Adjunctive Rifampicin Increases Antibiotic Efficacy in Group A Streptococcal Tissue Infection Models.

Biofilm has recently been highlighted as a complicating feature of necrotizing soft tissue infections (NSTI) caused by Streptococcus pyogenes (i.e., group A Streptococcus [GAS]) contributing to a persistence of bacteria in tissue despite prolonged antibiotic therapy. Here, we assessed the standard treatment of benzylpenicillin and clindamycin with or without rifampin in a tissue-like setting. Antibiotic efficacy was evaluated by CFU determination in a human organotypic skin model infected for 24 or 48 h with GAS strains isolated from NSTI patients. Antibiotic effect was also evaluated by microcalorimetric metabolic assessment in in vitro infections of cellular monolayers providing continuous measurements over time. Adjunctive rifampin resulted in enhanced antibiotic efficacy of bacterial clearance in an organotypic skin tissue model, 97.5% versus 93.9% (P = 0.006). Through microcalorimetric measurements, adjunctive rifampin resulted in decreased metabolic activity and extended lag phase for all clinical GAS strains tested (P < 0.05). In addition, a case report is presented of adjunctive rifampin treatment in an NSTI case with persistent GAS tissue infection. The findings of this study demonstrate that adjunctive rifampin enhances clearance of GAS biofilm in an in vitro tissue infection model.

Associations between capsular serotype, multilocus sequence type, and macrolide resistance in Streptococcus agalactiae isolates from Japanese infants with invasive infections.

SUMMARY Streptococcus agalactiae (group B streptococcus; GBS) isolates (n = 150) from infants with invasive infections between 2006 and 2011 were analysed for capsular serotype, multilocus sequence type, and antibiotic susceptibility. In cases with late-onset disease (n = 115), primary meningitis was predominant (62.6%), but represented only 39.1% in cases with early-onset disease (n = 23). The most common serotype was III (58.7%), followed by Ia (21.3%) and Ib (12.7%). Sequence types (STs) of serotype III strains included ST17 (50.0%), ST19 (26.1%), ST335 (18.2%), ST27 (4.5%), and ST1 (1.1%). Predominant STs of serotypes Ia and Ib were ST23 (81.3%) and ST10 (84.2%), respectively. No penicillin-resistant strains were detected, but 22·0% of strains had mef(A/E), erm(A), or erm(B) genes, which mediate macrolide resistance. A new ST335, possessing an mef(A/E) gene belonging to clonal complex 19 gradually increased in frequency. Improved prevention of invasive GBS infections in infants requires timely identification, and ultimately vaccine development.

A comprehensive model for the humoral coagulation network in humans.

Coagulation is an important process in hemostasis and comprises a complicated interaction of multiple enzymes and proteins. We have developed a mechanistic quantitative model of the coagulation network. The model accurately describes the time courses of coagulation factors following in vivo activation as well as in vitro blood coagulation tests of prothrombin time (PT, often reported as international normalized ratio (INR)) and activated partial thromboplastin time (aPTT). The model predicts the concentration-time and time-effect profiles of warfarin, heparins, and vitamin K in humans. The model can be applied to predict the time courses of coagulation kinetics in clinical situations (e.g., hemophilia) and for biomarker identification during drug development. The model developed in this study is the first quantitative description of the comprehensive coagulation network.

Sudden cardiac death from thrombotic thrombocytopenic purpura.

Clinical thrombotic thrombocytopenic purpura (TTP) is characterized by a pentad of microangiopathic hemolytic anemia, thrombocytopenia, neurological symptoms, renal involvement, and fever. A case of TTP in which early symptoms and signs were suggestive of ischemic heart disease, renal failure, and severe thrombocytopenia developed to a rapid outcome of death. The postmortem examination revealed coronary artery microthrombi, typical of TTP. The clinical presentation of this TTP was atypical: severe thrombocytopenia, striking renal and CNS symptoms were present, but fever and anemia were not present. Thrombotic thrombocytopenic purpura is an uncommon condition that carries a high fatality rate if untreated. Awareness of this syndrome and its high risk of sudden death underlines the importance of rapid diagnosis and treatment.

Fibrinolytic profiles in patients with small cell carcinoma of the lung.

1. Elevated levels of fibrinogen were observed in 100% of untreated patients with SCCL. The elevated fibrinogen tended to normalize with complete remission in response to combination chemotherapy. 2. FDPs were increased in 33% of patients in the limited disease group and in 37% in the extensive disease group. Elevated levels of D-dimers were seen in 26% in the limited disease group and in 50% in the extensive disease group. Levels of FDPs did not parallel levels of D-dimers. Some cases of very advanced disease showed increases in both FDPs and D-dimers. 3. When FDPs were within normal limits, D-dimers tended to be elevated. 4. Levels of plasminogen, alpha 2-antiplasmin, and plasmin were and remained within normal limits throughout the course of treatment, while concentrations of FDPs and D-dimers increased. 5. Plasminogen, alpha 2-antiplasmin, plasmin, FDPs and D-dimers did not show any trend. 6. Peripheral blood measurements did not reflect the crucial role of plasmin in modulating blood fibrinolysis and the metastatic cascade. 7. Evidence of the action of the fibrinolytic system at tumor sites failed to correlate with results of laboratory tests.

[Statistical analysis of nuclear medicine in the Higashi Nippon Gakuen University Dental Hospital].

The number of radionuclide in vivo tests carried out at the Higashi Nippon Gakuen University Dental Hospital was statistically analyzed and discussed. The subjects were all patients admitted to the Division of Nuclear Medicine during the seven years between 1981 and 1989. The total number of the patients included those introduced through medical facilities in Toubetsu-cho and others. The results of this analysis were as follows: 1) The proportion of the first time patients admitted to the Higashi Nippon Gakuen University Dental Hospital was only 11 percent of all patients. 2) Cases of radionuclide in vivo tests at the Higashi Nippon Gakuen University Dental Hospital decreased in number, annually. However the proportion of tumor scintigraphy and bone scintigraphy increased gradually.

Factor VIII inhibitor in insulin-dependent diabetes mellitus.

Acquired factor VIII inhibitor was found in a 69-year-old white male with insulin-dependent diabetes mellitus. He presented with left lower abdominal pain and hematoma after a fall. Preoperative hemostasis studies were normal except for prolonged aPTT. Prolonged aPTT was not corrected by 1:1 mixture with normal fresh plasma and incubation showed further prolongation with time. Factor VIII:c was 3.5%. The inhibitor titer was 7.5 Bethesda units. The possible mechanism causing antibody to factor VIII was postulated to be an autoimmune process and/or increased immunogenicity owing to glycosylation of factor VIII coagulant protein.

Thrombophlebitis in cancer patients.

Five cancer patients (three with lesions in the lung and one each with breast and head and neck cancer) with multiple metastases developed "migratory thrombophlebitis." These patients were not ambulatory. None of the patients showed a picture of "consumptive coagulopathy," although a "hypercoagulable state" was observed. Fibrinogen levels were normal or increased, FDP were slightly increased, and AT-III was decreased. Prior to heparin therapy, values for PT and PTT were within normal range. Sodium heparin, 30,000 to 36,000 units per day, was administered by continuous intravenous infusion. Despite prolongation of the PTT to twice the baseline levels, signs and symptoms of thrombophlebitis persisted for several days. When thrombophlebitis was controlled with heparin, Coumadin therapy was instituted, but thrombophlebitis recurred at the original site and at new sites, even though the prothrombin time was in the therapeutic range (2 to 2 1/2 times the normal value). The antithrombotic action of heparin depends on a normal quantity of plasma AT-III. Long-term use of heparin is feasible, but the optimal time for discontinuation of heparin treatment has not been established. Heparin is superior to oral anticoagulation therapy to control thrombophlebitis associated with advanced cancer.

Nitroblue tetrazolium test in patients with sickle-cell anemia.

Forty-four patients who had sickle-cell anemia were examined to evaluate the reliability and usefulness of the nitroblue tetrazolium (NBT) test. The patients with sickle-cell anemia in painful crisis with bacterial infection often had low percentages of NBT reduction or negative results. The NBT test did not differentiate well between sickle-cell anemia with bacterial infection and without bacterial infection.