Drug sensitivity test of Campylobacter jejuni strains isolated from human diarrheal stools, chicken meat, and chicken feces, and gene mutation of quinolone-resistant strains

In basic studies on campylobacteriosis, we tested 53 strains from human diarrhea stools and 102 strains from chicken meat and feces obtained between 2002 and 2006 for drug sensitivity to different drugs and gene mutation in quinolone-resistant strains. 1) Of 15 drugs tested, all were resistant to one or more of the following 10 drugs: CEX, 99.4%: ABPC, 59.4%; NA, 40.6%; NFLX, 40.0%; TC and CPFX, 39.4%; PIPC, 38.1%; MINO, 30.3%; KM, 3.2%; and SM, 2.6%. 2) Of 155 drug-resistant strains, 28 (18.1%) were resistant to single drugs and 127 (81.9%) were resistant to multiple drugs. The most frequent pattern of multipledrug resistance was ABPC/PIPC/CEX, followed by ABPC/PIPC/CEX/TC/MINO/NA/NFLX/CPFX. 3) Mutation of GyrA (Thr86 --> Ile) was detected in 43 (97.7%) of 44 quinolone-resistant strains. We found that resistance to beta-lactams, quinolones, and tetracycline antibiotics was high, and most resistant strains were resistant to multiple drugs. We also found that most quinolone-resistant strains had GyrA mutation.     

Clinical effects of piperacillin and tazobactam/piperacillin on Haemophilus influenzae lower respiratory tract infection in pediatric patients

OBJECTIVE: The prevalence of beta-lactamase-nonproducing ampicillin-resistant (BLNAR) Haemophilus influenzae (H. influenzae) has been increasing in recent years. Piperacillin (PIPC) is one of a few beta-lactams possessing good activity against BLNAR H. influenzae. We studied clinical efficacy of piperacillin and its beta-lactamase inhibitor, tazobactam/piperacillin (TAZ/PIPC) in children with lower respiratory tract infection caused by H. influenzae including resistance strains. METHODS: Subjects were 20 children with lower respiratory tract infection caused by H. influenzae treated with PIPC 100mg/kg/day (7 cases) or TAZ/PIPC 125mg/kg/day (13 cases). We selected cases from which resistant H. influenzae strains might be detected. Patients received prior antimicrobial therapy within two weeks before admission, or with underlying diseases. We examined patient profiles, clinical efficacy, susceptibilities for 6 beta-lactam antibiotics [PIPC, TAZ/PIPC, ampicillin (ABPC), cefotaxime (CTX), ceftriaxone (CTRX), and meropenem (MEPM)] and analyzed 6 genotype patterns of beta-lactam resistant genes by PCR. RESULTS: Efficacy was 7/7 in patients in PIPC group and 12/13 in patients in TAZ/PIPC group. Diminished efficacy was seen in only one case complicated with severe RSV infection. The susceptibility of all strains but one beta-lactamase producing, ABPC resistant (BLP) strain to PIPC and of all to TAZ/ PIPC was below 0.25 microg/mL. The genotype of the 15 strains isolated from the sputum on administration was as follows; beta-lactamase nonproducing, ABPC-susceptible (gBLNAS) strains were 4, gBLP strain was 1, beta-lactamase nonproducing, and ABPC-resistant (gLow-BLNAR) strains were 2, beta-lactamase nonproducing, ABPC resistant (gBLNAR) strains were 8. CONCLUSION: PIPC and TAZ/PIPC were useful against lower respiratory tract infection caused by H. influenzae including BLNAR in children.     

Antimicrobial susceptibilities of Streptococcus pneumoniae and Haemophilus influenzae isolated from children with meningitis

Between April 2001 and March 2003, we studied minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) of 7 strains of Streptococcus pneumoniae and 8 strains of Haemophilus influenzae isolated from children with meningitis. The age range of the patients was from 4 months to 5 years. Susceptibilities of ampicillin (ABPC), cefotaxime (CTX), panipenem (PAPM), and vancomycin (VCM) in S. pneumoniae and those of ABPC, CTX, ceftriaxone (CTRX), and meropenem (MEPM) in H. influenzae were measured. MICs of ABPC, CTX, PAPM, and VCM to S. pneumoniae were < or = 0.06-2, < or = 0.06-0.5, < or = 0.06, and 0.25-0.5 microgram/ml and MICs of ABPC, CTX, CTRX, and MEPM to H. influenzae were 0.12-64, < or = 0.06-0.5, < or = 0.06-0.12, and < or = 0.06-0.25 microgram/ml, respectively. In 5 of all strains, difference between MIC and MBC to ABPC was observed. Four strains out of them had mutations of penicillin binding protein genes measured by PCR methods.     

Extended-spectrum beta-lactamase (ESBL) produced by Escherichia coli and Klebsiella pneumoniae isolated from Teikyou University Hospital--the first report

We studied the cefotaxime (CTX)-resistant (MIC > or = 32 micrograms/ml) clinical isolates of E. coli and K. pneumoniae in Teikyo University Hospital from 1990 to 1996. The incidence of CTX-resistant isolates was 0.4% (6/1,282) in E. coli and 0.6% (7/1,044) in K. pneumoniae, in 1990. In 1995, the incidence of CTX-resistance increased to 1.7% (50/2,910) in E. coli (p = 0.0013) and 7.2% (144/1,996) in K. pneumoniae (p < 0.0001). These species have been detected in the stool (86 isolates), urine (59 isolates), sputum (15 isolates), pus (15 isolates), throat (10 isolates) and others (12 isolates) in 1995. MIC50 of ampicillin (ABPC), ABPC with clavlanic acid (CVA) 5 micrograms/ml, piperacillin (PIPC), PIPC with CVA 5 micrograms/ml, ceftazidime, CTX, ceftizoxime, cefpodoxime, cefepime, aztreonam, cefmetazole, latamoxef, and imipenem used against 33 isolates (11 isolates of E. coli, 22 isolates of K. pneumoniae), which were detected in 1996-1997, was > 512 micrograms/ml, 8 micrograms/ml, > 512 micrograms/ml, 8 micrograms/ml, 4 micrograms/ml, > 512 micrograms/ml, 16 micrograms/ml, > 512 micrograms/ml, 256 micrograms/ml, 32 micrograms/ml, 2 micrograms/ml, 0.25 microgram/ml and 0.25 microgram/ml, respectively. This susceptibility pattern were very similar to the Toho-1 type beta-lactamases producing strains.     

Antibiotic susceptibility of Neisseria meningitidis from healthy and diseased persons in Japan

We examined the susceptibilities of 100 Neisseria meningitidis strains isolated between 1990 and 2004 to 12 antimicrobial agents, finding the MIC50 to be 0.031 microg/mL and that of MIC90 of benzylpenicillin (PCG), a type of penicillin, to be 0.063 microg/mL. Two strains showed intermediate resistance (MIC of 0.125-0.25 microg/mL). Two strains of the same origin also showed intermediate resistance (0.25-1 microg/mL) to ampicillin (ABPC). For cephems, MIC50 and MIC90 of cefotaxime (CTX) were both 0.004 microg/mL, while the MICs of ceftriaxone (CTRX) were all 0.004 microg/mL, showing the strongest antibacterial spectrum. The three carbapenems surveyed meropenem (MEPM), panipenem (PAPM), and imipenem (IPM) also had a strong antibacterial spectrum in ascending order, with the MIC50 and MIC90 of MEPM, which was lowest, being 0.008 microg/mL and 0.016 microg/mL. Some 97% of MICs for ciprofloxacin (CPFX) were 0.004 microg/mL but 3 strains showed resistance (0.125 microg/mL). No difference was seen between MICs of N. meningitidis strains originated from meningitis patients, patients other than meningitis, and healthy carriers. No difference was seen in MICs by serogroup (A, B, C, Y, W135 and NG).     

Nosocomial infections due to methicillin-resistant S. aureus (MRSA) at the Kagoshima University Hospital (2). Susceptibility to antibiotics]

Susceptibility to antibiotics of 123 MRSA strains isolated at the Kagoshima University Hospital in 1989 was examined. The results were as follows: 1) Susceptibility of MRSA strains was excellent to VCM, MINO, and RFP, followed by IMP, CLDM, and CPFX. However, most strains were resistant to PCG, MPIPC, ABPC, CET, CMZ, CZON, GM, and AMK. 2) Five strains highly resistant to RFP were isolated. Three of these strains were isolated on the ward for tuberculosis. This suggests easy development of resistance to RFP by MRSA. 3) Differences in susceptibility to antibiotics between coagulase type II and type VII strains were examined. The cumulative percentage of type II strains susceptible to CLDM (MICs less than 0.5 microgram/ml) was 15.3%, and that of type VII was 45.2%. Strains resistant to CLDM were more frequently isolated among type II than among type VII strains (p less than 0.001). A similar relationship between strains and antibiotics was also found with EM and CPEX. On the other hand, the cumulative percentage of type II strains susceptible to AMK (MICs less than 25 micrograms/ml) was 89.7%, and that of type VII was 9.7%. Strains resistant to AMK were more frequently isolated among type VII than among type II strains (p less than 0.001).     

Increasing fluoroquinolone low-sensitivity in enterotoxigenic Escherichia coli isolated from diarrhea of overseas travelers in Tokyo

Drug resistance trends were investigated for 1,318 enterotoxigenic Escherichia coli (ETEC) isolated from overseas traveler's diarrheal cases in Tokyo during 1988-1999. A total of 1.6% (21 strains) were nalidixic-acid resistant and fluoroquinolones (NFLX, OFLX, CPFX, LVFX, TFLX, SPFX; FQ) low-sensitive (or low-level-resistant). None of the strains were high-level-resistant to FQ. The FQ low-sensitive strains were isolated in 1996 for the first time, and increased from 3.4% in 1996 to 15.8% in 1999. Countries visited by travelers with the FQ low-sensitive ETEC were India (16 cases), Nepal (3 cases), Cambodia (1 case), and Egypt (1 case). Drug resistance-patterns of the FQ low-sensitive strains, including other drugs (CP, TC, SM, KM, ABPC, ST, NA, and FOM) tested, varied among the 6 types. Among those, multidrug resistant strains accounted for 57.1% (12 strains). The enterotoxin producing types of strains were LT (4 strains), ST (10 strains), and both (7 strains). The serotypes of the strains were classified into 16 types. The quinolone resistance determining regions (QRDRs) of the gyrA genes of the FQ low-sensitive strains were sequenced. The mutations of a Ser to a Leu at position 83 (Ser-83-->Leu) was found in 19 strains, and Asp-87-->Tyr was found in 2 strains.     

Antimicrobial activities and mechanisms of carbapenem resistance in clinical isolates of carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter spp

We tested the antimicrobial activities of meropenem (MEPM), imipenem (IPM), panipenem (PAPM), piperacillin (PIPC), cefepime (CFPM), aztreonam (AZT), amikacin (AMK), and levofloxacin (LVFX) against 106 clinical Pseudomonas aeruginosa isolates and 64 clinical Acinetobacter spp. isolates with reduced susceptibility to carbapenems. Using NCCLS breakpoints, the percentages of P. aeruginosa strains susceptible to AMK and Acinetobacter spp. strains susceptible to LVFX were found to be 51.1% and 55.6%, respectively, which represented the highest activity among 8 antimicrobial agents in each organism. Referring to the correlations among MICs of carbapenems, MEPM showed a higher activity than IPM and PAPM in both organisms; 29 of the 94 strains (30.9%) of IPM-resistant P. aeruginosa were susceptible to MEPM. Further study for resistance mechanisms to carbapenems by the disk diffusion method using 2-mercaptopropionic acid revealed that 8 of the 64 Acinetobacter spp. isolates (12.5%) were metallo-beta-lactamase producers, while none of 106 P. aeruginosa isolates were metallo-beta-lactamase producers. PCR analysis using blaIMP-specific primers confirmed that 4 of the 8 metallo-beta-lactamase-producing Acinetobacter spp. isolates detected by the disk diffusion method were carrying the blaIMP gene. The identification of metallo-beta-lactamase-producing Acinetobacter spp. isolates implies that metallo-beta-lactamase genes have been disseminated among various gram-negative pathogens.     

Prevalence and serotypes of verocytotoxin-producing Escherichia coli (VTEC) isolates from dairy cattle]

To clarify the source of infection and route of transmission of Verocytotoxin-producing Escherichia coli (VTEC) in humans, we collected fresh feces from healthy dairy cattle reared in Hokkaido, Fukushima, Kanagawa and Okinawa prefectures between June 1996 and March 1997, and attempted to isolate VTEC. The results are described below. 1) VTEC was isolated from 68 (27.1%) of 251 fecal samples tested. VTEC was isolated from 14 (28.0%) of 50 in Hokkaido, 13 (26.0%) of 50 in Fukushima, 20 (39.2%) of 51 in Kanagawa and 21 (21.0%) of 100 in Okinawa. There were no difference in the prevalence among the prefectures. 2) Toxin type and serotype of 85 isolates were determined. Thirty-three isolaties (38.8%) were classified into VT1 toxin and VT2 toxin, respectively, and 19 isolates (22.4%) were classified as the strain that produces both VT1 and VT2 toxins. The toxin types of these isolates were divided by serotypes. The VT1-producing isolates were the most frequent among O111:H-. The VT2-producing isolates included O2:H12, O2:H29, O2:H-, O82:H8, O82:HUT, O153:H19, O153:H42 and O153:H-. Among the isolates producing both VT1 and VT2 toxins, O153:H19 was relatively frequent. Based on findings that many bacterial strains coinciding with toxin types and serotypes of human-derived VTEC isolated from dairy cattle, it was suggested that dairy cattle are closely related to VTEC infection in human as a source of infection.     

Drug sensitivity, conjugative R plasmids and plasmid profiles of Salmonella isolated from humans with infectious enteritis

Using 92 Salmonella strains isolated from patients suspected of having infectious diseases of the intestinal tract who visited 13 hospitals in Japan during the six years between 1991 and 1996, we investigated the drug susceptibility, prevalence of conjugative R plasmid, and the plasmid profiles. 1) Of the bacterial isolates tested, 52.2% showed drug-resistance. Regarding the drug-resistance patterns, 70.8% of the isolates were resistant to a single drug, while 29.2% were multi drug-resistant. 2) Dividing the resistance patterns by the serotypes, among Salmonella Enteritidis isolates, single-drug resistance to SM was the most frequent, being detected in 27 isolates. Single-drug resistance to NA and two-drug resistance to SM/TC were the second-most frequent, each being detected in isolates. Among Salmonella Hadar isolates, four isolates showed two-drug resistance to SM/TC, and one isolate showed single-drug resistance to TC. Among Salmonella Typhimurium isolates, one isolate each showed three-drug resistance to ABPC/CER/KM and KM/TC/CP. Among Salmonella Agona isolates, one isolate each showed two-drug resistance to SM/TC and single-drug resistance to SM. Among Salmonella Derby isolates, two isolates showed single-drug resistance to SM. 3) The prevalence of conjugative R plasmid was investigated in 48 drug-resistant isolates, and six isolates (12.5%) contained the plasmid. 4) The prevalence of the plasmid was investigated in 29 drug-resistant S. Enteritidis isolates, and 22 isolates (75.9%) contained the plasmid. These isolated were classified by the plasmid profiles into types H1 to H7. 5) Regarding the plasmid profiles of the S. Enteritidis isolates, a position corresponding to 60 Kbp was the most frequently detected in 90.5%.     

Detection of inducible beta-lactamase in sputum--clinical studies on Pseudomonas respiratory infection

To investigate the clinical incidence of inducible beta-lactamase, we measured the beta-lactamase activity in the sputum of 5 patients with chronic respiratory tract infection due to P. aeruginosa, by using the spectrophotometric method. During the piperacillin (PIPC) therapy given twice a day with a single dose of 2-3 g, sputum samples were collected every 2 hours for 3 days, and on the second day, two grams of Cefmetazole (CMZ) was added to PIPC therapy. The antibiotics concentration of each collected sputum samples were also measured by HPLC. In one out of 5 patients, no beta-lactamase activity in sputum was detected throughout the 3 days. However in three out of 5 patients, after the addition of CMZ to PIPC, the beta-lactamase activity significantly increased 2-3 times (max: 0.03 units/ml) that on PIPC alone, and gradually decreased on the 3rd day when PIPC was given alone. Then the peak concentration of PIPC with the addition of CMZ decreased to 38-73%, compared with that of PIPC alone. These findings were supported by the fact that CMZ showed a high in vitro inducer activity against the isolates from the sputum. In the remaining one patient, high beta-lactamase activity (mean: 0.16 units/ml) and no antibiotics concentration was detected to be constant throughout the 3 days, and it was confirmed for the reason that one of the isolates constitutively produced large amounts of beta-lactamase. These results suggest that inducible and constitutive beta-lactamase would clinically cause undesirable effects in the treatment by some beta-lactams and have a possibility of indirect pathogenesis.     

Biological properties and drug susceptibility of verotoxin-producing Escherichia coli (VTEC) isolated from healthy goats in Okinawa Prefecture

Fecal samples from 116 healthy goats out of 25 randomly selected farms were examined for verotoxin-producing Escherichia coli (VTEC) during 1996 and 1998 in Okinawa Prefecture. VTECs were detected 204 (15.0%) from 1,361 E. coli strains, 36 (31.0%) goats out of 13 (52.0%) farms. Randomly selected 88 strains were further characterized according to VT types, serotypes, virulence markers, biochemical properties and drug susceptibility. VT types were classified as VT1 (46.6%), VT2 (6.8%), and VT1/VT2 (46.6%) by means of reversed latex agglutination test. The VTEC belonged to 18 different O serogroups: O1, O6, O22, O27, O48, O75, O76, O77, O78, O82, O91, O103, O111, O123, O125, O128, O146, and O158. Serotypes O91:H- (13 strains), O27:H- (10 strains), O22:H19 (6 strains) are considered to be predominant, whereas O serotypes O157 and O26 were not isolated. eaeA gene was detected only in 5 strains (5.7%):O103:H2 and O111:H-, in contrast, hlyA gene was found frequent in 45 strains (51.1%) belong to various O serogroups, except for O146 (8 strains). On the basis of 20 biochemical features in all isolates, characteristic patterns were divided into 14 distinct types:47 strains (57.3%) were classified as one type. The VTECs examined were resistant to streptomycin (26.7%), ampicillin (12.2%), kanamycin (8.9%), oxytetracyline (8.9%), and oxolinic acid (3.3%), respectively. The current results indicate that goats harbored VTEC at high frequencies and may be a potential reservoir of human VTEC infection.     

Ganglioside GM1 mimicry in Campylobacter strains from sporadic infections in the United States

To determine whether GM1-like epitopes in Campylobacter species are specific to O serotypes associated with Guillain-Barré syndrome (GBS) or whether they are frequent among random Campylobacter isolates causing enteritis, 275 random enteritis-associated isolates of Campylobacter jejuni were analyzed. To determine whether GM1-like epitopes in Campylobacter species are specific to O serotypes associated with Guillan-Barre syndrome (GBS) or whether they are frequent among random Campylobacter isolates causing enteritis, 275 enteritis-associated isolates, randomly collected in the United States, were analyzed using a cholera-toxin binding assay [corrected]. Overall, 26.2% of the isolates were positive for the GM1-like epitope. Of the 36 different O serotypes in the sample, 21 (58.3%) contained no strains positive for GM1, whereas in 6 serotypes (16.7%), >50% of isolates were positive for GM1. GBS-associated serotypes were more likely to contain strains positive for GM1 than were non-GBS-associated serotypes (37.8% vs. 15.1%, P=.0116). The results suggest that humans are frequently exposed to strains exhibiting GM1-like mimicry and, while certain serotypes may be more likely to possess GM1-like epitopes, the presence of GM1-like epitopes on Campylobacter strains does not itself trigger GBS.     

Change in antimicrobial susceptibility of Pseudomonas aeruginosa under restricted use of carbapenems

Since 2003, we have been restricting the length of carbapenems use in the treatment of infections. For this four-year period, we have compared annual data for Pseudomonas aeruginosa (P. aeruginosa) clinical isolates (85 isolates in 2003, 91 in 2004, 100 in 2005 and 100 in 2006) in drug sensitivity/resistance, MIC50/MIC90 and cross-resistance rate. The mean antimicrobial use density (AUD) for carbapenems decreased significantly (p < 0.01) from 22.5 +/- 4.0 before implementing restrictions to 6.7 +/- 1.8 after implementation. P. aeruginosa resistance (%) for carbapenems showed the following changes from 2003 to 2006: for IPM/CS, from 24.7% to 9.0%; for MEPM, from 11.8% to 2.0%; for BIPM, from 10.6% to 5.0%; for CAZ, from 15.3% to 2.0%; for CPFX, from 16.5% to 16.0%; and for AMK, from 2.4% to 0.0%. Comparison of sensitivity and resistance for IPM/CS, MEPM, BIPM, and CAZ between 2003 and 2006 shows that sensitivity increased as resistance decreased, but no change was seen in CPFX. MIC50 values were almost the same for IPM/CS, MEPM and BIPM. MIC90 values were the same for MEPM and BIPM, but was one tube higher for IPM/CS. Different combinations of cross-resistance to antimicrobial agents were detected. It is thus necessary to regularly survey of the antimicrobial sensitivity of P. aeruginosa in the hospital setting and to determine optimal use of antimicrobial agents.     

云南省玉溪市家鼠疫源地小肠结肠炎耶尔森菌监测分析

目的 了解云南省玉溪市家鼠鼠疫疫源地小肠结肠炎耶尔森菌的分布、病原学特征及对抗生素的敏感性。方法 从元江、新平两县采集褐家鼠、黄胸鼠、小家鼠、树鼩的盲肠和舌根以及猪咽拭标本、猪粪便和腹泻病人粪便,分离小肠结肠炎耶尔森菌及毒力基因检测。结果 从3 431份标本中分离到小肠结肠炎耶尔森菌71株,总检出率为2.07%。分离株包含15株致病株和56株非致病株,有3种生物型(1A、2、3型)、3种以上血清型(O∶3、O∶5、O∶8及未分型)及3种毒力基因型别。致病株均为3/O∶3生物血清型,毒力基因以ail^＋、ystA^＋、ystB^－、yadA^＋、virF^＋为主;非致病株,血清型属于O∶5、O∶8及未分型,毒力基因以ail^－、ystA^－、ystB^＋、yadA^－、virF^－为主;分离株对阿莫西林、阿莫西林/克拉微酸、氨苄西林高度耐药,对其他大部分常用抗生素敏感性较高。结论 小肠结肠炎耶尔森菌病在玉溪家鼠鼠疫疫原地宿主中传播流行;分离菌株的血清型/生物型,毒力基因型别多样性;头孢三、四代,喹诺酮类或氨基糖甙类抗生素适宜治疗小肠结肠炎耶尔森菌引起的感染。     

Isolation rates and pathogenicity of enterococci in obstetric and gynecological operations.

Isolation of enterococci in patients undergoing obstetric and gynecological operations was studied as well as reviewing the postoperative infection due to this organism during the period from 1985 to 1990. 1) In 126 cases undergoing abdominal total hysterectomy, vaginal specimens were obtained before and after (3rd day) the operation. The isolation rates increased after the operation (before 16.7%, after 35.7%). They increased not only in the group using PIPC, CEZ, CEPR, CMZ, and LMOX by drip infusion but also in the group without prophylactic use of antibiotics. On the other hand in the group using CP vaginal suppositories, the isolation rate decreased. However no statistical proof was obtained as to antibiotics especially in regard to cephem drugs as the reason for the increase. 2) Enterococci were isolated from the surgical field during abdominal total hysterectomy in only 2.0% (n = 88). 3) Isolation rates of enterococci inside the transvaginal drain following radical hysterectomy (n = 30) reached 86.7%. 4) E. faecalis was isolated in 20.0% of the cases with wound infection (n = 25). However isolated Enterococcus strains were not regarded to be the causative organism. 5) There was one case of postoperative enterococcal septicemia in treating stage Ib adenocarcinoma of the uterine cervix.     

Mutations of gyrA gene and parC gene in fluoroquinolone-resistant Escherichia coli isolates from sporadic diarrheal cases

We studied 107 isolates of Escherichia coli O153 from sporadic diarrhea cases in Fukui, Toyama, Aichi, and Saga prefectures from 1991 to 2005 for antimicrobial susceptibility and mechanisms of fluoroquinolone resistance, based on standard disk diffusion. Of 12 drugs tested, ampicillin displayed resistance to 72.9% of isolates, streptomycin to 48.6%, tetracycline to 46.7%, sulfisoxazole to 46.7%, trimethoprim/sulfamethoxazole to 29.9%, nalidixic acid (NA) to 29.9%, and ciprofloxacin (CPFX) to 24.3%. Ten of 32 isolates resistant to 3-6 drugs and 16 of 18 isolates resistant to 7-10 drugs were resistant both to NA and CPFX. Mutations of amino acid in quinolone resistance-determining regions of gyrA and parC genes were detected in 24 isolates resistant both to NA and CPFX, and in 1 isolate resistant to NA. The former possessed a combination of double substitution (S83L and D87L) in GyrA and a single substitution (S80I) in ParC. Some 12 of 24 isolates possessed another single substitution (E84V or E84G or A108T) in ParC. The 25 isolates were classified into 4 types as follows. 1 isolate as type 1: GyrA (S83L) and ParC (S80I); 12 isolates as type 2: GyrA (S83L and D87N) and ParC (S80I); 8 isolates as type 3: GyrA (S83L and D87N) and ParC (S80I and E84G/S80R and E84V); and 4 isolate as type 4: GyrA (S83L and D87N) and ParC (S80I and A108T). In the relationship between amino acid mutations and minimal inhibitory concentrations (MIC) of fluoroquinolone, MICs of CPFX, ofloxacin, and norfloxacin showed 1microg/mL, 2microg/mL and 8microg/mL in type 1; 8 approximately 32microg/mL, 8 approximately 32microg/mL and 16 approximately 256microg/mL in type 2; and 32 approximately 256microg/mL' 32 approximately 128microg/mL and 128-->512microg/ mL in types 3 and 4. These results suggest that most of multiple-antimicrobial-resitant E. coli O153 isolates from sporadic diarrhea cases were resistant to fluoroquinolones and possessed mutations at gyrA and parC genes associated with fluoroquinolone resistance.     

Increasing drug resistance in Vibrio cholerae O1 and non-O1 strains isolated from diarrheal cases in Japan

Drug resistance trends were investigated for 271 Vibrio cholerae O1 (V.c O1) and 401 V. cholerae non-O1 (V.c non-O1) strains isolated from mainly imported diarrheal cases during 1981-2001 in Japan. The results of drug resistance test using 8 drugs (CP, TC, SM, KM, ABPC, ST, NA, and NFLX) showed that 34.7% of the V. c O1 strains and 15.7% of V.c non-O1 strains were multi-drug or mono-drug resistant. The incidence of drug resistant strains has increased since 1991, and it has been remarkable in V.c O1 strains that increased from 1.2% in 1981-1985 to 70.8% in 1996-2001. The drug resistance patterns of the resistant strains classified into 6 types in V.c O1 and 21 types in V.c non-O1. The prevalent patterns recognized were SM (75.5%), CP.TC.SM.ST (10.6%) and CP.SM.ST (8.5%) in V.c O1, and SM (25.4%) and ABPC (25.4%) in V.c non-O1. Ten V.c O1 strains (3.7%) and 10 V.c non-O1 strains (2.5%) were multi-drug resistant including TC. Among those, 13 strains were isolated from travelers who returned to Japan from Thailand. One V.c O1 strain (0.4%) and 6 V.c non-O1 strains (1.5%) were NA high-resistant and fluoroquinolones low-sensitive. Among those, 4 strains were isolated from travelers who returned to Japan from India.     

Pneumococcal and Haemophilus influenzae meningitis in a children's hospital in Ethiopia: serotypes and susceptibility patterns

Streptococcus pneumoniae and Haemophilus influenzae are responsible for most pyogenic meningitis cases in children in Ethiopia. Resistance of S. pneumoniae and H. influenzae to penicillin and chloramphenicol respectively has been reported globally. Resistance has been related to specific serotypes of S. pneumoniae or to beta-lactamase-producing H. influenzae strains. This study describes the serotypes/ serogroups and susceptibility pattern of the two organisms causing meningitis in Ethiopian children. There were 120 cases of meningitis caused by S. pneumoniae (46) and H. influenzae (74) over a period of 3 years (1993-95). Nineteen children died from pneumococcal and 28 from haemophilus meningitis. Penicillin-resistant pneumococcal meningitis (4/8 = 50%) caused a greater mortality rate than penicillin-susceptible pneumococcal meningitis (15/38 = 39%). Common serotypes accounting for 76% of S. pneumoniae were type 14, 19F, 20, 1, 18 and 5; and serotypes 14, 19F and 7 (accounting for 17% of strains) showed intermediate resistance to penicillin G. 97% of the H. influenzae isolates were type b, and in only two cases beta-lactamase-producing. 72% of isolates of the S. pneumoniae we identified belong to serotypes preventable by a 9-valent vaccine. Our study highlights the possibility of resistant pyogenic meningitis in children in Ethiopia due to emerging resistant strains of S. pneumoniae and H. influenzae isolates.     

Nationwide surveillance of antimicrobial consumption and resistance to Pseudomonas aeruginosa isolates at 203 Japanese hospitals in 2010

Purpose

In Japan, a national surveillance study of antimicrobial consumption has never been undertaken. This study aimed to describe antimicrobial consumption and resistance to Pseudomonas aeruginosa in 203 Japanese hospitals, to identify targets for quality improvement.

Methods

We conducted an ecological study using retrospective data (2010). Antimicrobial consumption was collected in the World Health Organization (WHO) anatomical therapeutic chemical/defined daily dose (ATC/DDD) format. Rates of imipenem (IPM), meropenem (MEPM), ciprofloxacin (CPFX), or amikacin (AMK) resistance were expressed as the incidence of non-susceptible isolates. Additionally, hospitals were asked to provide data concerning hospital characteristics and infection control policies. Hospitals were classified according to functional categories of the Medical Services Act in Japan.

Results

Data were collected from 203 Japanese hospitals (a total of 91,147 beds). The total antimicrobial consumption was 15.49 DDDs/100 bed-days (median), with consumptions for penicillins, carbapenems, quinolones, and glycopeptides being 4.27, 1.60, 0.41, and 0.49, respectively. The median incidences of IPM, MEPM, CPFX, and AMK resistance were 0.15, 0.10, 0.13, and 0.03 isolates per 1,000 patient-days, respectively. Antimicrobial notification and/or approval systems were present in 183 hospitals (90.1 %). In the multivariate analysis, the piperacillin/tazobactam, quinolones, and/or total consumptions and the advanced treatment hospitals showed a significant association with the incidence of P. aeruginosa resistant to IPM, MEPM, CPFX, and AMK [adjusted R ² (aR ²) values of 0.23, 0.30, 0.22, and 0.35, respectively).

Conclusion

This is the first national surveillance study of antimicrobial consumption in Japan. A continuous surveillance program in Japan is necessary in order to evaluate the association among resistance, antimicrobial restriction, and consumption.