Kozo Kawasaki

Nationwide Surveillance of Macrolide-Resistant Mycoplasma pneumoniae Infection in Pediatric Patients

ABSTRACT We conducted nationwide surveillance to investigate regional differences in macrolide-resistant (MR) Mycoplasma pneumoniae strains in Japan. The prevalence of MR M. pneumoniae in pediatric patients gradually increased between 2008 and 2012. Although regional differences were observed, high levels of MR genes were detected in all seven surveillance areas throughout Japan and ranged in prevalence from 50% to 93%. These regional differences were closely related to the previous administration of macrolides.

Therapeutic Efficacy of Macrolides, Minocycline, and Tosufloxacin against Macrolide-Resistant Mycoplasma pneumoniae Pneumonia in Pediatric Patients

ABSTRACT The importance of macrolide-resistant (MR) Mycoplasma pneumoniae has become much more apparent in the past decade. We investigated differences in the therapeutic efficacies of macrolides, minocycline, and tosufloxacin against MR M. pneumoniae. A total of 188 children with M. pneumoniae pneumonia confirmed by culture and PCR were analyzed. Of these, 150 patients had a strain with an MR gene and 134 had one with an A-to-G mutation at position 2063 of M. pneumoniae 23S rRNA domain V. Azithromycin (n = 27), clarithromycin (n = 23), tosufloxacin (n = 62), or minocycline (n = 38) was used for definitive treatment of patients with MR M. pneumoniae. Defervescence within 48 h after the initiation of antibiotic therapy was observed in 41% of the patients in the azithromycin group, 48% of those in the clarithromycin group, 69% of those in the tosufloxacin group, and 87% of those in the minocycline group. The average number of days of fever after the administration of antibiotic treatment was lower in the minocycline and tosufloxacin groups than in the macrolide groups. The decrease in the M. pneumoniae burden, as estimated by the number of DNA copies, after 48 to 96 h of treatment was more rapid in patients receiving minocycline (P = 0.016) than in those receiving tosufloxacin (P = 0.049), azithromycin (P = 0.273), or clarithromycin (P = 0.107). We found that the clinical and bacteriological efficacies of macrolides against MR M. pneumoniae pneumonia was low. Our results indicated that minocycline rather than tosufloxacin can be considered the first-choice drug for the treatment of M. pneumoniae pneumonia in children aged ≥8 years.

Clinical efficacy of macrolide antibiotics against genetically determined macrolide-resistant Mycoplasma pneumoniae pneumonia in paediatric patients.

Background and objective:  Since 2000, the prevalence of macrolide‐resistant (MR) Mycoplasma pneumoniae has increased among paediatric patients in Japan. To determine the efficacy of macrolides against MR M. pneumoniae pneumonia, microbiological and clinical efficacies were compared during the antibiotic treatment.

Comparison of serological tests for detection of immunoglobulin M antibodies to Chlamydophila pneumoniae

Background and objective:  To evaluate an enzyme immunoassay (EIA) (AniLab C. pneumoniae) for detecting anti‐Chlamydophila pneumoniae‐specific IgM antibody, by comparing it with an ELISA, Hitazyme C. pneumoniae, and a micro‐immunofluorescence (MIF) test.

Evaluation of enzyme-linked immunosorbent assay for Chlamydophila pneumoniae-specific immunoglobulin M in acute respiratory tract infection

Background and objective:  The study evaluated a newly developed ELISA (Hitazyme Chlamydophila pneumoniae) for detecting anti‐C. pneumoniae‐specific IgM antibody, by comparing the ELISA assay to a microimmunofluorescence (MIF) test and immunoblotting.

Sivelestat relieves respiratory distress refractory to dexamethasone in all-trans retinoic acid syndrome : a report of two cases

Abstract:  Treatment with all‐trans retinoic acid (ATRA) improves the prognosis of patients with acute promyelocytic leukemia (APL), but ATRA syndrome may occur as a possible fatal side effect, especially in cases refractory to medication or involving pulmonary hemorrhage. We describe two patients with APL who suffered from intracranial hemorrhage. The first patient was a 16‐yr‐old girl who was treated with ATRA and then developed respiratory distress refractory to treatment with dexamethasone combined with anthracycline‐cytarabine cytoreduction therapy. Treatment with Sivelestat, a small molecule inhibitor of neutrophil elastase, achieved rapid improvement in oxygenation and chest radiograph findings, and the patient has been in complete remission for 24 months. The second patient was a 10‐yr‐old boy in whom pulmonary hemorrhage developed following administration of ATRA, dexamethasone and cytoreduction therapy. Aspiration and administration of Sivelestat improved oxygenation and he remained stable. Hematological improvement was also achieved, but the patient died of brain dysfunction because of cerebral edema accompanied by intracranial bleeding. The two cases suggest that Sivelestat may be effective as an additional agent in the treatment of refractory ATRA syndrome, and, therefore, prospective randomized studies of treatment protocols are warranted.

Natural alteration of antibody titers in a patient with immunoglobulin A deficiency after chickenpox over a 10-year period

months (26 months after she was diagnosed with DNH). It is well known that childhood cancer survivors are at high risk of developing a second neoplasm; particularly in patients at a young age at diagnosis, with escalated doses of alkylating agents, and with the use of anthracyclines or epipodophyllotoxins. Hawkins reported that a cumulative dose of CPA over 4400 mg/m causes acute myeloid leukemia with relative risk of over 2.7. We gave 1575 mg/m of CPA, which is very low compared with cases already reported. Recently bevacizumab, a recombinant humanized monoclonal antibody directed against the vascular endothelial growth factor, or sorafenib, a tyrosine kinase inhibiter, are clinically applied to inhibit angiogenesis. Theoretically these agents may not act directly against genomic DNA replication, and could be applied for DNH with an expectation for less secondary cancer. In conclusion, low-dose CPA proved most effective after multimodal treatment against DNH in our case. Further follow up is warranted for secondary malignancies.