Multidrug-resistant Salmonella Typhimurium infection from milk contaminated after pasteurization

An outbreak of multidrug-resistant Salmonella enterica serotype Typhimurium infections occurred in Pennsylvania and New Jersey. A case-control study implicated pasteurized milk from a dairy, and an inspection indicated the potential for contamination after pasteurization. Dairy cattle are the likely reservoir, and milk may be an important vehicle of Salmonella transmission to humans.     

Age-related clinical and microbiological characteristics of enteric fever in India

A retrospective, hospital-based study at Safdarjang Hospital, India, was undertaken between January 1999 and December 2003 to estimate age-related epidemiological, clinical and microbiological characteristics in enteric fever cases. A total of 750 blood-culture-proven cases of enteric fever were studied. The majority of cases occurred in children aged 5-12 years and 24.8% of cases were in children up to 5 years of age. Salmonella serotypes showed an age-related predilection, with paratyphoid fever more common in adults. Classically-described clinical features of the disease were comparable among patients under and above 5 years of age. Hepatomegaly, anaemia and complications in general were more frequent in children up to 5 years of age. The antimicrobial resistance pattern, irrespective of Salmonella serotype, did not reveal a statistically significant difference across age groups for the different antibiotics tested. Multidrug resistance was seen only in Salmonella enterica serotype Typhi but not in S. Paratyphi A isolates. However, resistance to nalidixic acid was comparable in both serotypes. Age-related differences of serotype isolation rates, clinical presentation and associated complications are noteworthy for better case management and policy planning. More epidemiological studies regarding reasons for age-related differential serotype patterns would enable and guide public health strategies to contain enteric fever in endemic locations.     

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.     

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.     

Reactogenicity and immunogenicity of live attenuated Salmonella enterica serovar Paratyphi A enteric fever vaccine candidates

Eight Salmonella enterica serovar Paratyphi A strains were screened as candidates to create a live attenuated paratyphoid vaccine. Based on biochemical and phenotypic criteria, four strains, RKS2900, MGN9772, MGN9773 and MGN9779, were selected as progenitors for the construction of ΔphoPQ mutant derivatives. All strains were evaluated in vitro for auxotrophic phenotypes and sensitivity to deoxycholate and polymyxin B. All ΔphoPQ mutants were more sensitive to deoxycholate and polymyxin B than their wild-type progenitors, however MGN10028, MGN10044 and MGN10048, required exogenous purine for optimal growth. Purine requiring strains had acquired point mutations in purB during strain construction. All four mutants were evaluated for reactogenicity and immunogenicity in an oral rabbit model. Three strains were reactogenic in a dose-dependent manner, while one strain, MGN10028, was well-tolerated at all doses administered. All ΔphoPQ strains were immunogenic following a single oral dose. The in vitro profile coupled with the favorable reactogenicity and immunogenicity profiles render MGN10028 a suitable live attenuated Paratyphi A vaccine candidate.     

Emergence of ceftriaxone-resistant Salmonella isolates and rapid spread of plasmid-encoded CMY-2-like cephalosporinase,Taiwan

Of 384 Salmonella isolates collected from 1997 to 2000 in a university hospital in Taiwan, six ceftriaxone-resistant isolates of Salmonella enterica serovar Typhimurium were found in two patients in 2000. The resistance determinants were on conjugative plasmids that encoded a CMY-2-like cephalosporinase. During the study period, the proportion of CMY-2-like enzyme producers among Escherichia coli increased rapidly from 0.2% in early 1999 to >4.0% in late 2000. Klebsiella pneumoniae isolates producing a CMY-2-like beta-lactamase did not emerge until 2000. The presence of bla(CMY)-containing plasmids with an identical restriction pattern from Salmonella, E. coli, and K. pneumoniae isolates was found, which suggests interspecies spread and horizontal transfer of the resistance determinant. Various nosocomial and community-acquired infections were associated with the CMY-2-like enzyme producers. Our study suggests that the spread of plasmid-mediated CMY-2-like beta-lactamases is an emerging threat to hospitalized patients and the public in Taiwan.     

Salmonella-associated deaths, Sweden, 1997-2003

We examined excess deaths after infection with Salmonella in a registry-based matched cohort study of 25,060 persons infected abroad and 5,139 infected within Sweden. The domestically infected have an increased standardized mortality ratio, whereas those who acquired Salmonella infection abroad had no excess risk of death.     

Estimate of illnesses from Salmonella enteritidis in eggs, United States, 2000

Results from our model suggest that eating Salmonella enterica serovar Enteritidis-contaminated shell eggs caused 182,060 illnesses in the United States during 2000. Uncertainty about the estimate ranged from 81,535 (5th percentile) to 276,500 illnesses (95th percentile). Our model provides but 1 approach for estimating foodborne illness and quantifying estimate uncertainty.     

Salmonella enterica serotype Uganda infection in New York City and Chicago

Outbreaks associated with distinct strains of Salmonella enterica serotype Uganda, a rare serotype, occurred in New York City and Chicago during the summer of 2001. Both outbreaks were linked to eating ready-to-eat pork products. This serotype may emerge as a more frequent cause of human infections.     

Beta-lactam resistance and Enterobacteriaceae, United States

Extended-spectrum cephalosporins (ESC) are an important drug class for treating severe Salmonella infections. We screened the human collection from the National Antimicrobial Resistance Monitoring System 2000 for ESC resistance mechanisms. Of non-Typhi Salmonella tested, 3.2% (44/1,378) contained blaCMY genes. Novel findings included blaCMY-positive Escherichia coli O157:H7 and a blaSHV-positive Salmonella isolate. CMY-positive isolates showed a ceftriaxone MIC > or =2 microg/mL.     

Emergence of Salmonella enterica serotype Paratyphi A as a major cause of enteric fever in Kathmandu, Nepal

We performed pulsed-field gel electrophoresis (XbaI) on 114 bloodstream isolates of Salmonella enterica serotype Paratyphi A and S. enterica serotype Typhi collected from febrile patients in Kathmandu, Nepal. Of the 56 S. Paratyphi A isolates, 51 (91%) were indistinguishable, which suggests the emergence of a single clone. In contrast, only 21 (36%) of the 58 S. Typhi isolates exhibited a common genotype, which is consistent with endemic disease from multiple sources.     

Purification of O-specific polysaccharide from lipopolysaccharide produced by Salmonella enterica serovar Paratyphi A

The O specific polysaccharide (OSP) of the lipopolysaccharide (LPS) of Salmonella enterica serovar Paratyphi A is a protective antigen and the target for vaccine development. LPS is the major constituent of the outer membrane of S. Paratyphi A with the OSP exposed on the surface, in addition to the cell associated LPS a large amount of free LPS was present in the fermentation broth. A purification method was developed to take advantage of both sources of LPS and to maximize recovery of OSP. After fermentation the bacterial cells were concentrated and washed, the permeate containing the free LPS was processed separately from the cells. The free LPS was concentrated and washed on a 100 kD ultrafiltration membrane to remove low molecular weight impurities. The LPS was then detoxified by separation of the lipid A from the OSP using acid hydrolysis at 100 °C, the precipitated lipid A was removed by 0.2 μm membrane filtration. Contaminants were then removed by acid precipitation in the presence of sodium deoxycholate. The OSP was concentrated and washed with 1 M NaCl then water using a 10 kD ultrafiltration membrane then sterile filtered through a 0.2 μm membrane filter. The cells were treated by acid hydrolysis at 100 °C, the remaining cells, cell debris and precipitate was removed by centrifugation. The filtrate was then treated in the same way as described above for the free LPS. The combined yield of purified OSP from free LPS plus the cells was greater than 880 mg/L of culture broth. The method developed yields large amounts of OSP, is scalable and compatible with cGMP so would be readily transferrable to developing country vaccine manufacturers for low cost production of vaccine against S. Paratyphi A.     

A randomized comparison of oral chloramphenicol versus ofloxacin in the treatment of uncomplicated typhoid fever in Laos

We conducted a randomized open trial of oral chloramphenicol (50mg/kg/day in four divided doses for 14 days) versus ofloxacin (15 mg/kg/day in two divided doses for 3 days) in 50 adults with culture-confirmed uncomplicated typhoid fever in Vientiane, Laos. Patients had been ill for a median (range) of 8 (2-30) days. All Salmonella enterica serotype typhi isolates were nalidixic acid-sensitive, four (8%) were chloramphenicol-resistant and three (6%) were multidrug-resistant. Median (range) fever clearance times were 90 (24-224) hours in the chloramphenicol group and 54 (6-93) hours in the ofloxacin group (P<0.001). One patient in the chloramphenicol group developed an ileal perforation. Three days ofloxacin was more effective than 14 days chloramphenicol for the in-patient treatment of typhoid fever, irrespective of antibiotic susceptibility, and was of similar cost.     

Distribution trends of Salmonella serovars in India (2001-2005)

A total of 3079 samples were received and identified at the National Salmonella and Escherichia Centre (NSEC), Central Research Institute, Kasauli, India during 2001-2005. Out of these, 2098 samples were from humans, 250 from animals, and 726 from meat, vegetables, seafood and the environment. The Salmonella strains isolated were distributed among 35 different Salmonella serovars. The most common serovars from humans were Salmonella Typhi (73%) and Salmonella Paratyphi A (24%) among typhoidal serovars, and Salmonella Worthington (28.2%) and Salmonella Typhimurium (22.5%) among non-typhoidal serovars. The other frequently isolated serovars from different sources were Salmonella Gallinarum, Salmonella Typhimurium, Salmonella Enteritidis and Salmonella Dublin. Analysis of the prevalence of the 10 most common serovars in 18 states indicated that different serovars are distributed in different parts of India. The results from this study may be helpful in formulating preventive strategies to control the spread of infection in the country.     

Excess mortality associated with antimicrobial drug-resistant Salmonella typhimurium

In a matched cohort study, we determined the death rates associated with drug resistance in Salmonella Typhimurium. We linked data from the Danish Surveillance Registry for Enteric Pathogens with the Civil Registration System and the Danish National Discharge Registry. By survival analysis, the 2-year death rates were compared with a matched sample of the general Danish population, after the data were adjusted for differences in comorbidity. In 2,047 patients with S. Typhimurium, 59 deaths were identified. Patients with pansusceptible strains of S. Typhimurium were 2.3 times more likely to die 2 years after infection than persons in the general Danish population. Patients infected with strains resistant to ampicillin, chloramphenicol, streptomycin, sulfonamide, and tetracycline were 4.8 times (95% CI 2.2 to 10.2) more likely to die, whereas quinolone resistance was associated with a mortality rate 10.3 times higher than the general population.     

Nontyphoidal Salmonella bacteremia cases in AIDS patients in a Dakar University Hospital (Senegal)

OBJECTIVES: This study had for aim to describe epidemiological, clinical and bacteriological aspects of nontyphoidal Salmonella bacteremia in patients with AIDS in the Dakar University Hospital Infectious Diseases Clinic. METHOD: This study was made on data recorded between 1January1996 and 31December2005. The strains were identified according to biochemical (API 20E, BioMérieux) and antigenic features. Their susceptibility to antibiotic drugs was tested by antibiogram. Screening for strains secreting of an extended-spectrum betalactamase was performed. RESULTS: Sixty-two cases of nontyphoidal Salmonella bacteremia were recorded in AIDS patients as follows: Salmonellaenteritidis bacteremia (32 cases), Salmonellatyphimurium bacteremia (11 cases), and Salmonella spp bacteremia (11 cases). The strains were susceptible to ciprofloxacin, ceftriaxone, aztreonam, amoxicillin plus clavulanic acid in at least 92% of the cases. Only 79% of them were susceptible to cotrimoxazole. The lethality rate was 55%. DISCUSSION: This lethality rate of nontyphoidal Salmonella bacteremia is high in AIDS patients. Therefore, the priority should be put on prevention and, in patients with AIDS, on food hygiene measures, antiretroviral treatment and efficient chemoprophylaxis. This should prove efficient to reduce incidence of nontyphoidal Salmonella bacteremia.     

The changing pattern of bloodstream infections associated with the rise in HIV prevalence in northeastern Thailand

A survey of bloodstream infections was conducted in the large regional hospital in Ubon Ratchatani, northeastern Thailand between 1989 and 1998, during the onset of the HIV epidemic. The incidence of Staphylococcus aureus, Escherichia coli, Klebsiella/Enterobacter and Pseudomonas aeruginosa bacteraemias remained constant whereas infections caused by Burkholderia pseudomallei, non-typhoid Salmonellae, Cryptococcus neoformans, Penicillum marneffei and to a lesser extent Streptococcus pneumoniae all rose. Burkholderia pseudomallei infections were unrelated to HIV, whereas the other infections were associated directly with HIV. Group D non-typhoid Salmonellae bloodstream infections (mainly Salmonella enteritidis) rose coincident with the increase in HIV seroprevalence, and preceded the increase in the other HIV-associated infections. Other non-typhoid Salmonella bacteraemias increased two years after the rise in group D infections, and invasive yeast infections increased four years later, coincident with the increase in AIDS. Increasing Group D non-typhoid Salmonella bloodstream infections are an early warning signal of an impending rise in AIDS.     

The emergence of multidrug resistance to antimicrobial agents for the treatment of typhoid fever

Resistance to chloramphenicol was reported in Salmonella Typhi in 1950 but it was not until 22 years later that the first outbreaks of chloramphenicol-resistant typhoid fever occurred. Multidrug-resistant (MDR) Salmonella Typhi emerged in the 1980s and today has an almost worldwide distribution. Genome analysis of Salmonella Typhi strain CT18, an MDR isolate from a patient admitted to The Centre for Tropical Diseases, Ho Chi Minh City, Viet Nam, in December 1993 revealed that the resistance plasmid pHCM1 is very closely related to plasmid R27 which was first isolated in 1961. There is a core region shared by the two plasmids with five regions of variation. Two of these regions contain the genes encoding resistance. The largest region is 34.955 kbp in length, is bordered by two almost identical IS10 elements and contains several integron-like structures including a truncated Tn10 element. The second region is 14.75I kbp and encodes a trimethoprim-resistance gene, dfrA14, associated with a class one integrase. Restriction enzyme analysis has shown that the variation in Salmonella Typhi plasmids, collected during the emergence of resistant Salmonella Typhi in Viet Nam, maps to five variable regions. These regions appear to be hot spots for DNA acquisition in IncHI1 plasmids.     

Development of a novel in-water vaccination protocol for DNA adenine methylase deficient Salmonella enterica serovar Typhimurium vaccine in adult sheep

Intensive livestock production is associated with an increased incidence of salmonellosis. The risk of infection and the subsequent public health concern is attributed to increased pathogen exposure and disease susceptibility due to multiple stressors experienced by livestock from farm to feedlot. Traditional parenteral vaccine methods can further stress susceptible populations and cause carcass damage, adverse reactions, and resultant increased production costs. As a potential means to address these issues, in-water delivery of live attenuated vaccines affords a low cost, low-stress method for immunization of livestock populations that is not associated with the adverse handling stressors and injection reactions associated with parenteral administration. We have previously established that in-water administration of a Salmonella enterica serovar Typhimurium dam vaccine conferred significant protection in livestock. While these experimental trials hold significant promise, the ultimate measure of the vaccine will not be established until it has undergone clinical testing in the field wherein environmental and sanitary conditions are variable. Here we show that in-water administration of a S. Typhimurium dam attenuated vaccine was safe, stable, and well-tolerated in adult sheep. The dam vaccine did not alter water consumption or vaccine dosing; remained viable under a wide range of temperatures (21-37°C); did not proliferate within fecal-contaminated trough water; and was associated with minimal fecal shedding and clinical disease as a consequence of vaccination. The capacity of Salmonella dam attenuated vaccines to be delivered in drinking water to protect livestock from virulent Salmonella challenge offers an effective, economical, stressor-free Salmonella prophylaxis for intensive livestock production systems.     

Diversity of Salmonella spp. and fungi in northern Greek rivers and their correlation to fecal pollution indicators

The prevalence and diversity of Salmonella spp., filamentous fungi, and yeasts and their correlation with fecal pollution indicators (total coliforms, fecal coliforms, enterococci) and total heterotrophic bacteria counts were investigated in 95 water samples from the northern Greek rivers Aliakmon and Axios. Salmonella spp. were isolated in 27.4% of the samples and a total of 19 serotypes were identified. The frequency of Salmonella isolation was higher in the Axios (36.8%) than in the Aliakmon (21.0%) river. Significantly (P<0.001) more Salmonella spp. were recovered during warm (41.4%) than cold (5.4%) months. Salmonella-positive samples showed significantly higher counts of total heterotrophic bacteria and coliforms. Filamentous fungi were isolated from 98.9% and yeasts from 17.9% of the samples with respective mean counts of 2.36 x 10(3) and 1.28 x 10(2)cfu/100mL. Totals of 23 genera of filamentous fungi and 3 genera of yeasts were identified. The most frequent filamentous fungi were Penicillium and Aspergillus, while Candida was the most prevalent yeast. A significant (P<0.001) positive correlation of the fecal pollution indicators was demonstrated only for filamentous fungi. The results of this study indicate that these rivers may be potential pathways for human and other animal contamination with Salmonella spp., filamentous fungi, and yeasts, which contribute to the pollution of marine waters and the surrounding environment.