The trend in transmitted drug resistance (TDR) and prevalence of non-B HIV-1 infected individuals newly diagnosed at participating HIV/AIDS clinics in the Tokai area were evaluated during the period 2009-2017.
Non-B subtype infections accounted for 11.2% of new diagnoses in the Tokai area. Most individuals were infected with CRF01_AE, followed by subtype C and CRF02_AG, A, F, G and BF recombinant virus. The estimated location of infection in Japan was most observed in the CRF01_AE, subtype C and CRF01_ AG. The number of cases were individuals have been infected with HIV-1 CRF02_AG has been increasing (1 case in 2009-2011, 4 cases in 2012-2014 and 7 cases in 2015-2017) among men who have sex with men (MSM),heterosexual and non-specific sexual communities. The molecular phylogenic analysis revealed that 8 of the 12 individuals infected with HIV-1s CRF02_AG belong to the same transmission cluster. These data suggested that HIV-1 CRF02_AG may rapidly spread among multiple communities in the Tokai area.
The overall prevalence of TDR in non-B subtype infected individuals (8.0% in 2009-2017) was slightly lower than that of the nationwide surveillance (9.1% in 2008-2011). The frequencies of TDR mutation in HIV 1 non-B subtype were nucleoside reverse transcriptase inhibitor (NRTI)-associated resistance (3.6%), protease inhibitor (PI) (3.6%) and non-nucleoside reverse transcriptase inhibitor (NNRTI) (1.8%). In the CRF01_ AE, TDR prevalence was 13.2%, and multiple drug resistance of the virus was observed.
It could be anticipated that an expansion in the number of foreign workers as the nation attempts to be the host country for the Olympic Games could lead to an increase in the number of foreigners in Japan. Therefore, non-B HIV-1s from immigration-related and international traveler carriers might lead to different HIV-1 trends in Japan. We need to evaluate effective prevention strategies and to strengthen epidemiological surveillance on TDR and circulating HIV-1s among newly diagnosed individuals in the Tokai area.
When an enterococcal infection is strongly suspected, intravenous vancomycin is generally selected for the initial treatment. Vancomycin is administered for a few days, at which time susceptibility testing often indicates penicillin-susceptible enterococci, leading to unnecessary adverse reactions and the development of antibiotic-resistant bacteria. In cases of penicillin-susceptible Enterococcus faecalis bacteremia, where treatment has been performed with vancomycin, a higher mortality rate has resulted than in cases treated with penicillin.
To solve these problems, a method capable of rapidly identifying a penicillin susceptible strain is desired ; however, mass spectrometry or genetic testing is expensive and requires proficiency, and many hospitals comprise different subjects. Therefore, we devised a method to rapidly identify the penicillin susceptibility of enterococci by observing what we refer to as the “peanut sign”, based on Gram staining.
Microscopic testing was performed on blood culture-positive gram-stained specimens. Gram-positive diplococci without a capsule with pointed elliptical ends were presumed to be enterococci. The enterococci with a peanut shell-like symmetrical notch present in the center of the bacterial cell on both sides were defined as having the “peanut sign”. We evaluated the results for microscopic testing and penicillin-susceptibility testing of enterococci between a medical technologist, who performs microscopic testing on a daily basis and a physician, who does not.
In the microscopic examination by the physician, the “peanut sign”returned a sensitivity of 78% and specificity of 96% to penicillin-resistant enterococci. In the microscopic examination by the medical technologist, the sensitivity was 94% and specificity was 78%. The kappa coefficient was 0.62, indicating “substantial agreement” between the findings of the physician and medical technologist.
Penicillin-susceptible enterococci can be rapidly identified by Gram staining results, with a substantial agreement noted for inter-rater reliability.
If a patientʼs condition is not urgent, then optimal antibiotics can be selected in real-time, either penicillin or vancomycin depending on positive or negative presence of the “peanut sign”. This may assist with appropriate administration of antimicrobials, maximizing therapeutic efficacy, minimizing the risk of unnecessary adverse reactions and preventing the development of antibiotic-resistant bacteria.
To evaluate the longitudinal trends of integrase (IN) polymorphisms and integrase strand transfer inhibitor (INSTI)-associated drug resistance mutations in the Tokai area, we analyzed newly diagnosed individuals with HIV-1 subtype B (n=882) that were divided into two periods 2009-2013 and 2014-2017.
Overall, 113 variable residues, 167 positions in the IN region were mutated in ＞1% of individuals. E138K (1.4% in 2014-2017) was observed as a non-polymorphic accessory resistance mutation. The frequency of E138K was relatively higher in the Tokai area, compared with other reports. Seven of 8 HIV-1 sequences carrying E138K belonged to the same transmission cluster, suggesting that the higher rates of E138K may be partly due to the circulating specific virus. In the polymorphic accessary mutation, the L74M/I and E157 Q showed an increase in the prevalence of HIV-1 in 2009-2013 compared with 2014-2017.
So far, no resistance mutation which confers any severely reduced INSTI susceptibility has been observed in the Tokai area. These data may provide useful information regarding the clinical response to current INSTIs and to the novel mechanism of action of drugs targeting HIV-1 integrase.
Invasive infection caused by hypervirulent (hypermucoviscous) Klebsiella pneumoniae (hvKP) characterized by liver abscess and/or metastatic abscess syndrome was first reported in Taiwan. Although it is now recognized world-wide, and not only in Asian countries, there are few epidemiological investigation reports in Japan. In 2017, the unusual number of six cases of hvKP infection were reported from different 3 hospitals in Kawasaki city during a 4-month period (Jan-Apr). We collected the epidemiological information of these cases and conducted a genetic analysis of the hvKP strains.
All 6 patients were males, 70-85 (median 73) years of age, with no epidemiological link. Septicemia occurred in 4 cases with a liver abscess accounting for 3 cases and with pneumoniae accounting for one case. The other two cases without septicemia developed only pneumoniae. All cases had some kind of underlying disease or medical history, including 2 cases of postoperative cancer (stomach and prostate), 2 cases of gastric ulcer, one case of diabetes mellitus and hypertension, one case of rheumatoid arthritis and one case of both hepatitis B virus (HBV) and HTLV-1 carrier. One of the liver abscess cases also had a history of liver abscess in the past. The initial symptoms were fever which developed in 4 cases, with hypochaondralgia and feeding difficulty developing in one case each. There were no characteristic differences between the initial symptoms. One fatal case suffering from a liver abscess and septicemia was the HBV and HTLV-1 carrier, and disseminated strongyloidiasis occurred complicated with hvKP meningitis. In another fatal case with postoperative cancer and rheumatoid arthritis, severe pneumoniae develped with septicemia. According to the molecular analysis, 6 strains and 4 strains were positive for rmpA (regulator of mucoid phenotype and magA (mucoviscosity-associated gene A), respectively. Four magA-positive strains were classified into capsular serotype K1 with the polymerase chain reaction (PCR) method and sequence type (ST) 23 with Multilocus sequence typing (MLST). Two magA-negative strains were capsular serotype K2, and ST86 or ST380. The hvKP isolates in this investigation were susceptible to almost all antibiotics tested. Similar characteristic strains have already been reported in Asian countries.
Even though the epidemiology of hvKP infection in Japan is yet unclear, it is probable that the hvKP strain has already been endemic around Kawasaki city. We should conduct appropriate surveillance to identify the incidence of invasive hvKP infection, considering the possibility that hvKP strains will acquire extreme antimicrobial resistance.
We report herein on two cases of bacteremia caused by daptomycin-resistant Corynebacterium striatum. In
these cases, daptomycin-resistant C. striatum was detected after receiving daptomycin for the treatment of multidrug-resistant C. striatum bacteremia, and ERIC-PCR band patterns were identical among the isolates of C. striatum before and after daptomycin therapy. We performed an in vitro assay to determine whether daptomycin resistance is induced in nine clinical isolates of C. striatum, including our two cases, after exposure to daptomycin in broth culture, and seven isolates showed emergence of daptomycin resistance.
To our knowledge, this is the first reported case of daptomycin-resistant C. striatum bacteremia in Japan. The use of daptomycin for the treatment of C. striatam infections should be avoided, considering the risk for rapid emergence of daptomycin resistance.
A 22-year-old woman, who had undergone intracardiac repair for pulmonary valve atresia with a ventricular septal defect when she was three years old, underwent right ventricular outflow tract reconstruction for re-stenosis. On the 22nd postoperative day, she was admitted to our hospital with a fever. She was diagnosed as having mediastinitis with infiltration of the lung contiguous to the site of the origin on contrast computed tomographic (CT) examination. She received cefazolin and vancomycin, and drainage was performed under general anesthesia the following day. There were many white blood cells but no bacteria in the pus on Gram staining ; on anaerobic culture and enriched broth culture, gram positive rods were detected which needed to be differentiated from Actinomyces spp. ; they were finally identified as Cutibacterium acnes by means of biochemical methods, 16S rRNA gene analysis, and time of flight mass spectrometry (TOF/MS). Cefazolin and vancomycin were changed to ampicillin ; after 5 weeks, infiltration of the lung lesion was still present. Ampicillin was then changed to oral amoxicillin and continued for a total of 10 weeks. She recovered completely. To our knowledge, there is no report of a case of mediastinitis caused by C. acnes with infiltration of the lung. We needed to differentiate the pathogen from contaminants on detecting C. acnes. In this case, we concluded that it was a pathogen because of the pure culture, and identification of C. acnes in several ways. Mediastinitis caused by C. acnes can infiltrate the lung. Surgery is not necessary for the management of the infiltrated lesion ; medical management with antibiotics is adequate. Its treatment is different from that of Actinomyces spp. The period of antibiotic administration needs to be determined by evaluating the CT image, because the period for treatment of the infiltrate lesion has not been established.