Molecular and Epidemiological Characteristics of Carbapenemase-Producing Klebsiella pneumoniae Clinical Isolates in Japan.

Carbapenemase-producing Enterobacteriaceae represent a serious public health threat worldwide. Carbapenemase genes, harbored on a transferable plasmid, have been isolated globally with distinct geographical features. Klebsiella pneumoniae, included in Enterobacteriaceae, also produces carbapenemase and often shows hypervirulence. Overlapping carbapenem resistance and hypervirulence in K. pneumoniae have been reported, but such strains have not yet been found in Japan. Here, we screened 104 carbapenemase-producing K. pneumoniae isolates collected from 37 hospitals and outpatient clinics in Japan between September 2014 and July 2015. PCR and DNA sequencing demonstrated IMP-1 in 21 isolates and IMP-6 in 83 isolates, 77 of which coharbored CTX-M-2. Most of the isolates showed low MICs toward imipenem and meropenem but high MICs toward penicillin and cephalosporins. Conjugation experiments with an Escherichia coli J53 recipient showed that most of the plasmids in IMP-6 producers were transferable, whereas only one-half of the plasmids in IMP-1 producers were transferable. PCR-based replicon typing and multiplex PCR identified five isolates belonging to the CG258 non-tonB79 cluster and no isolate belonging to the CG258-tonB79 cluster or sequence type 307 (ST307). Four K1-ST23 isolates, 10 K2-ST65 isolates, and 7 K2-ST86 isolates were detected that harbored virulence genes. The resistance genes in 85 isolates were transferable, but the virulence genes were not transferred. These results demonstrate the acquisition of IMP-type carbapenemase genes and CTX-M-type genes among hypervirulence isolates in Japan, warranting further attention and countermeasures. In this study, we have determined the molecular characteristics and epidemiology of IMP-6 producers that coharbored various CTX-M genes in Japan.IMPORTANCE Carbapenems serve as a last resort for the clinical treatment of multidrug-resistant infections. Therefore, the rapid spread of carbapenemase-producing strains represents a serious public health threat, further limiting antibiotic choices. The current findings of hypervirulent carbapenemase-producing Klebsiella pneumoniae clinical isolates in Japan demonstrate the potential broad spread and transfer of these genes, necessitating close surveillance.

Infective Endocarditis Complicated by Intraventricular Abscesses, Pericarditis, and Mycotic Aneurysm Due to an Emerging Strain of Serotype VI Streptococcus agalactiae.

An increasing number of invasive infections due to Streptococcus agalactiae in non-pregnant adults have been reported. We report a case of infective endocarditis complicated by intraventricular abscesses, pericarditis, and mycotic aneurysm due to S. agalactiae belonging to ST681 with a capsular serotype VI in a woman with diabetes. The patient also had a myocardial infarction and was treated with percutaneous coronary intervention, pericardiocentesis, and 6 weeks of antibiotic treatment. Invasive infections due to serotype VI S. agalactiae are common in Asian countries such as Taiwan and Japan, so continuous monitoring of invasive S. agalactiae strains is warranted.

Mycobacterium wolinskyi Peritonitis after Peritoneal Catheter Embedment Surgery.

Mycobacterium wolinskyi belongs to the Mycobacterium smegmatis group, which comprises rapidly growing non-tuberculous mycobacteria. The number of case reports on M. wolinskyi infections associated with postoperative wounds has increased in recent years. We herein report a case of peritonitis due to M. wolinskyi after peritoneal catheter embedment surgery. Identification was achieved based on 16S ribosomal RNA and rpoB gene sequencing of the isolate. The patient recovered following catheter removal and treatment with levofloxacin and minocycline for one month.

Infective endocarditis caused by Enterococcus faecalis treated with continuous infusion of ampicillin without adjunctive aminoglycosides.

Aminoglycosides are useful antimicrobial agents for treating infective endocarditis; however, they occasionally cause troublesome side effects, such as nephrotoxicity and ototoxicity. We herein report a case of infective endocarditis caused by Enterococcus faecalis that was treated successfully with continuous infusion of ampicillin without adjunctive aminoglycosides. The serum ampicillin concentrations were higher than the minimal inhibitory concentration for the target strain. Although the use of ampicillin monotherapy is currently avoided because double ß-lactam therapy is reportedly more effective, continuous penicillin administration remains an effective therapeutic choice for treating infective endocarditis.

Nocardia beijingensis pulmonary infection successfully treated with intravenous beta-lactam antibiotics and oral minocycline.

We report a case of pulmonary infection caused by a rare Nocardia species, Nocardia beijingensis, in a 48-year-old man who received multiple immunosuppressive therapy after renal transplantation. This pathogen was isolated from a bronchoscopic protected specimen brush and was identified as N. beijingensis by 16S rRNA gene sequence analysis. The patient was initially treated with imipenem/cilastatin followed by ceftriaxone and oral minocycline. Traditionally, trimethoprim-sulfamethoxazole (SXT) has been one of the first-line antibiotics chosen as an initial therapy for pulmonary nocardiosis, but this case was successfully treated without SXT. Considering recent reports about failures of both prophylaxis and treatment for nocardial infections with SXT and its various side effects, treatment with beta-lactam antibiotics and minocycline for pulmonary nocardiosis can be chosen in mild to moderate cases with confirmed susceptibility to these antibiotics in vitro.

Purulent pericarditis due to Streptococcus pneumoniae diagnosed by pneumococcal urinary antigen assay and 16S rDNA sequence of the pericardial fluid.

A 57-year old woman was admitted to our hospital with massive pericardial fluid. Culture of the pericardial fluid was negative, however, Binax NOW Streptococcus pneumoniae urinary antigen test was positive in pericardial fluid. 16S rDNA sequencing and PCR for lyt(A) gene of the pericardial fluid sample confirmed the microbiological diagnosis of S. pneumoniae. The patient was treated with surgical drainage and continuous intravenous infusion of penicillin G and its concentration in the serum and pericardial effusion was monitored. Incorporation of molecular methods such as antigen testing and nucleic acid sequencing would benefit the management of infectious diseases especially in culture negative cases.

[A case of acute renal failure involving high amounts of tenofovir after HAART start].

A 58-year-old man admitted for fever, nausea, vomiting, and anuria after the start of HAART, including tenofovir, had a viral load of 1.1 x 10(5) copies/mL, a CD4-positive lymphocyte count of 81/microL, and serum creatinine of 0.8 mg/dL before HAART. He underwent renal biopsy and temporary dialysis. We concluded that the patient had acute tubular necrosis because of potentially impaired renal function and the high amount of medication, and judging from the renal biopsy specimen and clinical course. When implementing HAART, physicians should be aware of and monitor potential patient misunderstanding of instructions on dosage and administration and for possible complications in medicinal combinations and potential side effects. TDF taken together with lopinavir may increase the plasma concentration of TDF or other medications that could worsen renal function. It should also be noted that renal dysfunction is a potential complication in the elderly.

[Case of Scedosporium apiospermum cutaneous soft tissue infection treated with voriconazole].

A 69-year-old man treated with corticosteroids and immunosuppressive agents for acutely exacerbated interstitial pneumonia was found to have an ingrown nail in the left big toe and that suppurated despite treatment by dermatologists. Culture of the pus expressed from the toe yielded Scedosporium apiospermum. The patient suffered liver dysfunction a few days later when treated with intravenous voriconazole (VRCZ), which was discontinued due to the high plasma VRCZ concentration. Discrete erythema and subcutaneous nodules developed in left leg 2 or 3 weeks later. Ultrasonography showed tubular structures with substantial echoes that were not connected to veins in the subcutaneous tissue of the left leg. These findings suggested a nodular lymphangitic pattern of spreading of S. apiospermum soft tissue infection. Oral VRCZ at 100 mg/day was started, and increased to 200 mg/day after the plasma VRCZ concentration was measured. VRCZ was stopped after about 2 months, by which time the man had fully recovered. Because VRCZ-induced liver dysfunction was reported significantly associated with plasma level, we treated this case safely by administering VRCZ while measuring the plasma concentration.