Empyema and bacteremia caused by Aeromonas hydrophila: Case report and review of the literature.

INTRODUCTION: Despite the advance in antibiotics and widespread chest tube drainage, acute empyema still shows a high mortality rate, accounting for 10-25%. We experienced a case of acute empyema caused by A. hydrophila, which is extremely uncommon, and reviewed all previously published articles. CASE PRESENTATION: A 76-year older man with a medical history of liver cirrhosis (LC) due to chronic hepatitis C and hepatic cell carcinoma was admitted to our institute. Elevated inflammatory reaction and effusions on chest CT were seen, and he was suspected of having acute empyema. Although an empiric antibiotic therapy of meropenem with chest tube drainage was performed as an initial treatment, he died within 8 hours of admission. Postmortem, both blood and left pleural fluid cultures yielded Aeromonas hydrophila. The final diagnosis was acute empyema caused by A. hydrophila. We reviewed previously reported empyema caused by Aeromonas species cases (4 A. hydrophila, and 1 A. veronii) in 4 previous reports written in English, including ours. Of 5, all were male, and the mean age was 52 years (range 27-76 years). All patients had LC due to alcohol or viral infections. As for antibiotics initially prescribed, third-generation cephalosporins were most frequently used in 3/5 (60%). Thoracentesis was performed in all patients (100%). As for prognosis, 2 (40%) survived, and 3 (60%) died. CONCLUSION: Physicians should be aware of the possibility of acute empyema caused by A. hydrophila among patients with chronic hepatic disease.

Efficacy and validity of guideline-concordant treatment according to the JRS guidelines for the managements of pneumonia in adults updated in 2017 for nursing and healthcare-associated pneumonia. A propensity-matching score analysis.

INTRODUCTION: Patients with nursing and healthcare-associated pneumonia (NHCAP) commonly receive empiric antibiotic therapy according to the guideline's recommendation corresponding to the patient's deteriorated conditions. However, it is unclear whether guideline-concordant treatment (GCT) could be effective or not. PATIENTS AND METHODS: To evaluate the efficacy and validity of GCT according to the current guideline for pneumonia, we conducted this retrospective study. NHCAP patients who were admitted to our institute between 2014 and 2017 were enrolled. Based on the initial antibiotic treatment, these patients were divided into two groups, the GCT group (n = 83) and the non-GCT group (n = 146). Propensity score matching (PSM) was used to balance the baseline characteristics and potential confounders between the two groups. After PSM, patients' characteristics, microbial profiles, and clinical outcomes were evaluated. RESULTS: Both groups were well-balanced after PSM, and 78 patients were selected from each group. There were no differences in patients' characteristics or microbial profiles between the two groups. As for outcomes, there were no differences in 30-day, in-hospital mortality rate, duration of antibiotic treatment, or admission. The severity of pneumonia was more severe in patients with the GCT group than those with the non-GCT group. Anti-pseudomonal agents as initial treatment were more frequently seen in patients with the GCT group than those in the non-GCT group. CONCLUSION: Unlike previous studies, GCT's recommendation for management of pneumonia by the JRS in 2017 would appear to be valid and does not increase the mortality rate.

Comparative study of SmartAmp assay and reverse transcription-polymerase chain reaction by saliva specimen for the diagnosing COVID-19.

INTRODUCTION: The pandemic of a novel coronavirus disease 2019 (COVID-19) caused by a severe acute respiratory coronavirus 2 (SARS-CoV-2) infection has been problematic worldwide. A new SARS-CoV-2 diagnostic test (SmartAmp) was licensed in Japan in July 2021. This method, which enables us to diagnose COVID-19 as well as a gene mutation on the virus, is promising to reduce medical costs and staff labor. PATIENTS AND METHODS: To analyze the diagnostic accuracy of the SmartAmp assay for diagnosing COVID-19, we performed this retrospective study at our institute during April and May 2021. We compared the results of the SmartAmp assay and real-time reverse transcription-polymerase chain reaction (rRT-PCR) using a saliva sample from individuals suspected as having COVID-19. RESULTS: Out of 70 samples tested, the SmartAmp assay had 50 (71%) positive and 20 (29%) negative results. Using rRT-PCR as a reference, the diagnostic accuracy displayed a sensitivity of 84%, a specificity of 95%, a positive predictive value of 97.7%, and a negative predictive value of 70.4%. On the other hand, false-negative cases were found in 7 (10%), and there was no significant difference of Ct-value between true positive and false negative cases (Mean Ct-value 25.2 vs. 27.5 cycles, p = 0.226 by Mann-Whitney U test). CONCLUSION: The SmartAmp assay is a valuable method to diagnose COVID-19 rapidly. However, the negative predictive value is not high enough to diagnose the disease, so that negative results should be considered for rRT-PCR testing if patients are suspected of having COVID-19.

Risk factors of first recurrence of Clostridioides difficile infection.

OBJECTIVES: Clostridioides difficile infection (CDI) often recurs. Approximately 25% of patients have recurrences after the initial treatment, and patients who have relapsed once are more likely to relapse. We aimed to identify the risk factors for initial CDI recurrence. METHODS: We performed a retrospective survey of patient backgrounds and treatment-related factors. Risk factors were analyzed using single and multiple logistic regression analyses. RESULTS: A total of 134 patients were included in the study. Prophylactic probiotic use and nasogastric tube feeding were independent risk factors for the initial recurrence of CDI. Patients using prophylactic probiotics had significantly higher recurrence rates than those not using prophylactic probiotics. CONCLUSION: Prophylactic probiotic use and nasogastric tube placement may be risk factors for the initial recurrence of CDI. It is noteworthy that CDI that occurs during the use of prophylactic probiotics may be prone to recurrence.

Combination of Sequential Organ Failure Assessment (SOFA) score and Charlson Comorbidity Index (CCI) could predict the severity and prognosis of candidemia more accurately than the Acute Physiology, Age, Chronic Health Evaluation II (APACHE II) score.

BACKGROUND: Candidemia has emerged as an important nosocomial infection, with a mortality rate of 30-50%. It is the fourth most common nosocomial bloodstream infection (BSI) in the United States and the seventh most common nosocomial BSI in Europe and Japan. The aim of this study was to assess the performance of the Sequential Organ Failure Assessment (SOFA) score for determining the severity and prognosis of candidemia. METHODS: We performed a retrospective study of patients admitted to hospital with candidemia between September 2014 and May 2018. The severity of candidemia was evaluated using the SOFA score and the Acute Physiology, Age, Chronic Health Evaluation II (APACHE II) score. Patients' underlying diseases were assessed by the Charlson Comorbidity Index (CCI). RESULTS: Of 70 patients enrolled, 41 (59%) were males, and 29 (41%) were females. Their median age was 73 years (range: 36-93 years). The most common infection site was catheter-related bloodstream infection (n=36, 51%).The 30-day, and in-hospital mortality rates were 36 and 43%, respectively. Univariate analysis showed that SOFA score ≥5, APACHE II score ≥13, initial antifungal treatment with echinocandin, albumin < 2.3, C-reactive protein > 6, disturbance of consciousness, and CCI ≥3 were related with 30-day mortality. Of these 7, multivariate analysis showed that the combination of SOFA score ≥5 and CCI ≥3 was the best independent prognostic indicator for 30-day and in-hospital mortality. CONCLUSIONS: The combined SOFA score and CCI was a better predictor of the 30-day mortality and in-hospital mortality than the APACHE II score alone.

The combined score of quick SOFA and the charlson comorbidity index could be a poor prognostic indicator for in-hospital mortality among patients with necrotizing fasciitis.

INTRODUCTION: While necrotizing fasciitis (NF) is a rare but rapidly progressive devastating soft tissue infectious disease showing a high in-hospital mortality rate of 20-30%, there are no evidence-based predictive tools. PATIENTS AND METHODS: For the purpose of examining which predictive tools could correctly reflect the severity and prognosis of NF, we retrospectively reviewed all patients who were diagnosed with NF at our institute. The disease severity was evaluated by quick SOFA (qSOFA), SOFA score, SIRS score, APACHE II score, LRINEC score and the combined score of qSOFA and CCI. RESULTS: A total of 27 patients were enrolled in this study. The median age was 68 years (range 39-96 years). With respect to the predictive values for in-hospital mortality among NF patients, the area under the ROC curve for qSOFA, SOFA score, APACHE II score, the combined score of qSOFA and CCI were 0.653 (p = 0.192), 0.588 (p = 0.12), 0.709 (p = 0.075) and 0.782 (p = 0.016) respectively. A univariate analysis showed that the combined score of qSOFA and CCI≥5 and the initial treatment failure were poor prognostic indicators for the in-hospital death among NF patients. The appropriate cut-offs of qSOFA and CCI were based on the Youden Index. CONCLUSION: We concluded that the combined score of qSOFA and CCI could reflect the severity and prognosis of NF for in-hospital death.

Usefulness of serum procalcitonin for necrotizing fasciitis as an early diagnostic tool.

INTRODUCTION: While the early diagnosis of necrotizing fasciitis (NF) is crucial and could lead to a favorable outcome, it is difficult to differentiate NF from cellulitis, resulting in delay for the appropriate treatment. PATIENTS AND METHODS: For the purpose of examining which diagnostic tools could correctly differentiate NF from cellulitis, we conducted this case-control study. We retrospectively reviewed all patients who were diagnosed with NF at our institute during 2014-2019. The patients who were diagnosed with cellulitis were randomly selected during the study period as the control group. The severity of NF is evaluated by serum-procalcitonin (PCT), LRINEC score, NTSI assessment and SIARI score. RESULTS: A total of 25 NF patients were enrolled in this study. The median age was 68 years (range 39-79) and 18 (72%) were male. Comparing NF and cellulitis groups, NF group showed a higher LRINEC score and serum PCT than cellulitis group did, even though there was no statistical significance in serum PCT. With respect to the diagnostic value for differentiating NF from cellulitis, the area under the ROC curve for of serum PCT and LRINEC scores were 0.928 [95% confidential interval (CI) 0.864-0.992, p < 0.001] and 0.846 (95% CI 0.757-0.936, p < 0.001). The appropriate serum-PCT cutoff value was 1.0 and had a sensitivity of 88%, a specificity of 89%, a positive predictive value of 81%, and a negative predictive value of 93%. CONCLUSION: Serum-PCT could be a useful diagnostic marker for differentiating diagnosis of NF from cellulitis.

Ceftriaxone versus tazobactam/piperacillin and carbapenems in the treatment of aspiration pneumonia: A propensity score matching analysis.

INTRODUCTION: Aspiration pneumonia (AP) accounts for 5.0-53.2% of hospitalized pneumonia and the treatment commonly used is by broad-spectrum antibiotics to cover anaerobes. Since ceftriaxone (CTRX) could generally cover oral streptococcus and anaerobes implicated in AP, it could be a useful option in the treatment of AP, instead of piperacillin-tazobactam/(PIPC/TAZ) or Carbapenems. PATIENTS AND METHODS: For the purpose of examining whether CTRX is as effective as broad-spectrum antibiotics for the treatment of AP, this retrospective study included consecutive community-onset patients who were admitted to our institute between 2014 and 2017. These patients were divided into two groups, a CTRX group (n = 25) and a PIPC/TAZ or carbapenems group (n = 97) based on the initial antibiotic treatment. Propensity score matching (PSM) was used to balance the potential confounders, and 23 patients were selected from each group. Patients among CTXR group received CTRX, while those among PIPC/TAZ or carbapenems group received PIPC/TAZ, or carbapenems and/or other agents. RESULTS: Both groups were well-balanced after PSM. There were no differences in 30-day mortality, duration of hospital stay or antibiotic treatments in the between them. The medical costs were much more expensive in the PIPC/TAZ or carbapenems group than in the CTR group (35,582 v. s. 8678 Japanese yen, p < 0.001). CONCLUSION: CTRX is one of the most useful antibiotic treatment for AP, which is not inferior to broad-spectrum antibiotic treatment. In addition, usage of CTRX in the treatment of AP is more economical than broad-spectrum antibiotic treatment, and could contribute to reduction of medical costs.

An unexpected case of Cardiobacterium valvarum prosthetic arthritis without cardiac lesions: Case report and literature review.

We report a case of prosthetic arthritis caused by Cardiobacterium valvarum, which has been exclusively reported to cause intravascular infections. A 81-year-old Japanese female complained prosthetic knee joint pain. Arthrocentesis cultured no pathogen, and surgical replacement of the implant surface was performed. Modified Levinthal medium culture and 16S rRNA sequencing has finally led to diagnosis of C. valvarum prosthetic knee arthritis without cardiac lesions. Fastidious bacteria such as C. valvarum can be candidate pathogens of orthopedic infections whose causative agents are sometimes unidentified. Further development of molecular diagnostics is expected, but also the importance of conventional methods should be noted.

Efficacy and validity of automated quantitative chemiluminescent enzyme immunoassay for SARS-CoV-2 antigen test from saliva specimen in the diagnosis of COVID-19.

INTRODUCTION: The pandemic of a novel coronavirus disease 2019 (COVID-19) caused by a severe acute respiratory coronavirus 2 (SARS-CoV-2) infection has been problematic worldwide. A new SARS-CoV-2 antigen test (LUMIPULSEⓇ) was licensed and widely used in Japan since May 2020. We conducted this study intending to whether the automated quantitative CLEIA antigen test using a saliva sample is effective and valid for the diagnosis of COVID-19. PATIENTS AND METHODS: We analyzed and compared the diagnostic accuracy of both the automated quantitative CLEIA antigen test and real-time RT-PCR (rRT-PCR) using a saliva sample from individuals suspected as having COVID-19. RESULTS: A total of 305 samples were collected and tested in Aichi Medical University Hospital and affiliated facilities from December 2020 until January 2021 at our institute. Using reverse-transcription PCR as a reference, the AUROC of the automated quantitative CLEIA antigen test was 0.903 (95% confidential interval 0.845-0.962, p < 0.001). The appropriate cut-off antigen level was 4.0 pg/mL and had a sensitivity of 77.8%, a specificity of 99.6%, a positive predictive value of 98%, and a negative predictive value of 94.5%. On the other hand, the diagnostic accuracy of the antigen test decreased among patients among patients with COVID-19 with threshold cycle (Ct-value)≥27, which shows the AUROC was 0.795 (95%CI 0.687-0.907, p < 0.001). CONCLUSION: While the automated quantitative CLEIA antigen test from saliva specimen could be one of the most useful diagnostic tests for the diagnosis of COVID-19 in general practice, clinicians should know the limitations of the antigen test.

Comparative evaluation of nasopharyngeal swab and saliva specimens for the molecular detection of SARS-CoV-2 RNA in Japanese patients with COVID-19.

Considering the issues of shortage of medical resources and the invasiveness and infection risk involved in the collection of nasopharyngeal swab specimens, there is a need for an effective alternative test specimen for SARS-CoV-2 RNA detection. Here, we investigated suitability of saliva as a non-invasively obtained specimen for molecular detection of SARS-CoV-2 RNA in Japanese patients with COVID-19. In total, 28 paired clinical specimens of saliva and nasopharyngeal swabs were collected from 12 patients at various time points after symptom onset. Each specimen was assayed using reverse transcription real-time polymerase chain reaction (rRT-PCR) on the BD MAX open system using primers and probes targeting the N-gene. The saliva and nasopharyngeal swab specimens showed 19 and 15 positive results, respectively. No invalid (PCR inhibition) result was observed for any specimen. The qualitative results of each specimen obtained in the period immediately after symptom onset were similar. Three convalescent patients presented saliva-positive results, whereas their nasopharyngeal swabs were negative at four different time points, suggesting that saliva may be superior to nasopharyngeal swabs in terms of obtaining stable assay result of SARS-CoV-2. In conclusion, our results suggest that saliva can potentially serve as an alternative to nasopharyngeal swabs as a specimen for SARS-CoV-2 rRT-PCR. As saliva can be collected by patients themselves, it may be an effective way to overcome the shortage of personal protective equipment and specimen sampling tools.

Could threshold cycle value correctly reflect the severity of novel coronavirus disease 2019 (COVID-19)?

The novel coronavirus disease 2019 (COVID-19) is diagnosed by positive result of reverse transcription polymerase chain reaction (RT-PCR) for the novel coronavirus. We concluded that cycle threshold value (Ct-value) of real-time RT-PCR (rRT-PCR) assay could decrease as patients recover. Results of rRT-PCR assay could remain positive among asymptomatic patients for longer than 2 weeks. The discharge criteria of COVID-19 patients using a negative result of rRT-PCR should be reconsidered.

Can presepsin uniformly respond to various pathogens? - an in vitro assay of new sepsis marker.

BACKGROUND: Presepsin (soluble CD14 subtype) is a novel biomarker of sepsis used for early diagnosis. Originally, CD14 is known as the pattern recognition receptor for the lipopolysaccharide (LPS)/LBP complexes, and the diagnostic value of this molecule for gram-positive bacteria, which contain less amount of LPS, is uncertain. To confirm its effectiveness in the diagnosis of bacteremia caused by gram positive bacteria, and to evaluate the interspecies difference of presepsin production against various bacterial strains, we conducted an in vitro assay to evaluate presepsin levels in response to five Gram negative and four Gram positive bacteria. RESULTS: Whole blood was yielded from five healthy volunteers and co-cultured with bacterial strains at 37 °C for 4 h. Twenty seven clinical isolates of nine species (E. coli, K. pneumoniae, E. cloacae, P. aeruginosa, S. maltophilia, S. aureus, S. pyogenes, B. cereus, and C. striatum) derived from blood cultures of non-neutropenic bacteremia patients were used. Culture supernatants were harvested and presepsin levels were measured. The presepsin level in the gram-negative bacteria 273 (218-352) pg/mL was significantly higher than in the gram-positive bacteria 200 (143-275) pg/mL (p = 0.0002). The presepsin levels were significantly lower in C. striatum, in comparison to other bacteria, and S. pyogenes showed similar results. And the presepsin levels in P. aeruginosa were significantly lower compared to E. cloacae, K. pneumoniae, and S. aureus. CONCLUSIONS: Presepsin production can also be evoked by gram-positive bacteria, and interspecies differences of presepsin response may exist, which should be considered in the diagnosis of sepsis, especially in certain gram-positive bacteremia such as S. pyogenes or C. striatum.

Observational study in a single institute in Japan: How many community-onset pneumonia patients would have Clostridioides difficile infections after treatment?

While community-onset pneumonia patients such as community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP) have several risk factors of Clostridium difficile infection (CDI), prognostic guidelines for pneumonia never mention the occurrence of CDI following treatment for pneumonia. For the purpose of examining the occurrence and prevalence of CDI, we reviewed all community-onset pneumonia patients who were admitted to our institute during the study period. A total of 406 patients were enrolled in this study. Among them, 257 patients (63%) were male, and the median age was 79 years (range 19-103 years). Surprisingly, 155 CAP (88%) and all HCAP (100%) patients had one or more risk factors for CDI. Furthermore, 70 CAP (40%) and 157 HCAP (69%) patients had more than 3 risk factors for CDI. Despite these facts, probiotic medication for prevention of CDI were prescribed for 12 (7%) CAP and 15 (7%) HCAP patients as the initial treatment. Finally, 3% and 9% of CAP and HCAP patients had CDI after completing the treatment for pneumonia. Regarding the duration of antibiotic therapy, 146 CAP (82%) and 176 HCAP (77%) patients received it for longer than 8 days, even though bacteremia was not confirmed in those patients. In addition, 27 CAP (15%) and 26 HCAP (11%) patients received a combination antibiotic therapy as an initial treatment. They seemed to be unnecessary. Physicians should acknowledge community-onset pneumonia has several risk factors for CDI, and should avoid a longer than necessary antibiotic therapy and unnecessary combination antibiotic therapy for pneumonia patients with risk factors for CDI.

In vivo study assessed meropenem and amikacin combination therapy against carbapenem-resistant and carbapenemase-producing Enterobacteriaceae strains.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE), especially for carbapenemase-producing Enterobacteriaceae (CPE), is an emerging cause that pose a significant threat to public health. However, efficient therapy has not been established. We assessed the antimicrobial efficacy of meropenem (MEPM) and amikacin (AMK) combination therapy. MATERIAL AND METHODS: Total eight isolates of Escherichia coli or Klebsiella pneumoniae, including CRE and/or CPE have carbapenemase genes were used. The relationship between phenotype and in vivo efficacy was assessed in neutropenic murine thigh infection model. Efficacy was determined using the change in bacterial density and survival rate. RESULTS: The combination therapy showed enhanced antimicrobial activities against CRE+/CPE+ and CRE+/CPE-K. pneumoniae isolates than MEPM monotherapy (0.63 ± 0.04 vs. 2.56 ± 0.24 ⊿log10 cfu/mL, p < 0.05; -1.05 ± 0.15 vs. -0.48 ± 0.30 ⊿log10 cfu/mL, p < 0.05). Likewise, the combination therapy showed enhanced antimicrobial activities against CRE+/CPE+ and CRE+/CPE-E. coli isolates than MEPM monotherapy (0.90 ± 0.68 vs. 1.86 ± 0.23 ⊿log10 cfu/mL, p < 0.05; -1.81 ± 0.06 vs. -0.88 ± 0.23 ⊿log10 cfu/mL, p < 0.05). Also, combination therapy group showed similar to higher survival rates in CRE + E. coli infection mice, compared to MEPM monotherapy group. CONCLUSION: Our results are the first supportive data to threat CRE infections with combination therapy of MEPM and AMK with in vivo model. The current results verify the promising utility of the combination therapy with MEPM and AMK against CRE isolates with a wide range of MEPM MICs.

Brevibacterium paucivorans bacteremia: case report and review of the literature.

BACKGROUND: Brevibacteria are obligate aerobic gram-positive rods that are associated with milk products and are also found on human skin. Brevibacterium has been reported as a rare cause of catheter related blood steam infection mainly in immunocompromised hosts such as malignancies or AIDS patients. CASE PRESENTATION: A 94-year old woman, which had a past history of diabetes mellitus and chronic heart failure, presented with high fever associated with decreased oral intake and appetite loss and was admitted to our institute. A physical examination at the time of presentation was unremarkable. On day 2, both blood cultures collected on admission became positive with coryneform organism within 24 h without Staphylococci and Brevibacterium species were identified by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Subsequently, genetic investigation by 16S ribosomal RNA analysis was performed in order to identify the organism. Finally, the result identified this pathogen as Brevibacterium paucivorans with 99.5% homology on the Ez taxon database. The patient was started empirically on meropenem and teicoplanin for broad-spectrum antibiotic coverage. The patient's fever finally abated and labs were also improved. On day 14, the antibiotic therapy was discontinued. The site of infections was unknown. We hereby report a case of Brevibacterium paicivorans bacteremia in an immunocompetent patient and review cases of Brevibacterium specises bacteremia previously reported. This is the first case of B. paucivorans bacteremia as far as we could search. CONCLUSION: Physicians and microbiologists should be aware that Brevibacteria are uncommon but important agents which could cause opportunistic infections in immunocompetent.

The First Report on Pharmacokinetic/Pharmacodynamic Study of Trimethoprim/Sulfamethoxazole against Staphylococcus aureus with a Neutropenic Murine Thigh Infection Model.

INTRODUCTION: With an increase in the incidence of Staphylococcus aureus infections in the healthcare settings and in the community, trimethoprim/sulfamethoxazole (TMP/SMX) has been suggested as a convenient treatment option. However, the appropriate dosage regimen of TMP/SMX is unclear. OBJECTIVE: This study aimed to examine the pharmacokinetics/pharmacodynamics (PK/PD) of TMP/SMX against S. aureus using a neutropenic murine thigh infection model. METHODS: Five S. aureus isolates with TMP/SMX (1:5 fixed ratio) minimum inhibitory concentrations (MICs) of 0.032-64 µg/mL were tested. The antimicrobial efficacy of TMP/SMX (1-689 mg/kg/day: dose shown as SMX dosage) was calculated as the change in bacterial density after 24 h of treatment. The plasma concentrations of TMP/SMX were detected using high-performance liquid chromatography. RESULTS: After TMP/SMX single dose (130 mg/kg), the half-life, area under the blood concentration curve (AUC0-∞), and the protein binding ratio of SMX were 1.5 h, 718.2 µg h/mL, and 73.0 ± 8.3%, respectively. The free AUC/MIC and free %time (%T) above the MIC of SMX were better correlated with the in vivo antimicrobial activity than Cmax/MIC (free AUC/MIC, R2 = 0.69; free %T > MIC, R2 = 0.71; free Cmax/MIC, R2 = 0.53). The distributed doses (2-3 times per day) of TMP/SMX (130, 260, and 390 mg/kg/day) showed higher antimicrobial activity than the single dosage. However, TMP/SMX did not show its antimicrobial activity at <100% free %T > MIC. CONCLUSIONS: The TMP/SMX treatment demonstrated that the free AUC/MIC of SMX was the better predictor of the PK/PD index of TMP/SMX.

Clinical manifestations and risk factors of community-onset Acinetobacter species pneumonia in Japan; case control study in a single institute in Japan.

To clarify the etiology, patients' characteristics and risk factors for community-onset AP (Acinetobacter species pneumonia), we conducted this case-control study. We reviewed all patients with community-onset AP at our institute from 2010 until 2018. We defined non-AP group as a control. The patients with non-Acinetobacter spp. pneumonia (non-AP) were randomly selected during the study period without clinical information based on medical records' list among patients with community-onset pneumonia. The age (±2 years) and sex were matched to the patients with community-onset AP, and the ratio was AP:non-AP group = 1:3. Patients' characteristics, clinical outcomes, pathogens isolated and drug susceptibility were evaluated by comparing AP and non-AP group. The mean age of community-onset AP group was 79 years. They were 8 males and 5 females. The 30-day and in-hospital mortality rates of community-onset AP were 23% (v.s. 3%, p = 0.049) and 31% (v.s. 5%, p = 0.029) respectively, which are higher than the control group. Heavy alcohol consumption (23% v.v. 0%, p = 0.023), higher Charlson Comorbidity index (3.2 v.s. 2.0, p = 0.046) and lobar pneumonia by chest radiology (50% v.s. 23%, p = 0.071) were seen more frequently in community-onset AP than in the control group. In conclusion, community-onset AP shows poor outcomes despite the appropriate antibiotic therapy. Heavy alcohol history might be a risk factor of AP. Patients with community-onset AP could have more comorbidity and poor general conditions than the control group.

Clostridioides difficile-related toxic megacolon after Cryptococcus neoformans cellulitis: A complex of two rare infections in an immunocompromised host.

A 76-year-old Japanese woman was admitted due to uncontrolled cellulitis of the right lower leg. She had deep vein thrombosis on the right limb. Moreover, she had a long history of rheumatoid arthritis treated with corticosteroids. Skin biopsy and lumbar puncture were performed to diagnose disseminated cryptococcosis. She was administered antifungal agents (liposomal amphotericin B and 5-fluorocytosine). On treatment day 14, debridement was performed, and cryptococcosis was controlled. However, she developed toxic megacolon due to Clostridioides difficile infection (CDI). On day 32, she was transferred to the intensive care unit due to severe acidosis and acute kidney injury secondary to CDI-related toxic megacolon. Vancomycin, metronidazole, and tigecycline were administered for treatment of CDI. After several weeks of intensive care, toxic megacolon was improved, but renal replacement therapy was discontinued according to the patient's will. On day 73, she died of renal failure. We experienced a complex of rare diseases, Cryptococcus neoformans cellulitis and Clostridioides difficile-related toxic megacolon. Both diseases were presumed to be the result of corticosteroid and methotrexate use. Hence, careful monitoring is required when treating immunocompromised hosts to reduce the risk of developing complications.

Infective endocarditis caused by Cardiobacterium hominis endocarditis: A case report and review of the literature.

BACKGROUND: While it has been increasing cases of C. hominis endocarditis in the past decades due to advances of diagnostic methods, the epidemiology and clinical manifestations of IE caused by C. hominis is still unknown. CASE PRESENTATION: A 62-year old man was admitted to our institute with fever, anorexia and general fatigue for the preceding one month. He had a past medical history of both aortic and mitral valves replacement due to cardiac diseases. He was diagnosed as IE caused by C. hominis according to the modified duke criteria. The patient received 2 weeks of combination therapy of intravenous ceftriaxone (CTRX) 2g and gentamycin 180mg daily followed by 4 weeks CTRX 2g daily alone. Oral moxifloxacin 400mg once daily was given for an additional 4 weeks. After the antibiotic therapy was discontinued, disease recurrence was not observed. We reviewed previously reported C. hominis IE cases in 60 publications including ours. Of 73 patients enrolled, 53 were male, the mean age was 52 years. The most common risk factor of IE was past history of cardiac diseases in 44/73 (60%). As for antibiotics initially prescribed, third-generation cephalosporins was most frequently used in 28/69 (41%). While the cure rate was 67/73 (93%), 31/73 patients (43%) received a surgical intervention. Embolic lesions to the central nervous system and vertebrae were seen in 16/72 (22%) and 5/72 (7%). CONCLUSION: IE caused by C. hominis has a favorable prognosis, showing the cure rate of 93%. Physicians should recognize the possible occurrence of emboli among IE patients.