Takafumi Okada

Rapid Effectiveness of Minocycline or Doxycycline Against Macrolide-Resistant Mycoplasma pneumoniae Infection in a 2011 Outbreak Among Japanese Children

BACKGROUND Mycoplasma pneumoniae is a major pathogen causing community-acquired pneumonia in children and young adults. Outbreaks typically occur at intervals of several years. In 2011, a widespread outbreak was associated with macrolide-resistant M. pneumoniae (MRMP) in Japanese children, often those of school age. METHODS Two hundred fifty-eight children were diagnosed with M. pneumoniae-associated pneumonia based on chest radiography, real-time polymerase chain reaction (PCR), and antibody titers between January and December 2011. Mycoplasma pneumoniae cultures obtained from nasopharyngeal samples using appropriate broth were subjected to real-time PCR, by which decreases in M. pneumoniae in patients treated with minocycline (MIN), doxycycline (DOX), or tosufloxacin (TFX) were calculated. Mutations of the 23S ribosomal RNA gene that confer high resistance to macrolides in M. pneumoniae were identified by DNA sequencing. RESULTS Among 202 M. pneumoniae isolates from M. pneumoniae-associated pneumonia patients, 176 (87.1%) were MRMP. Macrolide-resistant M. pneumoniae infection was significantly related to school age (P < .01) and initial administration of macrolides (P < .01). Minocycline or DOX (n = 125) or TFX or levofloxacin (n = 15) was used for definitive treatment of MRMP patients. Minocycline or DOX was significantly more effective than TFX (P ≤ .05) in achieving defervescence within 24 hours and in decreasing numbers of M. pneumoniae DNA copies 3 days after initiation. CONCLUSIONS Macrolides are inappropriate as first-choice agents against MRMP in terms of shortening the clinical course and decreasing M. pneumoniae. Control and prevention of MRMP outbreaks in children require early decreases in M. pneumoniae as well as improvement of clinical findings.

A comparative clinical study of macrolide-sensitive and macrolide-resistant Mycoplasma pneumoniae infections in pediatric patients.

In recent years, the increased prevalence of macrolide-resistant Mycoplasma pneumoniae (MR-M. pneumoniae) has become a significant issue in Japan. We isolated 94 strains of M. pneumoniae, and determined the minimum inhibitory concentrations (MICs) of macrolides and other antimicrobial agents for these strains. We also performed a comparative clinical evaluation of macrolide efficacy for cases of MR-M. pneumoniae infections and cases of macrolide-sensitive Mycoplasma pneumoniae infections (MS-M. pneumoniae). Of the 94 isolates of M. pneumoniae, 64 (68.1%) were classified as MS-M. pneumoniae and 30 (31.9%) as MR-M. pneumoniae strains. The clinical study included an assessment of 47 pediatric cases of MS-M. pneumoniae and 22 pediatric cases of MR-M. pneumoniae. The patient demographics, such as sex, age, the period from the onset of the infection to the first examination, laboratory findings, diagnosis, and the severity of symptoms, showed no significant difference between the two study groups. However, the efficacy of macrolide treatment was 91.5% for MS-M. pneumoniae and 22.7% for MR-M. pneumoniae, a statistically significant difference (P < 0.01). Although M. pneumoniae infection is generally considered a treatable condition, the increasing prevalence of macrolide-resistant strains of M. pneumoniae has become a significant clinical issue in pediatric patients, and it is therefore necessary to give careful consideration to the appropriate antimicrobial therapy for MR-M. pneumoniae infection.

Rapid detection of eight causative pathogens for the diagnosis of bacterial meningitis by real-time PCR

We aimed to detect causative pathogens in cerebrospinal fluid (CSF) collected from patients diagnosed with bacterial meningitis by real-time polymerase chain reaction (PCR). In addition to Streptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae described previously, five other pathogens, Neisseria meningitidis, Escherichia coli, Streptococcus agalactiae, Staphylococcus aureus, and Listeria monocytogenes, were targeted, based on a large-scale surveillance in Japan. Results in CSF from neonates and children (n = 150), and from adults (n = 18) analyzed by real-time PCR with molecular beacon probes were compared with those of conventional culturing. The total time from DNA extraction from CSF to PCR analysis was 1.5 h. The limit of detection for these pathogens ranged from 5 copies to 28 copies per tube. Nonspecific positive reactions were not recognized for 37 microorganisms in clinical isolates as a negative control. The pathogens were detected in 72.0% of the samples by real-time PCR, but in only 48.2% by culture, although the microorganisms were completely concordant. With the real-time PCR, the detection rate of H. influenzae from CSF was high, at 45.2%, followed by S. pneumoniae (21.4%), S. agalactiae (2.4%), E. coli (1.8%), L. monocytogenes (0.6%), and M. pneumoniae (0.6%). The detection rate with PCR was significantly better than that with cultures in patients with antibiotic administration (χ2 = 18.3182; P = 0.0000). In conclusion, detection with real-time PCR is useful for rapidly identifying the causative pathogens of meningitis and for examining the clinical course of chemotherapy.

Human bocavirus DNA detected in a boy with plastic bronchitis.

Title Human Bocavirus DNA Detected in a Boy With Plastic Bronchitis Author(s) Oikawa, Junko; Ogita, Junko; Ishiwada, Naruhiko; Okada, Takafumi; Endo, Rika; Ishiguro, Nobuhisa; Ubukata, Kimiko; Kohno, Yoichi Citation The Pediatric Infectious Disease Journal, 28(11): 1035-1036 Issue Date 2009-11 Doc URL http://hdl.handle.net/2115/53432 Rights This is a non-final version of an article published in final form in Pediatr. Infect. Dis. J., 28(11):1035-1036, November 2009. Type article (author version) File Information Pediatr. Infect. Dis. J._28(11)_1035-1036.pdf

Pandemic (H1N1) 2009-associated Pneumonia in Children, Japan

To describe clinical aspects of pandemic (H1N1) 2009 virus–associated pneumonia in children, we studied 80 such children, including 17 (21%) with complications, who were admitted to 5 hospitals in Japan during August–November 2009 after a mean of 2.9 symptomatic days. All enrolled patients recovered (median hospitalization 6 days). Timely access to hospitals may have contributed to favorable outcomes.

Prolonged Mycoplasma pneumoniae infection in an elderly patient with community-acquired pneumonia

An 81-year-old woman with no underlying systemic illness was hospitalized with fever, muscle weakness, and sputum without cough for 2 days. Chest imaging showed consolidation in the left lower lobe. Real-time polymerase chain reaction (PCR) for six respiratory bacteria and 12 respiratory viruses performed on sputum obtained on admission showed Mycoplasma pneumoniae DNA, with no evidence of other pathogens. M. pneumoniae was confirmed to be the causative agent by serologic data. Variation of mycoplasma quantity in subsequent sputa was analyzed because of persistent sputum production despite treatment with minocycline. Mycoplasma DNA gradually decreased, becoming undetectable 1 week after the completion of 2 weeks of minocycline therapy. Two weeks after the completion of the minocycline therapy, mycoplasma DNA in sputum was strongly detectable again, and oral treatment with clarithromycin was initiated. No pathogen DNA was detected during 2 weeks of clarithromycin therapy or at 2 weeks after completion of this therapy. Although susceptibility tests on three isolates (on admission, 1 week after starting minocycline, and 2 weeks after minocycline cessation), showed no resistance to minocycline or clarithromycin, the infection was, nonetheless, prolonged. Some elderly subjects with mycoplasma pneumonia may show a longer course than that in young persons with pneumonia.

Killing kinetics of minocycline, doxycycline and tosufloxacin against macrolide-resistant Mycoplasma pneumoniae

Macrolide-resistant Mycoplasma pneumoniae (MRMP) has emerged and is increasing worldwide. In a 2011 outbreak of MRMP infections in Japan, symptoms failed to improve in many patients who initially received macrolides; the therapeutic agent was then changed to minocycline (MIN), doxycycline (DOX) or tosufloxacin (TFX). In this study, the bactericidal effects of these three agents against MRMP were evaluated. Time-kill kinetics against MRMP and macrolide-susceptible M. pneumoniae (MSMP) were determined for 5 days at concentrations corresponding to the respective minimum inhibitory concentration (MIC) and 2 × MIC, i.e. 1 µg/mL and 2 µg/mL for MIN, 0.5 µg/mL and 1 µg/mL for DOX, and 0.5 µg/mL and 1 µg/mL for TFX. The post-antibiotic effects (PAE) of these agents in culture against MRMP were also examined based on their pharmacokinetic parameters in children. Following exposure of MRMP and MSMP to up to twice the respective MICs of MIN, DOX and TFX, viable cells initially numbering 106 CFU/mL had decreased similarly to 103 CFU/mL after 4 days. Clarithromycin and azithromycin showed good bactericidal action against MSMP but not against MRMP. PAEs against MRMP appeared superior with MIN and DOX compared with TFX. In infection with M. pneumoniae having a generation time exceeding 6 h, a therapeutic agent must be selected in consideration of pharmacokinetic parameters, not MICs alone.

Nationwide survey of Streptococcus pneumoniae drug resistance in the pediatric field in Japan

Streptococcus pneumoniae is a major causative pathogen of pneumonia in children. The Drug‐Resistant Pathogen Surveillance Group in Pediatric Infectious Disease conducted a nationwide surveillance of S. pneumoniae in 2000–2001, 2004, 2007, 2010 and 2012, and investigated changes in drug resistance of S. pneumoniae.

Nationwide survey of drug resistance of S. pneumoniae in the pediatric field in Japan

Streptococcus pneumoniae is a major causative pathogen of pneumonia in children. The Drug‐Resistant Pathogen Surveillance Group in Pediatric Infectious Disease conducted a nationwide surveillance of S. pneumoniae in 2000–2001, 2004, 2007, 2010 and 2012, and investigated changes in drug resistance of S. pneumoniae.

Immunochromatography test for rapid diagnosis of Mycoplasma pneumoniae infection

The sensitivity and specificity of a new rapid Mycoplasma pneumoniae antigen immunochromatography (IC) test, DK‐MP‐001, were determined using particle agglutination (PA) antibody response and loop‐mediated isothermal amplification (LAMP) gene detection as the gold standard. Of 165 patients, 59 were diagnosed with M. pneumoniae infection based on a ≥fourfold rise of serum PA antibody during the course of the illness. Of the first visit swabs, 60 were positive for M. pneumoniae on LAMP, and 49 were positive for M. pneumoniae antigen on IC test. Compared with PA antibody and LAMP, the sensitivity/specificity of the IC test were 81.4% (48/59) and 99.1% (105/106); and 81.7% (49/60) and 100% (105/105), respectively. IC test detected antigen in pharyngeal swabs more sensitively than in nasal swabs for the same subjects (P < 0.05). The IC test performs well enough to be used with pharyngeal swabs at the first examination.