistant patients treated with bedaquiline and delamanid: Results from a large global cohort.

The World Health Organization (WHO) recommends countries introduce new anti-TB drugs in the treatment of multidrug-resistant tuberculosis. The aim of the study is to prospectively evaluate the effectiveness of bedaquiline (and/or delamanid)- containing regimens in a large cohort of consecutive TB patients treated globally. This observational, prospective study is based on data collected and provided by Global Tuberculosis Network (GTN) centres and analysed twice a year. All consecutive patients (including children/adolescents) treated with bedaquiline and/or delamanid were enrolled, and managed according to WHO and national guidelines. Overall, 52 centres from 29 countries/regions in all continents reported 883 patients as of January 31st 2021, 24/29 countries/regions providing data on 100% of their consecutive patients (10-80% in the remaining 5 countries). The drug-resistance pattern of the patients was severe (>30% with extensively drug-resistant -TB; median number of resistant drugs 5 (3-7) in the overall cohort and 6 (4-8) among patients with a final outcome). For the patients with a final outcome (477/883, 54.0%) the median (IQR) number of months of anti-TB treatment was 18 (13-23) (in days 553 (385-678)). The proportion of patients achieving sputum smear and culture conversion ranged from 93.4% and 92.8% respectively (whole cohort) to 89.3% and 88.8% respectively (patients with a final outcome), a median (IQR) time to sputum smear and culture conversion of 58 (30-90) days for the whole cohort and 60 (30-100) for patients with a final outcome and, respectively, of 55 (30-90) and 60 (30-90) days for culture conversion. Of 383 patients treated with bedaquiline but not delamanid, 284 (74.2%) achieved treatment success, while 25 (6.5%) died, 11 (2.9%) failed and 63 (16.5%) were lost to follow-up.

International Society of Cardiovascular Infectious Diseases Guidelines for the Diagnosis, Treatment and Prevention of Disseminated Mycobacterium chimaera Infection Following Cardiac Surgery with Cardiopulmonary Bypass.

Mycobacterial infection-related morbidity and mortality in patients following cardiopulmonary bypass surgery is high and there is a growing need for a consensus-based expert opinion to provide international guidance for diagnosing, preventing and treating in these patients. In this document the International Society for Cardiovascular Infectious Diseases (ISCVID) covers aspects of prevention (field of hospital epidemiology), clinical management (infectious disease specialists, cardiac surgeons, ophthalmologists, others), laboratory diagnostics (microbiologists, molecular diagnostics), device management (perfusionists, cardiac surgeons) and public health aspects.

Strong and persistent correlation between baseline and follow-up HIV-DNA levels and residual viremia in a population of naïve patients with more than 4 years of effective antiretroviral therapy.

In a longitudinal study on 181 naïve patients who responded to therapy (mean follow-up 4 years), high baseline human immunodeficiency virus (HIV)-RNA values correlated with high levels of cellular HIV-DNA at all time points (p < 0.0001, p 0.045, p 0.0055, and p 0.0025, respectively) and negatively correlated with undetectable residual viremia (URV; <2.5 copies/mL) at T1, T2, and T3 (p 0.026, p 0.0149, and p 0.0002, respectively). Baseline high HIV-DNA levels predicted the persistence of high values (p 0.0001) and negatively correlated with URV (p 0.0254, p 0.0481, and p 0.0085). These results suggest that baseline viral load, cellular HIV-DNA, and URV were strongly correlated over long-term follow-up of antiretroviral therapy responders.

HIV coreceptor tropism in paired plasma, peripheral blood mononuclear cell, and cerebrospinal fluid isolates from antiretroviral-naïve subjects.

A survey of HIV coreceptor usage in cerebrospinal fluid (CSF) samples, peripheral blood mononuclear cells (PBMCs), and plasma samples from naïve seropositive patients was conducted. One hundred patients were enrolled in this study. Of the 100 patients, 36 had a primary or recent infection (P-RI), 31 had an early chronic infection (>350 CD4 cells) (ECI), and 33 had a late chronic infection (LCI). All 3 compartments were sampled in a subset of 33 participants, while the remaining 67 patients provided plasma samples and PBMCs only. Seventy-seven patients harbored the R5 virus in plasma samples and had a significantly higher median and percentage of CD4(+) T cells than patients with X4 virus (437 and 281 cells/µl, respectively; P = 0.0086; 20.6% and 18.6%, respectively). The X4 strain was detected more frequently in patients with LCI than in patients with P-RI or ECI (39.3%, 19.4%, and 9.6%, respectively; P = 0.0063). PBMC and plasma tropism was concordant in 90 patients, and 73 had the R5 strain. Among patients with discordant results, 4 had the R5 virus in their plasma and the X4 virus in PBMCs; 6 showed the opposite profile. Plasma, PBMC, and CSF tropism determinations were concordant in 26/33 patients (21 patients had R5, and 5 had X4). The tropism was discordant in 5/33 patients, with the X4 virus in plasma and R5 in CSF; the HIV tropism in PBMCs was X4 in 3 patients. The remaining 2/33 patients had the R5 virus in plasma and PBMCs and the X4 virus in CSF; one of these patients had a P-RI. The discordant tropism in CSF and blood may have implications for chemokine (C-C motif) receptor 5 (CCR5) antagonist use in patients with limited response to antiretroviral therapy (ART) or in responding patients evaluated for simplification of treatment.

[Off-label antibiotic use: malpractice or good clinical practice?]. / La prescrizione off-label di antibiotici: malpractice o buona pratica clinica?

In Italy, off-label drug use has been forbidden since 1998. However, Italian law allows off-label treatment for single cases only if treatment is considered irreplaceable, and completely under physician responsibility. To assess the consequences of such regulations for the infectious diseases specialist, we listed the indications of intravenous and oral antibiotics available in our hospital pharmacy service, and discussed them in a pool of nine infectious diseases specialists. Indications were compared with the recommended treatment of major bacterial syndromes as suggested by the major guidelines and textbooks. We found that standard treatment for several bacterial infections is off-label. The pool of specialists concluded that some off-label use of antibiotics is vital to daily practice in infectious diseases. Scientific societies should promote guidelines as the standard reference for good clinical practice, which should not be based only on the respect of drug labels.

Chlamydia pneumoniae infection in HIV-positive patients: prevalence and relationship with lipid profile.

OBJECTIVES: The aims of this study were to evaluate the prevalence and impact of Chlamydia pneumoniae infection in HIV-positive patients and to establish the relationship between C. pneumoniae infection and lipid profile. METHODS: Detection of C. pneumoniae was by polymerase chain reaction (PCR) on Peripheral Blood Mononuclear Cells (PBMCs) collected from 97 HIV-positive patients. Samples were collected after overnight fast in EDTA-treated tubes. On the same day, patients were also tested for routine chemistry, HIV viral load, CD3, CD8 and CD4 cell counts and lipid profile [cholesterol, high-density lipoproteins (HDLs), low-density lipoproteins (LDLs) and triglycerides]. RESULTS: The overall prevalence of C. pneumoniae was 39%. The prevalence of C. pneumoniae was inversely related to the CD4 lymphocyte count (P=0.03). In the naive group, C. pneumoniae-positive patients had both significantly higher HIV load (71 021+/-15 327 vs. 14 753+/-14 924 HIV-1 RNA copies/mL; P=0.03) and lower CD4 cell count (348.0+/-165.4 vs. 541.7+/-294.8; P=0.04) than C. pneumoniae-negative patients. Moreover, treatment-naive patients with C. pneumoniae infection had significantly higher mean levels of cholesterol (185.3+/-56.2 vs. 124.8+/-45.9 mg/dL; P=0.01), triglycerides (117.2+/-74.7 vs. 68+/-27.6 mg/dL; P=0.04) and LDL (122.4+/-60.1 vs. 55.6+/-58 mg/dL; P=0.05) than C. pneumoniae-negative patients. CONCLUSIONS: These data indicate that, in HIV-positive subjects, C. pneumoniae infection is relatively frequent and is associated with both low CD4 cell count and high HIV load. Furthermore, C. pneumoniae appears to be associated with hyperlipidaemia and might therefore represent a further risk factor for cardiovascolar disease in HIV-positive patients.

Isolation of a novel sequevar of Mycobacterium flavescens from the synovial fluid of an AIDS patient.

This report describes the characterisation of a mycobacterium involved in a case of septic arthritis in an AIDS patient that was treated successfully with specific anti-mycobacterial drugs. The biochemical and cultural features, and the mycolic acid pattern as assessed by high-performance liquid chromatography, were fully compatible with the isolate being Mycobacterium flavescens. However, the isolate's 16S rDNA sequence differed by five nucleotides from the two known sequevars of M. flavescens, thus indicating that this isolate belonged to a new 16S rDNA sequevar.

Serum pepsinogen and gastrin levels in HIV-positive patients: relationship with CD4+ cell count and Helicobacter pylori infection.

BACKGROUND: The relationship between serum parameters of gastric function and Helicobacter pylori infection in human immunodeficiency virus (HIV)-positive patients is almost unknown. AIMS: To investigate in HIV-infected patients: (i) the relationship between serum gastrin and serum pepsinogens over the progressive phases of HIV-related disease; (ii) the impact of H. pylori infection on gastrin and pepsinogen serum levels and its relation to antral histology; (iii) the prevalence of parietal cell autoantibodies. METHODS: Fifty-nine HIV-positive patients were studied by upper endoscopy plus gastric antral biopsy. Serum samples were tested for gastrin, pepsinogen A, pepsinogen C and parietal cell autoantibodies. RESULTS: In patients without overt acquired immunodeficiency syndrome (AIDS), or with a CD4+ count of > 100 x 10(6) cells/L, mean serum levels of gastrin and pepsinogen C were higher than in subjects with AIDS or with a CD4+ count of < 100 x 10(6) cells/L (P < 0.01). Only one patient was found to be positive for parietal cell autoantibodies. H. pylori infection was associated with increased values of gastrin and pepsinogen C only in HIV-positive patients without AIDS or with a CD4+ count of > 100 x 10(6) cells/L. Atrophy was more frequent in patients with overt AIDS than in those without overt AIDS (57% vs. 33%, P=N.S.), and/or in patients with a CD4+ count of < 100 x 10(6) cells/L than in those with a CD4+ count of > 100 x 10(6) cells/L (62% vs. 26%, P < 0.05). CONCLUSIONS: HIV-positive patients without overt AIDS have increased serum levels of gastrin and pepsinogen C compared with HIV-positive patients with overt AIDS.

Three-times weekly teicoplanin in the outpatient treatment of acute methicillin-resistant staphylococcal osteomyelitis: a pilot study.

Treatment of osteomyelitis requires prolonged hospital stay, lengthy antibiotic therapy and adequate surgical debridement. Outpatient parenteral antibiotic therapy (OPAT) is a new approach to reduce patient discomfort and hospital costs. Teicoplanin, a glycopeptide antibiotic with a long half-life (72 hours), is one of the most useful drugs for OPAT. We performed a pilot study to assess the safety and efficacy of three-times weekly teicoplanin in the treatment of methicillin-resistant (MR) acute staphylococcal osteomyelitis. Ten patients with acute post-traumatic osteomyelitis were enrolled. Pathogens were MR Staphylococcus aureus (5 patients) and MR coagulase-negative staphylococci (5 patients). After a loading dose of 400 mg b.i.d. for 3 days, patients were treated with an intravenous dose of 1000 mg on Mondays and Wednesdays and with a 1200 mg dose on Fridays. Teicoplanin trough levels were maintained within a 10 to 20 mg/L range. If hardware removal had been possible at enrollment, treatment was carried out for at least 4 weeks. If, on the contrary, hardware removal had not been possible, teicoplanin was administered as suppressive therapy until hardware removal. Treatment was successfully performed in 9 out of 10 patients, whereas in one patient only improvement was achieved. Side effects were not recorded. Three times weekly teicoplanin seems to be a valuable option in the treatment of acute MR staphylococcal osteomyelitis. Further studies are warranted in order to better define the role of this new administration schedule in this field.

High prevalence of HCV-RNA in the saliva cell fraction of patients with chronic hepatitis C but no evidence of HCV transmission among sexual partners.

The aims of this study were to evaluate the prevalence of HCV-RNA in different fractions of saliva taken from patients with chronic hepatitis C, to establish whether virologic parameters or disease severity exert any influence on the detectability of HCV-RNA in saliva, and to evaluate the prevalence of HCV infection in partners of HCV-infected subjects with respect to the presence of HCV-RNA in saliva. Sera samples and different fractions of saliva (whole saliva, surnatant, and cell fraction) from 48 subjects (45 with chronic hepatitis C and three healthy anti-HCV+ carriers) were examined for HCV-RNA by RT nested PCR and DEIA hybridization. HCV-RNA-positive sera were also tested for genotype and viral titer (bDNA2 method). Twenty-seven stable sexual partners (25 females and 2 males) were screened for anti-HCV antibodies at least twice over a minimum of 12 months. HCV-RNA was detected in the sera of 39/45 patients and of 22/39 viremic patients. In all of the latter, the presence of HCV-RNA was restricted to the cell fraction. Viral titer was significantly higher in patients with HCV-RNA in saliva than in those without (12.3 x 10(6) versus 4.6 x 10(6) eq/ml, P < 0.01). HCV-RNA positivity was unrelated to genotype, duration of disease, Hepatitis Activity Index scores or transaminase levels. Anti-HCV was positive in one of 13 sexual partners of patients with HCV-RNA in saliva and in 1/14 of those without (P = NS). In conclusion, HCV-RNA is detectable in the cell fraction of saliva in a high proportion of highly viremic patients with chronic hepatitis C, but its presence does not seem to be associated with an increased risk of HCV transmission among sexual partners.

Mycobacterium genavense in AIDS patients, report of 24 cases in Italy and review of the literature.

Mycobacterium genavense is a frequently missed agent of disseminated disease in AIDS patients. The increasing frequency with which such organism is being isolated in Italy suggested a comparison of local survey with data reported in literature. Isolates presumed to belong to the species M. genavense were centralized and identified by means of genomic sequencing and/or HPLC analysis of cell wall mycolic acids; clinical data were obtained from relevant patients' record and collected using a proper questionnaire. In 24 cases in which this organism has been isolated in Italy M. genavense was grown, prevalently from blood, in liquid medium after an average of six weeks of incubation. In overwhelming majority, patients were males, presented other opportunistic diseases and were characterized by very low CD4+ counts (average 23/microl); most frequent symptoms were fever, anemia and weight loss. All but two patients, who died before the mycobacterial infection was diagnosed, were treated with at least three drugs; the mean survival was close to one year. A review of literature reports revealed a wide overlapping of clinical and microbiological features.

H. pylori infection in HIV-positive patients. A serohistological study.

Sixty-seven consecutive patients infected with the human immunodeficiency virus (HIV-1), 72% of which with overt AIDS, were examinated by upper endoscopy due to various indications and evaluated for the prevalence of H. pylori infection. The infection was studied by performing both histological examination of gastric biopsies and serological testing for anti-H. pylori IgG antibodies. The H. pylori prevalence rate was 55% in histology; no significant differences were observed in HIV-infected subjects and those with overt AIDS (52% vs 63%, respectively; P = NS). Positive histological testing appeared to be directly related to the peripheral CD4+ lymphocyte count (minimum rates of 43% were detected in patients with CD4+ < 100 x 10(6)/liter and maximum rates of 78% in patients with CD4+ > 200 x 10(6)/liter, respectively; P < 0.05) and inversely related to the frequency of antibiotic treatments performed over the six months prior to endoscopy. Low CD4+ counts were also apparently associated with low-grade H. pylori infection. Serological testing was positive for anti-H. pylori IgG antibodies in 39% of patients; compared to histology, serology displayed a sensitivity of 57% and a specificity of 81%. The discrepancy between histological and serological positive results for H. pylori was noted to be higher in the more advanced phases of HIV infection. Based upon our results, the serological testing for anti-H. pylori IgG antibodies seems to require cautious interpretation in HIV-positive patients.

Isolation of an unusual mycobacterium from an AIDS patient.

A mycobacterium isolated from a clinical sample of an AIDS patient was identified as Mycobacterium interjectum by direct 16S rRNA sequence determination. High-performance liquid chromatography, however, revealed a mycolic acid pattern which was different from the one shared by the previously analyzed strains of this species.

AIDS and tuberculosis control programmes: an integrated approach at educational level.

In developing countries with a high prevalence of individuals co-infected by human immunodeficiency virus (HIV) and tuberculosis (TB), urgent public health measures should be implemented to prevent the spread of both diseases. This study was performed by a combined acquired immune deficiency syndrome (AIDS)-TB health team with the following aims: 1) to assess knowledge, attitudes and practice towards AIDS; 2) to identify target groups for health education (HE); 3) to evaluate HE impact; 4) to circulate correct information on AIDS and TB through target groups; and 5) to evaluate integration of AIDS and control TB activities. Secondary school students of Arua District, Uganda, participated in a standardized HE session (covering the key-points of AIDS and TB control) preceded by a pretest (multiple choice) questionnaire and followed 3 months later by the same questionnaire (post-test). The impact of HE on AIDS control was evaluated by comparing answers to pre- and post-test questionnaires and its influence on the TB programme by evaluating case-finding performances in the period preceding and following the survey. We analysed 1,478 questionnaires. The results of our study gave information on knowledge about AIDS, identified females and students < 16 yrs of age as good targets for HE, revealed that the impact of HE was significantly associated with improved knowledge, contributed to improved TB case-finding and offered suggestions for the integration of programmes. The survey represented an opportunity to create a stable AIDS/TB health team at district level.

Amphotericin B as primary therapy for cryptococcosis in patients with AIDS: reliability of relatively high doses administered over a relatively short period.

Thirty-one consecutive AIDS patients with cryptococcal disease were enrolled in a study of the efficacy and safety of short-course primary treatment with a relatively high dose of amphotericin B (1 mg/[kg.d] for 14 days); 26 patients also received flucytosine (100-150 mg/[kg.d], given either intravenously or orally). Twenty-five patients had cryptococcal meningitis confirmed by culture, three had presumed cryptococcal meningitis, and three had disseminated extrameningeal cryptococcosis. After successful primary treatment, all patients were given oral itraconazole or fluconazole as suppressive therapy, and their lifelong clinical and mycologic follow-up was planned. Successful primary therapy was defined as the resolution of symptoms and the documentation of negative cultures of cerebrospinal fluid and/or blood 2 months after the initial diagnosis. Therapy was successful in 29 (93.5%) of all 31 cases and in 26 (92.8%) of the 28 cases of culture-proven or presumed cryptococcal meningitis. Nephrotoxicity developed as a result of amphotericin B administration in seven cases; this adverse reaction required a reduction of the dose in two cases and the discontinuation of therapy in five. No deaths due to cryptococcosis were documented during primary therapy. Treatment failed in two cases. During a mean observation period of 10.7 months, three relapses of the underlying infection occurred. Our results indicate that an aggressive approach to the primary treatment of cryptococcosis in AIDS patients, with the administration of a relatively high dose of amphotericin B for a relatively short period, is effective and well tolerated.