zithromax and Opportunistic-Infections

To propose a formalized consensus agreement regarding the prescription of azithromycin in cystic fibrosis (CF).. Application of the Delphi method in 5 thematic fields: indications, contra-indications, dosage, precautions for use and treatment follow-up.. Thirty identified French CF centers participated in the process on 49 (61%), which comprised 3 rounds. Experts validated azithromycin as a long-term anti-inflammatory agent in children aged over 6 years, presenting with the classical form of CF, irrespective of the bacteriological status of the patient (except for non-tuberculous mycobacteria). Azithromycin administration should not be routine in the milder forms of the disease, and avoided in the presence of severe hepatic or renal involvement. In children whose weight is below 40 kg, a strong consensus recommended a single daily oral dose, administered three times weekly. However, in adults, the level of agreement was weaker. Minimal duration of treatment is 6 months, after which the drug should be discontinued if no observable effect is noted on clinical parameters, exacerbation rate and/or FEV1. Clinical monitoring of treatment tolerance is recommended (nausea, diarrhea, skin rash, tinnitus, deafness, arthropathy), without increasing the frequency of surveillance of sputum bacteria. However, it is essential to monitor sputum for fungi (expectoration, Aspergillus, broncho-pulmonary allergic aspergillosis).. This consensus statement defines an area for the prescription of azithromycin in CF, with the aim of better harmonization of its use.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Child; Consensus; Cystic Fibrosis; France; Humans; Opportunistic Infections; Practice Guidelines as Topic; Young Adult

Pseudomonas aeruginosa is an opportunistic pathogen of immunocompromised hosts. In cystic fibrosis (CF), P. aeruginosa causes acute and chronic lung infections that result in significant morbidity and mortality. P. aeruginosa possesses several traits that contribute to its ability to colonize and persist in acute and chronic infections. These include high resistance to antimicrobials, ability to form biofilms, plethora of virulence products, and metabolic versatility. In P. aeruginosa, a cell-to-cell communication process termed quorum sensing (QS) regulates many of these factors that contribute to its pathogenesis. Recent evidence suggests that the CF lung environment presents a specialized niche for P. aeruginosa. The relationship of P. aeruginosa QS, biofilm formation, and the CF lung environment is discussed.

Topics: Animals; Azithromycin; Biofilms; Cystic Fibrosis; DNA, Bacterial; Gene Expression Regulation, Bacterial; Humans; Immunity, Mucosal; Immunocompromised Host; Lung; Opportunistic Infections; Pseudomonas aeruginosa; Pseudomonas Infections; Quorum Sensing; Tobramycin

Four randomised, placebo-controlled trials have previously documented the clinical benefits of azithromycin (AZM) in cystic fibrosis (CF) patients. The present study examined whether the beneficial effect of AZM is equivalent when administered daily or weekly. A double-blind, randomised study was carried out in 208 CF patients aged 6-58 yrs who were assigned to AZM either 250 mg daily (n = 103) or 1,200 mg weekly (n = 105) for 6 months, with assessments at baseline and at 1, 3, 6 and 7 months. Patients were taken from five adult and children CF centres in South-east Queensland, Australia. Equivalence was demonstrated between the two groups (daily versus weekly) with respect to improvements in lung function (forced expiratory volume in one second and forced vital capacity), C-reactive protein, days spent in hospital, admission rates and nutrition (body mass index, z-scores) using 95% confidence intervals with a tolerance interval of +/-10%. In patients aged <18 yrs the daily group had significantly better improvements in z-scores for height and weight after 6 months. In children, a nutritional advantage for daily administration was found. Gastro-intestinal adverse effects were more common with weekly therapy. Apart from these findings, daily and weekly administered azithromycin demonstrated similar outcomes for cystic fibrosis patients.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Azithromycin; Child; Cystic Fibrosis; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Male; Middle Aged; Opportunistic Infections; Pneumonia, Bacterial; Vital Capacity

Mycobacterium avium complex infection is common in patients with AIDS. Experimentally infected mice have been treated successfully with azithromycin, a macrolide antibiotic. We report an uncontrolled phase I study in which male homosexuals with AIDS and M avium complex disease were given 500 mg azithromycin per day orally for 10, 20, or 30 days. Quantitative blood cultures showed a mean reduction in mycobacteraemia from 118 colony forming units (cfu)/ml to 43 cfu/ml in 3 patients treated for 10 days, and from 2028 cfu/ml to 136 cfu/ml in 21 patients treated for 20 or 30 days. Of the patients treated for 20 or 30 days, 15 of 21 with fever pretreatment and 12 of 18 with night sweats pretreatment reported resolution of these symptoms. The principal side-effects were loose stools or diarrhoea, but these did not result in cessation of therapy. Azithromycin, as a single oral agent, safely reduced M avium complex bacteraemia and associated symptoms in almost 75% of patients treated for at least 20 days. Further studies are needed to assess emergence of resistance.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Adult; Azithromycin; Bacteremia; Drug Administration Schedule; Drug Evaluation; Erythromycin; Follow-Up Studies; Homosexuality; Humans; Male; Mycobacterium avium-intracellulare Infection; Opportunistic Infections

Previous studies have suggested that azithromycin improves lung function in lung transplant recipients with bronchiolitis obliterans syndrome (BOS). However, these studies did not include a non-treated BOS control cohort or perform survival analysis. This study was undertaken to estimate the effect of azithromycin treatment on survival in lung transplant recipients with BOS.. We conducted a retrospective cohort study of consecutive lung transplant recipients who developed BOS between 1999 and 2007. An association between azithromycin treatment and death was assessed using univariate and multivariate time-dependent Cox regression analysis.. Of the 178 recipients who developed BOS in our study, 78 did so after 2003 and were treated with azithromycin. The azithromycin-treated and untreated cohorts had similar baseline characteristics. Univariate analysis demonstrated that azithromycin treatment was associated with a survival advantage and this beneficial treatment effect was more pronounced when treatment was initiated during BOS Stage 1. Multivariate analysis demonstrated azithromycin treatment during BOS Stage 1 (adjusted hazard ratio = 0.23, p = 0.01) and absolute forced expiratory volume in 1 second (FEV(1)) at the time of BOS Stage 1 (adjusted hazard ratio = 0.52, p = 0.003) were both associated with a decreased risk of death.. In lung transplant recipients with BOS Stage 1, azithromycin treatment initiated before BOS Stage 2 was independently associated with a significant reduction in the risk of death. This finding supports the need for a randomized, controlled trial to confirm the impact of azithromycin on survival in lung transplant recipients.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Bronchiolitis Obliterans; Cause of Death; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Forced Expiratory Volume; Humans; Lung Transplantation; Male; Middle Aged; Opportunistic Infections; Postoperative Complications; Proportional Hazards Models; Pseudomonas Infections; Retrospective Studies; Risk Factors; Survival Analysis

During infection, Pseudomonas aeruginosa employs bacterial communication (quorum sensing [QS]) to coordinate the expression of tissue-damaging factors. QS-controlled gene expression plays a pivotal role in the virulence of P. aeruginosa, and QS-deficient mutants cause less severe infections in animal infection models. Treatment of cystic fibrosis (CF) patients chronically infected with P. aeruginosa with the macrolide antibiotic azithromycin (AZM) has been demonstrated to improve the clinical outcome. Several studies indicate that AZM may accomplish its beneficial action in CF patients by impeding QS, thereby reducing the pathogenicity of P. aeruginosa. This led us to investigate whether QS inhibition is a common feature of antibiotics. We present the results of a screening of 12 antibiotics for their QS-inhibitory activities using a previously described QS inhibitor selector 1 strain. Three of the antibiotics tested, AZM, ceftazidime (CFT), and ciprofloxacin (CPR), were very active in the assay and were further examined for their effects on QS-regulated virulence factor production in P. aeruginosa. The effects of the three antibiotics administered at subinhibitory concentrations were investigated by use of DNA microarrays. Consistent results from the virulence factor assays, reverse transcription-PCR, and the DNA microarrays support the finding that AZM, CFT, and CPR decrease the expression of a range of QS-regulated virulence factors. The data suggest that the underlying mechanism may be mediated by changes in membrane permeability, thereby influencing the flux of N-3-oxo-dodecanoyl-L-homoserine lactone.

Topics: Anti-Bacterial Agents; Azithromycin; Base Sequence; Ceftazidime; Ciprofloxacin; DNA Primers; DNA, Bacterial; Gene Expression; Genes, Bacterial; Humans; Oligonucleotide Array Sequence Analysis; Opportunistic Infections; Polymerase Chain Reaction; Pseudomonas aeruginosa; Pseudomonas Infections; Quorum Sensing; Virulence

Babesiosis is a tick-borne zoonosis. Human cases of babesiosis occur worldwide but have been mainly described in North America and rarely in Europe. The disease manifestations show a broad clinical spectrum including a malaria-like syndrome. Fulminant and life-threatening infections have been described in the setting of asplenia and/or immunosuppression.. A 63-year-old splenectomized patient had been treated with rituximab because of B cell lymphoma. 4 weeks later, he developed signs of infection, anemia, subicterus, and dark urine. Laboratory investigation revealed hemolytic anemia, hemoglobinuria, and renal insufficiency. Blood smears showed Plasmodium-like intraerythrocytic parasites. He had not been exposed to malaria. He had taken frequent walks in the woods around Lake Constance in the south of Germany, where tick-borne diseases are endemic. Babesiosis was confirmed by polymerase chain reaction (PCR) and the parasite was identified as EU1. Serology was negative. Therapy with clindamycin and quinine induced remission. Following a relapse, retreatment with atovaquone and azithromycin was initiated. After several months, seroconversion occurred and the patient cleared the parasite 8 months after first admission.. Human babesiosis does occur in Germany. Patients with splenectomy and/or immunosuppression and malaria-like symptoms should be evaluated for babesiosis by blood smear and PCR.

Topics: Anti-Bacterial Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antimalarials; Antineoplastic Agents; Atovaquone; Azithromycin; Babesiosis; Drug Therapy, Combination; Humans; Immunologic Deficiency Syndromes; Lymphoma, B-Cell; Male; Middle Aged; Opportunistic Infections; Rituximab; Splenectomy

We describe a renal allograft patient with a Chlamydia trachomatis infection. A 43 year-old man was diagnosed with end-stage renal disease in 1985 which necessitated the transplantation of a cadaver kidney in 1986. The kidney was rejected two years later. A second transplantation was performed in 1991. At the beginning of 1998 symptoms and signs of chronic renal failure and dysuria set in. Routine microbiological studies were negative. Cell culture on McCoy cell line was positive for an active infection with C. trachomatis--initially 3+, then 2+, 1+ and negative following treatment. The patient was positive on the AMPLICOR CT/NG test (Roche Diagnostic Systems, Branchburg, USA) twice with OD values OVER--above 2 at 450 nm wavelength measured on an ELISA reader. The patient received treatment with azithromycin and doxycycline for 10 days following which the serum creatinine levels fell and the creatinine clearance values improved. Dynamic microbiological follow-up showed disappearance of C. trachomatis as evidenced by the negative PCR test. We conclude that the deterioration of renal function in our patient is complex but the infection with C. trachomatis is part of the complex of the underlying chronic renal failure and immunosuppressive treatment.

Topics: Adult; Azithromycin; Chlamydia Infections; Chlamydia trachomatis; Doxycycline; Drug Therapy, Combination; Humans; Kidney Transplantation; Male; Opportunistic Infections

We report two cases of cryptosporidiosis after CD34-selected PBSCT for lymphoma. While the first patient died of pulmonary cryptosporidiosis, treatment with paromomycin, azithromycin and subcutaneous low-dose rhIL-2 to improve numerical and functional T lymphocyte defects completely eliminated infection in the second patient. We conclude, that the removal of mature T lymphocytes by positive selection of CD34+ cells bears the risk of a delayed immune reconstitution resulting in an increased incidence of severe and sometimes fatal opportunistic infections. IL-2 might be useful in this situation by accelerating immune reconstitution and reducing the danger of opportunistic infections.

Topics: Adult; Antigens, CD34; Azithromycin; Cryptosporidiosis; Female; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Hodgkin Disease; Humans; Immunosuppression Therapy; Interleukin-2; Lung Diseases, Parasitic; Lymphocyte Subsets; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Opportunistic Infections; Paromomycin; Recombinant Proteins; Transplantation, Autologous

Two children with cancer received azithromycin for Cryptosporidium-associated diarrhea that was unresponsive to supportive care. One child had choleriform diarrhea requiring daily fluid replacement of up to 65% of his total body weight; the other had protracted diarrhea and wasting. In both cases, administration of azithromycin was followed by prompt clinical improvement.

Topics: Administration, Oral; Azithromycin; Child, Preschool; Combined Modality Therapy; Cryptosporidiosis; Diarrhea; Diarrhea, Infantile; Drug Evaluation; Erythromycin; Fluid Therapy; Humans; Infant; Male; Mediastinal Neoplasms; Neuroblastoma; Opportunistic Infections; Sarcoma