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In this paper, we examined the details of severe infections, treatment efficacies, and the prognoses of 23 Japanese patients with chronic granulomatous disease (CGD). We described the mean ages at diagnosis and follow-up, which were 2.8 years (range, 0.7-10 years) and 14.9 years (range, 0.2-28.4 years), respectively. There were three deaths, two from Aspergillus pneumonia and one from liver abscess. Eighteen of the 23 patients (78%) had a complete loss of gp91phox, and three had p22-phox and one had p67phox deficiencies. Aspergillus species were found in 45% of 174 severe infections. The mean height and weight of the 20 surviving patients were -0.8 +/- 1.3SD and -1.9 +/- 1.9SD below the means for age, respectively. Short stature and underweight (below the 10th percentile of the means) for age were seen in 22% and 17% of the patients, respectively. This growth retardation reflects the severity of the disease. At 20 years of age, there was 87% survival. Ongoing prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) or antifungal drugs was given in 16 and 11 patients, respectively. Interferon-gamma (IFN-gamma) was given once a week to 14 patients. Four patients underwent hematopoietic stem cell transplantation (HSCT) and are currently well. There were infections observed in three of 21 identified related carriers of X-linked CGD. A carrier with a liver abscess had 5% normal neutrophils during the acute phase of infection, which returned to 40% normal neutrophils after recovery. The high survival rate in this hospital results from regular follow-up and prophylaxis with TMP-SMX and anti-fungal drugs beginning at the time of diagnosis, along with treatment with weekly IFN-gamma.
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We describe a rare adverse reaction to trimethoprim-sulfamethoxazole (TMP-SMX; Septra, Bactrim) in an immune-competent female adolescent. She was prescribed TMP-SMX for a urinary tract infection, which she had developed while being treated in the hospital for an extensive leg cellulitis. Shortly after receiving her third dose of TMP-SMX, she developed an acute altered mental status with agitation as well as vivid visual and auditory hallucinations. After prompt discontinuation of TMP-SMX, the patient slowly began to improve and was able to return to her baseline mental status within 10 days. No residual mental status changes were present. Despite the recent emergence of multidrug-resistant bacterial pathogens, TMP-SMX, one of the first-generation broad-spectrum antibiotics, continues to be widely prescribed, in part because of its low cost and its easy availability. It is generally well tolerated and is associated with relatively few adverse effects. More common toxicities associated with TMP-SMX include hypersensitivity reactions, bone marrow suppression, and gastrointestinal side effects. Central nervous system toxicity is very rare; when reported, it has been in an immune-compromised or an elderly patient.
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Our whole genome sequence (WGS) pipeline was assessed for accurate prediction of antimicrobial phenotypes. For 2316 invasive pneumococcal isolates recovered during 2015 we compared WGS pipeline data to broth dilution testing (BDT) for 18 antimicrobials. For 11 antimicrobials categorical discrepancies were assigned when WGS-predicted MICs and BDT MICs predicted different categorizations for susceptibility, intermediate resistance or resistance, ranging from 0.9% (tetracycline) to 2.9% (amoxicillin). For β-lactam antibiotics, the occurrence of at least four-fold differences in MIC ranged from 0.2% (meropenem) to 1.0% (penicillin), although phenotypic retesting resolved 25%-78% of these discrepancies. Non-susceptibility to penicillin, predicted by penicillin-binding protein types, was 2.7% (non-meningitis criteria) and 23.8% (meningitis criteria). Other common resistance determinants included mef (475 isolates), ermB (191 isolates), ermB + mef (48 isolates), tetM (261 isolates) and cat (51 isolates). Additional accessory resistance genes (tetS, tet32, aphA-3, sat4) were rarely detected (one to three isolates). Rare core genome mutations conferring erythromycin-resistance included a two-codon rplD insertion (rplD69-KG-70) and the 23S rRNA A2061G substitution (six isolates). Intermediate cotrimoxazole-resistance was associated with one or two codon insertions within folP (238 isolates) or the folA I100L substitution (38 isolates), whereas full cotrimoxazole-resistance was attributed to alterations in both genes (172 isolates). The two levofloxacin-resistant isolates contained parC and/or gyrA mutations. Of 11 remaining isolates with moderately elevated MICs to both ciprofloxacin and levofloxacin, seven contained parC or gyrA mutations. The two rifampin-resistant isolates contained rpoB mutations. WGS-based antimicrobial phenotype prediction was an informative alternative to BDT for invasive pneumococci.
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The gamma-pyridone beta-carboxylic acids or 'quinolones' rival beta-lactam antibiotics in diversity of chemical structure and properties. Norfloxacin has a much wider spectrum than nalidixic acid which includes pseudomonas and Gram-positive cocci. It is also much more potent with MIC50 for Enterobacteriaceae of less than 0.06 mg/l. This high activity is reduced in the presence of urine--possibly due to pH, but probably not to clinically inadequate levels. The results of laboratory tests from around the world are reviewed; despite various techniques these are remarkably consistent. The wide spectrum of norfloxacin should make it useful for therapy of urinary tract infection, and for gut decontamination and enteric infections. The high potency should allow use of lower doses with possibly less toxicity than nalidixic acid.
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Disseminated toxoplasmosis is a life-threatening infection in transplant recipients, which results either from reactivation of latent infection or from organ-transmitted primary infection. Preventive measures and diagnostic screening methods differ between countries and are related to the seroprevalence of Toxoplasma spp. in the general population. Here we report a case of disseminated toxoplasmosis in a heart transplant recipient with previous immunity that occurred after cotrimoxazole prophylaxis for the prevention of Pneumocystis jirovecii pneumonia was stopped. Quantitative PCR proved useful for the diagnosis and monitoring of Toxoplasma infection. Decreasing parasitic burdens in sequential samples of cerebrospinal fluid, blood, and bronchoalveolar lavage fluid correlated with a favorable outcome and allowed modulation of the immunosuppressive drug regimen. The duration of anti-Toxoplasma treatment and the need for maintenance prophylaxis are discussed, as well as prophylaxis for solid-organ transplant recipients. Although a rare event in heart transplant recipients, Toxoplasma reactivation must be investigated promptly, since early treatment improves the prognosis.
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Incidence rates of IPD and associated mortality shown in this study highlight the need for pneumococcal vaccines in rural Africa, which must be effective in infants and young children.
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The efficacy of three different regimens of oral medication for pharyngeal gonorrhea was examined in a study of 119 patients. Of 34 patients treated with 1.4 g of pivampicillin plus 1.0 g of probenecid, both taken once a day for five days, 33 (97.1%) were cured. The other two regimens consisted of tablets containing sulfamethoxazole (400 mg) and trimethoprim (80 mg). Of 36 patients treated with a single ten-tablet dose on the first day, two five-tablet doses on the second day, and two three-tablet doses for the next three to five days, 35 (97.2%) were cured. Of 49 patients treated with a single ten-tablet dose on the first day and two five-tablet doses on the second day, 44 (89.8%) were cured. The cure rates for the three regimens were not significantly different (P greater than 0.05). Therefore, we conclude that a two-day trimethoprim-sulfamethoxazole regimen is quick, inexpensive, and reliable in the treatment of pharyngeal gonorrhea.
GSH levels were determined by an high-performance liquid chromatography method utilizing a fluorescent probe, monobromobimane. The bimane-GSH adduct formed in PBMC was also characterized by mass spectrometry. Methaemoglobin formation on exposure to dapsone hydroxylamine was determined spectrophotometrically.