IASR

ISSN 0915-5813

Vol. 42 No. 3 (No. 493) March 2021
Infectious Agents Surveillance Reporthttps://www.niid.go.jp/niid/en/iasr-e.html

Drug resistance mechanisms and testing of Acinetobacter spp. ............. 51
Current situation of MDRA overseas with a focus on Asia..................... 52
Measures to prevent nosocomial spread of imported drug-resistantbacteria..................................................................................................... 53
Commentary: Acinetobacter bereziniae..................................................... 55
Case report of a patient with TMB-1 metallo-β-lactamase-producing
Acinetobacter pittii .................................................................................. 56
Findings on multidrug-resistant Acinetobacter from Japan Nosocomial
Infections Surveillance data ................................................................... 58

National Institute of Infectious Diseases andTuberculosis and Infectious Diseases
Control Division,
Ministry of Health, Labour and Welfare

Treatment of patients with multidrug-resistant Acinetobacter infection .. 59
SARS-CoV-2 genome surveillance in Japan (as at 14 January 2021).... 61
An outbreak of tellurite-susceptible enterohemorrhagic Escherichia coli
O103 in a nursery school, Osaka City.................................................... 64
The first case of Haemophilus influenzae type a isolated from apediatric patient with invasive Haemophilus influenzae diseasein Japan, Tokyo Prefecture ..................................................................... 65<THE TOPIC OF THIS MONTH>
Multidrug-Resistant Acinetobacter Infection
The genus Acinetobacter comprises glucose non-fermentative, Gram-negative, rod-shaped bacteria that cause opportunistic
infections. Acinetobacter species can cause pneumonia and other respiratory tract infections, urinary tract infections, infections atsites of surgery or trauma, catheter-related bloodstream infections, sepsis, and other conditions in immunocompromised patients andothers.
Under the Infectious Diseases Control Law, disease due to multidrug-resistant Acinetobacter (MDRA) infection has been
designated as a Category V infectious disease under sentinel surveillance since February 2011 and as a Category V infectious disease
under notifiable disease surveillance since September 2014. The Infectious Diseases Control Law defines MDRA infection as thatcaused by Acinetobacter species that demonstrates resistance to three types of antimicrobials: broad-spectrum β-lactam agents,aminoglycosides, and fluoroquinolones. Laboratory criteria required for notification of an MDRA infection include resistance to three
types of drugs: carbapenems (e.g., imipenem), aminoglycosides (amikacin), and fluoroquinolones (e.g., ciprofloxacin). Only symptomaticpatients are subject to notification of MDRA infection and asymptomatic carriers are not subject to notification (for notification
criteria, see https://www.mhlw.go.jp/bunya/kenkou/kekkaku-kansenshou11/01-05-140912-4.html). In Japan, strains that meet thelaboratory criteria for notification are often defined as MDRA species.
Molecular Epidemiology of Multidrug-Resistant Acinetobacter Species
The clinically important species of the Acinetobacter genus is Acinetobacter baumannii, and the international clone lineages inparticular are associated with multidrug resistance and nosocomial outbreaks. Among the international clone lineages, A. baumannii
international clone II lineage corresponding to sequence type (ST) 2 (Pasteur scheme) or ST208 (Oxford scheme) based on multilocus
sequence typing (MLST) is the most globally widespread and has also caused nosocomial outbreaks in Japan. However, MDRA species
are isolated much less frequently in Japan than in other countries (see p.52 of this issue). Indeed, in Japan, MDRA species arevigilantly monitored as a drug-resistant bacteria imported from overseas (see p.53 of this issue).
Carbapenem resistance in Acinetobacter species is mainly conferred by their production of carbapenemases, including OXA-type
carbapenemases and metallo-β-lactamases (see pp.51, 56 of this issue). As the above-mentioned A. baumannii international clone IIlineages are frequently OXA-type carbapenemases, OXA-type carbapenemase producers are dominant globally. However, metallo-βlactamase producing MDRA has also been confirmed in Japan (see p.55 of this issue).
National Epidemiological Surveillance of Infectious Diseases (NESID)
Since MDRA infections became a Category V infectious disease for notifiable disease surveillance in September 2014, there havebeen 172 notified cases in total (as at January 5, 2021). Of these 172 patients, 122 (71%) were male, the median age was 71 years(range: 0-97 years) at diagnosis, and 116 (67%) were aged 65 years or older. The most common type of infection (including multipleFigure 1. Age distribution of notified multidrug-resistant Acinetobacter infection
cases by year, 2014-2020, Japan40

No. of notified cases

35

Age group（years）

30

75-

25

65-74

20

15-64

150 -14

10
50

2014＊
(n=15)

2015(n=38)

2016(n=33)

2017(n=28)

2018(n=24)

2019(n=24)

2020 （Year）(n=10)＊Week 38 (19 September)-week 52 (28 December) 2014

(National Epidemiological Surveillance of Infectious Diseases: as at 5 January 2021)1′（ 49′）（Continued on page 50′）

IASR Vol. 42 No. 3（Mar. 2021） 2′（ 50′）
（THE TOPIC OF THIS MONTH-Continued）
infections) was pneumonia in 92 patients (53%), followed by Figure 2. Number of years with a notification(s) multidrug-resistantAcinetobacter infection during 2014-2020, by prefecture,bacteremia/sepsis in 31 patients (18%), and urinary tractJapan
infection in 21 patients (12%). The most common type ofspecimen in which MDRA was detected (including detection
No. of years within multiple specimen types) was sputum from 106 patientsa notification(s)(62%), followed by blood from 21 (12%), urine from 20 (12%),0and pus from 10 (6%). The number of notified cases by year
1-2
revealed a decreasing trend ever since the highest number of
3-4
cases was notified in 2015, when there were 38 cases; for any
5-6
given year, at least half of the notified patients were 65 years
or older (Fig. 1 in p.49). According to the number of notified
cases by prefecture, the largest number of notifications werefrom Tokyo Prefecture (n = 29), followed by Saitama Prefecture(n = 27), Chiba Prefecture (n = 14), Kanagawa Prefecture(n = 14), and Hokkaido Prefecture (n = 9). Notified cases
occurred intermittently for at least five years in the top four
prefectures (Fig. 2), and there are concerns about MDRA
becoming endemic in these areas.
Of the total 172 notified cases, the suspected place of
infection was outside of Japan in 25 cases (15%), with Asian
countries accounting for many of those cases -- China (n = 8),
Vietnam (n = 4), South Korea (n = 3), Indonesia (n = 2), Thailand(National Epidemiological Surveillance of Infectious Diseases: as at 5 January 2021)(n = 2), and 1 case each from India, Croatia, Peru, Malaysia,Russia, and Taiwan. Carbapenem-resistant Enterobacteriaceae infection and vancomycin-resistant enterococcal infection are also
designated as Category V infectious diseases for notifiable disease surveillance; 0.4% and 1.7%, respectively, of their notifications had
the place of infection being suspected as outside of Japan (based on cases notified during 2015-2018, NESID Program Annual Report),suggesting that MDRA infections are characterized by a relatively larger proportion of cases with overseas transmission.
Japan Nosocomial Infections Surveillance (JANIS), Japan Ministry of Health, Labour and Welfare
The JANIS clinical laboratory division publishes summary data on isolates that fulfill the laboratory criteria needed for
notification of MDRA. These summary data differ from NESID data in that they do not distinguish between asymptomatic carriercases and symptomatic cases, and reports are restricted to isolates from medical institutions that participate in JANIS. Among the2,075 medical institutions included in the 2019 annual report, 29 (1.4%) institutions isolated MDRA strains from a total of 98 casepatients, and the annual number of case-patients with MDRA isolation has not increased since 2017 (see p.58 of this issue).
Treatment for MDRA and Precautions Regarding Antimicrobial Susceptibility Testing
Acinetobacter species were originally susceptible to many types of antimicrobials before resistant isolates started to emerge inEurope and the US circa the 1990s, and multidrug-resistant isolates began appearing in many countries, including in Asia, circa 2000.
Multidrug-resistant isolates exhibit resistance to almost all antimicrobials used to treat infections of Gram-negative bacteria.
Although colistin and tetracyclines are therapeutic options for infections of MDRA, their effectiveness and side effects are of concern,and isolates resistant to these antimicrobials have emerged. The development of novel antimicrobials, such as cefiderocol, a siderophore
cephalosporin, is awaited (see p.59 of this issue).
Antimicrobial susceptibility testing devices are becoming more common in the clinical setting. It should be noted that one suchdevice, VITEKⓇ 2 (bioMérieux), is unable to accurately determine amikacin resistance in Acinetobacter species; therefore, additional
confirmation using another antimicrobial susceptibility testing method is advised when deemed necessary (see p.51 of this issue).
Conclusion
A 2017 notice (HSB / TIDCD Notification No. 0328- 4) prescribes the promotion of testing for antimicrobial resistance genes atpublic health institutes in the event of an MDRA infection case notification, enabling the progressive development of the pathogen
surveillance system. Although the NESID system carries out surveillance for symptomatic cases of MDRA infection, both symptomaticpatients and asymptomatic carriers need to be covered for infection prevention and control. The 2014 notice “Measures against
nosocomial transmission in medical institutions” (HPB/MCPD Notification No. 1219-1) prescribes rigorous infection control measures, inline with outbreak response, at the point at which the first case of MDRA (including an asymptomatic carrier) is detected. In addition,
any suspicion of nosocomial transmission calls for reporting to the public health center, along with the rapid implementation ofappropriate measures such as seeking support from regional networks for infectious diseases prevention and control. In line withprevention measures, the notice warrants laboratory testing support from public health institutes as necessary, and strengthening oflaboratory testing systems is ongoing (see p.56 of this issue). In 2018, after a report of a suspected case of nosocomial infection, anotheradministrative communication was issued that called for rigorous prevention measures against nosocomial infections, including
MDRA infections (https://www.mhlw.go.jp/content/10900000/000343986.pdf), and continued response efforts in this endeavor arerequired.
The statistics in this report are based on 1) the data concerning patients and laboratory findings obtained by the National Epidemiological
Surveillance of Infectious Diseases undertaken in compliance with the Act on the Prevention of Infectious Diseases and Medical Care for Patientswith Infectious Diseases, and 2) other data covering various aspects of infectious diseases. The prefectural and municipal health centers andpublic health institutes (PHIs), the Department of Environmental Health and Food Safety, the Ministry of Health, Labour and Welfare, andquarantine stations, have provided the above data.

Infectious Disease Surveillance Center, National Institute of Infectious Diseases
Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, JAPAN Tel (+81-3)5285-1111