Cerebral Venous Sinus Thrombosis with Meningitis and Septicemia due to Haemophilus influenzae Type f in an Immunocompetent Child

Since the implementation of conjugate Haemophilus influenzae serotype b (Hib) vaccine, the rate of infections caused by Hib has dramatically decreased, and the proportion of infections caused by non-type b H. influenzae has increased. Cerebral venous sinus thrombosis (CVST) is rare; however, it should be considered as a potential complication of bacterial meningitis. Herein, we report about a child who developed CVST after being diagnosed with H. influenzae serotype f meningitis.

Asthma has an adverse effect on the production of antibody to vaccines

Asthma is considered a chronic inflammatory airway disease. Mounting evidence reports that patients with asthma are at significantly higher risk of developing communicable diseases such as invasive pneumococcal disease, Haemophilus influenza, varicella, measles, pertussis and tetanus. While impaired innate immunity may play a role in increased risk of developing these infections, suboptimal adaptive immune responses have also been reported to play a role in asthmatic subjects with regard to increased risk of infections. This review discusses the currently underrecognized immunological effect of asthma on antibody to vaccines and recommends that clinicians be aware of less optimal antibody production in response to vaccines in subjects with asthma.

A Case of Delayed Infective Endophthalmitis Associated with Exposure of Scleral Fixation Knot

PURPOSE: To report a case of delayed infective endophthalmitis associated with exposure of scleral fixation knot. CASE SUMMARY: A 35-year-old female was transferred from a local clinic with sudden onset right eye pain under suspicion of uveitis. The patient received vitrectomy, scleral encircling and lensectomy for rhegmatogenous retinal detachment before 16 years. In addition, she underwent secondary scleral fixation of intraocular lens (IOL) 1 year previously. Best-corrected visual acuity was hand motion and intraocular pressure was 28 mmHg. Slit lamp examination revealed diffuse keratic precipitates and anterior chamber reaction was 4 positive. Exposed scleral fixation knot outside conjunctiva at 2 o' clock combined with suppurative discharge was observed. On fundus examination, red reflex was decreased due to vitreous haze. She was diagnosed as infective endophthalmitis associated with exposure of scleral fixation knot. The patient received vitrectomy and intravitreal injection of antibiotics and vitreous culture. After 2 days, IOL removal, silicone oil tamponade and intravitreal injection of antibiotics were performed due to uncontrolled inflammation with accompanying hypopyon. Hemophilus influenza was isolated in the vitreous sample. Removal of silicone oil was performed at 1 month. There was no recurrent inflammation at 1 year and she received scleral fixation of IOL for the second time. At 1 year and 3 months, corrected visual acuity was 0.4 without signs of inflammation. CONCLUSIONS: In cases of exposed scleral fixation knot after IOL insertion, a risk of endophthalmitis exists. Meticulous care is required when fixation knot is exposed due to thinning of overlying conjunctiva.

Evaluation of Antibodies Against Haemophilus influenzae Type b in Korean Adults

PURPOSE: After the introduction of Haemophilus influenzae type b (Hib) vaccine in 1995 in Korea, it was included in the national immunization program in 2013. In the post-Hib vaccine era, some studies in other countries reported that invasive Hib disease affects adults, especially the elderly and immunocompromised persons, more often than it affects children. To evaluate disease susceptibility, quantitative and qualitative analysis of anti-polyribosylribitol phosphate (PRP) antibodies were carried out in Korean adults aged 20 to 85 years. METHODS: Sera were collected from 39 healthy adults (20 to 50 years of age) and from 30 elderly adults (75 to 85 years of age) who did not have immune-compromising conditions. The concentration of anti-PRP immunoglobulin G (IgG) and serum bactericidal indices (SBIs) were measured by enzyme-linked immunosorbent assay and serum bactericidal assay. RESULTS: Geometric mean concentrations of anti-PRP IgG and geometric mean SBIs were 0.88 µg/mL (95% confidence interval [CI], 0.17 to 3.85) and 354 (95% CI, 50 to 2,499) in young adults and 1.67 µg/mL (95% CI, 0.53 to 5.24) and 449 (95% CI, 146 to 1,376) in elderly adults, respectively. When the threshold of seropositivity for anti-PRP IgG was applied as 0.15 or 1.0 µg/mL, which is the protective antibody level in children, seropositive rates were 87.2% or 53.8% in young adults and 100% or 60% in elderly adults. The seropositivity rates of the SBI (SBI ≥4) were 82.1% and 100% in the groups, respectively. CONCLUSIONS: Most subjects in the adult and elderly adult groups display immunity to Hib based on quantitative and qualitative antibody levels, but not all. Because high immunization and low Hib circulation rates may reduce the natural Hib immunity in the population, monitoring Hib immunity as well as disease are needed continuously.

Pharmacokinetics of tilmicosin in healthy pigs and in pigs experimentally infected with Haemophilus parasuis

A comparative in vivo pharmacokinetic (PK) study of tilmicosin (TIL) was conducted in 6 crossbred healthy pigs and 6 crossbred pigs infected with Haemophilus (H.) parasuis following oral administration of a single 40 mg/kg dose. The infected model was established by intranasal inoculation and confirmed by clinical signs, blood biochemistry, and microscopic examinations. Plasma TIL concentrations were determined by a validated high-performance liquid chromatography method with ultraviolet detection at 285 nm. PK parameters were calculated by using WinNonlin software. After TIL administration, the main PK parameters of TIL in healthy and H. parasuis-infected pigs were as follows: Area under the concentration-time curve, maximal drug concentration, half-life of the absorption phase, half-life of the distribution phase, and half-life of the elimination phase were 34.86 ± 9.69 vs. 28.73 ± 6.18 µg · h/mL, 1.77 ± 0.33 vs. 1.67 ± 0.28 µg/mL, 2.27 ± 0.45 vs. 2.24 ± 0.44 h, 5.35 ± 1.40 vs. 4.61 ± 0.35 h, and 43.53 ± 8.17 vs. 42.05 ± 9.36 h, respectively. These results of this exploratory study suggest that there were no significant differences between the PK profiles of TIL in the healthy and H. parasuis-infected pigs.

Sphenoid Sinusitis with Haemophilus influenzae Septicemia / 대한내과학회지

Haemophilus influenzae grows both aerobically and anaerobically and is an exclusively human pathogen. We present a case of septicemia originating from unilateral sphenoid sinusitis caused by non-typeable H. influenzae. No reports of sinusitis presenting as septicemia in a healthy young immunocompetent adult in South Korea have previously been published.

Imbalance of Fecal Microbiota at Newly Diagnosed Type 1 Diabetes in Chinese Children / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recent studies have indicated that an imbalance of gut microbiota is associated with the development of type 1 diabetes mellitus (T1DM) and there is no literature regarding it in Chinese children yet. The aim of this study was to evaluate the alteration of gut microbiota between children with newly diagnosed T1DM and healthy controls and to determine if gut microbiota could partly explain the etiology of this disease.</p><p><b>METHODS</b>A case-control study was carried out with 15 children with T1DM and 15 healthy children. The fecal bacteria composition was investigated by high-throughput sequencing of the V3-V4 region of the 16S rDNA gene and analyzed by the estimators of community richness (Chao) indexes.</p><p><b>RESULTS</b>There was a notable lower richness of fecal bacteria in T1DM group than controls (156.53 ± 36.96 vs. 130.0 ± 32.85, P = 0.047). At the genus level, the composition of Blautia was increased in T1DM group than control group whereas the composition of Haemophilus, Lachnospira, Dialister, and Acidaminococcus was decreased. In addition, we found that the percentage of Blautia was correlated positively with HbA1c (ρ = 0.40, P = 0.031), the numbers of T1DM autoantibodies (ρ = 0.42, P = 0.023), and the titers of tyrosine phosphatase autoantibodies (IA-2) (ρ = 0.82, P = 0.000) in the study.</p><p><b>CONCLUSIONS</b>This study showed that gut microbiota was associated with the development of T1DM by affecting the autoimmunity, and the results suggested a potential therapy for T1DM via modulating the gut microbiota.</p>

A Case of Vertebral Osteomyelitis and Spinal Epidural Abscess Caused by Haemophilus aphrophilus / 대한내과학회지

Haemophilus aphrophilus is an aerobic, gram-negative oropharyngeal bacterium, commonly isolated from cases of HACEK endocarditis. In addition, H. aphrophilus has also been shown to cause invasive bone and joint infections. Although multiple cases of H. aphrophilus endocarditis have been described, no cases of invasive bone and joint infections caused by H. aphrophilus have been reported in Korea. Here we report the case of a 69-year old woman with a diagnosis of vertebral osteomyelitis and spinal epidural abscess with compressive myelopathy caused by H. aphrophilus, in which there was no objective evidence of infective endocarditis. She was successfully treated with intravenous administration of cefotaxime and drainage of the epidural abscess by laminectomy of the T3-7 vertebrae.

A Case of Vertebral Osteomyelitis with Bacteremia and Psoas Abscess Caused by Non-typeable Haemophilus influenzae / 대한내과학회지

Vertebral osteomyelitis is primarily seen in middle-aged individuals, with a mean age of presentation of ~60 years. Recent trends suggest an increase in the incidence of vertebral osteomyelitis due to longer life expectancy of patients with chronic debilitating diseases. Haemophilus influenzae is a small, fastidious, gram-negative bacillus, which is known to cause infections in young children. While invasive H. influenzae infections have become increasingly common in adult populations, bone infections caused by this organism remain extremely rare. The existing medical literature includes only 11 reports of vertebral osteomyelitis caused by H. influenzae since 1978, with no reports of H. influenzae-associated vertebral osteomyelitis observed in Korea. Here, we present the case of a 72-year old patient with hematogenous vertebral osteomyelitis and psoas abscess caused by non-typeable H. influenzae.

A Case of Vertebral Osteomyelitis with Bacteremia and Psoas Abscess Caused by Non-typeable Haemophilus influenzae / 대한내과학회지

Vertebral osteomyelitis is primarily seen in middle-aged individuals, with a mean age of presentation of ~60 years. Recent trends suggest an increase in the incidence of vertebral osteomyelitis due to longer life expectancy of patients with chronic debilitating diseases. Haemophilus influenzae is a small, fastidious, gram-negative bacillus, which is known to cause infections in young children. While invasive H. influenzae infections have become increasingly common in adult populations, bone infections caused by this organism remain extremely rare. The existing medical literature includes only 11 reports of vertebral osteomyelitis caused by H. influenzae since 1978, with no reports of H. influenzae-associated vertebral osteomyelitis observed in Korea. Here, we present the case of a 72-year old patient with hematogenous vertebral osteomyelitis and psoas abscess caused by non-typeable H. influenzae.

Decreased Expression of TLR-9 and Cytokines in the Presence of Bacteria in Patients with Otitis Media with Effusion

OBJECTIVES: Toll-like receptor (TLR)-9 recognizes unmethylated cytidine-phosphate-guanosine (CpG) motifs in bacteria. Therefore, the expression of TLR-9 may differ according to the results of bacterial culture, and thus a change in proinflammatory cytokine induction can also be expected. The authors aimed to assess the differences and relationships between the expression of TLR-9, cytokines, and nitric oxide synthase (NOS) in otitis media with effusion (OME) based on bacterial culture results. METHODS: Sixty-eight patients with OME were divided into culture-positive and culture-negative groups based on middle ear culture results. mRNA expression of TLR-9, NOS, and cytokines was measured and analyzed. RESULTS: Bacteria were detected in 38.2% of patients, and the distribution was as follows: coagulase negative Staphylococcus (10.3%), Staphylococcus aureus (8.8%), Streptococcus pneumonia (5.9%), and Bacillus spp. and Haemophilus influenza combined (2.9%). There were no significant differences in epidemiologic characteristics according to the culture results. Down-regulation of TLR-9 was observed in the culture-positive group (P=0.019). Cytokines including interleukin (IL)-12 (r=-0.582), tumor necrosis factor (TNF)-alpha (r=-0.569), interferon (IFN)-gamma (r=-0.442), IL-6 (r=-0.395) and inducible NOS (r=-0.256) tended to decrease with the detection of bacteria. CONCLUSION: The expression of TLR-9 significantly decreased in OME with confirmed bacterial pathogens. IL-12, TNF-alpha, IFN-beta, IL-6 expression tended to decrease with the detection of bacteria. The presence of bacterial pathogens in OME may be related to abnormalities in the innate immune system.

Isolation and Cloning of an ABC Transporter-Like Gene of Haemophilus parasuis and Its Use in a New Diagnostic PCR

The aim of this study was to identify a new gene of Haemophilus parasuis that could be used to develop a polymerase chain reaction (PCR) test for this porcine pathogen. H. parasuis genomic DNA was cloned into a set of expression vectors, and transformants expressing His-tagged polypeptides were identified by colony blotting. An ABC transporter-like gene was isolated. The cloned DNA fragment is 1,105 base pair and shows 78% similarity at the nucleotide level with an ABC transporter gene of H. ducreyi. Based on this sequence, two PCR primers were designed to amplify the entire 1,105-bp fragment in the proposed diagnostic PCR test. PCR amplification was able to detect a minimum of 1 x 10(4) CFU/ml of H. parasuis organisms. Fifteen different H. parasuis serovars were positive using the PCR test. No amplification was observed when the test was done using DNA from 16 other bacterial species commonly isolated from swine.

Haemophilus parainfluenzae Infective Endocarditis Confirmed by 16S rRNA Sequence Analysis from Culture Negative Tissue / 대한임상미생물학회지

Blood culture-negative infective endocarditis (CNE) can be a diagnostic dilemma. Herein, we report a case of CNE caused by Haemophilus parainfluenzae identified only via 16S rRNA sequence analysis directly from valve tissue. A 17-year-old boy presented with high spiking fever for one month. Pansystolic murmur (Grade III) and vegetation (0.65x0.26 cm and 0.62x0.55 cm) on the anterior mitral valve leaflet via transesophageal echocardiogram suggested the diagnosis of infective endocarditis (IE). However, blood culture performed on admission was negative even after 2 weeks of incubation. Gram stain and culture of a direct tissue specimen failed to identify causative microorganism, while 16S rRNA gene sequences (548 bp) showed 100% identity with those of Haemophilus parainfluenzae (GenBank: FJ939586.1). The 16S rRNA sequence analysis with a direct tissue specimen might be useful in cases of CNE.

Asymptomatic Bacteriuria Caused by Haemophilus influenzae in a Kidney Transplant Recipient

Haemophilus influenzae has rarely been implicated as the causative agent of urinary tract infections (UTIs). However, cases of UTIs caused by H. influenza in patients with anatomical or functional urinary tract abnormalities have been steadily reported. We report a case of asymptomatic bacteriuria caused by H. influenzae in a kidney transplant recipient. The patient was a 61-yr-old woman who visited the hospital for a routine follow-up after receiving a kidney transplant from a living-related donor; the patient showed no symptoms. Urine microscopy revealed white blood cell (WBC) count of >30/high power field (HPF). Urine culture on blood agar showed non-hemolytic, tiny, translucent, grayish colonies with satellitism around beta-hemolytic colonies of Staphylococcus epidermidis. The organism in the satellite colonies was identified as H. influenzae by using VITEK Neisseria/Haemophilus Identification Card (bioMerieux, Marcy L'Etoile, France) and found to require both X and V factors for growth. The organism did not produce beta-lactamase. Urine culture performed 1 week later revealed H. influenza again. The patient was not treated with antimicrobials. Urine culture performed using chocolate agar 7 weeks later did not reveal H. influenzae. Since H. influenzae does not grow in the media commonly used for urine culture such as blood agar, the use of these media could lead to underestimation of the true frequency of H. influenzae. If UTI is suspected in a patient with anatomical or functional urinary tract abnormality, chocolate agar should be considered for urine culture.

Asymptomatic Bacteriuria Caused by Haemophilus influenzae in a Kidney Transplant Recipient

Haemophilus influenzae has rarely been implicated as the causative agent of urinary tract infections (UTIs). However, cases of UTIs caused by H. influenza in patients with anatomical or functional urinary tract abnormalities have been steadily reported. We report a case of asymptomatic bacteriuria caused by H. influenzae in a kidney transplant recipient. The patient was a 61-yr-old woman who visited the hospital for a routine follow-up after receiving a kidney transplant from a living-related donor; the patient showed no symptoms. Urine microscopy revealed white blood cell (WBC) count of >30/high power field (HPF). Urine culture on blood agar showed non-hemolytic, tiny, translucent, grayish colonies with satellitism around beta-hemolytic colonies of Staphylococcus epidermidis. The organism in the satellite colonies was identified as H. influenzae by using VITEK Neisseria/Haemophilus Identification Card (bioMerieux, Marcy L'Etoile, France) and found to require both X and V factors for growth. The organism did not produce beta-lactamase. Urine culture performed 1 week later revealed H. influenza again. The patient was not treated with antimicrobials. Urine culture performed using chocolate agar 7 weeks later did not reveal H. influenzae. Since H. influenzae does not grow in the media commonly used for urine culture such as blood agar, the use of these media could lead to underestimation of the true frequency of H. influenzae. If UTI is suspected in a patient with anatomical or functional urinary tract abnormality, chocolate agar should be considered for urine culture.

Haemophilus parainfluenzae Infective Endocarditis Diagnosed by Direct 16S rRNA Sequencing of Vegetation

The HACEK group of microorganisms is responsible for approximately 3-6% of endocarditis cases and is a major cause of culture-negative endocarditis. Here, we report a case of Haemophilus parainfluenzae infective endocarditis that was diagnosed by direct PCR sequencing of 16S rRNA from resected vegetation. A healthy 26-yr-old man was admitted to the emergency room (ER) on March 27, 2011 because of intermittent high fever. The patient was prescribed cefpodoxime for 5 days at the ER. Six and 11 sets of blood cultures were performed at the ER and in a general ward, respectively, using BACTEC Plus Aerobic/F (Becton-Dickinson, USA) and Lytic Anaerobic/F Plus (BD) together. Echocardiography revealed a large vegetation at the posterior mitral valve leaflet. After performing mitral valvoplasty on hospital day (HD) 11, the vegetation tissue was cultured in thioglycolate broth, blood agar, Brucella agar, and MacConkey agar for 7 days, but no organism was grown. Direct PCR sequencing of 16S rRNA of the tissue revealed the presence of H. parainfluenzae. In the 17 sets of blood cultures, bacterial growth was detected in only 2 aerobic bottles of 5 sets taken at HD 9 after 10-day and 14-day incubation. The organism was identified as H. parainfluenzae by using the VITEK NHI card (bioMerieux, France). Direct PCR sequencing of vegetation could be useful in diagnosing bacterial pathogens in infective endocarditis patients, especially in culture-negative cases.

Bacterial diversity in the saliva of patients with different oral hygiene indexes

The objective of the present study was to evaluate the bacterial diversity in the saliva of patients with different oral hygiene indexes using of two 16S rRNA gene libraries. Each library was composed of samples from patients with different averages of the differentiated Silness-Löe biofilm index: the first library (A) with an index between 1.0 and 3.0 (considered a high index) and the second library (B) between 0 and 0.5 (considered a low index). Saliva DNA was extracted and the 16S rRNA gene was amplified and cloned. The obtained sequences were compared with those stored at NCBI and RDP GenBank. The saliva of patients with high index presented five known genera - Streptococcus, Granulicatella, Gemella, Veillonella and Peptostreptococcus - and 33.3% of nonculturable bacteria grouped into 23 operational taxonomic units (OTUs). The saliva of patients with low index differed significantly from the first library (p=0.000) and was composed of 42 OTUs distributed into 11 known genera - Streptococcus, Granulicatella, Gemella, Veillonella, Oribacterium, Haemophilus, Escherichia, Neisseria, Prevotella, Capnocytophaga, Actinomyces - including 24.87% of nonculturable bacteria. It was possible to conclude that there is greater bacterial diversity in the saliva of patients with low dental plaque in relation to patients with high dental plaque.

O objetivo do presente estudo foi avaliar a diversidade bacteriana da saliva de pacientes com diferentes índices de higiene bucal através da construção de duas bibliotecas do gene 16S rRNA. Cada biblioteca foi composta por amostras de saliva de pacientes com índice de biofilme dental de Silness-Löe diferenciado, sendo a primeira (A) com índice de 1,0 a 3,0 (denominada de alto índice) e a segunda (B), entre 0 a 0,5 (denominada de baixo índice). O DNA da saliva foi extraído e o gene 16S rRNA foi amplificado, clonado e sequenciado. As sequências obtidas foram comparadas com aquelas armazenadas no GenBank do NCBI e RDP. A saliva de pacientes com alto índice de biofilme dental apresentou cinco gêneros conhecidos: Streptococcus, Granulicatella, Gemella, Veillonella e Peptostreptococcus e 33,3% de bactérias não-cultivadas, agrupados em 23 unidades taxonômicas operacionais (UTOs). A saliva de pacientes com baixo índice de biofilme dental, foi diferente significativamente da primeira (p=0,000) e foi composta de 42 UTOs, distribuídas em 11 gêneros conhecidos: Streptococcus, Granulicatella, Gemella, Veillonella, Oribacterium, Haemophilus, Escherichia, Neisseria, Prevotella, Capnocytophaga, Actinomyces, além de 24,87% de bactérias não-cultivadas. Pode-se concluir que existe maior diversidade bacteriana na saliva de pacientes com baixo índice de biofilme dental em relação a pacientes com alto índice de biofilme dental.

The Clinical Experience of Pediatric Flexible Bronchoscopy at a Single Institution / 소아알레르기및호흡기학회지

PURPOSE: This study was performed to investigate the indications, bronchoscopic findings, results of bronchoalveolar lavage, and complications and to report the clinical features of using flexible bronchoscopy for respiratory diseases in children. METHODS: We studied 105 patients who underwent flexible bronchoscopy at the Department of Pediatrics, Dong-A University Medical Center from June 2001 to June 2008. A bronchoalveolar lavage (BAL) was performed if need, and the BAL fluid was cultured for bacteria and fungi. We performed an acid-fast bacilli (AFB) smear and culture. RESULTS: The most common indication for flexible bronchoscopy was suspected pulmonary tuberculosis (37 cases, 35.2%). The most common abnormal finding was excessive secretion, which was found in 53 cases (50.4%). BAL bacterial cultures were performed in 10 of 38 cases, and Hemophilus influenza was the most common organism and was found in three cases (7.8%). There were 17 AFB culture-positive cases (49.3%) among the 37 suspected pulmonary tuberculosis cases. Among these 17, the Tb-polymerase chain reaction (Tb-PCR) was conducted for four cases (23.5%) but only two cases (50%) were positive. TB-specific antigen-induced interferon-gamma was performed in four cases (23.5%), and all four cases (100%) were positive. CONCLUSION: Pediatric flexible bronchoscopy has made it possible to vary the indication and subjects. It was also safe and effective if used carefully. Further study should be conducted to develop safe and useful technology to overcome the limitations.

Antibiotic Resistance and Treatment Update of Community-Acquired Pneumonia / 대한내과학회지

The emergence of penicillin-resistant S. pneumoniae has issued in the management of community-acquired pneumonia (CAP). However, the clinical outcome did not match with penicillin resistance. Thus, recent (Jan/2008) change of penicillin breakpoints for nonmeningeal strain was done and this made prevalence of penicillin resistance under 5% worldwide. Macrolide resistance of S. pneumoniae in Korea is prevalent (70-80%). Thus, the Korean CAP guideline did not include macrolide monotherapy as empiric therapy. Fluoroquinolone resistance of pneumococcus is very low, however, concerning of the increase of resistance is present.Some new antibiotics for the multidrug resistant S. pneumoniae should be reserved for the future. Macrolide resistance of Mycoplasma pneumoniae is reported in various regions in the world, however, data of the clinical significance is rare. Increased beta-lactamase production of Haemophilus influenzae urges us to use beta-lactam/beta-lactamase or 3rd generation cephalosporin if Haemophilus is pathogen. Pneumococcal vaccine usage is an effective way to prevent invasive diseases by S. pneumoniae (including resistant pathogen). The rate of pneumococcal vaccination in Korea is very low (0.8% in adult). Strategies to control resistance that include effective antimicrobial treatment, vaccination, infection control, appropriate policies and regulations, 'antibiotic stewardship' and education of appropriate antibiotic use, are greatly in need.

Antibiotic Resistance and Treatment Update of Community-Acquired Pneumonia / 대한내과학회지

The emergence of penicillin-resistant S. pneumoniae has issued in the management of community-acquired pneumonia (CAP). However, the clinical outcome did not match with penicillin resistance. Thus, recent (Jan/2008) change of penicillin breakpoints for nonmeningeal strain was done and this made prevalence of penicillin resistance under 5% worldwide. Macrolide resistance of S. pneumoniae in Korea is prevalent (70-80%). Thus, the Korean CAP guideline did not include macrolide monotherapy as empiric therapy. Fluoroquinolone resistance of pneumococcus is very low, however, concerning of the increase of resistance is present.Some new antibiotics for the multidrug resistant S. pneumoniae should be reserved for the future. Macrolide resistance of Mycoplasma pneumoniae is reported in various regions in the world, however, data of the clinical significance is rare. Increased beta-lactamase production of Haemophilus influenzae urges us to use beta-lactam/beta-lactamase or 3rd generation cephalosporin if Haemophilus is pathogen. Pneumococcal vaccine usage is an effective way to prevent invasive diseases by S. pneumoniae (including resistant pathogen). The rate of pneumococcal vaccination in Korea is very low (0.8% in adult). Strategies to control resistance that include effective antimicrobial treatment, vaccination, infection control, appropriate policies and regulations, 'antibiotic stewardship' and education of appropriate antibiotic use, are greatly in need.