TMPRSS2 gene polymorphism common in East Asians confers decreased COVID-19 susceptibility.

COVID-19 has a wide range of clinical presentations, and the susceptibility to SARS-CoV-2 infection and the mortality rate also vary by region and ethnicity. Here, we found that rs12329760 in the TMPRSS2 gene, a missense variant common in East Asian populations, contributes to protection against SARS-CoV-2 infection. TMPRSS2 is a protease responsible for SARS-CoV-2 entry and syncytium formation. rs12329760 (c.478G>A, p. V160M) was associated with a reduced risk of moderate symptoms. The enzymatic activity of Met160-TMPRSS2 was lower than that of Val160-TMPRSS2, and thus the viral entry and the syncytium formation of SARS-CoV-2 were impaired. Collectively, these results indicate that the genetic variation in TMPRSS2, which is common in East Asians, is one of the molecular determinants of COVID-19 susceptibility.

Periprosthetic knee joint infection caused by Sneathia sanguinegens.

Sneathia sanguinegens is a fastidious, Gram-negative, rod-shape organism rarely isolated from human specimens. In the present report, we describe a case of periprosthetic knee joint infection due to the organism, which occurred in a female patient receiving immunosuppressants for underlying lupus nephritis. The causative organism was isolated from the synovial fluid in the affected knee joint through inoculating the material on chocolate agar and incubation for 15 days under 5% CO2. Moreover, the organism was capable to be subcultured on chocolate agar with incubation for a few days under 5% CO2, demonstrating that this uncommon organism, although generally considered as a strict anaerobe, is culturable in aerobic condition if appropriate media and a sufficient incubation time are given. The patient was treated with intravenous cefepime, an antibiotic highly active to the isolated organism in an in vitro study, in addition to intraarticular debridement and exchanging a polyethylene insert in the affected joint. The antimicrobial therapy with cefepime was given for 19 days and, thereafter, changed with oral levofloxacin. Although the patient showed full recovery after administration of levofloxacin for 100 days, an in vitro study conducted later revealed that levofloxacin was inactive to the isolated organism.

Optimal First-Line Antibiotic Treatment for Pediatric Complicated Appendicitis Based on Peritoneal Fluid Culture.

PURPOSE: Consensus is lacking regarding the optimal antibiotic treatment for pediatric complicated appendicitis. This study determined the optimal first-line antibiotic treatment for pediatric patients with complicated appendicitis based on peritoneal fluid cultures. METHODS: This retrospective study examined the cases of pediatric patients who underwent appendectomy for complicated appendicitis at our institution between 2013 and 2019. Peritoneal fluid specimens obtained during appendectomy were cultured for the presence of bacteria. RESULTS: Eighty-six pediatric patients were diagnosed with complicated appendicitis. Of them, bacteria were identified in 54 peritoneal fluid samples. The major identified bacteria were Escherichia coli (n=36 [66.7%]), Bacteroides fragilis (n=28 [51.9%]), α-Streptococcus (n=25 [46.3%]), Pseudomonas aeruginosa (n=10 [18.5%]), Enterococcus avium (n=9 [16.7%]), γ-Streptococcus (n=9 [16.7%]), and Klebsiella oxytoca (n=6 [11.1%]). An antibiotic susceptibility analysis showed E. coli was inhibited by sulbactam/ampicillin in 43.8% of cases versus cefmetazole in 100% of cases. Tazobactam/piperacillin and meropenem inhibited the growth of 96.9-100% of the major identified bacteria. E. coli (100% vs. 84.6%) and P. aeruginosa (100% vs. 80.0%) were more susceptible to amikacin than gentamicin. CONCLUSION: Tazobactam/piperacillin or meropenem is a reasonable first-line antibiotic treatment for pediatric complicated appendicitis. In the case of aminoglycoside use, amikacin is recommended.

Infective endocarditis caused by Nocardia nova: A case report and literature review of nocardial endocarditis.

Although a variety of microorganisms have caused infective endocarditis, Nocardia species have rarely been reported as a causative agent of the disease. We describe a case of nocardial endocarditis, occurring to a 22-year-old Japanese woman during long-term corticosteroid therapy for adult-onset Still's disease and diagnosed after the rupture of cerebral mycotic aneurysm. Echocardiography showed that the causative organism, isolated from the blood and identified as Nocardia nova with an analysis of 16S ribosomal RNA sequences, affected the posterior papillary muscle of the left ventricle. Nocardia-like organisms were also detected in the pus around the raptured aneurysm. After treatment with imipenem/cilastatin plus amikacin for 3 months followed by oral trimethoprim/sulfamethoxazole for 1 year, no relapse of nocardiosis occurred during a follow-up for 3 years. To our knowledge, the present case is the first reported endocarditis due to N. nova.

Characteristics of invasive Acinetobacter infection: A multicenter investigation with molecular identification of causative organisms.

We examined microbiological and clinical characteristics of invasive Acinetobacter infection occurring in four hospitals located in the Minami-Ibaraki Area. Glucose-non-fermentative Gram-negative bacilli isolated from the blood and the cerebrospinal fluid in independent cases between 2001 and 2014 were consecutively collected and those possibly to be Acinetobacter species were re-identified using molecular methods. Of 158 strains identified as Acinetobacter species, 155 were classified into 16 officially designated species, including 42 Acinetobacter pittii and 40 Acinetobacter baumannii. Imipenem non-susceptibility was detected only in 4 strains, none of which demonstrated multidrug resistance. Retrospective analyses of 154 cases for which medical records were fully available showed that the most common cause of infection was primary bloodstream infection (134 cases), of which 128 were related to intravascular catheter use. The mortality on day 28 after the onset was independently associated with cerebrovascular disease, moderate to severe renal disease, the Pitt bacteremia score, and infection other than primary bloodstream infection but not with appropriate empiric antimicrobial therapy. Isolation of A. baumannii was significantly associated with septic shock but not with the 28-day mortality. These findings, obtained in a region where drug-resistant Acinetobacter strains were much less prevailing, indicated that non-baumannii Acinetobacter species were common pathogens, that the most predominant cause of invasive Acinetobacter infection was intravascular catheter-related infection, that virulence of A. baumannii might be higher than those of other species but its association with mortality was unclear, and that administration of broad-spectrum antibiotics targeting Acinetobacter species might be deferrable in a certain situation.

Hematogenous pleural infection caused by Achromobacter xylosoxidans in a patient undergoing maintenance hemodialysis.

A 78-year-old Japanese man, undergoing maintenance hemodialysis for 20 years and having received coronary artery bypass grafting two months before, was hospitalized because of fever with subclinical left-sided pleurisy. Achromobacter xylosoxidans strains exhibiting identical genomic patterns on a macrorestriction analysis were isolated from the blood and the pleural effusion obtained on admission. Physical and radiological examinations did not reveal any lesions in either chest wall or lung adjacent to the effusion, indicating that the organism in the effusion had entered the pleural space via the bloodstream. Immunocompromising conditions due to undergoing maintenance hemodialysis and the presence of the antecedently accumulated pleural effusion may have been associated with the development of hematogenous dissemination. The patient fully recovered only with antibiotic therapy. To our knowledge, the present report is the first describing a case of hematogenous pleural infection caused by A. xylosoxidans.

Cellulitis Complicated with Bacteremia Due to Sphingobacterium Species: A Report of Two Cases and a Literature Review.

Sphingobacterium species rarely cause human infection. We herein report two cases of cellulitis complicated with bacteremia due to this genus. The patients, both in their 70s and receiving corticosteroid therapy for their underlying diseases, had antecedent skin injuries in their affected limbs. The patients' symptoms improved promptly and completely with the administration of cefazolin, which did not inhibit the growth of isolated organisms at a concentration of 4 µg/mL.

Cefotaxime-non-susceptibility of Haemophilus influenzae induced by additional amino acid substitutions of G555E and Y557H in altered penicillin-binding protein 3.

Cefotaxime-non-susceptible Haemophilus influenzae has rarely been isolated from clinical specimens. Although several reports have shown that amino acid (AA) alteration in penicillin-binding protein 3 (PBP3), encoded by the ftsI gene, reduces activity of cefotaxime, precise mechanisms conferring the non-susceptibility have been unclear. We analyzed the ftsI gene of two clinically isolated cefotaxime-non-susceptible H. influenzae strains, 16-11 and 20-07 (minimum inhibitory concentrations [MICs]: 16 and 8 µg/mL, respectively), and found that their deduced AA sequences of PBP3 included two AA substitutions of G555E and Y557H in addition to previously described AA alterations. To clarify whether the two additional substitutions are requisite for cefotaxime non-susceptibility, we produced transformants of Rd KW20 (cefotaxime MIC: ≤0.06 µg/mL) with the ftsI gene of 16-11. Cefotaxime MICs against transformants M1 and M2, of which deduced PBP3s were altered with that of 16-11 entirely and partially (only the N-terminal side up to the AA position 519), were 8 and 0.25 µg/mL, respectively. We also produced M2-555/7 through site-directed mutagenesis inducing additional substitutions of G555E and Y557H into the PBP3 of M2, against which cefotaxime MIC was 8 µg/mL. These findings show that the additional substitutions of G555E and Y557H in PBP3 with previously described alterations cause cefotaxime non-susceptibility. An additional substitution of either G555E or Y557H alone in altered PBP3 reduced cefotaxime activity but the elevation of MICs were within the category of susceptibility. To our knowledge, this is the first study clarifying a genetic factor in the PBP3 causing cefotaxime non-susceptibility among H. influenzae strains.

Pericarditis caused by Campylobacter fetus subspecies fetus associated with ingestion of raw beef liver.

Campylobacter fetus is an organism residing primarily in the gastrointestinal tracts of cattle and sheep and transmitting to humans through ingestion of contaminated food products or surface water. The organism has caused various extraintestinal infections but, to date, purulent pericarditis due to the organism has rarely been described. We report a case of purulent pericarditis due to C. fetus subsp. fetus, occurring in a patient having several predisposing conditions, including receiving hemodialysis therapy, recent surgery for cecal cancer, and administration of esomeprazole. The patient mentioned having eaten homemade raw beef liver two weeks before the onset, suggesting that the ingested food product was contaminated with C. fetus and the organism transmitted to the pericardium through the bloodstream although blood culture was negative. The causative organism, recovered from the pericardial effusion, was unidentifiable with commercial systems but determinable with molecular methods at the subspecies level. The patient fully improved with pericardiocentesis and subsequent administration of ciprofloxacin, to which the organism was considered susceptible, for a total of four weeks. This is the first case of C. fetus pericarditis in which a history of ingesting a raw food product was clearly mentioned.

Thoracic empyema caused by Campylobacter rectus.

We report a case of thoracic empyema caused by Campylobacter rectus, an organism considered as a periodontal pathogen but rarely recovered from extraoral specimens. The patient fully recovered through drainage of purulent pleural fluid and administration of antibiotics. The present case illustrates that C. rectus can be a cause of not only periodontal disease but also pulmonary infection.

High-level aminoglycoside resistance in Enterococcus faecalis and Enterococcus faecium causing invasive infection: Twelve-year surveillance in the Minami Ibaraki Area.

We examined prevalence of high-level aminoglycoside resistance (HLAR) in Enterococcus faecalis and Enterococcus faecium causing invasive infection in the Minami Ibaraki Area. Ten strains of both species each, recovered from the blood or the cerebrospinal fluid between 2003 and 2014, were randomly selected every year. High-level resistance to gentamicin (HLR-GM) and streptomycin (HLR-SM) was detected in 34% (41 of 120 strains) and 18% (21) of E. faecalis and 9% (11) and 39% (48) of E. faecium, respectively. In comparisons of the proportions among three four-year periods, HLR-SM among E. faecium was significantly lower in the 2011-2014 period. All strains with HLR-GM were positive for the aac(6')-Ie-aph(2″)-Ia gene. The ant(6')-Ia gene was detected in all with HLR-SM except for one E. faecalis strain. The present study showed that prevalence of HLR-GM among E. faecalis and E. faecium causing invasive infection in this area was nearly equivalent to that described in previous studies in Japan and that proportions of strains with HLAR did not vary during the study period except for that of HLR-SM among E. faecium.

Prospective intervention study with a microarray-based, multiplexed, automated molecular diagnosis instrument (Verigene system) for the rapid diagnosis of bloodstream infections, and its impact on the clinical outcomes.

The Verigene Gram-positive blood culture test (BC-GP) and the Verigene Gram-negative blood culture test (BC-GN) identify representative Gram-positive bacteria, Gram-negative bacteria and their antimicrobial resistance by detecting resistance genes within 3 h. Significant benefits are anticipated due to their rapidity and accuracy, however, their clinical utility is unproven in clinical studies. We performed a clinical trial between July 2014 and December 2014 for hospitalized bacteremia patients. During the intervention period (N = 88), Verigene BC-GP and BC-GN was used along with conventional microbiological diagnostic methods, while comparing the clinical data and outcomes with those during the control period (N = 147) (UMIN registration ID: UMIN000014399). The median duration between the initiation of blood culture incubation and the reporting time of the Verigene system results was 21.7 h (IQR 18.2-26.8) and the results were found in 88% of the cases by the next day after blood cultures were obtained without discordance. The hospital-onset infection rate was higher in the control period (24% vs. 44%, p = 0.002), however, no differences were seen in co-morbidities and severity between the control and intervention periods. During the intervention period, the time of appropriate antimicrobial agents' initiation was significantly earlier than that in the control period (p = 0.001) and most cases (90%; 79/88) were treated with antimicrobial agents with in-vitro susceptibility for causative bacteria the day after the blood culture was obtained. The costs for antimicrobial agents were lower in the intervention period (3618 yen vs. 8505 yen, p = 0.001). The 30-day mortality was lower in the intervention period (3% vs. 13%, p = 0.019).

Native valve endocarditis caused by Neisseria elongata Subsp. nitroreducens.

Neisseria elongata, a normal resident in the human oral cavity, rarely causes invasive infections. We herein report a case of endocarditis caused by Neisseria elongata subsp. nitroreducens that occurred in a patient without any apparent cardiac complications. The patient received aortic valve replacement following the administration of intravenous beta-lactam for five weeks. To our knowledge, this is the first published case in Japan of N. elongata infection in a patient without a prosthetic device.

A fatal case of iliopsoas abscess caused by Salmonella enterica serovar Choleraesuis that heterogeneously formed mucoid colonies.

Salmonella enterica subsp. enterica serovar Choleraesuis, an organism highly adapted to swine, rarely causes invasive human infection. We describe a fatal case of Salmonella ser. Choleraesuis infection developing iliopsoas abscess. A part of organisms recovered from the blood formed mucoid colonies, which became reactive to anti-O antigen antisera after either heat treatment or subculture through semisolid agar.

A case of secondary syphilis demonstrating nephrotic syndrome and a solitary intrahepatic mass in a human immunodeficiency virus-1-infected patient.

A 37-year-old, human immunodeficiency virus-1-infected Japanese man was referred because of nephrotic syndrome following emergence of generalized skin rash. Serological tests for syphilis turned out to be positive within ten months of the referral. Abdominal echography incidentally revealed a solitary intrahepatic mass without a detectable blood flow in segment 7. The patient's signs and symptoms, as well as the intrahepatic mass, resolved promptly after administration of amoxicillin. We consider that, in the present case, secondary syphilis caused the nephrotic syndrome and the intrahepatic mass, both of which have rarely been reported to date.

Pulmonary nocardiosis in patients with connective tissue disease: A report of two cases.

Reported here are 2 patients with connective tissue disease who developed pulmonary nocardiosis. Case 1 involved a 73-year-old man with malignant rheumatoid arthritis treated with prednisolone 25 mg/day. Chest X-rays revealed a pulmonary cavity and bronchoscopy detected Nocardia species. The patient was successfully treated with trimethoprim/sulfamethoxazole. Case 2 involved a 41-year-old woman with systemic lupus erythematosus. The patient received remission induction therapy with 50 mg/day of prednisolone and tacrolimus. Six weeks later, a chest CT scan revealed a pulmonary cavity; bronchoscopy resulted in a diagnosis of pulmonary nocardiosis. The patient had difficulty tolerating trimethoprim/sulfamethoxazole, so she was switched to and successfully treated with imipenem/cilastatin and amikacin.