Emergence of multidrug-resistant Salmonella enterica serotype Typhi with decreased ciprofloxacin susceptibility in Bangladesh

During 1989-2002, we studied the antimicrobial resistance of 3928 blood culture isolates of Salmonella enterica serotype Typhi (S. Typhi) in Dhaka, Bangladesh. Overall 32% (1270) of the strains were multidrug-resistant (MDR, resistant to chloramphenicol, ampicillin and trimethoprim-sulphamethoxazole); first detected in 1990 (rate of 8%), increased in 1994 (44%), declined in 1996 (22%, P<0.01 compared to 1994) and re-emerged in 2001 (36%) and 2002 (42%, P<0.01 compared to 1996). An increased MIC of ciprofloxacin (0.25 microg/ml) indicating decreased susceptibility to ciprofloxacin was detected in 24 (18.2%) out of 132 randomly selected strains during 1990-2002; more frequently in MDR than susceptible strains (46.3% vs. 5.5%, P<0.001), and the proportion of them rose to 47% in 2002 from 8% in 2000 (P<0.01). Ciprofloxacin (5 microg) disk diffusion zone diameters of < or =24 mm as break-point had 98% sensitivity and 100% specificity when compared with a ciprofloxacin MIC of 0.25 microg/ml as break-point for decreased susceptibility; being a useful and easy screen test. All strains were susceptible to ceftriaxone. The emergence of MDR S. Typhi with decreased ciprofloxacin susceptibility will further complicate the therapy of typhoid fever because of the lack of optimum treatment guidelines.     

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.     

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.     

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.     

Surveillance of antimicrobial resistance of Salmonella enterica serotype Typhi in seven Asian countries

Two hundred and four Salmonella enterica serotype Typhi (S. Typhi) isolates were collected from seven Asian countries during 2002-2004. Multidrug-resistant S. Typhi (resistant to > or = 3 antibiotics) was detected in 84 (41.2%) isolates and 142 (69.6%) showed reduced susceptibility to ciprofloxacin (minimum inhibitory concentration=0.125-1.0 mg/l). This study highlights the worsening situation of antimicrobial resistance of S. Typhi in Asia.     

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。     

鼠伤寒沙门菌临床分离株对喹诺酮类药物耐药机制的研究

目的 研究引起儿童腹泻鼠伤寒沙门菌对喹诺酮类抗菌药物的耐药机制.方法 采用K-B法测定62株鼠伤寒沙门菌对常用抗菌药物的敏感性;应用PCR法和DNA测序法检测喹诺酮耐药决定区(QRDRs)和质粒介导的喹诺酮耐药基因;采用接合试验测定耐药基因的转移性;PFGE法测定耐药菌株的同源性.结果 62株肠伤寒沙门菌中有40株对环丙沙星耐药(MIC≥0.5 μg/ml),其中28株为低水平耐药,12株为高水平耐药,且所有对环丙沙星耐药菌株同时对其他多种抗菌药物耐药;40株环丙沙星耐药菌株分属于4种PFGE型,分别是A型7株、B型4株、E型1株、D型28株;两株对环丙沙星高水平耐药菌株同时存在gyrA和parC两个位点的突变,其余环丙沙星耐药菌株仅发现gyrA 1个位点的突变,未检测到qnr和qepA基因;62株鼠伤寒沙门菌中有23株为aac-(6′)-Ib-cr阳性,其中19株PFGE分型为D型.结论 腹泻患儿分离的肠伤寒沙门菌对环丙沙星耐药率高,喹诺耐耐药决定区gyrA基因的点突变和携带aac-(6′) -Ib-cr基因是导致鼠伤寒沙门菌对环丙沙星耐药的主要原因.     

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.     

Bacteremia and antimicrobial drug resistance over time, Ghana

Bacterial distribution and antimicrobial drug resistance were monitored in patients with bacterial bloodstream infections in rural hospitals in Ghana. In 2001-2002 and in 2009, Salmonella enterica serovar Typhi was the most prevalent pathogen. Although most S. enterica serovar Typhi isolates were chloramphenicol resistant, all isolates tested were susceptible to ciprofloxacin.     

Antibiogram pattern and seasonality of Salmonella serotypes in a North Indian tertiary care hospital

The antibiogram pattern and seasonal distribution of Salmonella serotypes were analysed retrospectively over a 6-year period from January 1999 to December 2004. Blood cultures received in the Bacteriology Laboratory were processed by standard procedures and the Salmonella spp. isolates were identified with specific antisera and standard biochemical tests. Antimicrobial susceptibility testing was carried out by a standard disc diffusion method and the minimum inhibitory concentration (MIC) of ciprofloxacin for 332 representative Salmonella isolates was determined by E test. Salmonella Typhi (75.7%) was the predominant serotype among 830 Salmonella spp. isolated during the study period followed by S. Paratyphi A (23.8%). The maximum number of enteric fever cases occurred during April-June (dry season) followed by July-September (monsoon season). There was a decrease in multidrug-resistant (MDR) S. Typhi, but MDR S. Paratyphi A isolates increased. There was also a dramatic increase in nalidixic acid-resistant isolates. All isolates were susceptible to third-generation cephalosporins and ciprofloxacin except one S. Typhi strain which demonstrated high-level ciprofloxacin resistance with a MIC of 16 mug/ml. A knowledge of the seasonal distribution and antibiotic resistance pattern of Salmonella in a particular geographical region is helpful in the delineation of appropriate control measures required for prevention of enteric fever.     

Decreased susceptibility to ciprofloxacin in Salmonella enterica serotype typhi, United Kingdom

In 1999, 23% of Salmonella enterica serotype Typhi isolates from patients in the United Kingdom exhibited decreased susceptibility to ciprofloxacin (MIC 0.25-1.0 mg/L); more than half were also resistant to chloramphenicol, ampicillin, and trimethoprim. Increasing numbers of treatment failures have been noted. Most infections have been in patients with a recent history of travel to India and Pakistan.     

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.     

Ciprofloxacin-resistant Salmonella enterica Typhimurium and Choleraesuis from pigs to humans, Taiwan

We evaluated the disk susceptibility data of 671 nontyphoid Salmonella isolates collected from different parts of Taiwan from March 2001 to August 2001 and 1,261 nontyphoid Salmonella isolates from the National Taiwan University Hospital from 1996 to 2001. Overall, ciprofloxacin resistance was found in 2.7% (18/671) of all nontyphoid Salmonella isolates, in 1.4% (5/347) of Salmonella enterica serotype Typhimurium and in 7.5% (8/107) in S. enterica serotype Choleraesuis nationwide. MICs of six newer fluoroquinolones were determined for the following isolates: 37 isolates of ciprofloxacin-resistant (human) S. Typhimurium (N = 26) and Choleraesuis (N = 11), 10 isolates of ciprofloxacin-susceptible (MIC <1 mg/mL) (human) isolates of these two serotypes, and 15 swine isolates from S. Choleraesuis (N = 13) and Typhmurium (N = 2) with reduced susceptibility to ciprofloxacin (MIC >0.12 microg/mL). Sequence analysis of the gryA, gyrB, parC, parE, and acrR genes, ciprofloxacin accumulation, and genotypes generated by pulsed-field gel electrophoresis with three restriction enzymes (SpeI, XbaI, and BlnI) were performed. All 26 S. Typhimurium isolates from humans and pigs belonged to genotype I. For S. Choleraesuis isolates, 91% (10/11) of human isolates and 54% (7/13) of swine isolates belonged to genotype B. These two genotypes isolates from humans all exhibited a high-level of resistance to ciprofloxacin (MIC 16-64 mg/mL). They had two-base substitutions in the gyrA gene at codons 83 (Ser83Phe) and 87 (Asp87Gly or Asp87Asn) and in the parC gene at codon 80 (Ser80Arg, Ser80Ile, or Ser84Lys). Our investigation documented that not only did these two S. enterica isolates have a high prevalence of ciprofloxacin resistance nationwide but also that some closely related ciprofloxacin-resistant strains are disseminated from pigs to humans.     

An outbreak of multidrug-resistant Salmonella enterica serotype Oranienburg in Michigan dairy calves

The objectives of this study were to report an outbreak of highly drug-resistant Salmonella enterica serotype Oranienburg in dairy calves, and conduct an epidemiological investigation of Oranienburg identified on a dairy herd during a study to determine whether discontinuing feeding medicated milk replacer to preweaned dairy calves resulted in increased antimicrobial susceptibility in enteric bacteria. Calf fecal samples and swabs of calf and maternity pens were collected monthly over 18 months. Samples were streaked onto XLT-4 agar and characteristic colonies were subjected to biochemical tests to confirm Salmonella. Strain relatedness was examined by Xbal and BlnI pulsed-field gel electrophoresis analysis on 62 randomly selected isolates. Antimicrobial susceptibility testing, using automated microbroth dilution, was conducted using a panel containing tetracycline, amikacin, amoxicillin-clavulanic acid, ampicillin, ceftiofur, ceftriaxone, cephalothin, chloramphenicol, ciprofloxacin, cefoxitin, gentamicin, kanamycin, nalidixic acid, streptomycin, sulfamethoxazole, and trimethoprim-sulfamethoxazole. A total of 190 Salmonella spp. were isolated from 604 calf and 36 pen samples, of which 86% were Oranienburg and 97% were resistant to at least 9 agents. Environmental isolates had lower levels of resistance than fecal isolates. Pulsed-field gel electrophoresis analysis identified three strains: the most common strain was consistently present before the outbreak and at its peak. One strain was exclusively an environmental isolate, with little antimicrobial resistance. Multiresistant isolates with resistance to ciprofloxacin appeared early in the outbreak, and were replaced by multiresistant isolates with resistance to cephalothin. The differences in strains and resistance patterns suggest that the strains of Oranienburg found in fecal isolates may have different origins from environmental isolates.     

Cases of typhoid fever imported into England, Scotland and Wales (2000-2003)

Although typhoid fever is no longer endemic in most of the developed world, it remains a major infectious disease in less developed regions and imported cases continue to occur in returning travellers, immigrants or migrant workers. We analysed all 692 isolates of Salmonella enterica subspecies enterica serovar Typhi from cases in England, Scotland and Wales that were sent to the Laboratory of Enteric Pathogens at the Health Protection Agency, Centre for Infections, London, UK between 2000 and 2003. The country of acquisition was known for 416 isolates (60%), and the majority of these (70%) came from India or Pakistan. Overall, 24 countries were listed, mainly in Asia and Africa. A total of 48 phage types were detected, 41% of which were Vi-phage type E1. Antimicrobial susceptibility testing revealed that 22% of isolates were multidrug resistant (MDR) (defined as resistance to chloramphenicol, ampicillin and co-trimoxazole) and 39% were quinolone resistant. A significant number of isolates (n=49) were sensitive to nalidixic acid by disk test but exhibited low-level ciprofloxacin resistance, suggesting a novel mechanism of resistance and reinforcing the need for minimum inhibitory concentration determination. Overall, 13% of isolates were both MDR and likely to show a poor response to a fluoroquinolone. A third-generation cephalosporin (e.g. ceftriaxone) should be considered as empirical therapy in regions of the Indian subcontinent where resistance is now at high levels as well as in patients returning from these areas. This study helps to describe the epidemiology of antimicrobial drug resistance in typhoid fever.     

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.     

Multidrug-resistant strains of Salmonella enterica Typhimurium, United States, 1997-1998

To evaluate multidrug-resistant strains of Salmonella enterica serotype Typhimurium, including definitive type 104 (DT104) in the United States, we reviewed data from the National Antimicrobial Resistance Monitoring System (NARMS). In 1997 to 1998, 703 (25%) of 2,767 serotyped Salmonella isolates received at NARMS were S. Typhimurium; antimicrobial susceptibility testing and phage typing were completed for 697. Fifty-eight percent (402) were resistant to > or = 1 antimicrobial agent. Three multidrug-resistant (> or = 5 drugs) strains accounted for (74%) 296 of all resistant isolates. Ceftriaxone resistance was present in 8 (3%), and nalidixic acid resistance in 4 (1%), of these multidrug-resistant strains. By phage typing, 259 (37%) of S. Typhimurium isolates were DT104, 209 (30%) were of undefined type and 103 (15%) were untypable. Fifty percent (202) of resistant (> or = 1 drug) isolates were DT104. Multidrug-resistant S. Typhimurium isolates, particularly DT104, account for a substantial proportion of S. Typhimurium isolates; ceftriaxone resistance is exhibited by some of these strains.     

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.     

Characteristics of gonococci isolated from men with urethritis in Dubai.

Neisseria gonorrhoeae were collected from men attending out-patient clinics in Dubai. The susceptibility to a range of therapeutic antibiotics and their auxotype and serotype was determined. The plasmid content of all penicillinase-producing strains was also analysed. Thirty-six strains of N. gonorrhoeae were isolated from specimens collected from 79 patients over a 24-day period. Of the 36 isolates, 9(25%) were penicillinase-producing N. gonorrhoeae (PPNG) and 15 (42%) were chromosomally resistant N. gonorrhoeae (CMRNG). CMRNG exhibited higher levels of resistance to cefuroxime, chloramphenicol, tetracycline and erythromycin than PPNG. All isolates were susceptible to ceftriaxone and spectinomycin. Three (8%) isolates showed reduced susceptibility (MIC, > or = 0.25 mg/l) to ciprofloxacin. Six isolates of PPNG carried the 4.4 MD and three the 3.2 MD penicillinase encoding plasmid. The total gonococcal population was phenotypically diverse, with 12 serovars, 6 auxotypes and 21 A/S classes. Gonorrhoea was found to be a major cause of urethritis in Dubai and the strains exhibited high levels of resistance to penicillin.