A technology of genetic analysis has been applied for clinical use. By using such technology, we can detect the pathogens earlier than the conventional microorganism tests. In order to understand the current status of the genetic test for infectious diseases, a 2nd questionnaire survey was conducted among member physician of the Japanese Association for Infectious Diseases (JAID) between October and November, 2018. Valid responses were obtained from 201 physicians. A percentage of infectious disease specialists certified by the JAID was 50.7%. A percentage of the respondents who answered the genetic testing in hospital was important and necessary for the diagnosis of infectious diseases and infection control was 92.5% and 89.6%,respectively. Of the respondents, 89.1% answered that the genetic testing in hospital was useful for rapid detection of the difficult-to-culture pathogens. A percentage of respondents who answered that it is useful for detection of drug-resistant or virulence genes and comprehensive detection of pathogens was 84.1% and 60.2%, respectively. The percentage was significantly higher in comparison with 1st surveillance (78.4% and 50.4% in 1st survey, respectively). A percentage of respondents who performed the genetic testing for infectious disease in hospital and outsourced was 36.3% and 33.8%, respectively. Of the respondents, 17.9% answered to implement the fully automated platform was 17.9%, and the percentage was significantly higher in comparison with 1st surveillance (7.4% in 1st surveillance). Of the respondents, 7.0% answered to implement multiplex panel. Of them, 57.1% answered to perform it in all medical departments, 35.7% answered to perform only when requested from physician, and 7.1% answered to perform in limited medical departments. This questionnaire survey revealed that the most physicians recognized the importance and necessity of genetic testing for infectious diseases. In addition, the fully automated platforms had been implemented into the large hospitals in Japan. On the other hand, their operation varied by hospital. Therefore, further investigation is needed to clear an optimal operation of fully automated platforms in Japan.
When considering measures against antimicrobial resistance (AMR), it is important to manage the use of antibiotic drugs by outpatients in cooperation with community pharmacies as well as to consider whether the number of antibiotic prescriptions is appropriate or not.
I calculated the number of antibiotic prescriptions for outpatients from prescriptions dispensed by a community pharmacy. The number of antibiotic prescriptions per 1,000 visits was 125 in 2009, 199.3 in 2011,173.3 in 2014, 171.1 in 2016, 103.0 in 2017 and 38.6 in 2018.
Compared to 2011, the number of outpatient antibiotic prescriptions in 2018 had decreased by 80.6%,and the number of 3rd generation oral cephalosporins, macrolides, and new quinolones had decreased by 89.6%. The goal of the National Action Plan on AMR was attained by these results.
The number of antibiotics prescribed was positively correlated with the prescribed dose (potency). Increases or decreases in prescribed doses of antibiotics can be estimated by checking the number of antibiotic prescriptions.
Even if only approximate, it is still possible to monitor any tendency of outpatient antibiotic prescriptions using a simple method, and it is considered that this method can be helpful in reducing unnecessary and inappropriate usage of antibiotics.
We analyzed 341 Enterobacteriaceae strains isolated from 339 urine specimens collected from 320 children admitted to our hospital for febrile urinary tract infection between 2009 and 2018. The annual change in antimicrobial susceptibility was investigated. Patientsʼ ages ranged from 11 days to 14 years and 9 months (median 174 days).
Resistance rates to cefotaxime and levofloxacin have gradually increased in the past few years, which suggests that continuing the surveillance of antimicrobial resistance is necessary.
A 17-day-old female infant presenting with fever and diarrhea was admitted to our hospital. We performed a sepsis work-up for neonatal fever. The blood test did not show any increase of inflammatory reaction and urinalysis revealed nothing in particular, either. The cerebrospinal fluid cell count was not raised and bacterial cultures of blood, cerebrospinal fluid and urine were all negative. Human parechovirus was finally detected with a multiplex PCR system (FilmArray Meningitis/Encephalitis Panel) in the cerebrospinal fluid. We diagnosed her as having human parechovirus infection and started maintenance intravenous fluid administration only. Five days later, her temperature became normal and she was discharged another three days later. The differential diagnosis of severe infections such as sepsis, meningitis or encephalitis is essential for neonatal fever. The early diagnosis of the pathogen results is of benefit in both severe central nervous infection cases and relatively mild cases. However, the spread of rapid diagnostic procedures in Japan is limited at present to some pathogens, and a definitive diagnosis is often delayed. The multiplex PCR system that we used in this case may be useful for early diagnosis and for prevention of unnecessary treatment such as antimicrobial agents and antiviral drugs. Convenience and cost are considered as future problems of the multiplex PCR test. The reduction of costs and the continuous review of an appropriate panel are needed. It is also important to select appropriate cases to examine.
A 39-year-old woman was treated for pulmonary hypertension with treprostinil administered via a Hickman catheter. She developed a fever and inflammatory signs at the exit site of the Hickman catheter were observed. On day 2, antimicrobial therapy (ceftriaxone) was started and the Hickman catheter was exchanged. Rhizobium radiobacter was detected from the catheter tip culture. Fever reduction was not observed and her blood culture remained positive despite treatment. We switched antimicrobial therapy from ceftriaxone to tazobactam/piperacillin plus amikacin, but the treatment was not effective. Although enhanced computed tomography scan and transesophageal echocardiography were performed, there were no findings of infectious foci. On day 28, the catheter was exchanged again, but the blood culture on day 29 was still positive. On day 40, we exchanged the catheter again, and this time we exchanged the catheter kit and the injection cap that connected the catheter and drug bag. R. radiobacter was detected from the injection cap. She was afebrile from day 41, and on day 46 her blood culture became negative. Therefore, we diagnosed the problem as catheter related blood stream infection by R. radiobacter, and concluded that the location of infection was the injection cap. Antimicrobial therapy was continued until day 59, and she was subsequently discharged. We experienced a case of catheter related blood stream infection from a Hickman catheter, and it was difficult ―to find the source of infection.
Mycobacterium haemophilum is a non-tuberculous mycobacterium that causes systemic infections involving the skin and soft tissue, pulmonary system, bones and joints, particularly in immunocompromised patients. We report herein on a rare case of cutaneously disseminated M. haemophilum infection accompanying blood stream infection in a patient following renal transplantation. A 41-year-old Japanese woman who had undergone a kidney transplant 5 years previously was referred to us due to prolonged undetermined fever. She was taking prednisolone, tacrolimus, everolimus, and mycophenolate mofetil at the time of hospitalization. In addition to the high fever, the patient suffered from chronic erythema emerging over her body. The results of Gram staining were suggestive of mycobacterium infection, and a genetic analysis based on sequencing of the hsp65 and rpoB genes finally identified this case to be a disseminated M. haemophilum infection. After we initiated combination therapy including clarithromycin, ciprofloxacin, and rifabutin, the patientʼs dermatological condition ameliorated and she was discharged 3 months later in remission.
Diagnosis of non-tuberculous mycobacterial infection is challenging from the aspect of both the clinical and laboratory approaches. In this case, careful observation of Gram staining in laboratory was a clue to the diagnosis of the infection. Among non-tuberculous mycobacteria, M. haemophilum is clinically a rare pathogen. Difficulty in identifying the pathogen may be a reason for its lower prevalence. M. haemophilum prefers a lower temperature (30-32℃) and requires iron or hemin (e.g. a blood agar plate) for proliferation, although we noticed that a chocolate agar plate in 5% CO2 at 35℃ gave the best culture conditions in this case. In case of refractory and unidentified dermatologic diseases, attention should be paid to the possibility of mycobacterial infection.
An 11-year-old boy, who had undergone repair of a total anomalous pulmonary venous connection (TAPVC) and double outlet right ventricle (DORV) during infancy, presented with a headache. Sinusitis and dental caries were also observed. Computed tomography (CT) scan revealed a mass on the left frontal lobe of his brain. He was diagnosed as having a brain abscess (BA) based on the magnetic resonance imaging (MRI) findings. The BA was drained, and the patient was treated with 300mg/kg cefotaxime and 40mg/kg metronidazole per day intravenously as empirical therapy. The melting temperature mapping method revealed Streptococcus intermedius in the intracranial pus 4.5 h after drainage. The echocardiogram showed no infective endocarditis. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDITOF MS) detected the same organism from the pus 3 days after drainage. The organism was pansusceptible, and treatment was continued because the presence of anaerobic, Gram-negative bacilli was suspected in the sinus cavity and dental plaque. The brain abscess, however, grew to 5cm 3 weeks after the drainage even under continued antibiotic therapy. A craniotomy was performed, and the entire abscess, including the abscess wall, was excised. Antibiotics were continued for 6 weeks, and the patient recovered completely. Rapid detection empirical therapy by administering appropriate antibiotics and total excision of the abscess successfully treated the patient. Thus, the use of rapid diagnostic tests and the melting temperature mapping method had significant impacts on effective antimicrobial stewardship.
Most of prosthetic joint infection (PJI) cases require surgical treatment and appropriate antimicrobial therapy over a long period, so identification of the causative microorganisms is very important to give appropriate antimicrobial therapy for affected patients. However, the utility of joint fluid cultures has been questioned based on relatively high false negative rates because of previous antimicrobial therapy and biofilm formation in PJI. In PJI patients with negative results of joint fluid cultures, PCR testing of the infected joint fluid or tissue is reported to be useful to identify the causative microorganisms.
We report herein on a case of PJI caused by Pseudomonas aeruginosa which was detected with PCR of periprosthetic joint fluid. The patient was treated successfully with intravenous, combined antimicrobial therapy followed by long-term oral antimicrobial therapy, which targeted P. aeruginosa, without surgery. In cases with high clinical suspicion of PJI but negative cultures, PCR tests might be helpful to identify the causative microorganisms.