Therapeutic efficacy of macrolides, minocycline, and tosufloxacin against macrolide-resistant Mycoplasma pneumoniae pneumonia in pediatric patients.

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.

Nationwide surveillance of macrolide-resistant Mycoplasma pneumoniae infection in pediatric patients.

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.

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. METHODS: Samples from a total of 30 children with M. pneumoniae pneumonia, as confirmed by PCR and serology, were analyzed. Primers for domain V of 23S rRNA were used, and DNA sequences of the PCR products were compared with the sequence of an M. pneumoniae reference strain. RESULTS: Isolates from 21 patients demonstrated point mutations, and these patients were defined as MR. The remaining nine patients, whose isolates showed no point mutations, were categorized as control (macrolide-sensitive) patients. The number of M. pneumoniae in nasopharyngeal samples from the control group decreased rapidly 48 h after initiation of macrolide treatment and showed a close relationship with clinical outcome. In contrast, the number of M. pneumoniae 48 h after initiation of macrolide treatment were significantly higher in samples from MR patients than in samples from macrolide-sensitive patients. In 15 of 21 MR patients, fever persisted for more than 48 h after the initiation of macrolide treatment. When treatment was changed to minocycline, fever disappeared within 48 h in all these MR patients. There were no differences between MR patients who demonstrated a reduction in fever and those in whom fever persisted after 48 h of macrolide treatment. CONCLUSIONS: The microbiological and clinical efficacies of macrolides for treating patients with MR M. pneumoniae pneumonia were low. These results show that macrolides are clearly less effective in patients with MR M. pneumoniae pneumonia.

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. METHODS: Antibodies in sera from three groups of patients were measured: eight serum samples collected serially from a patient with acute C. pneumoniae pneumonia, 34 serum samples with Hitazyme-ELISA false-positive results, and 137 serum samples from patients with community-acquired pneumonia. RESULTS: The IgM antibody titre in the patient with acute C. pneumoniae pneumonia showed almost identical variation with the EIA, ELISA and MIF tests. Among the 34 samples found to be false-positive for IgM with ELISA, EIA revealed no positive cases. When a true positive case was defined as one for which a positive reaction was obtained with at least two tests, the sensitivities of the EIA, ELISA and MIF tests were 97.1%, 100% and 74.3%, with specificities of 100%, 37.3% and 100%, respectively. CONCLUSIONS: EIA was highly sensitive and specific as compared with the MIF test, and the ELISA test showed the lowest specificity. Consequently, the AniLab-EIA, rather than the Hitazyme-ELISA, is recommended as the routine method for accurately diagnosing acute C. pneumoniae infection.

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. METHODS: One hundred patients with acute respiratory tract infections (58 children and 42 adults) were enrolled in the study. Paired sera were obtained from all subjects for serological testing of C. pneumoniae. RESULTS: C. pneumoniae IgM positivity was observed in 36 (62.0%) children and 11 (26.1%) adults. However, MIF test or immunoblot revealed only four positive reactions in these patients. These four IgM-positive patients were also positive by ELISA. A significant increase in IgG and/or IgA antibody titres in paired sera was observed in three of the four patients. Of the remaining 96 patients, no significant increase in IgG or IgA antibody titre in the paired sera was observed. To confirm the positive reactivity of ELISA, positive sera were also analysed by recombinant enzyme immunoassay. Forty-three cases that were IgM-positive only by ELISA were all negative by recombinant enzyme immunoassay and the ELISA results were considered to be false-positives. CONCLUSIONS: These results indicate that a newly developed ELISA for detecting anti-C. pneumoniae-specific IgM antibody frequently generates false-positive findings in patients with acute respiratory tract infections, at the current cut-off level. Further studies are needed to determine an appropriate cut-off level and the possible causes of the false-positive results in the ELISA.

Mycoplasma pneumoniae pneumonia in the elderly.

BACKGROUND: Mycoplasma pneumoniae is one of the most common causes of community-acquired pneumonia (CAP). This infection occurs predominantly in school-aged children and younger adults, but may also occur in the elderly. MATERIAL/METHODS: To investigate the frequency and clinical characteristics of M. pneumoniae pneumonia in the elderly, we analyzed 210 hospitalized patients with M. pneumoniae pneumonia over a 15-year period. RESULTS: Thirty-two (15.2%) were 60 years of age or older. The frequencies of a comorbid illness with the age >or=60-years group were significantly higher than those of the age <60-years group (p<0.0001). The symptoms were almost identical in both age groups, but the fever magnitude was significantly lower in the age >or=60-years group than the age <60-years group (p<0.0001). One or more additional etiological factors were found more frequently in the age >or=60-years group than in the age <60-years group (37.5% vs 10.1%, p=0.0003). The diagnostic sensitivity for M. pneumoniae pneumonia using the Japanese CAP guidelines scoring system was significantly lower in the age >or=60-years group than in the age <60-years group (50% vs 90%, p <0.0001). CONCLUSIONS: Our results indicate that the frequency of M. pneumoniae pneumonia in the elderly was low but not rare. The symptoms and severity of the illness from this infection were almost identical in both age groups and the mortality rate was low even in the elderly. It seems to be difficult to distinguish between M. pneumoniae pneumonia and bacterial pneumonia in the elderly.

Clinical features of severe Mycoplasma pneumoniae pneumonia in adults admitted to an intensive care unit.

Community-acquired pneumonia (CAP) due to Mycoplasma pneumoniae is usually mild, but some cases develop a severe life-threatening pneumonia. To investigate the clinical features of severe M. pneumoniae pneumonia in adults admitted to an intensive care unit, a multi-centre CAP surveillance study was performed. Among all hospitalized CAP cases between January 2000 and December 2004, there were 227 cases with M. pneumoniae pneumonia without the complication of other pathogens. A total of 13 of the cases required admission to an intensive care unit because of acute respiratory failure (ARF), and the remaining 214 cases (non-ARF) were low to moderately severe. The clinical features of ARF cases were compared with those of non-ARF cases. The underlying conditions in both types of case were identical, whereas clinical findings on admission clearly differed between the two groups. A regimen of an antibiotic effective against M. pneumoniae was begun on average at 9.3 days after the onset of symptoms in ARF cases, which was significantly later than for non-ARF cases (P<0.0001). However, two of the ARF cases progressed to respiratory failure despite the fact that adequate antibiotics were initially administered within 3 days after the onset of symptoms. All ARF cases received corticosteroids with adequate antibiotics, and their condition improved promptly. These results indicate that the clinical features, excluding underlying conditions, clearly differed between severe M. pneumoniae pneumonia and low to moderately severe pneumonia. The delayed administration of adequate antibiotics may contribute to the severity of M. pneumoniae pneumonia. Early corticosteroid therapy with adequate antibiotics should be considered.

Design and burn-up analyses of new type holder for silicon neutron transmutation doping.

We have developed a new silicon irradiation holder with a neutron filter to increase the irradiation efficiency. The neutron filter is made of an alloy of aluminum and B4C particles. We fabricated a new holder based on the results of design analyses. This filter has limited use in applications requiring prolonged use due to a decrease in the amount of (10)B in B4C particles. We investigated the influence of (10)B reduction on doping distribution in a silicon ingot by using the Monte Carlo Code MVP.

A new irradiation method with a neutron filter for silicon neutron transmutation doping at the Japan research reactor no. 3 (JRR-3).

We studied a new silicon irradiation holder with a neutron filter designed to make the vertical neutron flux profile uniform. Since an irradiation holder has to be made of a low activation material, we applied aluminum blended with B4C as the holder material. Irradiation methods to achieve uniform flux with a filter are discussed using Monte-Carlo calculation code MVP. Validation of the use of the MVP code for the holder's analyses is also discussed via characteristic experiments.

In vitro activities of 11 antimicrobial agents against macrolide-resistant Mycoplasma pneumoniae isolates from pediatric patients: results from a multicenter surveillance study.

Macrolide-resistant Mycoplasma pneumoniae is emerging in several countries, and it is mainly observed in children. To our knowledge, we conducted the first multicenter prospective epidemiological study of macrolide-resistant M. pneumoniae in order to investigate regional differences in the susceptibility of macrolide-resistant M. pneumoniae to antibacterial agents. The in vitro activities of 11 antimicrobial agents against macrolide-resistant M. pneumoniae isolates from 5 different areas of Japan were investigated. Among 190 M. pneumoniae isolates from pediatric patients, 124 (65.2%) isolates showed macrolide resistance and possessed an A2063G transition in domain V of the 23S rRNA. These isolates showed high resistance to erythromycin, clarithromycin, and azithromycin with minimum inhibitory concentrations (MICs) ≥ 16 µg/ml. Conversely, quinolones such as garenoxacin, moxifloxacin, tosufloxacin, and levofloxacin exhibited potent antimycoplasmal activity. No regional differences were observed with respect to the MICs among the 5 areas in Japan.

Assessment of the usefulness of sputum Gram stain and culture for diagnosis of community-acquired pneumonia requiring hospitalization.

BACKGROUND: The usefulness of sputum Gram stain and culture in guiding microbiological diagnosis of community-acquired pneumonia (CAP) is controversial. We evaluated the role of sputum examination at a university teaching hospital. MATERIAL/METHODS: Three hundred forty-seven adult patients with CAP were enrolled in this study. Before administering antibiotic therapy, sputum was collected and its quality evaluated. Samples were gram stained and those of good quality were assessed for a predominant morphotype. RESULTS: Sputum samples were obtained from 216 patients (62%), and of these 124 (57%) samples were good quality and 80 (65%) showed a predominant morphotype. Sputum culture yielded a causative organism in 70 (88%) of the 80 samples with a predominant morphotype. In the cases of patients who had received previous antibiotic treatment, a good quality samples showing a predominant morphotype and positive culture was less frequently obtained from than from those who had not (p<0.0001). The sensitivity and specificity of the gram-positive diplococci identification in the sputum culture of S. pneumoniae were 68.2% and 93.8%, respectively, and the sensitivity and specificity of the gram-negative coccobacilli identification in the sputum culture of H. influenzae were 76.2% and 100%, respectively. CONCLUSIONS: Gram stain of sputum samples was useful in guiding microbiological diagnosis of CAP in 23% of patients. The Gram stain and culture of sputum samples obtained from patients who have received antibiotic treatment was unreliable. The presence of gram-positive diplococci and gram-negative coccobacilli was highly specific for the culture of S. pneumoniae and H. influenzae, respectively.

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

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.

Safety from thromboembolism using intravenous immunoglobulin therapy in Kawasaki disease: Study of whole-blood viscosity.

BACKGROUND: High-dose intravenous infusions of immunoglobulin (IVIG) are well established as a standard therapy for Kawasaki disease (KD) for reducing the risk of coronary artery aneurysms. IVIG therapy might increase the blood viscosity both in vitro and in vivo, which has been reported as a risk factor for cardiovascular or cerebrovascular thromboembolism in adults. METHODS: We measured the whole-blood viscosity in vitro, serum IgG and albumin, and blood hematocrit in 10 patients with KD and 10 with non-KD (five with acute encephalitis, one with sepsis, one with idiopathic thrombocytopenic purpura, one with Guillain-Barré syndrome, one with insulin-dependent diabetes mellitus, and one with Evans syndrome) before and after IVIG therapy. RESULTS: The blood viscosity increased significantly after IVIG therapy in the patients with non-KD, but did not increase in those with KD. CONCLUSION: The results of the present study suggest that the use of IVIG therapy for KD might be relatively safe, with no risk of thromboembolism due to hyperviscosity.