The Association between Insulin Resistance and Cardiovascular Disease Risk: A Community-Based Cross-Sectional Study among Taiwanese People Aged over 50 Years.

BACKGROUND AND AIMS: Previous studies have implied that insulin resistance (IR) could represent a major underlying abnormality leading to cardiovascular disease (CVD). The aim of this study was to evaluate the relationships between IR (estimated by the homeostasis model assessment of IR (HOMA-IR) index) and CVD risk among middle-aged and elderly Taiwanese individuals. METHODS: In this cross-sectional, community-based study, a total of 320 participants were interviewed to collect demographical parameters and blood samples. The recruited participants were divided into tertiles according to their levels of HOMA-IR. The Framingham risk score (FRS) was calculated according to the 2008 general CVD risk model from the Framingham Heart Study. RESULTS: The HOMA-IR index was significantly correlated with the FRS, with a Pearson's coefficient of 0.22. In the multiple logistic regression model, a higher HOMA-IR level was significantly associated with a high FRS (FRS ≥ 20%) (highest tertile vs. lowest tertile of HOMA-IR, crude OR = 3.69; 95% CI = 1.79-7.62), even after adjusting for smoking, fasting plasma glucose (FPG), and systolic blood pressure (SBP) (highest tertile vs. lowest tertile of HOMA-IR, adjusted OR = 11.51; 95% CI = 2.55-51.94). The area under the receiver operating characteristic curve for the HOMA-IR index as the predictor of high FRS was 0.627, and the optimal HOMA-IR cutoff value was 1.215 (sensitivity = 83.6%, specificity = 42.9%). CONCLUSIONS: We considered that HOMA-IR is an independent factor but that it cannot be used solely for evaluating the CVD risk due to the low AUC value. Further prospective cohort studies are warranted to better assess the relationship between CVD risk and insulin resistance.

Correction: Non-invasive in vivo molecular imaging of intra-articularly transplanted immortalized bone marrow stem cells for osteoarthritis treatment.

[This corrects the article DOI: 10.18632/oncotarget.21315.].

Non-invasive in vivo molecular imaging of intra-articularly transplanted immortalized bone marrow stem cells for osteoarthritis treatment.

Pathophysiology of osteoarthritis (OA) is characterized by progressive loss of articular cartilage in the knee-joints. To impart regenerative ability in lowly metabolizing chondrocytes, the bone marrow stem cells (BMSCs) has recently been recognized as a superior alternative treatment for OA. However, study of primary BMSCs-mediated chondrogenesis is difficult due to progressive cellular aging and replicative senescence. To obtain a therapeutic cell population for OA, BMSCs were immortalized by human papilloma virus (HPV)-16 E6/E7 along with mCherry luciferase (mCL), a gene marker for non-invasive imaging, and designated as iBMSCs-mCL. Next, their cell morphology, population doubling time (PDT) and colony forming ability (CFU) were evaluated. Furthermore, pluripotency and immunophenotypic markers were investigated. To deduce therapeutic ability, iBMSCs-mCL were intra-articularly injected into right knee of anterior cruciate ligament transaction (ACLT)-OA mice model and tracked through non-invasive bioluminescence imaging. Cell morphology of iBMSCs-mCL was similar to parental BMSCs. PDT and CFU ability of iBMSCs-mCLs were significantly increased. Pluripotency and immunophenotypic markers were highly expressed in iBMSC-mCL. Long-term survival and tri-lineage differentiation particularly chondrogenic potential of iBMSCs-mCL were also demonstrated in vitro and then in vivo which was monitored through non-invasive imaging. Intensive bioluminescent signals in iBMSCs-mCL administered knee-joint indicated a marked in vivo survival and proliferation of iBMSCs-mCL. Immunohistochemical staining for type II collagen (IHC of Col II) and alcian blue & safranin o staining of proteoglycans also corroborated cartilage regeneration by iBMSCs-mCL. Conclusively, iBMSCs-mCL maintains stemness and in vivo cartilage regeneration potential suggesting a promising avenue for development of OA therapeutics.

Correction: Chronic Hepatitis C Virus Infection Is Associated with the Development of Rheumatoid Arthritis: A Nationwide Population-Based Study in Taiwan.

[This corrects the article DOI: 10.1371/journal.pone.0113579.].

Cordyceps militaris Treatment Preserves Renal Function in Type 2 Diabetic Nephropathy Mice.

Diabetic nephropathy is derived from long-term effects of high blood glucose on kidney function in type 2 diabetic patients. Several antidiabetic drugs and herbal medications have failed to prevent episodes of DN. Hence, this study aimed to further investigate the renal injury-reducing effect of antidiabetic CmNo1, a novel combination of powders of fruiting bodies and mycelia of Cordyceps militaris. After being administered with streptozotocin-nicotinamide and high-fat-diet, the diabetic nephropathy mouse model displayed elevated blood glucose and renal dysfunction markers including serum creatinine and kidney-to-body weight ratio. These elevated markers were significantly mitigated following 8 weeks CmNo1 treatment. Moreover, the chronic hyperglycemia-induced pathological alteration in renal tissue were also ameliorated. Besides, immunohistochemical study demonstrated a substantial reduction in elevated levels of carboxymethyl lysine, an advanced glycation end product. Elevated collagenous deposition in DN group was also attenuated through CmNo1 administration. Moreover, the enhanced levels of transforming growth factor-ß1, a fibrosis-inducing protein in glomerulus were also markedly dampened. Furthermore, auxiliary risk factors in DN like serum triglycerides and cholesterol were found to be increased but were decreased by CmNo1 treatment. Conclusively, the results suggests that CmNo1 exhibit potent and efficacious renoprotective action against hyperglycemia-induced DN.

Lovastatin lowers the risk of breast cancer: a population-based study using logistic regression with a random effects model.

BACKGROUND: Laboratory studies have demonstrated statin-induced apoptosis of cancer cells, including breast cancer cells, and evidence is accumulating on the mechanism of statin-induced apoptosis. However, despite numerous epidemiological studies, no consensus has been reached regarding the relationship between statin use and breast cancer risk. METHODS: This retrospective case-control study enrolled 4332 breast cancer patients and 21,660 age-matched controls registered in the National Health Insurance program of Taiwan, which covers approximately 99% of the population. The study cases were women for whom a diagnosis of breast cancer (ICD-9-CM code 174.X) had been recorded in LHID2005 between January 1, 2004 and December 31, 2010. A logistic regression model was adjusted for potential confounding factors, including the level of urbanization, and the Charlson Comorbidity Index was applied to assess potential comorbidities. We also considered possible bias caused by random urbanization, because nutrition and lifestyle factors are related to breast cancer incidence. RESULTS: Our results showed that lovastatin was associated with a lower risk of breast cancer (adjusted OR 0.596; 95% CI 0.497-0.714; p < 0.001), and atorvastatin exhibited a protective tendency against breast cancer (adjusted OR 0.887; 95% CI 0.776-1.013; p < 0.077). CONCLUSIONS: Although no consensus has been established regarding the relationship between statin use and breast cancer risk, our study indicated that lovastatin is a potential chemopreventive agent against breast cancer. Further detailed research is warranted.

Correction: Association of Sjögren's Syndrome in Patients with Chronic Hepatitis Virus Infection: A Population-Based Analysis.

[This corrects the article DOI: 10.1371/journal.pone.0161958.].

Hydrogen Sulfide Modulates the S-Nitrosoproteome and the Mitochondrial Morphology in Endothelial Cells.

BACKGROUND: Hydrogen sulfide (H2S) is one of the endogenous gaseous molecules promoting the production of nitric oxide (NO) which has cardioprotective functions. However, the role of the H2S-mediated protein S-nitrosoproteome and its subsequent physiological response remains unclear. METHODS: Endothelial cells EAhy 926 were treated with 50 µM of H2S for 2 hours. The NO bound S-nitrosoproteins were purified by a biotin-switch and then digested by trypsin. Resulting peptides from control and H2S treatment were separately labeled by isobaric tag for relative and absolute quantitation 114/115, quantified by liquid chromatography tandem-mass spectrometry and analyzed by ingenuity pathway analysis (IPA) software. The microP software was applied to analyze the morphological changes of mitochondria. RESULTS: With the treatment of H2S, 416 S-nitrosylated proteins were identified. IPA analysis showed that these proteins were involved in five signaling pathways. The NO-bound cysteine residues and the S-nitrosylation levels (115/114) were shown for ten S-nitrosoproteins. Western blot further verified the S-nitrosylation of thioredoxin-dependant peroxide reductase, cytochrome c oxidase and cytochrome b-c1 complex that are involved in the mitochondrial signaling pathway. H2O2-induced mitochondrial swelling can be reduced by the pretreatment of H2S. CONCLUSIONS: The H2S-mediated endothelial S-nitrosoproteome has been confirmed. In the present study, we have proposed the cardioprotective role of H2S via maintaining mitochondrial homeostasis.

Association of Sjögrens Syndrome in Patients with Chronic Hepatitis Virus Infection: A Population-Based Analysis.

OBJECTIVE: The association between Sjögren's syndrome (SS) and chronic hepatitis virus infection is inconclusive. Hepatitis B (HBV) and hepatitis C virus (HCV) infections are highly prevalent in Taiwan. We used a population-based case-control study to evaluate the associations between SS and HBV and HCV infections. MATERIALS AND METHODS: We identified 9,629 SS patients without other concomitant autoimmune diseases and 38,516 sex- and age-matched controls without SS from the Taiwan National Health Insurance claims data between 2000 and 2011. We utilized multivariate logistic regression to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of the associations between SS and HBV and HCV infections. Sex- and age-specific (<55 and ≥55 years) risks of SS were evaluated. RESULTS: The risk of SS was higher in patients with HCV than in those without chronic viral hepatitis (OR = 2.49, 95% CI = 2.16-2.86). Conversely, HBV infection was not associated with SS (OR = 1.10, 95% CI = 0.98-1.24). Younger HCV patients were at a higher risk for SS (<55 years: OR = 3.37, 95% CI = 2.62-4.35; ≥55 years: OR = 2.20, 95% CI = 1.84-2.62). Men with HCV were at a greater risk for SS (women: OR = 2.26, 95% CI = 1.94-2.63; men: OR = 4.22, 95% CI = 2.90-6.16). Only men with chronic HBV exhibited a higher risk of SS (OR = 1.61, 95% CI = 1.21-2.14). CONCLUSION: HCV infection was associated with SS; however, HBV only associated with SS in men.

Association between sleep duration and sleep quality, and metabolic syndrome in Taiwanese police officers.

OBJECTIVES: This study's objective was to examine association between sleep duration and sleep quality, and metabolic syndrome (MetS) and its components in Taiwanese male police officers. MATERIAL AND METHODS: Male police officers who underwent annual health examinations were invited to join the study and eventually a total of 796 subjects was included in it. The study subjects were divided into 5 groups according to the length (duration) of sleep: < 5, 5-5.9, 6-6.9, 7-7.9 and ≥ 8 h per day, and the global Pittsburgh Sleep Quality Index was used to categorize their sleep quality as good or poor. To analyze the association between sleep problems and MetS, adjusted odds ratio and respective 95% confidence intervals (CI) were computed. RESULTS: The prevalence of MetS in Taiwanese male police officers was 24.5%. Abdominal obesity had the highest proportion (36.2%) among 5 components of MetS. More than 1/2 of the police officers (52.3%) had poor sleep quality. Police officers with higher scores of sleep disturbances had a higher prevalence of MetS (p = 0.029) and abdominal obesity (p = 0.009). After adjusting for age, low-density lipoprotein cholesterol, smoking status, alcohol drinking habit, physical habitual exercise, snoring and type of shift work, the police officers who slept less than 5 h were 88% more likely to suffer from abdominal obesity than those who slept 7-7.9 h (95% CI: 1.01-3.5). Sleep quality was not associated with MetS and its components. CONCLUSIONS: The police officers who slept less than 5 h were more likely to experience abdominal obesity in Taiwan, and those with higher scores of sleep disturbances had a higher prevalence of MetS and abdominal obesity. It is recommended that police officers with short sleep duration or sleep disturbances be screened for MetS and waist circumference in order to prevent cardiovascular diseases.

Zerumbone enhances the Th1 response and ameliorates ovalbumin-induced Th2 responses and airway inflammation in mice.

Zerumbone is a sesquiterpene compound isolated from the rhizome of wild ginger, Zingiber zerumbet Smith. The rhizomes of the plant are used as a spice and traditional medicine. Zerumbone was shown to possess anticarcinogenic, anti-inflammatory, and antioxidant properties. However, the antiallergic activity and the underlying mechanism of zerumbone have not been reported. Herein, we investigated the immunomodulatory effects of zerumbone on antigen-presenting dendritic cells (DCs) in vitro and its potential therapeutic effects against ovalbumin (OVA)-induced T helper 2 (Th2)-mediated asthma in mice. In the presence of zerumbone, lipopolysaccharide-activated bone marrow-derived DCs enhanced T cell proliferation and Th1 cell polarization in an allogeneic mixed lymphocyte reaction. In animal experiments, mice were sensitized and challenged with OVA, and were orally treated with different doses of zerumbone after sensitization. Circulating titers of OVA-specific antibodies, airway hyperresponsiveness to methacholine, histological changes in lung tissues, the cell composition and cytokine levels in bronchoalveolar lavage fluid, and cytokine profiles of spleen cells were assessed. Compared to OVA-induced hallmarks of asthma, oral administration of zerumbone induced lower OVA-specific immunoglobulin E (IgE) and higher IgG2a antibody production, attenuated airway hyperresponsiveness, prevented eosinophilic pulmonary infiltration, and ameliorated mucus hypersecretion. Zerumbone treatment also reduced the production of eotaxin, keratinocyte-derived chemokine (KC), interleukin (IL)-4, IL-5, IL-10, and IL-13, and promoted Th1 cytokine interferon (IFN)-γ production in asthmatic mice. Taken together, these results suggest that zerumbone exhibits an antiallergic effect via modulation of Th1/Th2 cytokines in an asthmatic mouse model.

Hepatitis B virus infection and the risk of male infertility: a population-based analysis.

OBJECTIVE: To evaluate the risk of male infertility among patients with hepatitis B virus (HBV) infection. DESIGN: A nationwide, population-based cohort study. SETTING: Not applicable. PATIENT(S): Men infected with HBV (n = 5,138) and men without HBV infection (n = 25,690). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Male infertility, as defined by the International Classification of Diseases, Ninth Revision, Clinical Modification. RESULT(S): The incidence of infertility was 1.59 times higher in patients with HBV infection than in those without HBV infection (2.21 vs. 1.39 per 1,000 person-years). The risk of developing infertility remained significant among patients with HBV infection (hazard ratio 1.52, 95% confidence interval 1.20-1.92) after adjusting for covariates in a multivariate Cox proportional hazards model. CONCLUSION(S): The data show an increased incidence and risk of infertility among men with HBV infection compared with men without HBV.

Chronic hepatitis C virus infection is associated with the development of rheumatoid arthritis: a nationwide population-based study in taiwan.

OBJECTIVE: The association between chronic hepatitis virus infection and rheumatoid arthritis (RA) remains debatable. This nationwide population-based cohort study assessed the risk of RA among patients with a chronic infection of hepatitis B and/or C virus. MATERIALS AND METHODS: We used data extracted from the claims of 1,000,000 randomly sampled individuals covered under the Taiwan National Health Insurance program. Among the 49,892 persons identified in 2000-2010 with chronic hepatitis virus infection, 35,652 had chronic HBV infection alone, 10,253 had chronic HCV infection alone, and 3,987 had chronic HBV/HCV dual infections. The comparison cohort comprised 199,568 persons matched on sex, age and calendar year without chronic hepatitis virus infection. All study participants were free of RA at baseline and traced through 2011 with new RA cases identified. RESULTS: After adjusting for covariates, chronic HCV infection alone was significantly associated with an increased risk for RA (hazard ratio (HR)  = 2.03, 95% confidence interval (CI)  = 1.27-3.22). The increased risk for RA among participants with chronic HCV infection remained significant after restricting the analysis to those who were prescribed disease-modifying anti-rheumatic drugs. The corresponding HR for the overall sample was 1.89 (95% CI  = 1.15-3.11). However, HBV carriers did not appear to be at a significantly higher risk for RA. CONCLUSION: Our data imply that chronic HCV infection is associated with RA development.

Synergistic anabolic actions of hyaluronic acid and platelet-rich plasma on cartilage regeneration in osteoarthritis therapy.

Osteoarthritis (OA) is a common disease associated with tissue inflammation, physical disability and imbalanced homeostasis in cartilage. For advanced treatments, biological approaches are currently focused on tissue regeneration and anti-inflammation. This study was undertaken to evaluate the therapeutic efficacies of hyaluronic acid (HA) and platelet-rich plasma (PRP) (HA+PRP) on OA. Articular chondrocytes were obtained from five OA patients. The optimal HA and PRP concentrations were evaluated by MTT assay. The expressions of chondrogenic and inflammatory genes were analyzed by RT-PCR. Signaling pathway was examined by immunoblotting and the expressions of OA pathology-related chemokines and cytokines was demonstrated by real-time PCR-based SuperArray. The therapeutic efficacies of HA+PRP were then demonstrated in 3D arthritic neo-cartilage and ACLT-OA model. Here we showed that HA+PRP could greatly retrieve pro-inflammatory cytokines-reduced articular chondrocytes proliferation and chondrogenic phenotypes, the mechanism of which involve the sequential activation of specific receptors CD44 and TGF-ßRII, downstream mediators Smad2/3 and Erk1/2, and the chondrogenic transcription factor SOX9. The real-time PCR-based SuperArray results also indicated that OA pathology-related chemokines and cytokines could be efficiently suppressed by HA+PRP. Moreover, the cartilaginous ECM could be retrieved from inflammation-induced degradation by HA+PRP in both 2D monolayer and 3D neo-cartilage model. Finally, the intra-articular injection of HA+PRP could strongly rescue the meniscus tear and cartilage breakdown and then decrease OA-related immune cells. The combination of HA+PRP can synergistically promote cartilage regeneration and inhibit OA inflammation. This study might offer an advanced and alternative OA treatment based on detailed regenerative mechanisms.

The Translational Proteome Modulated by 20(S)-Protopanaxadiol in Endothelial Cells.

BACKGROUND: 20(S)-protopanaxadiol (PPD), a natural compound of dammarane ginsenoside purified from the ginseng plant, exhibits strong anticancer properties. It has also been reported to have strong antioxidant activity and plays a role in cardiovascular protection. However, the downstream signaling mechanism PPD employs is still unclear and requires further elucidation. METHODS: Endothelial cells (ECs) EAhy 926 were used to investigate the growth promoting effect of PPD. The protein lysates extracted from both mock- and PPD-treated cells were separated by two-dimensional gel electrophoresis (2-DE) to monitor protein changes. After image analysis, proteins with significant change in the expression level were further identified by mass spectrometry. Western blot was applied to further confirm the protein variations in the 2-DE assay. RESULTS: In the current study, we found that treatment with PPD (10 µg/ml) significantly increased ECs healing. The translational proteome was established according to 16 up-regulated and 8 down-regulated proteins identified in 2-DE. These proteins were reported to function as energy homeostasis and in the prevention of oxidative stress. The elevated expressions of heme oxygenase 1 (HO-1) and glutathione synthetase (GSS) were further confirmed in the western blot analysis. CONCLUSIONS: According to the information obtained from translational proteome, we delineated that PPD mediated vascular homeostasis through the up-regulation of anti-oxidative proteins. Additional functional investigations are necessary regarding the HO-1 and GSS proteins. KEY WORDS: Dammarane sapogenins; Endothelial cell; Glutathione synthetase; Heme oxygenase 1; Proteome; 20(S)-protopanaxadiol.

Potential Osteoporosis Recovery by Deep Sea Water through Bone Regeneration in SAMP8 Mice.

The aim of this study is to examine the therapeutic potential of deep sea water (DSW) on osteoporosis. Previously, we have established the ovariectomized senescence-accelerated mice (OVX-SAMP8) and demonstrated strong recovery of osteoporosis by stem cell and platelet-rich plasma (PRP). Deep sea water at hardness (HD) 1000 showed significant increase in proliferation of osteoblastic cell (MC3T3) by MTT assay. For in vivo animal study, bone mineral density (BMD) was strongly enhanced followed by the significantly increased trabecular numbers through micro-CT examination after a 4-month deep sea water treatment, and biochemistry analysis showed that serum alkaline phosphatase (ALP) activity was decreased. For stage-specific osteogenesis, bone marrow-derived stromal cells (BMSCs) were harvested and examined. Deep sea water-treated BMSCs showed stronger osteogenic differentiation such as BMP2, RUNX2, OPN, and OCN, and enhanced colony forming abilities, compared to the control group. Interestingly, most untreated OVX-SAMP8 mice died around 10 months; however, approximately 57% of DSW-treated groups lived up to 16.6 months, a life expectancy similar to the previously reported life expectancy for SAMR1 24 months. The results demonstrated the regenerative potentials of deep sea water on osteogenesis, showing that deep sea water could potentially be applied in osteoporosis therapy as a complementary and alternative medicine (CAM).

Rosuvastatin-regulated post-translational phosphoproteome in human umbilical vein endothelial cells.

Statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, are widely prescribed as cholesterol-lowering drugs. Statins have recently been found to have pleiotropic effects that are independent of their lipid-lowering properties. Phosphorylation of serine, threonine, and tyrosine residues of functional proteins are considered to be important in the endothelial signaling cascade. In this study, protein phosphorylation status in human umbilical vein endothelial cells (ECs) after rosuvastatin treatment was examined. The proteins were collected from rosuvastatin-treated ECs and then the phosphorylated peptides purified by a Fe(3+)-immobilized metal-affinity chromatography bead system were examined by liquid chromatography-tandem mass spectrometry analysis. Alterations of the phosphorylation status of proteins were noticed after rosuvastatin treatment. There were 277 and 530 phosphorylated proteins identified from the control and rosuvastatin-treated ECs, respectively. Among those proteins, T78, in addition to S156 of the Ras-GTPase-activating protein, was phosphorylated after rosuvastatin treatment. Rosuvastatin reduced the phosphorylation of Y455 in HSP90 protein. Decreased phosphorylation of T211 with a concurrent increase in the T291 phosphorylation of Akt1 was observed under rosuvastatin treatment. Increased S633 phosphorylation was detected in endothelial nitric oxide synthase. Western blot analysis further showed an earlier and greater S633 phosphorylation than that of S1177 in endothelial nitric oxide synthase after rosuvastatin treatment. Changes in the phosphorylation status of these proteins may alter the protein's function and affect endothelial physiology. The current study provides new insights leading to a better understanding of the pleiotropic effects of statins on the vascular system.

Virally inactivated human platelet concentrate lysate induces regulatory T cells and immunosuppressive effect in a murine asthma model.

BACKGROUND: Platelet concentrate lysates (PCLs) are increasingly used in regenerative medicine. We have developed a solvent/detergent (S/D)-treated PCL. The functional properties of this preparation should be unveiled. We hypothesized that, due to transforming growth factor-ß1 (TGF-ß1) content, PCLs may exert immunosuppressive and anti-inflammatory functions. STUDY DESIGN AND METHODS: PCL was prepared by S/D treatment, oil extraction, and hydrophobic interaction chromatography. The content of TGF-ß in PCL was determined by enzyme-linked immunosorbent assay. Cultured CD4+ T cells were used to investigate the effects of PCL on expression of transcription factor forkhead box P3 (Foxp3), the inhibition of T-cell proliferation, and cytokine production. The regulatory function of PCL-converted CD4+ T cells was analyzed by suppressive assay. The BALB/c mice were given PCL-converted CD4+ T cells before ovalbumin (OVA) sensitization and challenge using an asthma model. Inflammatory parameters, such as the level of immunoglobulin E (IgE), airway hyperresponsiveness (AHR), bronchial lavage fluid eosinophils, and cytokines were assayed. Recombinant human (rHu) TGF-ß1 was used as control. RESULTS: PCL significantly enhanced the development of CD4+Foxp3+-induced regulatory T cells (iTregs). Converted iTregs produced neither Th1 nor Th2 cytokines and inhibited normal T-cell proliferation. PCL- and rHuTGF-ß-converted CD4+ T cells prevented OVA-induced asthma. PCL- and rHuTGF-ß-modified T cells both significantly reduced expression levels of OVA-specific IgE and significantly inhibited the development of AHR, airway eosinophilia, and Th2 responses in mice. CONCLUSION: S/D-treated PCL promotes Foxp3+ iTregs and exerts immunosuppressive and anti-inflammatory properties. This finding may help to understand the clinical properties of platelet lysates.

Lemierre syndrome complicating multiple brain abscesses caused by extended-spectrum ß-lactamase-producing Klebsiella pneumoniae cured by fosfomycin and meropenem combination therapy.

A woman aged 56 years of age had a community-acquired left neck abscess and internal jugular vein thrombosis with septicemia due to extended-spectrum ß-lactamase (ESBL)-producing Klebsiella pneumoniae. Even though she was treated with intravenous meropenem, the bacteremia persisted. She was complicated with multiple brain abscesses, seizure, and leucopenia. After a combination of intravenous fosfomycin and meropenem, her clinical condition became stable. Combination treatment was continued for 2 months and she recovered. In individual cases of Lemierre syndrome with brain abscess caused by ESBL-producing Enterobacteriaceae, fosfomycin combination therapy may be the alternative choice.