Seroepidemiology of Hepatitis Viruses and Hepatitis B Genotypes of Female Marriage Immigrants in Korea

PURPOSE: The Korean society has moved rapidly toward becoming a multicultural society. This study aimed to estimate the seroprevalence of hepatitis viruses and investigate hepatitis B virus (HBV) genotypic diversity in female marriage immigrants. MATERIALS AND METHODS: Screening program was conducted at support centers for multicultural families in 21 administrative districts in Korea between July 2011 and January 2017. A total of 963 female marriage immigrants were included in this study. Blood samples were tested for hepatitis viral markers and HBV genotype. RESULTS: Subjects' median age was 33 years (20–40 years), and they originated from nine countries including Vietnam (n=422, 43.8%), China (n=311, 32.3%), the Philippines (n=85, 8.8%), Cambodia (n=58, 6.0%), and Japan (n=39, 4.0%). About 30% (n=288) of subjects required hepatitis A vaccination. HBsAg positive rate was 5.4% (n=52). Positive HBsAg results were the highest in subjects from Southeast Asia (6.6%, n=38). Anti-HBs positive rate was 60.4% (n=582). About 34% (n=329) of subjects who were negative for anti-HBs and HBsAg required HBV vaccinations. Genotypes B and C were found in 54.6% (n=12) and 45.4% (n=10) of the 22 subjects with HBV, in whom genotypes were tested. Eight (0.8%) subjects were positive for anti-HCV. Positive anti-HCV results were the highest in subjects from Central Asia (7.9%, n=3). CONCLUSION: Testing for hepatitis viral marker (hepatitis A virus IgG and HBsAg/anti-HBs) is needed for female marriage immigrants. Especially, HBV genotype B is different from genotype C of Koreans. Therefore, interest and attention to vaccination programs for female marriage immigrants are necessary for both clinicians and public health institutes.

Complication of Amebic Liver Abscess: Biliary Fistula / 고신대학교의과대학학술지

In amebic liver abscess, communication between liver abscess and intrahepatic bile ducts is an uncommon cause of bile leak. This condition can be treated surgically or endoscopically. However, these treatment modalities are related with high morbidity and mortality. A 49-year-old man was diagnosed with amebic liver abscess. Percutaneous drainage was performed due to poor medical response and for the purpose of preventing abscess rupture. Liver abscess-biliary communication was found at follow-up imaging study. He was treated successfully with medical therapy and supportive care without further interventions.

Long-term outcomes of two rescue therapies in lamivudine-refractory patients with chronic hepatitis B: combined lamivudine and adefovir, and 1-mg entecavir

BACKGROUND/AIMS: Adefovir (ADV) and lamivudine (LAM) combination therapy (ADV+LAM) has been a useful option for patients with LAM-resistant (LAM-r) chronic hepatitis B (CHB). However, the long-term outcomes of LAM+ADV and 1-mg entecavir (ETV) rescue therapies have still been limited. The aim of this study was to determine the long-term outcomes of these two rescue therapies. METHODS: Sixty patients with LAM-r CHB underwent rescue therapy with LAM+ADV (n=36) or 1-mg ETV (n=24). We determined the duration of rescue therapy, timing and type of mutation, undetectable serum hepatitis B virus (HBV) DNA by PCR (lower limitation of detection, < 140 copies/mL), biochemical response (alanine aminotransferase < 40 IU/mL), and the incidence of hepatitis B virus e antigen (HBeAg) seroconversion and virologic breakthrough. RESULTS: Baseline characteristics did not differ between the two therapy groups. The duration of rescue therapy was 56 months (range, 14-100 months) in the ADV+LAM group and 42 months (range, 12-73 months) in the ETV group (P=0.036). The cumulative rates of HBV DNA undetectability and HBeAg seroconversion up to 6 years were 88.6% and 43.0%, respectively, in the ADV+LAM group, and 45.8% and 31.8% in the ETV group. The rate of virologic breakthrough and resistance was 14.4% in the ADV+LAM group and 71.9% in the ETV group (P=0.001). CONCLUSIONS: Combination of LAM and ADV therapy for up to 6 years achieved modest rates of virological suppression and resistance. ETV is not an optimal therapy because the risk of viral breakthrough to ETV increases over time.

Clinical characteristics and the usefulness of the QuantiFERON-TB Gold In-Tube test in hematologic patients with hepatic or splenic lesions

BACKGROUND/AIMS: Hepatic or splenic lesions in hematologic patients are not defined well because they are not easy to evaluate due to limitations of invasive procedures. Management typically depends on the clinical diagnosis with few microbiological data. METHODS: We reviewed the medical records of consecutive hematologic patients with hepatic or splenic lesions in the infectious diseases unit from April 2009 to December 2010 at the Catholic Hematopoietic Stem Cell Transplantation Center in Korea. RESULTS: Twenty-six patients were identified. Their mean age was 46.0 +/- 14.7 years, and 16 (61.5%) were male. Underlying diseases were acute myelogenous leukemia (n = 15, 57.7%) and myelodysplastic syndrome (n = 6, 23.1%). Among the nine nontuberculous infectious lesions, two bacterial, six fungal, and one combined infection were identified. The numbers of confirmed, probable, and possible tuberculosis (TB) cases were one, three, and four, respectively. Two patients had concurrent pulmonary TB. QuantiFERON-TB Gold In-Tube (QFT-GIT, Cellestis Ltd.) was positive in seven cases, among which six were diagnosed with TB. The sensitivity and specificity of QFT-GIT were 75% and 81.3%. Nine (34.6%) were defined as noninfectious causes. CONCLUSIONS: Causes of hepatic or splenic lesion in hematologic patients were diverse including TB, non-TB organisms, and noninfectious origins. TB should be considered for patients not responding to antibacterial or antifungal drugs, even in the absence of direct microbiological evidence. QFT-GIT may be useful for a differential diagnosis of hepatosplenic lesions in hematologic patients.

Trismus in cephalic tetanus from a foot injury

No abstract available.

Posaconazole Treatment in Korea: Single-Center Experience Over 5 Years

PURPOSE: Posaconazole is a second-generation triazole with a broad spectrum. However, there is a lack of data to support a significant role for posaconazole in the treatment of invasive fungal infection (IFI), especially in Korea. Until recently, posaconazole was available only through the Korean Orphan Drug Center. This study was designed to review the use of posaconazole at a single-center in Korea. MATERIALS AND METHODS: Data from patients who received posaconazole treatment at Catholic Blood and Marrow Transplantation Center were retrospectively reviewed between January 2007 and September 2012. RESULTS: A total of 11 cases (3 males and 8 females, median age 52 years) received posaconazole. Five patients were given the drug for mucormycosis, two for invasive aspergillosis, and four for unspecified IFI for which galactomannan (GM) assays were negative. The treatment duration ranged from 4-250 days. Three patients received posaconazole for management refractory IFI, two for intolerance of previous antifungal therapy, and six for long-term maintenance treatment. The overall successful response rate to posaconazole was 55% (six of eleven patients). Five of eleven patients died during the study period. However, only one death was attributed to the progression of IFI. None of the patients discontinued posaconazole therapy due to adverse events. CONCLUSION: Posaconazole is an attractive oral antifungal agent for salvage treatment of IFI, particularly upon diagnosis of mucormycosis or in cases in which mucormycosis cannot be ruled out due to a negative GM.

Epidemiology and Clinical Features of Bloodstream Infections in Hematology Wards: One Year Experience at the Catholic Blood and Marrow Transplantation Center

BACKGROUND: The aim of this study was to investigate the clinical features and epidemiology of bloodstream infections (BSIs) in 2 distinctive hematological wards of the Catholic Blood and Marrow Transplantation (BMT) center. MATERIALS AND METHODS: We retrospectively reviewed the medical data of patients who developed BSIs from June 2009 to May 2010 in 2 hematologic wards at the Catholic BMT center. Ward A is a 44-bed unit mainly conducting conventional high dose chemotherapy and ward B is a 23-bed unit exclusively conducting BMT. RESULTS: Overall, 222 BSI episodes were developed from 159 patients. Acute myeloid leukemia in ward A and multiple myeloma in ward B were more frequent than in ward B and A, respectively. Sex, age, presence of neutropenia, shock, Pitt bacteremia score, type of central catheter, level of C-reactive protein, duration of admission days, type of BSI, overall mortality and distribution of organisms were not different between the 2 wards. There were 202 monomicrobial and 20 polymicrobial BSI episodes, including 2 fungemia episodes. The incidence rate of overall BSIs per 1,000 patient-days was higher in ward A than in ward B (incidence rate ratio 2.88, 95% confidence interval 1.97-4.22, P<0.001). Among 243 organisms isolated, the number of gram positives, gram negatives and fungi were 122, 119 and 2, respectively. Escherichia coli was the most common organism in both ward A and B (27.6% and 42.4%), followed by viridians streptococci (18.6% and 15.2%) and Klebsiella pneumoniae (13.3% and 9.0%). Extended spectrum beta-lactamase (ESBL) producers accounted for 31.9% (23/72) of E. coli and 71.0% (22/31) of K. pneumoniae. Out of 19 Enterococcus faecium, 7 isolates (36.8%) were resistant to vancomycin. The crude mortality rates at 7 and 30 days after each BSI episode were 4.5% (10/222) and 13.1% (29/222), and were significantly higher in the patients with shock compared with those without shock (20.5% vs. 1.1%, P<0.001 and 38.5% vs. 7.7%, P<0.001, respectively). CONCLUSIONS: The incidence rate of BSIs was higher in patients receiving chemotherapy than those receiving BMT, but the distribution of organisms was not different between the 2 wards. E. coli was the most common causative BSI organism in hematologic wards followed by viridians streptococci and K. pneumoniae.

Clinical Impact of Cytochrome P450 2C19 Genotype on the Treatment of Invasive Aspergillosis under Routine Therapeutic Drug Monitoring of Voriconazole in a Korean Population

BACKGROUND: Genetic polymorphisms of cytochrome P450 enzymes, especially CYP2C19 influence voriconazole pharmacokinetics. However, the impact of CYP2C19 genetic polymorphisms on the therapeutic efficacy and toxicity of voriconazole therapy are not well established. MATERIALS AND METHODS: In this prospective observational study, we analyzed all consecutive adult patients with hematologic diseases who were treated for invasive aspergillosis (IA) with voriconazole between January 2011 and June 2012. CYP2C19 genotype and routine therapeutic drug monitoring of voriconazole were performed. The target range for voriconazole trough levels was 1-5.5 mg/L. RESULTS: A total of 104 consecutive patients were enrolled, including 39 homozygous extensive metabolizers (EMs, 38%), 50 heterozygous extensive metabolizers (HEMs, 48%), and 15 poor metabolizers (PMs, 14%). The initial voriconazole trough levels were 1.8, 2.7, and 3.2 mg/L in EMs, HEMs, and PMs, respectively (P = 0.068). Out-of-range initial trough levels were most frequently observed in EMs (46%) followed by HEMs (26%) and PMs (0%) (P = 0.001). The frequency of initial trough levels 5.5 mg/L differed significantly among the 3 groups (P = 0.005). However, treatment response, all-cause and IA-attributable mortality, and the occurrence of voriconazole-related adverse events did not differ significantly among the 3 groups (P = 0.399, P = 0.412, P = 0.317, and P = 0.518, respectively). CONCLUSIONS: While none of the initial voriconazole trough levels in PMs was outside the target range, subtherapeutic initial trough levels were frequent in EMs. Although there was no significant relationship between CYP2C19 genotype and either the clinical outcomes of IA or toxicity of voriconazole, further large-scale multicenter studies using clinical data from homogeneous populations are required.

Prognosis of Invasive Pulmonary Aspergillosis in Patients with Hematologic Diseases in Korea / 결핵및호흡기질환

BACKGROUND: The aim of this study was to investigate therapeutic outcomes and assess factors associated with therapeutic outcomes in hematologic patients with invasive pulmonary aspergillosis (IPA). METHODS: We analyzed all consecutive cases of IPA in adults with hematologic diseases from January 2008 to January 2009 at a Catholic Hematopoietic Stem Cell Transplantation (HSCT) Center in Seoul, Korea. RESULTS: A total of 54 patients were identified. Underlying diseases were acute myelogenous leukemia (n=25), acute lymphoblastic leukemia (n=10), myelodysplastic syndrome (n=7), chronic myelogenous leukemia (n=3), multiple myeloma (n=3), severe aplastic anemia (n=2) and other hematologic diseases (n=4). Twenty six patients (48.2%) were assessed as having a favorable response, of which 16 patients (29.6%) showed complete response. Overall 12-week mortality and IPA attributable mortality were 38.9% (n=21) and 33.3% (n=18), respectively. In multivariate analysis, uncontrolled underlying disease (odds ratio [OR], 7.31; 95% confidence interval [CI], 1.49~35.94; p=0.014) was associated with an unfavorable response, and for 12-week mortality, uncontrolled underlying disease (OR, 11.79; 95% CI, 1.49~93.46; p=0.020) and hypoalbuminemia (OR, 9.89; 95% CI, 1.42~68.99; p=0.021) were significantly poor prognostic factors. CONCLUSION: IPA still remains as a poor therapeutic outcome, especially in patients with refractory hematologic diseases.

Two Cases of Saccharomyces cerevisiae Fungemia in Patients with Hematologic Malignancies

Saccharomyces cerevisiae, also known as "baker's yeast" or "brewer's yeast", and is considered to be a frequent colonizer of human mucosal surfaces. Although it is a very uncommon cause of infections in humans, it can cause wide range of clinical syndromes, including pneumonia, empyema, liver abscess, peritonitis, urinary tract infection, cellulitis, unexplained fever, or septic shock, particularly in immunocompromised hosts. Fungemia is the most severe and well-proven manifestation of S.cerevisiae infections. According to previous studies, the conditions related to immunosupression, such as cancer, HIV infection, use of corticosteroid, neutropenia, stem cell transplantation, solid organ transplantation, burns and heart surgery, appear to be predisposing factors to fungemia. The antifungal agent of choice has not been established. We report two cases of S.cerevisiae fungemia in patients with hematologic malignancies. One was primary fungemia, and the other was presumed to be a catheter related one. Both cases showed a good prognosis with the complete negative conversion of fungemia.

A Case of Coccidioidal Meningitis

A 35-year-old man with known coccidioidal meningitis developed a severe headache and vomiting during routine treatment. Hydrocephalus was visible on brain imaging, and CSF study revealed pleocytosis, lowering of glucose, and increased intracranial pressure. Dexamethasone and mannitol was used for intracranial pressure control. Intrathecal amphotericin B administration and switching to itraconazole resulted in gradual improvement of symptoms. After 4 months of discontinuing amphotericin B intrathecal administration, the patient developed severe headaches with vomiting, diplopia and tandem gait. Coccidioidal meningitis aggravation was suspected based on brain MRI and CSF studies. Ventriculo-peritoneal shunt insertion was performed for intracranial pressure control and the combined therapy of intrathecal amphotericin B administration and fluconazole was maintained. This combined regimen kept the meningitis stable for 1 month.

Molecular Epidemiologic Analysis of Community-Onset Extended Spectrum Beta-Lactamase (ESBL) Producing Escherichia coli Using Infrequent-Restriction-Site Polymerase Chain Reaction (IRS-PCR) with Comparison by Pulsed-Field Gel Electrophoresis (PFGE)

BACKGROUND: We evaluated the ability of infrequent restriction site-polymerase chain reaction (IRS-PCR) to perform molecular epidemiologic analysis of Community-Onset Extended Spectrum Beta-Lactamase (ESBL) producing Escherichia coli, and also assessed the use of PFGE as an alternative method. MATERIALS AND METHODS: IRS-PCR assay was performed using combinations of adaptors for XbaI and HhaI restriction sites on clinical isolates of E. coli (n=51). We compared the discriminatory power, quality and efficiency of IRS-PCR to PFGE. RESULTS: In E. coli, PFGE discriminated 39 (76.4%) and IRS-PCR discerned 41 (80.3%) of the total 51 strains. It took much less time to complete IRS-PCR (one day) than PFGE (at least 4 days). CONCLUSIONS: IRS-PCR is a more sensitive and rapid alternative to PFGE for molecular epidemiologic analysis of E. coli.

Real-Time Nucleic Acid Sequence-Based Amplification to Predict the Clinical Outcome of Invasive Aspergillosis

Monitoring the response to therapy for invasive aspergillosis (IA) is essential for the management of patients with hematologic diseases. We evaluated the correlation between the outcome of real-time nucleic acid sequence-based amplification (RTi-NASBA) for Aspergillus 18S rRNA and the clinical outcome of IA. A total of 157 serum samples from 29 patients with IA were tested for RTi-NASBA. The treatment response and mortality were compared with the NASBA outcome (whether the NASBA value was converted to negative or not) at 12 weeks after the start of antifungal therapy. At 12 weeks, there was a moderate correlation between the treatment failure and persistently positive NASBA (kappa = 0.482; P = 0.019). Deaths attributable to IA were more prevalent in patients without negative conversion of NASBA than in those with negative conversion (50% vs 5%; P = 0.013). Significant factors of treatment failure at 12 weeks were the status of hematologic disease (nonremission; P = 0.041) and the NASBA outcome (failure of negative conversion; P = 0.024). Survival was significantly better in patients with negative conversion of NASBA than those with persistently positive values (P = 0.036). This study suggests that the serial monitoring of RTi-NASBA could be useful for prediction of the clinical outcome in hematologic patients with IA.

Successful Treatment of Pneumonia caused by Aspergillus terrerus and Cytomegalovirus after Chemotherapy for Acute Myelogenous Leukemia

We report a case of pneumonia caused by Aspergillus terreus and cytomegalovirus (CMV) in a patient with acute myleogenous leukemia (AML) after remission induction chemotherapy. A 19-year-old woman underwent chemotherapy for AML. Twenty-three days after completing chemotherapy, she experienced a neutropenic fever with a rapidly-progressive pulmonary infiltration. In those days, her serum galactomannan immunoassay was 4.7 and she was treated with intravenous voriconazole (6 mg/kg q12h for 2 doses, followed by 4 mg/kg q12h) because of persistent fever and radiological worsening, despite the administration of amphotericin B deoxycholate (1 mg/kg q24h) for 7 days. A chest CT showed wedge-shaped consolidation with a central hypodense lesion and an air-crescent sign in the right middle lobe. With maintenance therapy of oral voriconazole for 10 weeks, a partial response was shown and neutrophil count was still less than 100/mm3. A lobectomy of the right middle lobe was performed. A. terreus was discovered from the lung tissue. At the same time, giant cells with intranuclear inclusions were found and immunohistochemical staining for CMV was positive. Ganciclovir (5 mg/kg q12h) was added to voriconazole therapy for 3 weeks after surgery, and then cord blood hematopoietic stem cell transplantation (HSCT) was performed. During HSCT, foscarnet (60 mg/kg q12h) was substituted for ganciclovir, and both antiviral agents were used alternatively due to CMV DNAemia. After 83 days from HSCT, the patient achieved successful engraftment and discharged without worsening the pneumonia.

A Case of Pseudomembranous Colitis after Voriconazole Therapy

This is a case report on a 35-year-old man with acute myelogenous leukemia who presented fever and intermittent mucoid loose stool to the emergency center. He had been taking voriconazole for invasive pulmonary aspergillosis. The flexible sigmoidoscopy was consistent with the diagnosis of pseudomembranous colitis.

Invasive Tracheobronchial Aspergillosis : Case Reports and a Literature Review

Invasive tracheobronchial aspergillosis (iTBA) is an uncommon clinical manifestation of invasive aspergillosis and this is usually limited to the large airways. Its pathophysiology and clinical features are obscure, but some fatal cases of iTBA in immunocompetent patients have also been reported. We describe 4 cases of iTBA in the patients with hematologic malignancies, that was early diagnosed by bronchoscopy, a computed tomography and successfully treated by proper antifungal treatment. And we also review the cases of iTBA reported in Korea.

Application of Infrequent-Restriction-Site Polymerase Reaction (IRS-PCR) to the Molecular Epidemiologic Analysis of Methicillin Resistant Staphylococcus aureus (MRSA)

BACKGROUND: We investigated the usefulness of infrequent-restriction-site polymerase chain reaction (IRS-PCR) compared with pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) on the molecular epidemiologic analysis of methicillin-resistant Staphylococcus aureus (MRSA). MATERIALS AND METHODS: We used fifty clinical isolates of MRSA collected from 10 university hospitals located in Seoul. We performed three procedures on these isolates: PFGE using SmaI, IRS-PCR using XbaI-Hha I or EagI-Hha I, and MLST using seven house-keeping genes. We determined the clusters of molecular types by dendrogram using the unweighted pair group method with arithmetic mean (UPGMA) and Dice coefficients. RESULTS: MLST analysis showed that isolates exhibited ST1, ST5, ST72, ST89, and ST239. In PFGE, the isolates clustered into 5 major groups with 80% similarity, which subsequently became classified into 18 subgroups with 95% similarity. In IRS-PCR using EagI-HhaI restriction enzymes, there was little resolution among the patterns of isolates. However, XbaI-HhaI IRS-PCR showed 5 groups with a 90% similarity. These groups were then classified into 9 subgroups with a 95% similarity. There were no significant differences among the isolates from different hospitals. CONCLUSIONS: The XbaI-HhaI IRS-PCR method could be a useful tool in the molecular epidemiology of MRSA. Its resolution power was good enough to analyze isolates, because the patterns of IRS-PCR were closely correlated with those of MLST and showed diverse groups.

A Case of Visual and Auditory Hallucinations during Intravenous Voriconazole Therapy

Voriconazole is a triazole with broad spectrum antifungal activity, and it is currently considered to be the first-line agent for the treatment of invasive aspergillosis. We report here on a case of visual and auditory hallucinations during intravenous treatment with voriconazole in association with a high trough level. A 28-year-old man with acute myelogenous leukemia was admitted for re-induction remission chemotherapy. During the persistent neutropenic fever, intravenous voriconazole was administered for the suspected invasive fungal pneumonia. He began to have visual hallucinations on the 1st day and auditory hallucinations on the 3rd day of voriconazole therapy. The plasma peak and trough concentration levels of voriconazole were 9.9 and 7.4 microg/ml, respectively, on the 3rd day. The hallucinations resolved after changing to amphotericin B deoxycholate, and the plasma concentration of voriconazole dropped to less than 0.5 microg/ml. The genotype of the CYP2C19 alleles was classified as a heterozygous extensive metabolizer. We suggest that therapeutic drug monitoring of voriconazole is indicated for a case that is suspicious for a voriconazole-related adverse event.

Liver Abscess by Aspergillus and Enterococcus faecium in a Patient with Acute Myeloid Leukemia: A Case Report and Literature Review

We report a case of liver abscess caused by Aspergillus and Enterococcus faecium in a patient with acute myeloid leukemia. As far as we know, this is the first case of hepatic aspergillosis in Korea. After remission induction chemotherapy, the female patient presented with abdominal pain and was found to have liver abscess. The patient was treated with antibiotics against E. faecium, which was isolated from the abscess drainage. However, the therapeutic response was unsatisfactory and a left lateral sectionectomy of the liver was conducted after 21 days of treatment. The liver tissue showed typical pathologic findings of aspergillosis and voriconazole was administered. Allogeneic hematopoietic stem cell transplantation was performed successfully after 4 months. The possibility of aspergillosis should be considered when an immunocompromised patient with hepatic abscess poorly responds to the use of broad spectrum antibiotics.

Efficacy of Vancomycin against Staphylococcus aureus according to Inoculum Size in a Neutropenic Mouse Infection Model

BACKGROUND: Staphylococcus aureus is one of the most important gram-positive pathogens in many clinical situations. Use of vancomycin against methicillin resistant S aureus (MRSA) has been anecdotally associated with treatment failure, which could be attributable to an inoculum effect (IE). Using a neutropenic mouse thigh infection model, we tried to evaluate the in vivo IE of vancomycin against S. aureus. MATERIALS AND METHODS: Twenty strains of S aureus were used. Minimum inhibitory concentrations (MICs) were determined by the Clinical and Laboratory Standards Institute guideline. Six-week-old specific-pathogen-free, female CD-1 mice weighing 23-27 grams were used. The neutropenic mice received inoculations of 5.02-5.74 log10 CFU/thigh in one thigh (low inoculum, LI), and 7.22-7.73 log10 CFU/thigh in the other thigh (high inoculum, HI) before therapy. The mice were treated with 6 hourly subcutaneous doses of vancomycin (3.125-100 mg/kg) for 24 h. Single-dose serum pharmacokinetics of vancomycin was determined. Dose-response data were analyzed by an Emax model using non-linear regression. Static doses and area under the curve (AUC)/MIC for bacteriostatic effect at each inoculum were calculated and compared. The ratio of static dose and AUC/MIC between HI and LI (IE index) provided the magnitude of IE for each organism. RESULTS: Five methicillin-susceptible S aureus (MSSA) strains and 15 MRSA strains were used. Vancomycin MICs of the 20 strains varied by 4-fold (0.5-2 mg/L). The AUC/MIC ratio was the major parameter determining the efficacy of vancomycin against S aureus . Mean (range) static dose on LI and HI was 20.7 (11.8-35.1) and 136.7 (32.1-314), respectively. The mean IE index of static dose between them was 7.39. Mean (range) of AUC/MIC on LI and HI was 27.0 (6.61-66.6) and 152.3 (46.2-344), respectively, which produced a mean IE index of AUC/MIC of 7.47. The IE indices of the MSSA strains were significantly higher than those of the MRSA strains (11.3 vs. 6.1 on static dose [P=0.018], 11.4 vs. 6.2 on AUC/MIC [P=0.034]). CONCLUSIONS: With a 100-fold inoculum increment of S aureus , at least a 7-fold dose of vancomycin would be required to show the same bacteriostatic effect. Thus, IE as well as MICs is an important parameter in selecting and adjusting a dose and dosage interval along with the resistance profile in the treatment of S. aureus infections. IE to vancomycin observed in the in vivo neutropenic mouse model was more evident for MSSA strains than for MRSA strains.