Candidatus Mycoplasma haemohominis in Human, Japan.

Hemotropic mycoplasmas are common pathogens in animals, but it remains unclear what role these pathogens play in human infections. We report clinical and biologic characterization of Candidatus Mycoplasma haemohominis infection in a 42-year-old man in Japan. The patient had severe hemophagocytic syndrome 1 month after an accidental needlestick injury. Metagenomic deep sequencing identified Candidatus M. haemohominis and determined its draft genome for an isolate from serum of the patient. A high copy number of the Candidatus M. haemohominis genome was detected in serum and bone marrow samples. Electron microscopy examination showed morphologic characteristics of Candidatus M. haemohominis. Levofloxacin monotherapy induced resistance caused by a gyrase A gene mutation in the quinolone resistance-determining region, but a combination treatment with moxifloxacin and minocycline was effective. We identified Candidatus M. haemohominis in a patient who had life-threatening symptoms related to multiple organ infection. Human infection with this mycoplasma might occur more frequently than has been generally recognized.

Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of japanese society of chemotherapy, the japanese association for infectious diseases, and the japanese society for clinical microbiology in 2016: General view of the pathogens' antibacterial susceptibility.

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from the patients in Japan was conducted by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2016. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period between February 2016 and August 2016 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical Laboratory Standards Institute. Susceptibility testing was evaluated in 1062 strains (143 Staphylococcus aureus, 210 Streptococcus pneumoniae, 17 Streptococcus pyogenes, 248 Haemophilus influenzae, 151 Moraxella catarrhalis, 134 Klebsiella pneumoniae, and 159 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was 48.3%, and those of penicillin-susceptible S. pneumoniae was 99.5%. Among H. influenzae, 14.1% of them were found to be ß-lactamase-producing ampicillin-resistant strains, and 41.1% to be ß-lactamase-non-producing ampicillin-resistant strains. Extended spectrum ß-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo ß-lactamase were 4.5% and 0.6%, respectively.

High burden of Aspergillus fumigatus infection among chronic respiratory diseases.

Aspergillus fumigatus (AF) is a ubiquitous fungus in our environment and causes severe airway disorders. Chronic respiratory diseases (CRDs) are a series of chronic airway and lung diseases. Although both are chronic disorders, however, the relationships between AF and CRDs are still unclear. Therefore, we examined 104 Aspergillus species (spp.) isolated samples in our hospital during three consecutive years to further elucidate the relationships between Aspergillus spp. and CRDs. Based on sample isolates, we then grouped these into two groups, AF and non-AF, to retrospectively analyse the clinical features and to clarify the relationships between AF and CRDs. Importantly, the manifestation of CRD was more frequent in the AF group than in the non-AF group ( p = 0.035). Among CRDs, lung fibrosis was more evident in the AF group ( p = 0.025). Moreover, diabetes mellitus was tended to be evident in AF group than non-AF group ( p = 0.035). In conclusion, CRDs, especially lung fibrosis, were highly prevalent in AF group than non-AF group.

Serotype distribution of Streptococcus pneumoniae isolated from adult respiratory tract infections in nationwide Japanese surveillances from 2006 to 2014.

BACKGROUND AND OBJECTIVE: Reports on the efficacy of pneumococcal conjugate vaccines (PCVs) have been received from many countries. However, in countries where the 7-valent PCV (PCV7) and 13-valent PCV (PCV13) were introduced, overall coverage of the serotypes by the vaccine gradually decreased due to pneumococcal serotype replacement. The aim of this study is to assess the distribution of pneumococcal serotypes and to also provide basic data on adult respiratory infection in Japan. METHODS: We analyzed 1086 Streptococcus pneumoniae strains that had been isolated from respiratory tract infection specimens in adult patients from 2006 to 2014. Capsular typing was performed by the Quellung reaction and multiplex PCR. RESULTS: Among all 1086 strains, serotype 3 was the most common and was identified in 160 strains (14.7%), followed by serotypes 19F, 6B, 19A and 23F. From 2006-10 to 2012-14, the coverage rate of PCV7 tended to gradually decrease. Particularly, serotypes 6B and 19F of penicillin non-susceptible strains decreased. On the other hand, serotypes 19A and 15A of penicillin non-susceptible strains increased. However, coverage by PCV13 of penicillin-resistant S. pneumoniae (PRSP) (penicillin G minimum inhibitory concentration ≥2 µg/mL) remained high (88.7% [2006-10], 88.0% [2012-14]). CONCLUSIONS: In Japan, PCV13 vaccination of adults became available from June 2014. Our study demonstrated that most PRSP (88.0%) still remain covered by PCV13. At present, the introduction of PCV13 in adult clinical practice seems to be highly significant. However, there is a possibility that the distribution has been changing, and careful screening should be continued in the future.

Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2012: General view of the pathogens' antibacterial susceptibility.

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from the patients in Japan was conducted by Japanese Society of Chemotherapy, Japanese association for infectious diseases and Japanese society for Clinical Microbiology in 2012. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period between January and December in 2012 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical Laboratory Standard Institutes. Susceptibility testing was evaluated in 1236 strains (232 Staphylococcus aureus, 225 Streptococcus pneumoniae, 16 Streptococcus pyogenes, 231 Haemophilus influenzae, 147 Moraxella catarrhalis, 167 Klebsiella pneumoniae and 218 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was 51.3%, and those of penicillin-intermediate S. pneumoniae was 0.4%. Among H. influenzae, 5.6% of them were found to be ß-lactamase-producing ampicillin-resistant strains, and 37.2% to be ß-lactamase-non-producing ampicillin-resistant strains. Extended spectrum ß-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo ß-lactamase were 4.2% and 3.2%, respectively. Continuous national surveillance is important to determine the actual situation of the resistance shown by bacterial respiratory pathogens to antimicrobial agents.

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.

Effect of interventions by an antimicrobial stewardship team on clinical course and economic outcome in patients with bloodstream infection.

BACKGROUND: Bloodstream infections (BSIs) represent one of the most severe and clinically important conditions in the hospital setting. We have organized an interdisciplinary antimicrobial stewardship team (AST) at our hospital and performed consultations focusing on BSI patients since 2013. This study aimed to evaluate the impact of AST interventions on the diagnosis, treatment, and clinical outcomes of BSI patients. METHODS: We conducted a retrospective quasi-experimental study of BSI patients at a single Japanese university hospital. AST provided recommendations to attending physicians regarding appropriate diagnosis, therapy, and management of BSI patients after reviewing medical charts. RESULTS: We identified a total of 308 cases of BSI from January to December, 2012 (pre-intervention group) and 324 cases of BSI from April, 2013 to March, 2014 (post-intervention group). No significant differences in the in-hospital mortality or 30-day mortality rates were observed between both the groups. Inappropriate therapy was initiated in a significantly lower proportion of patients in the post-intervention group (18.5% vs. 11.4%; P = 0.012). Multivariate analysis confirmed that inappropriate therapy was significantly associated with in-hospital mortality (odds ratio, 2.62; 95% confidence interval, 1.42-4.82; P = 0.002). CONCLUSIONS: An interdisciplinary AST intervention approach decreases the use of inappropriate therapy and may improve clinical outcomes in BSI patients.

Terminal-stage prognostic analysis in candidemia.

BACKGROUND: Candidemia has an extremely high mortality rate but is not always the direct cause of death. Therefore, determining the effect of candidemia on death is extremely difficult. METHODS: We investigated prognostic factors in patients with culture-proven candidemia at 2 Japanese university teaching hospitals from April 2009 through May 2013. To examine the effects of comorbid conditions, the Charlson comorbidity index was determined, and patients were subjectively classified into 3 clinical prognostic stages (terminal [death expected within 1 month], semiterminal [death expected within 6 months], and nonterminal [expected to live more than 6 months]). The Cox proportional hazard model was used for univariate and multivariate analyses of factors possibly affecting survival. RESULTS: On univariate analysis, factors identified as associated with an increased mortality rate were: admission to an internal medicine department, Candida glabrata, immunosuppression, hypotension, hypoxemia, and a terminal prognostic stage. Factors associated with a decreased mortality rate were: serum albumin, endophthalmitis investigation, and nonterminal prognostic stage. The mortality rate was significantly related to the prognostic stage on multivariate analysis (P < 0.0001), was increased by age (P = 0.0014), and was decreased by a delayed start of antifungal therapy (P = 0.0374). CONCLUSION: In contrast to earlier studies, the present study has found that later antifungal usage is associated with a decreased mortality rate in cases of candidemia. More important than candidemia in causing the deaths of patients with candidemia were the patients' background and comorbidity status. Therefore, rigorous methods should be used when investigating causes of death in terminally ill patients with candidemia.

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.

Iliopsoas abscess caused by Aspergillus fumigatus complicated by pulmonary aspergillosis.

We report a case of iliopsoas abscess caused by Aspergillus fumigatus with pulmonary complications. A 60-year-old man was admitted to the Showa University Hospital Department of Gastroenterology with fulminant hepatitis B on April 14, 2010, and treated with steroids. Although fulminant hepatitis B was improved by steroid and symptomatic therapy, he developed a fever on hospital day 39. The chest X-ray film showed a nodular lesion in the right middle-lower lung field, and both the (1 â†’ 3)-ß-D: -glucan and Candida mannan antigen tests were positive. The ß-D: -glucan level increased despite treatment with fluconazole and other drugs, including low-dose micafungin. Abdominal computed tomography showed a low-density area in the right iliopsoas muscle. He was then referred to the Department of Clinical Infectious Diseases. A. fumigatus was isolated from the iliopsoas lesion and the pulmonary lesion after specimens were obtained by aspiration and bronchofiberscopy, respectively, leading to a diagnosis of fungal iliopsoas abscess. Steroid therapy was tapered early, the abscess was drained, and the micafungin dose was increased. This treatment led to improvement of the fever, inflammatory reaction, ß-D: -glucan level, and lesions of the lung and iliopsoas muscle. In preparation for discharge, treatment was changed to voriconazole (parenteral â†’ per oral) followed by itraconazole (per oral). His clinical course was satisfactory, and there was no recurrence after antifungal therapy was stopped. We conclude that after invasive pulmonary aspergillosis developed, A. fumigatus spread hematogenously to create an extremely rare iliopsoas abscess. The ß-D: -glucan level closely reflected the response to treatment and was useful for follow-up.

Measurement of antifungal drug levels in cerebrospinal fluid for cryptococcal meningoencephalitis.

We report a rare case of cryptococcal meningoencephalitis in which antifungal therapy was monitored by measuring the cerebrospinal fluid (CSF) levels of the antifungal drugs. A 78-year-old man with diabetes mellitus being treated with oral agents. He had no history of human immunodeficiency virus infection. The patient showed abnormal behavior and fever (>38°C) on November 20, 2009, and was admitted for disturbance of consciousness on November 24. CSF examination showed an increased cell count, and a yeast-like fungus, suggesting cryptococcal meningoencephalitis, was observed by India ink staining. Initial treatment was liposomal amphotericin B (L-AMB) plus flucytosine. Cryptococcus neoformans was isolated by CSF culture on day 2. MIC was 0.25 µg/ml for amphotericin B (AMPH-B), 4 µg/ml for flucytosine, 4 µg/ml for fluconazole (FLCZ), and 0.03 µg/ml for voriconazole (VRCZ). Despite treatment, his disturbance of consciousness persisted. The CSF level of AMPH-B was ≤0.05 µg/ml on day 8. Therefore, L-AMB was switched to fosfluconazole. The CSF level of FLCZ was sufficient (22.6 µg/ml) on day 25, but there was a decrease in glucose and the fungus could still be detected in CSF smears. Consequently, FLCZ was switched to VRCZ. On day 47, CSF level of VRCZ was 1.97 µg/ml, exceeding its MIC, so treatment was continued. On day 77, the patient was generally lucid, and CSF smears did not detect any fungi. The patient was then transferred for rehabilitation. On day 84, voriconazole was discontinued, with no evidence of fungal recurrence.

Days of Antibiotic Spectrum Coverage Trends and Assessment in Patients with Bloodstream Infections: A Japanese University Hospital Pilot Study.

The antibiotic spectrum is not reflected in conventional antimicrobial metrics. Days of antibiotic spectrum coverage (DASC) is a novel quantitative metric for antimicrobial consumption developed with consideration of the antibiotic spectrum. However, there were no data regarding disease and pathogen-specific DASC. Thus, this study aimed to evaluate the DASC trend in patients with bloodstream infections (BSIs). DASC and days of therapy (DOT) of in-patients with positive blood culture results during a 2-year interval were evaluated. Data were aggregated to calculate the DASC, DOT, and DASC/DOT per patient stratified by pathogens. During the 2-year study period, 1443 positive blood culture cases were identified, including 265 suspected cases of contamination. The overall DASC, DASC/patient, DOT, DOT/patient, and DASC/DOT metrics were 226,626; 157.1; 28,778; 19.9; and 7.9, respectively. A strong correlation was observed between DASC and DOT, as well as DASC/patient and DOT/patient. Conversely, DASC/DOT had no correlation with other metrics. The combination of DASC and DOT would be a useful benchmark for the overuse and misuse evaluation of antimicrobial therapy in BSIs. Notably, DASC/DOT would be a robust metric to evaluate the antibiotic spectrum that was selected for patients with BSIs.

Mold colonization of fiberglass insulation of the air distribution system: effects on patients with hematological malignancies.

We investigated mold colonization of air handling units (AHUs) of heating, ventilating, and air conditioning (HVAC) systems and its effects, including invasive pulmonary mycoses and febrile neutropenia, in patients with hematological malignancies. Sample collection with transparent adhesive tape and culture swabs revealed that AHUs were heavily colonized with molds, including thermotolerant, variously distributed Penicillium spp. Cases of nosocomial invasive pulmonary mycosis were not clustered in specific patient rooms but did occur frequently when the HVAC systems were not in use, prior to intervention (i.e., sealing and disuse of AHUs in private room), and during construction of a new hospital building. Multivariate logistic regression analysis of initial episodes of febrile neutropenia showed that the rate of febrile neutropenia was significantly associated with the duration of neutropenia (odds ratio [OR]: 1.16; 95% confidence interval [CI]: 1.07-1.27) and with sex (OR: 0.469; CI: 0.239-0.902). An evaluation of private rooms showed that female patients also had a lower rate of fever after intervention (OR: 0.0016; 95% CI: 0.000-0.209). The reduced rate of febrile neutropenia after intervention suggests that mold colonization of AHUs had adverse effects on patients with hematological malignancies.

Clinical viability of Fungitell, a new (1→3)-ß-D: -glucan measurement kit, for diagnosis of invasive fungal infection, and comparison with other kits available in Japan.

Fungitell, a (1→3)-ß-D: -glucan (ß-D: -glucan) measurement kit, was approved in the United States in 2004. Three other kits for measurement of ß-D: -glucan, Fungitec G test MK (G-MK), ß-Glucan test Wako (Wako), and ß-Glucan test Maruha (Maruha), are commonly used for diagnosis of invasive fungal diseases in Japan. We evaluated the clinical viability of the Fungitell kit and compared it with the 3 kits generally used in Japan. The plasma ß-D: -glucan values measured with each kit showed some differences, possibly because different ß-D: -glucan standards, blood pretreatment methods, and kinds of horseshoe crab (a raw material for the main reagent) are used in each kit. Measures of diagnostic efficiency, for example the sensitivity, specificity, and positive and negative predictive values, varied among the kits. Although the areas under the receiver operating characteristic curves of the kits were not significantly different, the sensitivity of the Fungitell kit was the highest, followed by that of the G-MK kit. The sensitivity of the Wako and Maruha kits was low, but the specificity of these tests was higher than that of the G-MK or Fungitell kits. These inconsistent ß-D: -glucan measurements could interfere with diagnosis of invasive fungal infection. Early establishment of an international standard method for measurement of ß-D: -glucan is required.

Two-way analysis for detecting factors affecting ventilator-associated pneumonia.

The "clinically required ventilation period" for assessing ventilator-associated pneumonia (VAP) has not been studied because this period could not be clinically predicted. We addressed this problem using both rate analysis and failure-time analysis. A total of 325 patients who had received mechanical ventilatory support in the intensive care unit of a university hospital were reviewed. The total ventilation period and the ventilation period before VAP were compared using logistic regression and the Cox proportional hazard model for univariate and multivariate analyses. The Frechet distribution model was also used. Fifty patients were excluded for having pneumonia before intubation or for being admitted to a department in which no VAP occurred; 12 patients had VAP. Discrepancies in both methods caused by time-dependent bias were observed in patients emergently admitted (odds ratio, 1.435; hazard ratio, 0.3928). This reduced hazard ratio remained with the multivariate Frechet distribution model. Longer operation time significantly increased the VAP rate in the logistic model only. Low body mass index increased the rate of VAP in both models, especially in female patients (hazard ratio, 0.1707; 95% confidence interval, 0.02105-0.6728). The results of rate analysis and failure-time analysis were similar for most factors but differed somewhat for several factors, such as emergency admission. Unknown factors might be obscured by this type of difference, and this two-way method might be able to reveal artificial effects.

[Case of multiple vertebral osteomyelitis due to Streptococcus pneumoniae].

We report a rare case of multiple vertebral osteomyelitis due to Streptococcus pneumoniae. A 73-year-old man admitted for back pain and a low-grade fever was found in laboratory studies to have severe leukocytosis and increased C-reactive protein, but neither computed tomography (CT) nor vertebral magnetic resonance imaging (MRI) clarified the cause of infection in the painful hip lesion, and paralysis developed. in the left leg MRI eventually indicated a vertebral abscess involving multiple lesions at C4-7 and L4-5. We had started antibiotics before blood culture clarified Streptocccus pneumonaie, and antibiotics acted more effectively thereafter. The clinical course was good, little paralysis remained.

Epidemiology and risk factors for mortality in bloodstream infections: A single-center retrospective study in Japan.

BACKGROUND: Few published data are available on the morbidity and mortality of bloodstream infections (BSIs) in Japan. We sought to investigate the epidemiology of BSIs, the involvement of antimicrobial resistance, and the factors that influence patient prognosis. METHODS: This single-center study retrospectively evaluated patients who were found to have positive blood cultures at a tertiary teaching hospital between January 2012 and December 2016. RESULTS: A total of 2,105 patients with BSIs were included; 1,786 survived and 319 died, and the 30-day mortality rate was 15.2% over the 5-year study period. BSIs caused by yeasts were independently associated with 30-day mortality. The 30-day mortality rate of BSIs caused by extended-spectrum beta lactamase-producing gram-negative bacteria was significantly higher than that of BSIs caused by nonproducing bacteria. DISCUSSION: The differences in mortality may be caused by differences in the distribution of pathogens and in the delivery of health care. CONCLUSIONS: This study reported epidemiology and antimicrobial resistance data of BSIs in Japan and identified several risk factors associated with 30-day mortality. National surveillance of BSIs is required in Japan for comparison with other countries.