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The in vitro activity of clarithromycin alone and in combination with its primary human metabolite, 14-hydroxy-clarithromycin, was determined against 203 strains of Haemophilus influenzae. Microdilution broth MICs and MBCs of both clarithromycin and 14-hydroxy-clarithromycin were determined. The clarithromycin MIC50 was 4 mg/l and the MIC90 was 8 mg/l. The hydroxy metabolite was 2-4-fold more active with an MIC50 and MIC90 of 2 mg/l. The MBCs were equal to the MICs. The microbicidal effect of combinations of clarithromycin and 14-hydroxy-clarithromycin was tested using a microdilution checkerboard technique and the fractional inhibitory index was calculated. The combination was additive in 92% and synergistic in 8% of all strains of H. influenzae tested; no antagonism was found. The results were independent of the site of isolation of the strain or presence of beta-lactamase. These findings suggest the potential clinical utility of clarithromycin for the treatment of H. influenzae infections.
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Myeloid-derived suppressor cells (MDSC) play a significant role in tumor-induced immune suppression. Targeting their function could improve antitumor therapies. Previously, we demonstrated that phosphodiesterase 5 (PDE5) inhibition in MDSCs augmented antitumor immunity in murine models. Here, we show how the addition of the PDE5 inhibitor, tadalafil, in a patient with end-stage relapsed/refractory multiple myeloma reduced MDSC function and generated a dramatic and durable antimyeloma immune and clinical response. Strategies targeting MDSC function with PDE5 inhibitors represent a novel approach that can augment the efficacy of tumor-directed therapies.
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Many factors influence the metabolism of warfarin, including disease states, medications, age, and diet. Data collected in this case suggested clarithromycin may have contributed to the increase in the effect of warfarin. Inhibition of the cytochrome P450 oxidizing system appears to be the reason for the increase. Numerous drugs and disease states affect the rate at which this system metabolizes drugs.
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Acute oropharyngeal and respiratory tract infections are due to a wide spectrum of microorganisms. The aim of this study was to compare and evaluate the in vitro activity of four antiseptics (cetyltrimethylammonium naproxenate, chlorhexidine, benzydamine, hexetidine) to four antibiotics (amoxicillin, amoxicillin-clavulanate, clarithromycin, cefaclor) on strains of Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes and Streptococcus pneumoniae.
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A 47-year-old man presented to a local physician with a chief complaint of sputum and cough for 3 months. Chest X-ray showed bilateral consolidation in the upper lung fields, and the patient was suspected to have pulmonary tuberculosis: he was then referred to our hospital. Smear and culture of both sputum and gastric juice showed acid-fast bacilli, and we started administration of rifampicin, isoniazid, ethambutol, and pyrazinamide. Results of the culture and identification test showed the causative bacillus to be Mycobacterium scrofulaceum (M. scrofulaceum). We stopped pyrazinamide and added clarithromycin to the treatment regimen, which resulted in symptomatic relief and radiological improvement. The frequency of pulmonary nontuberculous mycobacteriosis is increasing: in contrast, pulmonary infection by M. scrofulaceum has been decreasing. Nevertheless, M. scrofulaceum infection should be considered in the differential diagnosis from tuberculosis when the results of radiological findings and sputum culture suggest pulmonary tuberculosis.
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A 37-year-old Hispanic man with advanced acquired immunodeficiency syndrome developed extensive pulmonary disease with persistent cough, fever, night sweats, worsening dyspnea, and weight loss. Sputum samples showed scant growth of acid-fast bacilli. He failed to respond to the standard tuberculosis regimen of isoniazid, rifampin, ethambutol, and pyrazinamide. Subsequently, Mycobacterium szulgai was identified, and susceptibility tests showed it to be resistant to all four of those agents. Therapy was changed to clarithromycin, doxycycline, ciprofloxacin, and amikacin. Within 2 weeks, the patient's condition improved significantly, and 6 months after treatment, extensive pulmonary infiltrates had nearly resolved. Fewer than 1% of all human isolates of mycobacteria consist of M. szulgai, which is relatively susceptible to standard antimycobacterial agents. To our knowledge, this is the first reported case of M. szulgai with resistance to all primary antituberculosis drugs.
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In all, 22 of 223 men (9.87%) demonstrated H pylori IgA antibodies in their seminal plasma. After treatment, mean seminal H pylori IgA levels demonstrated significant decrease (1.55 ± 0.4 vs 0.52 ± 0.26; 95% confidence interval, 0.83-1.21; P = .001) concomitant with improved progressive as well as nonprogressive sperm motility. H pylori IgA antibodies demonstrated significant negative correlation with progressive sperm motility, nonprogressive sperm motility, normal sperm morphology, and significant positive correlation with immotile sperm motility.
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Ceftaroline, the active form of ceftaroline fosamil, is a broad-spectrum cephalosporin with bactericidal activity against pathogens causing community-acquired pneumonia (CAP), including Streptococcus pneumoniae. Ceftaroline was evaluated for the treatment of CAP in 2 randomized, double-blind, multicenter trials: Ceftaroline Community Acquired Pneumonia Trial versus Ceftriaxone in Hospitalized Patients (FOCUS) 1 and FOCUS 2.
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We report a case of fatal pulmonary infection caused by Mycobacterium abscessus in a young patient with cystic fibrosis, who underwent bipulmonary transplantation after a 1-year history of severe lung disease. Fifteen days after surgery he developed septic fever with progressive deterioration in lung function. M. abscessus, initially isolated from a pleural fluid specimen, was then recovered from repeated blood samples, suggesting a disseminated nature of the mycobacterial disease. Drug susceptibility testing assay, performed on two sequential isolates of the microorganism, showed a pattern of multidrug resistance. Despite aggressive therapy with several antimycobacterial drugs, including clarithromycin, the infection persisted, and the patient died.
To our knowledge, this is the first case report of parotitis caused by M. fortuitum and its successful medical treatment.
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We aim to determine infections occurring in patients with non-small cell lung cancer during radiotherapy (RT).
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Forty Wistar albino rats were divided into five groups of eight animals. After the crushed wound model was made on the back of the rats, wounds were closed with a simple suture and Staphylococcus aureus ATCC 29213 strain was used to create infection. All rats apart from the controls were given oral gavage with antibiotics, including cephalexin, amoxicillin-clavulanate, clarithromycin (CAM), or levofloxacin for 5 days. Wounds were evaluated qualitatively and quantitatively on 5th day approximately 18 h after the last treatment.
An urban AIDS clinic
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The decrease in the expression of GPI-anchored complement regulator and the complement after removal of a chronic microbial stimulus suggests that the gastric epithelium appears to undergo an aggressive stress of complement during H. pylori infection. Conclusively, DAF and HRF20 may play an important protective role against complement-mediated damage induced by chronic microbial stimuli in such a pathological condition.
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The impact on the INR was analyzed using a paired samples t test comparing INR values and warfarin doses before and after azithromycin exposure. There was a significant change in the INR between the 2 groups (before vs after azithromycin exposure, P < 0.001). This change was clinically significant given that the values before and after exposure to azithromycin lead to a decrease in warfarin from a mean weekly dose of 30 mg to 29.2 mg (P = 0.001). However, changes in the INR did not result in vitamin K administration or adverse bleeding events.
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One hundred nine of 514 NASPGHAN members completed an Internet-based questionnaire on H. pylori infection.
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Both once-daily triple (rabeprazole, levofloxacin, and furazolidone) and twice-daily quadruple therapy (rabeprazole, bismuth subcitrate, doxycycline, and furazolidone) for 10 days achieved encouraging results. Subsequent studies should be performed to evaluate antibiotic resistance, doses, dosing intervals, duration of treatment, and safety of these two regimes.
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Adults from Ciudad Juarez with H. pylori infections identified by culture or histology received rabeprazole 20 mg, clarithromycin 0.5 g and amoxicillin 1 g, each b.d. for 7 days. Outcome was assessed by 13C-urea breath test carried out 4+ weeks after treatment.
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Patients with H. pylori-positive active duodenal ulcer were randomly assigned to receive triple therapy with amoxycillin 1000 mg b.d. + clarithromycin 500 mg b.d. + omeprazole 20 mg daily for 10 days (ACT-10) or dual therapy with clarithromycin 500 mg t.d.s. + omeprazole 40 mg daily for 14 days (Dual). No additional acid suppression was provided following eradication therapy. Endoscopy, with biopsy for culture and histology, as well as 13C-urea breath testing (13C-UBT) were performed pre-treatment to assess H. pylori infection. H. pylori eradication was established at 4-6 weeks follow-up with culture (2 antral, 1 corpus biopsies), histology (2 antral biopsies), and 13C-UBT. Ulcer healing by endoscopy and change in clinical symptoms were also assessed at 4-6 weeks.
Clarithromycin is a relatively new macrolide antibiotic that offers twice-daily dosing. It differs from erythromycin only in the methylation of the hydroxyl group at position 6. Although the side-effect profile of erythromycin is established, including gastroenteritis and interactions with other drugs subject to hepatic mixed-function oxidase metabolism, experience with the newer macrolides is still being recorded. Cardiotoxicity has been demonstrated after both intravenous and oral administration of erythromycin but has never been reported with the newer macrolides. We report a case of ventricular dysrhythmias that occurred after six therapeutic doses of clarithromycin. The dysrhythmias resolved after discontinuation of the drug.
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In general, proton pump inhibitor-C-I and proton pump inhibitor-C-A are equally effective and therefore other factors such as local prevalence of resistant strains, cost of therapy and options for second-line treatment should determine which regimen should be preferred. When using RBC, the RBC-C-I combination is somewhat superior to RBC-C-A.
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The aim of this study was to examine the effect of clarithromycin, a CYP3A4 inhibitor, on the enantioselective disposition of lansoprazole among three different CYP2C19 genotype groups in healthy Japanese subjects. These subjects included 6 each of homozygous extensive metabolizers (homEMs), heterozygous extensive metabolizers (hetEMs), and poor metabolizers (PMs). In the EMs of CYP2C19, clarithromycin markedly increased Cmax and the AUC0-infinity of (S)-lansoprazole and (S)-hydroxylansoprazole compared with those of the corresponding (R)-enantiomers. Clarithromycin significantly increased Cmax and the AUC0-infinity of (S)-lansoprazole in the homEMs by 110% and 115%, respectively, and in the hetEMs by 105% and 103%, respectively, compared with placebo. Furthermore, clarithromycin slightly prolonged the elimination half-life of (R)-lansoprazole in the homEMs and hetEMs but did not alter that of (S)-lansoprazole. In the of PMs CYP2C19, clarithromycin significantly increased Cmax and the AUC0-infinity and significantly prolonged the elimination half-lives of (R)- and (S)-lansoprazole by 51% and 49%, respectively. The present study suggests that there are significant drug interactions between (R)- or (S)-lansoprazole and clarithromycin in EMs by inhibiting the CYP3A4-catalyzed sulfoxidation primarily during the first pass, whereas in PMs, the overall metabolism of lansoprazole is inhibited.
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Some patients with Mycoplasma pneumoniae infection are clinically resistant to antibiotics such as erythromycin, clarithromycin, or clindamycin. We isolated M. pneumoniae from such patients and found that one of three isolates showed a point mutation in the 23S rRNA gene. Furthermore, 141 EM-sensitive clinical isolates of M. pneumoniae were cultured in broth medium containing 100 microg/ml of erythromycin (EM). Among 11 EM-resistant strains that grew in the medium, point mutations in the 23S rRNA were found in 3 strains at A2063G, 5 strains at A2064G and 3 strains at A2064C. The relationship between the point mutation pattern of these EM-resistant strains and their resistance phenotypes to several macrolide antibiotics was investigated.
Symptomatic lung involvement and an increased susceptibility to pulmonary infections are uncommon in GD and, if present, are often associated with more severe disease manifestations. To our knowledge, this is the first published report on the association of GD and pulmonary aspergillosis and mycobacterial infection. It illustrates the increased susceptibility of untreated GD patients to opportunistic pulmonary infections and ineffective eradication of these infections despite adequate therapy.