Antimicrobial susceptibility patterns of Salmonella enterica serotype typhi in eastern Nepal

The aim of the present study was to evaluate antimicrobial susceptibility patterns with special reference to multidrug resistance, susceptibility to ciprofloxacin, and bacteriophage typing of Salmonella enterica serotype Typhi isolated from blood sent for culture in a tertiary-care teaching hospital in eastern Nepal during January 2000-December 2004. In total, 132 strains of S. enterica Typhi, isolated from 2,568 blood culture samples collected from cases of suspected enteric fever, were tested for susceptibility to commonly-used antimicrobials by the disc-diffusion method. There were 35 multidrug-resistant strains. None of the isolates were resistant to ciprofloxacin. Of 52 isolates tested for minimum inhibitory concentration (MIC) of ciprofloxacin, 36 (69.23%) showed reduced susceptibility (MIC >0.25 mg/L). Of 112 strains tested for nalidixic acid susceptibility, 86 (76%) were resistant. Strains with reduced susceptibility to ciprofloxacin and resistance to nalidixic acid could be correlated. The commonest phage type was El. Nalidixic acid susceptibility could be a useful screening test for the detection of decreased susceptibility of S. Typhi to ciprofloxacin, a drug which is commonly used even for minor ailments in this area.     

Salmonella enterica serovar Typhi de sensibilité diminuée à la ciprofloxacine

The use of fluoroquinolone (FQ) as first line therapy for typhoid fever should be reconsidered because of the emergence of Salmonella Typhi and Paratyphi A strains with decreased susceptibility to FQ, mainly from Asia. Relapse can occur when ciprofloxacin MIC is over 0.12 mg/l, as illustrated by our case report. Azithromycin can be used successfully for patients infected with reduced ciprofloxacin susceptibility isolates. Literature review led us to suggest a new therapeutic strategy for uncomplicated typhoid fever, the antibiotic was chosen according to nalidixic acid susceptibility and ciprofloxacin MIC of the strain. High-dose intravenous ceftriaxone (4 g per day) is always efficient in first line therapy. Depending on FQ susceptibility testing results, it is relayed by oral therapy with a FQ (ciprofloxacin 500 mg bid for 7 days) if the isolate has maintained susceptibility, or azithromycin (1 g first day and 500 mg per day, 7 days) if the isolate is resistant to nalidixic acid or has a ciprofloxacin MIC superior to 0.12 mg/l.     

The treatment of multidrug-resistant and nalidixic acid-resistant typhoid fever in Viet Nam

Multidrug-resistant (MDR) Salmonella Typhi (resistant to chloramphenicol, ampicillin, and trimethoprim-sulphamethoxazole) and isolates with reduced susceptibility to fluoroquinolones (indicated by resistance to nalidixic acid, NaR) have caused epidemics and become endemic in southern Viet Nam during the 1990s. Short courses of ofloxacin have proved acceptable for treating MDR/NaS isolates of S. Typhi (ofloxacin MIC90 = 0.06 mg/l) causing uncomplicated disease. Ofloxacin (10-15 mg/kg/d) given for 2, 3, or 5 d cured >90% of patients with an average fever clearance time (FCT) of 4 d. Less than 3% of patients relapsed or had a positive post-treatment stool culture. In contrast, the response of NaR isolates (ofloxacin MIC90 = 0.5 mg/l) to such regimens is poor. For example, ofloxacin (20 mg/kg/d) given for 7 d cured only 75% of patients, with an FCT of 7 d, and 19% of patients had positive post-treatment faecal cultures. Currently available alternatives for NaR infections include ceftriaxone, cefixime, and azithromycin. These antimicrobials are reasonably effective but expensive. New, effective, and affordable regimens are needed to treat these NaR infections. Short courses of the new generation fluoroquinolones or combinations of the available antimicrobials are possible options.     

Reduced fluoroquinolone susceptibility in Salmonella enterica serotypes in travelers returning from Southeast Asia.

During 1995 to 1999, we collected 1,210 Salmonella isolates; 629 were from Finnish travelers returning from abroad. These isolates were tested for susceptibility by determining MICs to ciprofloxacin, nalidixic acid, and seven additional antimicrobial agents. From 1995 to 1999, the annual proportion of reduced ciprofloxacin susceptibility (MIC > 0.125 microg/mL) among all travelers' isolates increased from 3.9% to 23.5% (p<0.001). The increasing trend was outstanding among the isolates from Southeast Asia; isolates from Thailand alone increased from 5.6% to 50.0% (p<0.001). The reduced fluoroquinolone susceptibility was nonclonal in character and significantly associated with multidrug resistance. A point mutation in the quinolone resistance-determining region of gyrA was present in all isolates with reduced susceptibility. These data provide further evidence for the rapid spread of multidrug-resistant pathogens from one continent to another.     

MIC法测定空肠弯曲菌对氯霉素、环丙沙星、萘啶酮酸和红霉素的敏感性的研究

[目的]研究空肠弯曲菌对氯霉素、环丙沙星、萘啶酮酸和红霉素四种抗生素的敏感性。[方法]采用MIC法,在5%O2、10%CO2、85%N2的微需氧环境中,测定了空肠弯曲菌对氯霉素、环丙沙星、萘啶酮酸和红霉素四种抗生素的敏感性。[结果]14号菌株,17号菌株同时出现了对环丙沙星和萘啶酮酸的耐药性,11号菌株出现了对红霉素的耐药性。[结论]耐药性菌株的出现与农业和畜牧业中大量使用抗生素的使用相符合,应提高警惕。     

Activity of nalidixic acid and fluoroquinolones on Escherichia coli strains isolated from non-complicated urinary infections (reseau TSN - France, 1999 - 2001)

OBJECTIVE: The authors studied the susceptibility of 1,647 non-repeat isolates of Escherichia coli to quinolones and fluoroquinolones. METHOD: The strains were isolated from non-complicated urinary infections in women 18-64 years of age. Data was provided by the TSN Database France, a real time electronic database which collects antibiotic susceptibility results and patient demographic data. The data was collected from 1999 to 2001 in 63 French hospital laboratories, each using their own routine test methods. Quantitative data was interpreted (S, I, R) according to CA-SFM breakpoint guidelines. RESULTS: Ninety-eight and 94,6 % of the strains were susceptible to ciprofloxacin and nalidixic acid respectively. Cross resistance was assessed as well as intrinsic difference in activity within the fluoroquinolone class. Current fluoroquinolones are still highly efficient, and ciprofloxacin is the most active. CONCLUSION: Since 1996, little change in resistance to fluoroquinolones has been observed. These results confirm the choice of fluoroquinolones as first intention therapy as recommended by consensus conferences.     

Increasing spectrum in antimicrobial resistance of Shigella isolates in Bangladesh: resistance to azithromycin and ceftriaxone and decreased susceptibility to ciprofloxacin

Antimicrobial resistance of Shigella isolates in Bangladesh, during 2001-2002, was studied and compared with that of 1991-1992 to identify the changes in resistance patterns and trends. A significant increase in resistance to trimethoprim-sulphamethoxazole (from 52% to 72%, p < 0.01) and nalidixic acid (from 19% to 51%, p < 0.01) was detected. High, but unchanged, resistance to tetracycline, ampicillin, and chloramphenicol, low resistance to mecillinam (resistance 3%, intermediate 3%), and to emergence of resistance to azithromycin (resistance 16%, intermediate 62%) and ceftriaxone/cefixime (2%) were detected in 2001-2002. Of 266 recent isolates, 63% were resistant to > or =3 anti-Shigella drugs (multidrug-resistant [MDR]) compared to 52% of 369 strains (p < 0.007) in 1991-1992. Of 154 isolates tested by E-test in 2001-2002, 71% were nalidixic acid-resistant (minimum inhibitory concentration [MIC] > or =32 microg/mL) and had 10-fold higher MIC90 (0.25 microg/mL) to ciprofloxacin than that of nalidixic acid-susceptible strains exhibiting decreased ciprofloxacin susceptibility, which were detected as ciprofloxacin-susceptible and nalidixic acid-resistant by the disc-diffusion method. These strains were frequently associated with MDR traits. High modal MICs were observed to azithromycin (MIC 6 microg/mL) and nalidixic acid (MIC 128 micdrog/mL) and low to ceftriaxone (MIC 0.023 microg/mL). Conjugative R-plasmids-encoded extended-spectrum beta-lactamase was responsible for resistance to ceftriaxone/cefixime. The growing antimicrobial resistance of Shigella is worrying and mandates monitoring of resistance. Pivmecillinam or ciprofloxacin might be considered for treating shigellosis with caution.     

Prevalence and mechanisms of quinolone resistance among selected nontyphoid Salmonella isolated from food animals and humans in Korea

The aim of this study was to investigate the prevalence and mechanism of quinolone resistance among selected nontyphoid Salmonella (NTS) isolates. A total of 1279 NTS isolated from food animals (n=692) and humans (n=587) between 1995 and 2009 were investigated by serotyping, antimicrobial susceptibility testing, screening for plasmid-mediated quinolone resistance (PMQR) genes qnr, aac(6')-Ib-cr, and qepA and mutations in the quinolone resistance-determining region (QRDR) of gyrA and parC by PCR, and DNA sequencing. Three hundred thirty (47.7%) of 692 animal isolates and 177 (30.2%) of 587 human isolates were resistant to nalidixic acid. Most animal (94.8%, 313/330) and human (99.4%, 176/177) NTS exhibited decreased ciprofloxacin susceptibility (minimum inhibitory concentration [MIC]: 0.125-2?mg/L). None of them carried qnr or qepA gene. However, aac(6')-Ib was identified in six animal isolates, of which four carried aac(6')-Ib-cr gene. Based on antimicrobial resistance profile, year of isolation, MIC for quinolones and fluoroquinolones, and isolation frequency of serotype, 114 animal and 83 human isolates were tested for QRDR mutations. All contained a single mutation within the QRDR of gyrA at either codon 87 or 83, and 41 of them contained an additional mutation in parC. The most prevalent mutation was Asp87-Tyr (n=107), followed by Asp87-Gly (n=28), Asp87-Asn (n=26), Ser83-Tyr (n=22), and Ser83-Phe (n=14). Point mutations in parC were observed outside the QRDR, which included 40 isolates with Thr57-Ser substitution and 1 Salmonella Typhimurium with a novel Glu51-Lys substitution. In conclusion, a point mutation within the QRDR of gyrA was primarily responsible for quinolone resistance and reduced susceptibility to fluoroquinolones in NTS in Korea. To our knowledge, this is the first report of occurrence of aac(6')-Ib-cr gene among NTS in Korea. The spread of NTS carrying aac(6')-Ib-cr is of serious concern and should be carefully monitored.     

Life-threatening infantile diarrhea from fluoroquinolone-resistant Salmonella enterica typhimurium with mutations in both gyrA and parC

Salmonella Typhimurium DT12, isolated from a 35-day-old infant with diarrhea, was highly resistant to ampicillin, tetracycline, chloramphenicol, streptomycin, gentamycin, sulfamethoxazole/trimethoprim, nalidixic acid, and fluoroquinolones. The patient responded to antibiotic therapy with fosfomycin. Multidrug-resistance may become prevalent in Salmonella infections in Japan, as shown in this first case of a patient infected with fluoroquinolone-resistant Salmonella.     

Antimicrobial susceptibility breakpoints and first-step parC mutations in Streptococcus pneumoniae: redefining fluoroquinolone resistance

Clinical antimicrobial susceptibility breakpoints are used to predict the clinical outcome of antimicrobial treatment. In contrast, microbiologic breakpoints are used to identify isolates that may be categorized as susceptible when applying clinical breakpoints but harbor resistance mechanisms that result in their reduced susceptibility to the agent being tested. Currently, the National Committee for Clinical Laboratory Standards (NCCLS) guidelines utilize clinical breakpoints to characterize the activity of the fluoroquinolones against Streptococcus pneumoniae. To determine whether levofloxacin breakpoints can identify isolates that harbor recognized resistance mechanisms, we examined 115 S. pneumoniae isolates with a levofloxacin MIC of >2 mg/mL for first-step parC mutations. A total of 48 (59%) of 82 isolates with a levofloxacin MIC of 2 mg/mL, a level considered susceptible by NCCLS criteria, had a first-step mutation in parC. Whether surveillance programs that use levofloxacin data can effectively detect emerging resistance and whether fluoroquinolones can effectively treat infections caused by such isolates should be evaluated.     

中国常用益生菌菌种的耐药性研究

采用肉汤稀释法,对中国益生菌保健品行业常用的9株双歧杆菌和22株乳杆菌,共计31株益生菌进行了24种抗生素的耐药性检测。结果表明:31株益生菌均对下列抗生素敏感:氨苄西林、青霉素、亚胺培南、庆大霉素、阿莫西林、阿莫西林/棒酸、加替沙星、红霉素、克林霉素、四环素、利福平和头孢噻肟;而对萘啶酮酸、万古霉素和磷霉素的耐药率较高。     

Salmonella enterica Serotype Typhi with nonclassical quinolone resistance phenotype

We report Salmonella enterica serotype Typhi strains with a nonclassical quinolone resistance phenotype (i.e., decreased susceptibility to ciprofloxacin but with susceptibility to nalidixic acid) associated with a nonsynonymous mutation at codon 464 of the gyrB gene. These strains, not detected by the nalidixic acid disk screening test, can result in fluoroquinolone treatment failure.     

大肠埃希菌体外对氟喹诺酮类药物交叉耐药的研究

目的探讨大肠埃希菌在体外对氟喹诺酮类药物的交叉耐药性。方法采用多步诱导法,对32株临床分离的氟喹诺酮类敏感大肠埃希菌分别进行环丙沙星、左氧氟沙星、加替沙星的诱导性耐药试验;用琼脂稀释法测定药物敏感性。结果22株大肠埃希菌诱导出稳定的高耐氟喹诺酮菌株;与原株比较,耐药株的MIC分别增加了32-3 000倍,三种氟喹诺酮药物诱导的耐药株对三种药物存在交叉耐药性;进行测序的1株诱导高度耐药菌株的gyrA发生Ser83→Leu、Asp87→Asn,parC发生ser80→Ile的氨基酸替换,而测序的一株敏感菌株未发现氨基酸改变。结论在低浓度抗菌药物的长期压力下,可诱导大肠埃希菌产生对氟喹诺酮类药物的获得性耐药,氟喹诺酮药物之间存在交叉耐药性。     

四环素诱导表皮葡萄球菌对氟喹诺酮类耐药性研究

目的　为研究氟喹诺酮类抗菌药物非特异性耐药机制建立细菌筛选方法,并研究其耐药特点及遗传稳定性。方法　使用高浓度四环素作诱导剂,分步诱导敏感表皮葡萄球菌产生高耐突变株,并从中选择对环丙沙星和司帕沙星耐药菌株。结果　经过4 步四环素诱导突变后,获得的突变株对四环素的M IC增加了500 倍,这些菌株中约有1/3 对环丙沙星和司帕沙星中度耐药,MIC比亲代株增加了60 倍。子代菌与亲代菌相比主要生化反应无改变,连续传代培养证明突变株对氟喹诺酮类药物的抗药性可稳定遗传。结论　采用四环素诱导突变的方法可使细菌获得对氟喹诺酮类的耐药性,提示用其它抗菌药物治疗感染失败的患者换用氟喹诺酮类药物时应慎重     

Rational basis for optimizing antibiotic dosing regimens

Adjustment of the antibiotic dosage is usually done taking into account pharmacokinetic parameters. However, as the bacterial response to the antimicrobial effect varies it is important to correlate pharmacokinetics with antimicrobial susceptibility data, the latter measured by determining the Minimum Inhibitory Concentration (MIC). It is now widely accepted that the ratio between the maximum antibiotic concentration achieved in serum and the MIC of the pathogen correlates with efficacy of aminoglycosides and fluoroquinolones. The ratio between the area under the serum concentration-time curve and the MIC correlates with efficacy of aminoglycosides and fluoroquinolones but also of vancomycin, tetracyclines, azithromycin, and quinupristin/dalfopristin. Finally the time for which antibiotic concentration in serum remains above the MIC correlates with efficacy of beta-lactams, most macrolides, and clindamycin. All the above mentioned pharmacodynamic parameters should be considered for optimizing antibiotic dosage.     

Minimum inhibitory concentration (MIC) of some antibiotics against Vibrio cholerae O139 isolates from Pondicherry.

The antibiotic susceptibility pattern of Vibrio cholerae O139, Bengal, an emerging intestinal pathogen has been determined by the Kirby Bauer technique and the MIC values of some antibiotics against these strains by agar dilution technique. All the strains were susceptible to tetracycline, norfloxacin, ciprofloxacin and a majority was susceptible to gentamicin (95.7%) and nalidixic acid (82.9%). Only 51% were susceptible to cefotaxime and most strains were resistant to furazolidone (95.7%), ampicillin (87.3%) and co-trimoxazole (91.5%). The study shows the importance of judicious use of antibiotics in cholera cases and the need for monitoring the susceptibility status of these strains particularly because of their ability to cause extra-intestinal infections like septicaemia.     

Emerging resistance to newer antimicrobial agents among Shigella isolated from Finnish foreign travellers

In Finland, most cases of shigellosis are related to travel abroad. Antimicrobial drug resistance of 1814 Shigella strains isolated from Finnish patients during 1990-2005 was studied using discs of 12 antimicrobial agents. Since 2000, the E-test has been performed to determine ciprofloxacin minimum inhibitory concentrations of nalidixic acid-resistant isolates. The proportion of multi-resistant strains (resistant to >or =4 antimicrobials) was highest among isolates from China and India, but is increasing significantly in other parts of Asia. Resistance to nalidixic acid has become common among the strains from the Far East, and the first isolates also resistant to ciprofloxacin were detected during 2004-2005. All the ciprofloxacin-resistant isolates belonged to the S. flexneri 2a serotype. All the nalidixic acid-resistant S. flexneri strains had reduced susceptibility to ciprofloxacin, whereas 23% of the nalidixic acid-resistant S. sonnei strains were still completely susceptible to ciprofloxacin.     

Community-acquired urinary tract infections in 15 to 65 years old female patients in France. Susceptibility of E. coli according to history: AFORCOPI-BIO network 2003

OBJECTIVES: A multicenter study was implemented in order to determine the distribution and antibiotic susceptibility patterns of strains isolated from 15 to 65 year old female patients with community-acquired urinary tract infections. PATIENTS AND METHODS: From October to December 2003, 11 French private laboratories consecutively collected 420 clinical strains with medical data. Minimal inhibitory concentrations of antibiotics on E. coli were determined using the agar dilution method in a coordinating center and interpretation followed the recommendations of the Comité de l'antibiogramme de la Société fran?aise de microbiologie. RESULTS: Escherichia coli was the most prevalent pathogen (80%) followed by Proteus mirabilis (4%), Klebsiella spp (2%), other Enterobacteriaceae (4%), Enterococcus spp (3%), Staphylococcus aureus (2%), Staphylococcus saprophyticus (2%), and Streptococcus agalactiae (2%). The susceptibility of E. coli strains was 61% for amoxicillin (AMX), 93% for nalidixic acid (NAL), 97% for norfloxacin (NOR) and ciprofloxacin (CIP), 77% for cotrimoxazole (SXT), 99% for fosfomycin, gentamicin and cefotaxime. The susceptibility of E. coli was lower in case of previous treatment with beta-lactam antibiotics for AMX (84 vs 95% p=0.02) and SXT (62 vs 81% p=0.02). In the same way, previous treatment with quinolones was associated with decreased susceptibility for NAL (84 vs 95% p=0.02) and SXT (62 vs 81% p=0.02). CONCLUSIONS: In 2003, fluoroquinolones, third generation cephalosporins, aminoglycosides, and fosfomycin kept a good activity on E. coli collected from community-acquired urinary tract infections in 15 to 65 years old female patients in France.     

Antibiotic susceptibility of campylobacter isolates from sewage and poultry abattoir drain water.

In this study, the in vitro susceptibility of 209 campylobacter strains to the quinolones nalidixic acid, flumequine, ciprofloxacin, enrofloxacin, and to ampicillin, tetracycline and erythromycin was tested by the disk diffusion method. The strains were isolated from poultry abattoir effluent (DWA) and two sewage purification plants (SPA and SPB). Sewage purification plant SPA received mixed sewage, including that from a poultry abattoir, whereas SPB did not receive sewage from any meat-processing industry. The quinolone resistance of the DWA isolates ranged from 28% for enrofloxacin to 50% for nalidixic acid. The strains isolated from the sewage purification plants were more susceptible to the quinolones with a range of 11-18% quinolone resistance for SPB isolates to 17-33% quinolone resistance for SPA isolates. The susceptibility criteria as recommended by National Committee Clinical Laboratory Standards (USA) cannot readily be employed for campylobacter isolates. This investigation shows that the resistance of campylobacter bacteria is highest in the plant receiving sewage from a poultry slaughterhouse. Monitoring of antibiotic resistance of aquatic Campylobacter spp. is important, as surface waters are recognized as possible sources of infection.     

广西壮族自治区1994-2013年伤寒流行病学特征及菌株耐药分析

目的 分析1994-2013年广西地区伤寒流行特征、菌株耐药特征及其变迁。方法 采用描述流行病学方法分析1994-2013年广西地区伤寒疫情报告资料,对分离自伤寒病例475株沙门菌,利用纸片扩散法及肉汤微量稀释法检测抗菌药物最小抑菌圈和抑菌浓度（MIC）,依据CLSI 2012版敏感判定标准,判定菌株的耐药情况。结果 20年间广西地区共报告伤寒病例57 928例,年均发病率为6.29/10万,病死率为0.03%。<20岁人群发病较高,发病无性别差异,病例以农民和学生为主,主要分布在广西北部地区,全年均有发病,发病高峰在5-10月。2001-2013年发生13起大的暴发疫情,传播方式以水型为主。475株菌对第三代头孢类抗生素头孢噻肟和氟喹诺酮类诺氟沙星的敏感率为100%,对四环素、氯霉素、氨苄西林、庆大霉素的敏感率约为98%,对环丙沙星的敏感率为89.89%;对链霉素、复方新诺明的敏感性较低,为67.73%和65.89%。发现1株环丙沙星耐药、47株环丙沙星敏感性降低的菌株。暴发株与散发株耐药情况无差别。有28株菌耐≥3种抗生素,首次发现1株同时对氨苄西林、氯霉素、链霉素、复方新诺明、四环素、萘啶酸（ACSSxT-NAL）耐药的多重耐药菌株。多耐药株多见于伤寒小范围暴发疫情。结论 广西地区伤寒发病水平仍较高,且菌株出现对临床常用的氟喹诺酮类药物敏感性降低及多重耐药现象,应加强疫情及耐药监测。