Analysis of Staphylococcal Toxins and Clinical Outcomes of Methicillin-Resistant Staphylococcus aureus Bacteremia.

It is well known that methicillin-resistant Staphylococcus aureus (MRSA) produces many virulence factors, such as hemolysins, leukocidins, proteases, enterotoxins, exfoliative toxins, and immune-modulatory factors. The aim of study was to identify staphylococcal pathogenicity that may affect the prognosis of patients with MRSA bacteremia. We obtained 149 MRSA strains from blood cultures between January 2009 and December 2014 in our institution. We collected information on patient characteristics, laboratory data, staphylococcal toxin genes, and susceptibility of the strain toward anti-MRSA agent and analyzed them as factors contributing to 30-d mortality. The "survival" and "dead" groups consisted of 103 and 46 patients, respectively. Multiple logistic regression analysis showed a four-fold increase in the risk of mortality in patients exhibiting isolated MRSA with staphylococcal enterotoxins (SEs) genes as well as toxic shock syndrome toxin-1 (TSST-1) genes [odds ratio: 3.89; 95% confidence interval: 1.20-12.60; p=0.024]. Kaplan-Meier analysis also showed significantly higher mortality in patient with isolated MRSA with SEs and TSST-1 genes. After adjusting for confounders, the coexistence of SEs and TSST-1 were independently associated with the 30-d mortality compared with treatment and susceptibility. The coexistence of superantigenic toxin genes greatly affects the clinical course and prognosis of patients with MRSA bacteremia.

A molecular analysis of quinolone-resistant Haemophilus influenzae: validation of the mutations in Quinolone Resistance-Determining Regions.

The mechanism of quinolone-resistance is considered to be amino acid mutations in the type II topoisomerase. We validated the genetic mechanisms of quinolone resistance in Haemophilus influenzae. We obtained 29 H. influenzae strains from a nationwide surveillance program in Japan (including 11 quinolone-resistant strains [moxifloxacin: MFLX or levofloxacin MIC ≥2 µg/ml]). We analyzed the sequences of the Quinolone Resistance-Determining Regions (QRDRs) in GyrA, GyrB, ParC and ParE. Furthermore, we induced resistance in susceptible strains by exposing them to quinolone, and investigated the relationship between mutations in the QRDRs and the MICs. Five amino acid substitutions in GyrA (at Ser84 and Asp88) and ParC (at Gly82, Ser84 and Glu88) were found to be closely related to the MICs. The strains with a MFLX MIC of 0.125-1 and 2-4 µg/ml had one and two mutations, respectively. The strains with a MFLX MIC of ≥8 µg/ml had three or more mutations. The strains with induced resistance with MFLX MICs of 0.5-1 and ≥2 µg/ml also had one and two mutations, respectively. We confirmed that these five mutations strongly contribute to quinolone resistance and found that the degree of resistance is related to the number of the mutations. In addition, the three strains of 18 susceptible strains (16.7%) also had a single mutation. These strains may therefore be in the initial stage of quinolone resistance. Currently, the frequency of quinolone-resistant H. influenzae is still low. However, as has occurred with ß-lactams, an increase in quinolone use may lead to more quinolone-resistant strains.

[A case of cysticercosis with multiple lesions in the brain and femoral muscles].

A 37-year-old Nepalese man was admitted to Showa University Hospital because of a loss of consciousness and seizures. He had lived in Nepal, Qatar, Singapore, and India before the age of 34 years. He had no history of having eaten raw pork. His physical findings were normal excluding an abnormal visual field, and a positive serum antibody test result for Taenia solium, CT and MRI examinations showed multiple nodular lesions in his brain and thigh. We resected a cyst from his left thigh and diagnosed him as having cysticercosis based on the presence of characteristic hooklets and suckers on a pathological examination. Later, the Asian type of Cysticercus cellulosa was identified using a mitochondrial DNA test. Albendazole (800 mg/day) and prednisolone (60 mg/day) were administered for 14 days. All cysticercus were smaller on Day7 and had almost disappeared on Day 14. No adverse effects from the treatment occurred. Cysticercosis is rare in Japan, and cases requiring treatment for a large number of cysticercus in the brain and thigh are rare. We report a case of neurocysticercosis that had a good clinical course.

Changes in the Distribution of Capsular Serotypes of Streptococcus pneumoniae Isolated from Adult Respiratory Specimens in Japan.

OBJECTIVE: The objective of this study was to assess whether the distribution of pneumococcal capsular types has been changed, while also providing basic data on changes in the distribution after the introduction of Pneumococcal conjugated vaccine (PCV)13 in adult medical practice. METHODS: We analyzed 431 Streptococcus pneumoniae strains (200 in 2006 and 231 in 2012) that had been isolated from respiratory infection specimens from adult patients. Capsular typing was performed by the Quellung reaction and multiplex polymerase chain reaction. RESULTS: A comparison of the 2006 and 2012 strains revealed that the number and proportion of strains by serotype increased from 30 (15%) to 46 (20%) for serotype 3, from 4 (2%) to 14 (6%) for serotype 6A, and from 4 (2%) to 13 (6%) for serotype 6C, whereas the number and proportion of strains by serotype decreased from 8 (4%) to 0 (0%) for serotype 4 and from 24 (12%) to 17 (7%) for serotype 6B. From 2006 to 2012, the coverage rate significantly decreased from 39 to 28.1% for PCV7 (p=0.017). CONCLUSION: Our study showed a decrease in the vaccine coverage of PCV7. However, PCV13 covered serotypes 3 and 6A, which are prevalent, as well as penicillin-resistant S. pneumoniae strains. At present, PCV13 in adult clinical practice seems to be highly significant. However, there is a possibility that the distribution has changed, and careful screening should be continued in the future.

More accurate measurement of vancomycin minimum inhibitory concentration indicates poor outcomes in meticillin-resistant Staphylococcus aureus bacteraemia.

Meticillin-resistant Staphylococcus aureus (MRSA) is an important pathogen associated with community-acquired and nosocomial infections. The aim of this study was to validate the vancomycin (VAN) minimum inhibitory concentration (MIC) and administration of VAN that may affect the prognosis of patients with MRSA bacteraemia. In total, 140 clinical MRSA strains from blood cultures were collected from January 2009 to December 2013 at a university hospital in Tokyo (Japan). Patient background, their clinical situation and the susceptibility of isolates to anti-MRSA agents in all cases were reviewed, and factors contributing to 30-day mortality were analysed. Susceptibility to anti-MRSA agents was measured by a microdilution susceptibility testing method. The VAN MIC was further evaluated at 0.25 µg/mL intervals from 0.5 µg/mL to 2.0 µg/mL. Multiple logistic regression analysis revealed a 4-fold increase in mortality of patients with a VAN MIC ≥1.5 µg/mL [odds ratio (OR)=3.952, 95% confidence interval (CI) 1.471-10.614; P=0.006]. A one-score increase in the Charlson co-morbidity index resulted in a 1.2-fold increase in the risk of death (OR=1.199, 95% CI 1.054-1.364; P=0.006). However, no significant difference was found in the ratio of the VAN 24-h area under the concentration-time curve to MIC between VAN MIC ≥1.5 µg/mL and <1.5 µg/mL. A significant increase in the MICs of teicoplanin and daptomycin was observed in strains with high VAN MICs. For patients with high VAN MICs, administration of these anti-MRSA antibiotics may have a poor outcome owing to cross-resistance.