The clinical and economic burden of community-onset complicated skin and skin structure infections in Korea

Background/Aims@#To investigate epidemiologic characteristics, clinical and economic burdens, and factors associated with mortality in complicated skin and skin structure infection (cSSSI) patients in Korea. @*Methods@#A retrospective, observational, nationwide study was conducted between April to July 2012 at 14 tertiary-hospitals in Korea. Eligible patients were hospitalized adults with community acquired cSSSI, who underwent surgical intervention and completed treatment between November 2009 and October 2011. Data on demography, clinical characteristics, outcomes and medical resource utilization were collected through medical record review. Direct medical costs were calculated by multiplying quantities of resources utilized by each unit price in Korea. @*Results@#Of 473 patients enrolled, 449 patients (except 24 patients with no record on surgical intervention) were eligible for analysis. Microbiological testing was performed on 66.1% of patients and 8.2% had multiple pathogens. Among culture confirmed pathogens (n = 297 patients, 340 episodes), 76.2% were gram-positive (Staphylococcus aureus; 41.2%) and 23.8% were gram-negative. The median duration of hospital stay was 16 days. Among treated patients, 3.3% experienced recurrence and 4.2% died in-hospital. The mean direct medical costs amounted to $4,195/ person, with the greatest expenses for hospitalization and antibiotics. The in-hospital mortality and total medical costs were higher in combined antibiotics therapy than monotherapy (p < 0.05). Charlson’s comorbidity index ≥ 3, standardized early warning scoring ≥ 4, sub-fascia infections and combined initial therapy, were all found to be associated with higher mortality. @*Conclusions@#Korean patients with community-onset cSSSI suffer from considerable clinical and economic burden. Efforts should be made to reduce this burden through appropriate initial treatment.

Cluster of Serogroup W-135 Meningococcal Disease in 3 Military Recruits

We describe a group of 3 cases of invasive meningococcal disease that occurred in a military training camp in April 2011. All three patients were hospitalized. Ultimately, two patients recovered and one died. One patient had meningitis, one patient had septicemia and meningitis, and the other had no definite septicemia or meningitis. Neisseria meningitidis serogroup W-135 was detected in the serum and cerebrospinal fluid (CSF) of all patients by real-time polymerase chain reaction. In the one case of mortality, two strains were isolated from the patient's blood and CSF. Using multilocus sequence typing analysis, these strains were identified as a novel sequence type, ST-8912. Special attention is required for the meningococcal disease in military camp because the military personnels are in high risk of contact transmission.

Liver Abscess and Empyema due to Lactococcus lactis cremoris

Lactococcus lactis cremoris infections are very rare in humans. We experienced liver abscess and empyema due to L. lactis cremoris in an immunocompetent adult. A 42-yr-old man was admitted with fever and abdominal pain. Abdominal computed tomography (CT) revealed a liver abscess and chest CT showed loculated pleural effusion consistent with empyema. L. lactis cremoris was isolated from culture of the abscess material and blood. The patient was treated with pus drainage from liver abscess, video-assisted thoracoscopic decortications for empyema, and antibiotics including cefotaxime and levofloxacin. The patient was completely recovered with the treatment. To our knowledge, this is the first report of a L. lactis cremoris infection in Korea.

Comparison of Clinical Characteristics of Pneumococcal and non-Pneumococcal Streptococcal Pneumonia

BACKGROUND: Although Pneumococcal (SPN) pneumonia is the most common cause of community-acquired pneumonia, non-pneumococcal streptococcal (NSPN) pneumonia is also frequently reported. However, there are insufficient data on characteristics of NSPN pneumonia which makes it difficult to decide treatment plans or to assess the prognosis. MATERIALS AND METHODS: Between March 2002 and February 2009, medical records including clinical and epidemiological data on patients aged > or =18 years with community-acquired streptococcal pneumonia were reviewed retrospectively. Clinical characteristics were compared between community-acquired NSPN pneumonia and SPN pneumonia. RESULTS: During the 7 year study periods, 248 patients were hospitalized with community-acquired streptococcal pneumonia and 30 of them had NSPN pneumonia. There were 12 cases of Streptococcus constellatus, 7 cases of S. anginosus, 4 cases of S. mitis, 3 cases of S. pyogenes, 2 cases of S. oralis, 1 case of S. alactolyticus and 1 case of S. agalactiae. There was no difference in percentage of patients with a chronic underlying disease between SPN and NSPN pneumonia groups. The most common was chronic obstructive pulmonary disease (SPN 29.8%, NSPN 16.7%) followed by diabetes mellitus (SPN 22.0%, NSPN 13.3%). Bacteremia (SPN 7.3%, NSPN 20.0%, P=0.04) and empyema (SPN 1.4%, NSPN 53.3%, P<0.001) were more common in NSPN pneumonia. However, there was no significant difference in the CURB-65 pneumonia severity score and 30-day mortality between the two groups. According to multivariate analysis results, the significant risk factor for NSPN pneumonia was the history of frequent alcohol drinking (Adjusted OR 3.81, 95% CI 1.36 to 10.67). CONCLUSION: Pneumonia caused by NPSN is more commonly accompanied by bacteremia and empyema compared to SPN pneumonia, but there was no difference in the 30-day mortality between the two groups. NSPN pneumonia should be considered if a patient with a history of chronic alcoholism presents with pneumonia and pleural effusion, especially when Gram positive diplococci is seen in the sputum Gram stain.

Clinical Features of Invasive Pneumococcal Disease in Korea

BACKGROUND: Streptococcus pneumoniae is one of the most important causes of pneumonia, meningitis, bacteremia, and other invasive diseases in children and adults. The 23-valent polysaccharide pneumococcal vaccine (PPV) has been recommended to adults with high risk conditions by the Korea Society of Infectious Diseases in 2007, but there is no data on the epidemiology of invasive pneumococcal disease in Korean adults to support this recommendation. Therefore, we performed a study to investigate the epidemiology of invasive pneumococcal disease in Korean population. MATERIALS AND METHODS: We collected clinical and microbiologic data of patients diagnosed with invasive pneumococcal disease (IPD) in 3 university-hospitals located in Seoul and Gyeonggi-do from January 2002 to December 2007. RESULTS: A total of 168 patients were diagnosed with IPD in the selected hospitals during the study period. Invasive pneumonia and meningitis were the most common forms of IPDs. The mean length of hospitalization of patients with IPD was 18.5+/-26.7 days and mortality rate of IPD was 18.6%. Among the isolates from patients with IPD, 59.7% was susceptible to penicillin and 38.3% was susceptible to erythromycin. Mortality rate of IPD increased with age and in patients with Eastern Cooperative Oncology Group performance status 4. CONCLUSIONS: Epidemiology of IPD in Korean population was described. Further studies should be performed to secure the risk factors of invasive pneumococcal diseases and to confirm the appropriateness of recommendation for vaccination with the 23-valent PPV.

A Case of Secondary Syphilis with Jarisch-Herxheimer Reaction Presenting as Hypersensitivity Pneumonit

Jarisch-Herxheimer reaction (JHR) is a self-limited, acute febrile hypersensitivity reaction that occurs after antibiotic therapy against spirochetes disease. When occurring in the text of syphilis therapy, the JHR begins typically 1-2 hour after the administration of penicillin and is characterized by fever, chills, myalgias, and exacerbation of skin lesions. Rarely, severe JHR can occur in the form of endocarditis, fulminant hepatitis, and hypersensitivity pneumonitis. Recently, we experienced an interesting case of JHR complicated by the hypersensitivity pneumonitis after treating secondary syphilis. Proper differential diagnosis is required to differentiate this reaction from drug-induced hypersensitivity reaction.

Mediastinal Tuberculous Lymphadenitis with Periodic Fever

A 60-year-old man undergoing maintenance hemodialysis presented with periodic fever, which resembled Pel-Ebstein fever of Hodgkin's lymphoma. Despite scores of diagnostic evaluations, origin of the fever remained obscure. On positron emission tomography/computed tomography scan, focal hot uptakes were seen in the mediastinum and mediastinoscopic biopsy showed many acid-fast bacilli with chronic granulomatous inflammation and necrosis. After a week of anti-tuberculosis medication, the patient remained afebrile without recourse to antipyretics.

A Case of Aortic Aneurysm Rupture Infected by Clostridium septicum in a Patient with Colon Cancer

Infected aortic aneurysm a life-threatening disease entity. Clostridium septicum is a very rare pathogen of infected aneurysms that carries a high mortality rate and demonstrates a strong association with an derlying colonic or hematologic neoplasm. Herein, we report a case of ruptured aortic aneurysm infected by C. septicum in a patient with colon cancer. This is the first reported case of infected aneurysm caused by C. septicum in Korea. Early diagnosis, appropriate antibiotic therapy, and prompt surgical interventions are required considering the rapid downhill progression of C. septicum-induced infected aneurysm.

A Case of Secondary Syphilis with Jarisch-Herxheimer Reaction Presenting as Hypersensitivity Pneumonit

Jarisch-Herxheimer reaction (JHR) is a self-limited, acute febrile hypersensitivity reaction that occurs after antibiotic therapy against spirochetes disease. When occurring in the text of syphilis therapy, the JHR begins typically 1-2 hour after the administration of penicillin and is characterized by fever, chills, myalgias, and exacerbation of skin lesions. Rarely, severe JHR can occur in the form of endocarditis, fulminant hepatitis, and hypersensitivity pneumonitis. Recently, we experienced an interesting case of JHR complicated by the hypersensitivity pneumonitis after treating secondary syphilis. Proper differential diagnosis is required to differentiate this reaction from drug-induced hypersensitivity reaction.

Mediastinal Tuberculous Lymphadenitis with Periodic Fever

A 60-year-old man undergoing maintenance hemodialysis presented with periodic fever, which resembled Pel-Ebstein fever of Hodgkin's lymphoma. Despite scores of diagnostic evaluations, origin of the fever remained obscure. On positron emission tomography/computed tomography scan, focal hot uptakes were seen in the mediastinum and mediastinoscopic biopsy showed many acid-fast bacilli with chronic granulomatous inflammation and necrosis. After a week of anti-tuberculosis medication, the patient remained afebrile without recourse to antipyretics.

A Case of Aortic Aneurysm Rupture Infected by Clostridium septicum in a Patient with Colon Cancer

Infected aortic aneurysm a life-threatening disease entity. Clostridium septicum is a very rare pathogen of infected aneurysms that carries a high mortality rate and demonstrates a strong association with an derlying colonic or hematologic neoplasm. Herein, we report a case of ruptured aortic aneurysm infected by C. septicum in a patient with colon cancer. This is the first reported case of infected aneurysm caused by C. septicum in Korea. Early diagnosis, appropriate antibiotic therapy, and prompt surgical interventions are required considering the rapid downhill progression of C. septicum-induced infected aneurysm.

Candida Spondylodiscitis with Epidural Abscess Treated with Voriconazole / 대한의진균학회지

Candida spondylodiscitis with epidural abscess is rarely reported and known to be the late complication of candidemia. A 48-years-old man presented with 4 weeks of progressively aggravating low back pain. He had a history of fungemia caused by Candida albicans 4 months earlier, for which he had been treated successfully with systemic fluconazole. The MRI of lumbar spine demonstrated the spondylodiscitis with multiple epidural abscesses at the L2/3 level. Along with the surgical interventions including abscess drainage, the intravenous amphotericin B administration was begun. Culture of drained pus yielded the growth of Candida albicans. After therapy with parenteral amphotericin B for 2 weeks followed by oral fluconazole for 8 weeks, the back pain resolved. However the low back pain and inflammation relapsed during oral fluconazole therapy. Thereafter oral voriconazole had been administered for 24 weeks and the patient showed complete recovery and no recurrence.

Candida Spondylodiscitis with Epidural Abscess Treated with Voriconazole / 대한의진균학회지

Candida spondylodiscitis with epidural abscess is rarely reported and known to be the late complication of candidemia. A 48-years-old man presented with 4 weeks of progressively aggravating low back pain. He had a history of fungemia caused by Candida albicans 4 months earlier, for which he had been treated successfully with systemic fluconazole. The MRI of lumbar spine demonstrated the spondylodiscitis with multiple epidural abscesses at the L2/3 level. Along with the surgical interventions including abscess drainage, the intravenous amphotericin B administration was begun. Culture of drained pus yielded the growth of Candida albicans. After therapy with parenteral amphotericin B for 2 weeks followed by oral fluconazole for 8 weeks, the back pain resolved. However the low back pain and inflammation relapsed during oral fluconazole therapy. Thereafter oral voriconazole had been administered for 24 weeks and the patient showed complete recovery and no recurrence.

Persistent bacteremia and fungemia-risk factors and clinical significance / 대한내과학회지

BACKGROUDN: Persistent bloodstream infection is known to cause high mortality and a prolonged hospital stay. We performed a study examining risk factors and the clinical significance of persistent bacteremia and fungemia. METHODS: This was a case-controlled study. Medical records of patients with bacteremia or fungemia in one university hospital in Korea from May 1999 to February 2005 were retrospectively reviewed. Patients with persistent positive blood cultures regardless of antibiotic treatment for more than three days were assigned to the persistent group. Patients with positive blood cultures only on the same calendar days with the persistent group but negative on follow-up were assigned to the short-term group. RESULTS: A total of 64 patients were enrolled in the persistent group, and 146 patients in the short-term group among 1,737 patients with positive blood cultures. The persistent group was associated with previous antibiotic usage within 1 month (p=0.033), nosocomial infection (p=0.026), having an abscess (p=0.008), and infection by mixed organisms (p=0.001), independently. Candida sp. as a causative organism, treatment with inappropriate empirical antibiotics, having a central venous catheter, or ICU care at the time of blood culture was higher in the persistent group as well. The persistent group had a prolonged number of hospital-days (p=0.010), but there was no difference in mortality between the two groups. CONCLUSIONS: Patients with a persistent bloodstream infection should be assessed about previous antibiotic usage within 1 month, nosocomial infection, having an abscess, infection by mixed organisms, Candida sp. as a causative organism, treatment with inappropriate empirical antibiotics, having central venous catheter, or ICU care at the time of blood culture.

Usefulness of Computerized Restricted Antibiotics Use and Control Program in a Tertiary Care Hospital

BACKGROUND: Excessive and inappropriate use of antimicrobial agents remains one of the most important factors affecting antibiotic resistance. We have developed the computerized control program for antibiotic use and evaluated utility of the program. MATERIALS AND METHODS: A computerized antibiotic control program was designed to restrict 15 antibiotics use, based on the mandatory approval by Infectious diseases specialists. The program was integrated into computerized order-entry system, and automatically stopped physician's antibiotics prescription in cases of no approval. We analyzed cases of disapproval on the restricted antibiotics use during the period from January to December, 2004 and evaluated the usefulness of the program. RESULTS: Total consumption of 15 restricted antibiotics out of whole antibiotics use was 14,457 (defined daily dose) DDD/144,692 DDD (9.99%). Total numbers of prescriptions for restricted antibiotics were 3,285:glycopeptides, 1,450 cases (44.1%); anti-pseudomonal cephalosporins, 699 cases (21.2%); carbapenem, 608 cases (18.5%). Three hundred eighty cases (11.65%) were not approved:'Inappropriate empirical use' was the most common with 34.5%. 'Unnecessary use' was 21.1% which included no evidence of infection, prophylactic use or long-term use. 'Incorrect regimen' as third reason (17.9%) means wrong choice of antibiotics due to misunderstanding of infection focus or organism. In addition, less expensive or more narrow-spectrum drugs were replaced in 17.6% of cases by infectious diseases specialists. CONCLUSIONS: A computerized antibiotic control program can improve inappropriate empirical antibiotic therapy and prevent unnecessary antibiotic use. It may contribute to make cost-effective mana gement and provide the better-quality of patient care.

Epidemiology and Clinical Significance of Bacteriuria Caused by Vancomycin-Resistant Enterococci

BACKGROUND: Vancomycin-resistant enterococci (VRE) have been important pathogen of nosocomial infections and isolated most commonly from urine specimens. However, the clinical significance of VRE bacteriuria remains unknown. The objectives of this study are to describe the frequency, related factors and outcomes of VRE bacteriuria, and to compare epidemiologic data and outcomes between the subgroups: symptomatic urinary tract infection (UTI), asymptomatic bacteriuria, and colonization. MATERIALS AND METHODS: For patients with urine culture positive for VRE between August 1, 2002 and June 30, 2005, we collected clinical data and performed a retrospective analysis. According to Centers for Disease Control and Prevention (CDC), patients were classified as symptomatic UTI, asymptomatic bacteriuria, colonization and undetermined. RESULTS: Total 144 episodes (2.88%), in 58 patients, of 5,008 urine specimens were positive for VRE during the study period. Frequency of antimicrobial exposure history, especially 3rd generation cephalosporin, indwelling urinary catheter, and ICU stay at the time of culture was high in patients with VRE bacteriuria. In VRE bacteriuria, symptomatic UTI was only 24.5%. Instead the majority of the patients (71.4%) was colonized in urine with VRE or had asymptomatic bacteriuria. In comparison between symptomatic UTI group and combined group of asymptomatic bacteriuria and colonization, most demographic data and clinical features including hospital day and mortality had no significant difference except one, male sex. CONCLUSION: Most patients with VRE bacteriuria were classified as asymptomatic bacteriuria and colonization and only one-fourth of patients with VRE bacteriuria require antibiotic therapy. Therefore, clinicians should decide to initiate antibiotic therapy after consideration of clinical significance of VRE bacteriuria.

Immunogenicity and Safety of Half Dose Intradermal Injection Compared to Full Dose Intramuscular Injection of Influenza Vaccine in Healthy Adults

BACKGROUND: Influenza is the representative respiratory infectious disease causing significant high morbidity. Vaccination is the most effective method to prevent influenza. To cope with both unstable supply and increasing demand of influenza vaccine with more flexibility, we studied the safety and immunogenicity of half dose intradermal injection of influenza vaccine in healthy adults compared with full dose intramuscular injection method. MATERIALS AND METHODS: We conducted a randomized, open-label trial in healthy adults of age 15 to 64 years. Subjects were randomly assigned to receive either a recommended dose of influenza vaccine (Fluarix(R), Injection Prefilled Syringe, GlaxoSmithKline, hemagglutinin antigen (HA) 15 microgram) via intramuscular route (designated as control group) or a half recommended dose (HA 7.5 microgram) via intradermal route (designated as experimental group). Blood samplings were done before and more than 28 days after vaccination. We measured the changes in hemagglutination-inhibition (HAI) antibody titers and compared geometric mean titers, seroconversion rates, seroconversion factors and seroprotection rates of each group. Local and systemic adverse events were assessed after vaccination. RESULTS: In antibody titer against all three antigens (A/H1N1, A/H3N2, B) was more evident in intramuscular injection group but intradermal group with half dose showed acceptable immunogenicity fulfilling criteria for Committee for Proprietary Medicinal Products (CPMP). Likewise, seroprotection rates for all three viral strains showed no significant difference between the two groups. Although local reactions were significantly more frequent and lengthy in intradermal group than in intramuscular group, the reactions were mild and transient. CONCLUSION: Compared with intramuscular injection of full dose influenza vaccine, intradermal injection of half dose resulted in comparable immunogenicity in healthy adults. Intradermal administration of half dose influenza vaccine could be a practical alternative plan to expand the supplies of influenza vaccine, but further studies will be needed in high risk groups.

Usefulness of Computerized Restricted Antibiotics Use and Control Program in a Tertiary Care Hospital

BACKGROUND: Excessive and inappropriate use of antimicrobial agents remains one of the most important factors affecting antibiotic resistance. We have developed the computerized control program for antibiotic use and evaluated utility of the program. MATERIALS AND METHODS: A computerized antibiotic control program was designed to restrict 15 antibiotics use, based on the mandatory approval by Infectious diseases specialists. The program was integrated into computerized order-entry system, and automatically stopped physician's antibiotics prescription in cases of no approval. We analyzed cases of disapproval on the restricted antibiotics use during the period from January to December, 2004 and evaluated the usefulness of the program. RESULTS: Total consumption of 15 restricted antibiotics out of whole antibiotics use was 14,457 (defined daily dose) DDD/144,692 DDD (9.99%). Total numbers of prescriptions for restricted antibiotics were 3,285:glycopeptides, 1,450 cases (44.1%); anti-pseudomonal cephalosporins, 699 cases (21.2%); carbapenem, 608 cases (18.5%). Three hundred eighty cases (11.65%) were not approved:'Inappropriate empirical use' was the most common with 34.5%. 'Unnecessary use' was 21.1% which included no evidence of infection, prophylactic use or long-term use. 'Incorrect regimen' as third reason (17.9%) means wrong choice of antibiotics due to misunderstanding of infection focus or organism. In addition, less expensive or more narrow-spectrum drugs were replaced in 17.6% of cases by infectious diseases specialists. CONCLUSIONS: A computerized antibiotic control program can improve inappropriate empirical antibiotic therapy and prevent unnecessary antibiotic use. It may contribute to make cost-effective mana gement and provide the better-quality of patient care.

Epidemiology and Clinical Significance of Bacteriuria Caused by Vancomycin-Resistant Enterococci

BACKGROUND: Vancomycin-resistant enterococci (VRE) have been important pathogen of nosocomial infections and isolated most commonly from urine specimens. However, the clinical significance of VRE bacteriuria remains unknown. The objectives of this study are to describe the frequency, related factors and outcomes of VRE bacteriuria, and to compare epidemiologic data and outcomes between the subgroups: symptomatic urinary tract infection (UTI), asymptomatic bacteriuria, and colonization. MATERIALS AND METHODS: For patients with urine culture positive for VRE between August 1, 2002 and June 30, 2005, we collected clinical data and performed a retrospective analysis. According to Centers for Disease Control and Prevention (CDC), patients were classified as symptomatic UTI, asymptomatic bacteriuria, colonization and undetermined. RESULTS: Total 144 episodes (2.88%), in 58 patients, of 5,008 urine specimens were positive for VRE during the study period. Frequency of antimicrobial exposure history, especially 3rd generation cephalosporin, indwelling urinary catheter, and ICU stay at the time of culture was high in patients with VRE bacteriuria. In VRE bacteriuria, symptomatic UTI was only 24.5%. Instead the majority of the patients (71.4%) was colonized in urine with VRE or had asymptomatic bacteriuria. In comparison between symptomatic UTI group and combined group of asymptomatic bacteriuria and colonization, most demographic data and clinical features including hospital day and mortality had no significant difference except one, male sex. CONCLUSION: Most patients with VRE bacteriuria were classified as asymptomatic bacteriuria and colonization and only one-fourth of patients with VRE bacteriuria require antibiotic therapy. Therefore, clinicians should decide to initiate antibiotic therapy after consideration of clinical significance of VRE bacteriuria.

Immunogenicity and Safety of Half Dose Intradermal Injection Compared to Full Dose Intramuscular Injection of Influenza Vaccine in Healthy Adults

BACKGROUND: Influenza is the representative respiratory infectious disease causing significant high morbidity. Vaccination is the most effective method to prevent influenza. To cope with both unstable supply and increasing demand of influenza vaccine with more flexibility, we studied the safety and immunogenicity of half dose intradermal injection of influenza vaccine in healthy adults compared with full dose intramuscular injection method. MATERIALS AND METHODS: We conducted a randomized, open-label trial in healthy adults of age 15 to 64 years. Subjects were randomly assigned to receive either a recommended dose of influenza vaccine (Fluarix(R), Injection Prefilled Syringe, GlaxoSmithKline, hemagglutinin antigen (HA) 15 microgram) via intramuscular route (designated as control group) or a half recommended dose (HA 7.5 microgram) via intradermal route (designated as experimental group). Blood samplings were done before and more than 28 days after vaccination. We measured the changes in hemagglutination-inhibition (HAI) antibody titers and compared geometric mean titers, seroconversion rates, seroconversion factors and seroprotection rates of each group. Local and systemic adverse events were assessed after vaccination. RESULTS: In antibody titer against all three antigens (A/H1N1, A/H3N2, B) was more evident in intramuscular injection group but intradermal group with half dose showed acceptable immunogenicity fulfilling criteria for Committee for Proprietary Medicinal Products (CPMP). Likewise, seroprotection rates for all three viral strains showed no significant difference between the two groups. Although local reactions were significantly more frequent and lengthy in intradermal group than in intramuscular group, the reactions were mild and transient. CONCLUSION: Compared with intramuscular injection of full dose influenza vaccine, intradermal injection of half dose resulted in comparable immunogenicity in healthy adults. Intradermal administration of half dose influenza vaccine could be a practical alternative plan to expand the supplies of influenza vaccine, but further studies will be needed in high risk groups.