Variations in the pathophysiology of respiratory syncytial virus infection depend on the age at onset.

BACKGROUND: Lower respiratory tract infections due to respiratory syncytial virus are associated with morbidity and mortality in infants and children. Thus precise elucidation of respiratory syncytial virus lower respiratory tract infection pathophysiology is important. METHODS: Medical records of hospitalized patients were reviewed. Patients were divided into three groups. Group I: patients who improved without oxygen supply. Group II: patients who received oxygen supply, but not nasal high-flow cannula therapy. Group III: patients who received nasal high-flow cannula. Patients were also divided by age group into the <6 months and ≥6 months groups. Parameters for differentiating the severity among groups were then evaluated. Further, serum concentration of high-mobility group box-1 and several cytokines (Inerleukin-6, soluble tumor necrosis factor receptor-1/2, Interleukin-18, Interferon-gamma responsive protein-100) were evaluated. RESULTS: One hundred eighty-nine were enrolled. An analysis of variance for those <6 months showed overall differences including younger age, lower pH, and increased partial pressure of carbon dioxide (pCO2), bicarbonate (HCO3-), and base excess at the time of admission. On the other hand, analysis of variance for ≥6 months revealed that, in addition to a lower pH and increased pCO2, patients showed differences including decreased serum total protein and albumin, and increased aspartate aminotransferase (AST), alanin aminotransferase (ALT), lactate dehydrogenase (LDH), Ferritin and C-reactive protein (CRP) levels. Further, evaluation of serum cytokines showed that IL-6, s tumor necrotizing factor receptor-1/2, and high-mobility group box-1 were higher in Group II/III among the ≥6 months age group, but not for those in the <6 months group. CONCLUSIONS: The pathophysiology of severe respiratory syncytial virus lower respiratory tract infection varies according to the age at onset. In late infancy and childhood, a certain proportion of patients show a hyperinflammatory status.

Surveillance on susceptibility of strains isolated from pediatric infections.

During the period from January to December 2015, 104 Streptococcus pneumoniae strains, 129 Haemophilus influenzae strains and 54 Moraxella catarrhalis strains isolated from clinical specimens of pediatric infections in the national 16 institutions, studied susceptibilities of total 28 antibiotics, the capsular serotype for S. pneumoniae, the capsular b type and ß-lactamase production capability for H. influenzae, and the ß-lactamase production capability for M. catarrhalis were measured. In S. pneumoniae, the results showed that 68 strains (65.4%) were PSSP, 32 (30.8%) were PISP, and 4 (3.8%) were PRSP. The susceptibilities of TBPM and GRNX among oral antibiotics, and PAPM among injectable antibiotics demonstrated the lowest value with MIC90 ≤ 0.06 µg/mL. The most frequent distribution of S. pneumoniae serotypes was seen in 15B, followed by 19A, and 35B. Serotype strains contained in 13-valent pneumococcal conjugate vaccine (PCV13) were 19 strains (18.3%). In H. influenzae, the results showed that BLNAS accounted for 40 strains (31.0%), BLNAI for 28 strains (21.7%), BLNAR for 47 strains (36.4%), ß-lactamase producing for 14 strains (10.8%). The susceptibilities of quinolones demonstrated the lowest outcome among oral antibiotics with MIC90 ≤ 0.06 µg/mL, and CTRX and TAZ/PIPC (TAZ4 fixed) among injectable antibiotics with MIC of 0.25 µg/mL. There was no detection of capsular type b strains. In M. catarrhalis, all the isolates were ß-lactamase producing strains. The susceptibilities of TBPM, CPFX, TFLX and GRNX among oral antibiotics, and TAZ/PIPC (TAZ4 fixed), PAPM, MEPM and DRPM among injectable antibiotics demonstrated the lowest outcome with MIC of ≤0.06 µg/mL.

Non-invasive discrimination of acute focal bacterial nephritis with pyelonephritis.

BACKGROUND: The appropriate antimicrobial treatment period for febrile urinary tract infection (UTI) can be changed, depending on whether the patient has acute focal bacterial nephritis (AFBN). The aim of this study was to clarify the characteristics of AFBN compared with those of acute pyelonephritis (APN) and establish a strategy to detect AFBN. METHODS: A total of 77 patients diagnosed with febrile UTI were enrolled. They were divided into APN (n = 64) and AFBN groups (n = 13). The clinical data and other laboratory biomarkers were retrospectively analyzed. RESULTS: The time required for fever resolution after antimicrobial treatment was significantly longer in the AFBN group than in the APN group (2.77 days vs 1.11 days, respectively, P < 0.001). Also, the time to disappearance of pyuria after antimicrobial treatment was longer in the AFBN group than in the APN group (6.22 days vs 2.32 days, respectively, P = 0.001). Fever lasting >1.75 days after antimicrobial treatment had a sensitivity of 92% and specificity of 79% for the detection of AFBN, while pyuria disappearance after 4 days had a sensitivity of 88% and specificity of 85%. When patients fulfilled both cut-offs, the sensitivity and specificity were 89% and 97%. CONCLUSION: Acute focal bacterial nephritis was associated with fever of significantly longer duration after antimicrobial treatment, and it took a longer time for pyuria to disappear. Children with febrile UTI should be evaluated for AFBN if the fever persists ≥48 h after the initiation of antimicrobial treatment and if pyuria lasts for 4 days.

Serotype replacement of Streptococcus pneumoniae due to seven-valent pneumococcal conjugate vaccine in Japan.

BACKGROUND: This study examined the trends for the serotypes of S. pneumoniae that have caused infections before (2010) and after (2012) the introduction of PCV-7 in Japan. METHODS: We examined 458 strains of Streptococcus pneumoniae obtained from 22 pediatric institutions throughout Japan from January to June 2010 (immediately after the introduction of the seven-valent pneumococcal conjugate vaccine [PCV-7]), and 370 strains obtained from 19 institutions from January to June 2012 (after PCV-7 became widely used). The samples were collected from children aged 0-14 years with conditions such as respiratory tract infections (upper airway inflammation, bronchitis, and pneumonia), meningitis, and sepsis. RESULTS: The most frequent serotype in the 2010 strains was 19F (17.3%), followed by 6B (16.8%), and 23F (15.1%). The most frequent serotype in the 2012 strains was 6C (10.0%), followed by 19F (9.7%), 15A (8.9%) and 15B (8.9%), indicating a significant change in the distribution. The serotypes contained in PCV-7 were detected in 280 strains (61.1%) in 2010 and in 81 strains (21.9%) in 2012 (P < 0.01). The serotypes contained in PCV-13 were detected in 356 strains (77.7%) in 2010 and in 146 strains (39.5%) in 2012 (P < 0.01). A total of 129 subjects who had not been vaccinated with PCV-7 and 127 subjects who had been vaccinated with PCV-7 at least once, were compared with regard to the 2012 strains. The serotypes contained in PCV-7 were found in 21 strains (16.5%) in those who had been vaccinated and in 37 strains (28.7%) in those who had not been vaccinated (P < 0.05). CONCLUSIONS: The increased use of PCV-7 led to decreases in the serotypes contained in PCV-13 and increases in the serotypes not contained in PCV-13, suggesting serotype replacement.

Effects of Intrapartum Antibiotic Prophylaxis on Neonatal Acquisition of Group B Streptococci.

OBJECTIVES: To assess the incidence of colonization with group B streptococci (GBS) among neonates as influenced by maternal GBS carriage and intrapartum antibiotic prophylaxis (IAP). STUDY DESIGN: Between October 2014 and May 2015, nasopharyngeal and rectal swab samples were collected from 730 neonates at 1 week and 1 month after birth. GBS and capsular serotype were identified by real-time polymerase chain reaction and by culture. IAP at delivery was determined retrospectively from hospital records. RESULTS: Sixty-four neonates (8.8%) were GBS-positive by real-time polymerase chain reaction and culture. Among neonates born to mothers who were GBS carriers (n = 107), 94.4% (101/107) had maternal IAP; 19.6% nonetheless were GBS-positive, compared with 6.5% of neonates born to noncarrier mothers (P <.01). Among neonates born to mothers receiving IAP, more were positive only at 1 month of age than at both 1 week and 1 month. The frequency of GBS in neonates born to mothers receiving IAP was significantly lower than that in neonates born to mothers not receiving IAP (P <.05). Capsular serotypes V (25%) and III (23.4%) were common, followed by Ib (15.6%), Ia (14.1%), II (7.8%), IV (6.3%), nontypeable (4.7%), and VI and VIII (each 1.6%). CONCLUSIONS: Delayed colonization with GBS occurs in infants born to GBS carrier mothers receiving IAP. GBS should be considered in all infants at 1 month after birth with signs of infection.

Invasive Haemophilus influenzae infections in children in Kamikawa subprefecture, Hokkaido, Japan, 2006-2015: The effectiveness of H. influenzae type b vaccine.

We evaluated 24 children with invasive Haemophilus influenzae infections between 2006 and 2015 in Kamikawa subprefecture of Hokkaido, Japan. The most frequent disease was pneumonia in 12 cases (50.0%), followed by meningitis in 7 (29.2%) and bacteremia in 5 (20.8%). Patients ranged in age from 3 months to 12 years of age. Seventeen (70.8%) of the total were less than 2 years old. The incidence rate of H. influenzae infection varied from 15.1 to 36.3 per 100,000 population in the Kamikawa area during the period from 2006 through 2011. The corresponding rate decreased to 10.4 per 100,000 population in 2012, and there were no cases after 2013. Meningitis occurred in 1-2 patients annually from 2006 to 2011, showing an incidence rate of 4-10 per 100,000 population per year, while no cases were reported during or after 2012. No patients with invasive H. influenzae infection died, but sequelae were seen at discharge in 1 patient with meningitis, that had hydrocephalus and developmental delay. In Japan, introduction of the H. influenzae type b (Hib) vaccine was in November 2008. Initially, this vaccination was voluntary, resulting in a low vaccination rate. According to the national policy, and the self-pay burden for vaccination was decreased in December 2010, and the vaccination rate increased markedly to over 90%. This report provides a meaningful demonstration that introduction of the Hib vaccine markedly reduced invasive H. influenzae infections, exerting a beneficial effect in Japan, as it has in the world.

Pediatric community-acquired pneumonia treated with a three-day course of tebipenem pivoxil.

We evaluated the efficacy and safety of a 3-day treatment regimen of tebipenem pivoxil for pediatric community-acquired pneumonia. Tebipenem pivoxil was administered to 49 patients, and its effectiveness was evaluated in 36 patients 2-4 days after initiation of treatment. Thirty-two patients were cured 7-15 days after initiation of treatment. Body temperature was significantly lower on the day following initial administration (median 38.8 to 37.0 °C, n = 33). Leukocyte counts and C-reactive protein levels were significantly reduced by Day 2-4 of treatment (median 16,100 to 7800 white blood cells/µL, and 5.6 to 1.5 mg/dL, respectively; n = 28). Six of the 49 patients had mild diarrhea. Thus, we concluded that 3-day treatment with tebipenem pivoxil was safe and efficacious for treating pediatric community-acquired pneumonia.

Invasive pneumococcal diseases in children in Hokkaido, Japan from April 2000, to March 2015.

In Japan, the 7-valent pneumococcal conjugate vaccine (PCV-7) became commercially available as a voluntary vaccine in March 2010. It was included in the routine immunization schedule in April 2013 and was replaced by PCV-13 in November 2013. We evaluated 146 cases of invasive pneumococcal disease (IPD) in 142 children (2 developed the disease twice, and 1 developed it three times) treated in the northern district of Hokkaido, Japan from April 2000 to March 2015, before and after the introduction of PCV-7. The incidence rate per 100,000 people aged <5 years showed an increasing trend between April 2000 and March 2010, and reached 87.5 per 100,000 people per year between April 2009 and March 2010, which was immediately before the introduction of PCV-7. Subsequently, the incidence rate started to show a decreasing trend and reached as low as 9.5 per 100,000 people per year between April 2013 and March 2014. However, the incidence rate showed an increasing trend again between April 2014 and March 2015, reaching 33.4 per 100,000 people per year. Serotyping was performed for the 77 strains collected between April 2000 and March 2010. The most frequently isolated serotype was 6B (31.2%), followed by 23F (14.3%) and 19F (13.0%). Among them, 55 strains were covered by PCV-7 (71.4%), and 64 strains were covered by PCV-13 (83.1%). Of the 33 strains collected between April 2010 and March 2015, 14 were covered by PCV-7 (42.4%) and 16 were covered by PCV-13 (48.4%), showing a significant decrease (p < 0.01).

The change of susceptibility of Streptococcus pneumoniae strains isolated from pediatric patients at Asahikawa Kosei Hospital between 2011 and 2015.

The susceptibility of 1578 Streptococcus pneumoniae strains isolated from pediatric patients at Asahikawa Kosei Hospital between 2011 and 2015 was tested to penicillin G (PCG), cefotaxime (CTX), ceftriaxone (CTRX), cefditoren (CDTR), meropenem (MEPM), erythromycin (EM) and levofloxacin (LVFX). Although no significant differences were observed, the percentage of strains with a minimal inhibitory concentration (MIC) of PCG of <0.1pg/mL increased from 55.5% (2011) to 64.0% (2015), whereas that of strains with MIC of ≥2µg/mL decreased from 14.8% to 9.5%. From 2011 to 2015, the percentage of strains with MIC ≤0.12ug/mL increased from 18.9% to 28.9% for CTX, from 20.5% to 30.2% for CTRX, from 29.2% to 40.9% for CDTR, and from 69.6% to 80.6% for MEPM. EM-resistant strains with MIC ≥22µg/mL accounted for as much as approximately 90% each year. One LVFX-resistant strain with MIC 8pg/mL has been detected each year since 2013.

Clinical evaluation of 3-day tebipenem pivoxil therapy in children with community-acquired pneumonia.

A 4mg/kg dose of tebipenem pivoxil (TBPM-PI) was administered twice daily for 3 days to 34 pediatric patients with pneumonia who had chest X-ray findings indicative of pneumonia and CRP values of at least 3.0 mg/dL. The clinical effects of this regimen were evaluated by retrospectively examining medical charts for the period from April 2012 to March 2015. The patients were 6 months to 8 years old, with serum CRP values ranging from 3.06 to 14.25 mg/dL. Fever resolved within 24 hours and respiratory symptoms improved within 3 to 5 days after the start of treatment in all 34 patients. Although CRP was positive in 28 of 30 patients at the end of the treatment period, none of these children showed worsening of pneumonia. Eight patients (23.5%) experienced adverse drug reactions including diarrhea. These results indicate that a 3-day course of TBPM-PI is useful for treating pediatric pneumonia.

The change of macrolide resistance rates in group A Streptococcus isolates from children between 2002 and 2013 in Asahikawa city.

This study targeted patients in the Department of Pediatrics, Asahikawa Kosei Hospital, between January 2002 and December 2013. In patients suspected of having hemolytic streptococcal infection, Group A Streptococcus (GAS) strains isolated from a throat swab were examined for antimicrobial susceptibility testing. The MICs were measured by the broth microdilution method. The annual number of GAS strains examined for antimicrobial susceptibility testing ranged from 28 to 65 strains, for a total of 574 strains. Some of the isolates obtained from 2006 to 2009 and from 2011 to 2013 were analyzed to determine their emm types. An erythromycin (EM) resistant strain was not detected until 2004, but one EM-resistant strain appeared in 2005. Subsequently, EM-resistant strains rapidly increased, and 48 of 65 strains (73.8%) examined in 2009 were resistant. In 2010, the number of EM-resistant strains decreased to 12 of 36 strains (33.3%). However, it gradually increased afterwards, and 37 of 60 strains (61.7%) were resistant in 2013. Out of 574 strains examined, 184 exhibited EM-resistance, and the overall resistance rate was 31.9%. Partitioning the 124 strains examined between 2006 and 2008 according to emm types, only emm28 strains, which exhibited a high resistance rate, and emm12 strains demonstrated resistance. For the 142 strains examined between 2011 and 2013, the resistance rate of emm28 strains was similarly high; the resistance of emm12 strains significantly increased, and emm1 strains exhibited a high resistance rate. The number of emm types associated with the resistant strains increased.

Pediatric invasive streptococcal infection in northern and eastern regions of Hokkaido, Japan from 2010 to 2012.

BACKGROUND: The frequency of occurrence of pediatric invasive streptococcal infection in Japan has not been studied, therefore the aim of this study was to survey the northern and eastern regions of Hokkaido from 2010 to 2012. METHOD: Survey sheets were sent to the pediatric departments at 17 facilities where children in the subject region can be hospitalized. Responses were obtained from all of the 17 facilities. RESULTS: Seven patients developed group A streptococcal infection over the 3 years, and their ages ranged from 1 day after the birth to 15 years old. Sepsis was diagnosed in five children, and empyema and arthritis in the knee were found in one child each, respectively. The number of cases in children under 15 years old was six excluding the child who was 15 years old, and the incidence rate per 100,000 population was 1.00. Eight children developed group B streptococcal infection, and their ages ranged from 0 days to 2 months after birth. Two cases were the early onset type (age within 7 days) and six cases were the late onset type. Five children developed sepsis and three children developed meningitis. The frequency of occurrence was 0.24 per 1000 births; which was 0.06 per 1000 births for the early onset type and was 0.18 per 1000 births for the late onset type. No reports for group C or group G hemolytic streptococcal infection were obtained. CONCLUSIONS: The incidence rates identified in the present survey are similar to those in other advanced countries, and appear to be valid.

Susceptibility and emm type of Streptococcus pyogenes isolated from children with severe infection.

Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of various antimicrobial agents were measured against 12 strains of Streptococcus pyogenes isolated from children with invasive infections between 2003 and 2012. The patients ranged in age from 1 day to 15 years, with patients younger than 5 years, including three neonates, accounting for a half of the patients. The disease was sepsis in four patients, skin and soft tissue infection in three patients, retropharyngeal abscess in two patients, pneumonia plus sepsis in one patient, empyema in one patient, and pyogenic arthritis in one patient. One patient with sepsis died, while cure without sequelae was achieved in all the remaining patients. When classified by type, emm1 (six strains) was the most prevalent type, followed by emm12 (two strains). The MIC90/MBC90 values were 0.015/0.015 µg/mL for penicillin G, 0.03/0.03 µg/mL for ampicillin, 0.015/0.03 µg/mL for cefotaxime, 0.03/0.03 µg/mL for ceftriaxone, 0.008/0.008 µg/mL for panipenem, 0.008/0.008 µg/mL for meropenem, and ≤0.004/≤0.004 µg/mL for doripenem, indicating the superior antimicrobial activities of carbapenem.

Antibiotic susceptibility in relation to genotype of Streptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae responsible for community-acquired pneumonia in children.

Streptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae are the main pathogens causing community-acquired pneumonia (CAP). We identified S. pneumoniae (n = 241), H. influenzae (n = 123), and M. pneumoniae (n = 54) as causative pathogens from clinical findings and blood tests from pediatric CAP patients (n = 903) between April 2008 and April 2009. Identification of genes mediating antimicrobial resistance by real-time PCR was performed for all isolates of these three pathogens, as was antibiotic susceptibility testing using an agar dilution method or broth microdilution method. The genotypic (g) resistance rate was 47.7 % for penicillin-resistant S. pneumoniae (gPRSP) possessing abnormal pbp1a, pbp2x, and pbp2b genes, 62.6 % for ß-lactamase-nonproducing, ampicillin-resistant (gBLNAR) H. influenzae possessing the amino acid substitutions Ser385Thr and Asn526Lys, and 44.4 % for macrolide-resistant M. pneumoniae (gMRMP) possessing a mutation of A2063G, A2064G, or C2617A. Serotype 6B (20.3 %) predominated in S. pneumoniae, followed by 19F (15.4 %), 14 (14.5 %), 23F (12.0 %), 19A (6.2 %), and 6C (5.4 %). Coverage for the isolates by heptavalent pneumococcal conjugate vaccine (PCV7) and PCV13, respectively, was calculated as 68.5 and 80.9 %. A small number of H. influenzae were identified as type b (6.5 %), type e (0.8 %), or type f (0.8 %); all others were nontypeable. Proper use of antibiotics based on information about resistance in CAP pathogens is required to control rapid increases in resistance. Epidemiological surveillance of pediatric patients also is needed to assess the effectiveness of PCV7 and Hib vaccines after their introduction in Japan.

Neonatal pleural empyema caused by emm type 6 group A streptococcus.

Since the mid-1980s, there have been increasing reports of severe invasive group A streptococcal (GAS) disease in children and adults. There are few reports, however, of neonatal invasive disease, particularly neonatal pleural empyema caused by GAS. Although many mechanisms have been reported for the pathophysiology of invasive GAS infections, similar reports for neonates were unable to be located. Reported herein is the case of a 3-day-old girl with pleural empyema caused by GAS that demonstrated a high invasive capacity for human epithelial cells.

Risk factors for poor outcome in congenital cytomegalovirus infection and neonatal herpes on the basis of a nationwide survey in Japan.

BACKGROUND: Congenital cytomegalovirus (CMV) infection and neonatal herpes are major mother-to-child infections, and analyses of the important clinical issues, including risk factors for prognosis, are essential. METHODS: A secondary survey of congenital CMV infection and neonatal herpes was performed using questionnaires for cases reported in the primary survey between 2006 and 2008. RESULTS: Univariate analysis of 71 cases of congenital CMV infection showed that intrauterine growth restriction (IUGR) or other specific findings on fetal ultrasonography (US), microcephaly, intracranial calcification, disseminated intravascular coagulation, abnormal findings on computed tomography, and the use of i.v. gammaglobulin were all significantly correlated with poor outcome (death or severe sequelae). Multivariate analysis showed that only IUGR was significantly associated with poor outcome. Hearing impairment is one of the major abnormalities associated with congenital CMV infection. Automatic auditory brainstem response (automatic ABR) appeared to be useful for detection of hearing impairment in comparison with conventional ABR. Moreover, univariate analysis showed that specific fetal US or abnormal magnetic resonance imaging findings were correlated with sensorineural hearing loss. In 24 cases of neonatal herpes, fever and seizure were correlated with poor outcome on univariate analysis. All patients received acyclovir treatment, although substantial numbers of patients in severe clinical categories (disseminated or central nervous system diseases) received a low dose of acyclovir (<60 mg/kg per day). CONCLUSIONS: This secondary survey has identified the risk factors associated with outcome and important issues in diagnosis and treatment of two mother-to-child infections: congenital CMV and neonatal herpes, in Japan.

[Susceptibility in parenteral antibiotics in Streptococcus pneumoniae isolated from children with invasive pneumococcal disease].

Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of commonly used clinical antimicrobial drugs were examined for 76 strains of Streptococcus pneumoniae isolated between 2006 and 2011 from pediatric patients with invasive pneumococcal infection. Patients from whom bacterial strains were isolated ranged from 4 months to 6 years old and included 50 infants (65.8%) 1 year old and 10 (13.2%) less than 1 year old, i.e., 79.1% of all patients studied. In diagnosis, 38 (50.0%) had occult bacteremia, 34 (44.7%) pneumonia, 3 (3.9%) meningitis, and 1 (1.3%) sepsis. Infections in all but one case who died of sepsis were treated without sequelae. The most frequent capsular serotype among isolates was 6B (20 strains, 26.3%), followed by 19 F (13 strains, 17.1%) and 14 (9 strains, 11.8%). Serotypes for 55 strains (72.4%) corresponded to those contained in heptavalent pneumococcal conjugate vaccine. In classification by resistance based on mutations in penicillin-binding protein genes, 32 were penicillin-resistant S. pneumoniae (42.1%), 35 penicillin intermediate-resistant S. pneumoniae (46.1%), and 11 penicillin-susceptible S. pneumoniae (11.8%). MIC90/MBC90 of drugs were as follows: ampicillin 4/4 microg/mL, cefotaxime 0.5/0.5 microg/mL, ceftriaxone 1/2 microg/ mL, panipenem 0.125/0.125 microg/mL, meropenem 0.5/0.5 microg/mL, and doripenem 0.25/0.25 microg/mL.

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.