Salmonella enterica subsp. enterica serovar Typhimurium and Lactobacillus spp. interactions in vitro elicit improved antimicrobial production

@#Antimicrobial resistance (AMR) is a global health crisis. Despite the drug discovery efforts, AMR is increasing, and discoveries are nearly nil. It is thus critical to design new strategies. Probiotics are tapped as alternatives to antibiotics for the treatment of gut-associated diseases. Lactobacillus species, common in food products, can inhibit the growth of gut pathogens. Here, we demonstrate the antimicrobial activities of Lactobacillus species – Lactobacillus paracasei, Lactobacillus casei, and Lactobacillus delbrueckii subsp. bulgaricus are enhanced when cocultured with Salmonella enterica subsp. enterica serovar Typhimurium. Cell-free culture supernatants (CFCS) from cocultures of Lactobacillus spp. and Salmonella enterica serovar Typhimurium more potently inhibit pathogen growth than their monoculture counterparts. Interestingly, we discovered that Salmonella enterica serovar Typhimurium could enhance the production of antimicrobials from Lactobacillus spp., most evident in L. delbrueckii subsp. bulgaricus. Also, L. delbrueckii subsp. bulgaricus CFCS upregulates key Salmonella virulence genes, hilA and sipA. Whether this increases Salmonella’s pathogenicity in vivo or reduces pathogen fitness and growth inhibition in vitro warrants further investigation. We propose that these probiotic isolates may be utilized for innovative natural food processing and preservation strategies to control Salmonella food contaminations. Importantly, our findings that Salmonella elicits an enhanced antimicrobial activity from Lactobacillus spp. provide evidence of a pathogen-mediated elicitation of antimicrobial production. Therefore, extending this phenomenon to other microbial interactions may help augment the strategies for drug discovery.

Disseminated Salmonella Infection Coexisting with Thymoma.

A 21-year-old boy presented with high grade fever, diffuse chest pain and exertional breathlessness of one month duration. Radiologically he had a large lobulated anterior mediastinal mass with necrotic thick enhancing septaes. Histopathology of the mass was suggestive of thymoma and culture from the necrotic aspirate yielded Salmonella typhi. The same pathogen was isolated in subsequent blood and sputum cultures. This current report describes the rare association of salmonella infection with thymoma.

Differences in Clinical and Laboratory Findings between Group D and Non-Group D Non-Typhoidal Salmonella Gastroenteritis in Children / 대한소아소화기영양학회지

PURPOSE: To investigate the differences in clinical features and laboratory findings between group D and non-group D non-typhoidal Salmonella (NTS) gastroenteritis in children. METHODS: A retrospective chart review of children diagnosed with NTS confirmed by culture study was performed. The clinical features and laboratory findings of group D and non-group D NTS were compared. RESULTS: From 2003 to 2012, 75 cases were diagnosed as NTS at our center. The number of group D and non-group D patients was 45 and 30, respectively. The mean age was higher in group D than in non-group D patients (5.1 years vs. 3.4 years, p=0.038). Headaches were more frequently observed (p=0.046) and hematochezia was less frequently observed (p=0.017) in group D than in non-group D NTS gastroenteritis patients. A positive Widal test result was observed in 53.3% of group D and 6.7% of non-group D NTS cases (O-titer, p=0.030; H-titer, p=0.039). There were no differences in white blood cell counts, level of C-reactive protein and rate of antimicrobial resistance between group D and non-group D cases. CONCLUSION: The more severe clinical features such as headache, fever, and higher Widal titers were found to be indicative of group D NTS gastroenteritis. Additionally, group D NTS gastroenteritis was more commonly found in older patients. Therefore, old age, fever, headache, and a positive Widal test are more indicative of group D NTS than non-group D NTS gastroenteritis. Pathophysiological mechanisms may differ across serologic groups.

Differences in Clinical and Laboratory Findings between Group D and Non-Group D Non-Typhoidal Salmonella Gastroenteritis in Children / 대한소아소화기영양학회지

PURPOSE: To investigate the differences in clinical features and laboratory findings between group D and non-group D non-typhoidal Salmonella (NTS) gastroenteritis in children. METHODS: A retrospective chart review of children diagnosed with NTS confirmed by culture study was performed. The clinical features and laboratory findings of group D and non-group D NTS were compared. RESULTS: From 2003 to 2012, 75 cases were diagnosed as NTS at our center. The number of group D and non-group D patients was 45 and 30, respectively. The mean age was higher in group D than in non-group D patients (5.1 years vs. 3.4 years, p=0.038). Headaches were more frequently observed (p=0.046) and hematochezia was less frequently observed (p=0.017) in group D than in non-group D NTS gastroenteritis patients. A positive Widal test result was observed in 53.3% of group D and 6.7% of non-group D NTS cases (O-titer, p=0.030; H-titer, p=0.039). There were no differences in white blood cell counts, level of C-reactive protein and rate of antimicrobial resistance between group D and non-group D cases. CONCLUSION: The more severe clinical features such as headache, fever, and higher Widal titers were found to be indicative of group D NTS gastroenteritis. Additionally, group D NTS gastroenteritis was more commonly found in older patients. Therefore, old age, fever, headache, and a positive Widal test are more indicative of group D NTS than non-group D NTS gastroenteritis. Pathophysiological mechanisms may differ across serologic groups.

A Case of Salmonella Infection Complicated by Rhabdomyolysis and Acute Kidney Injury / 계명의대학술지

Rhabdomyolysis a clinical syndrome characterized by injury to skeletal muscle and release of intracellular contents into the systemic circulation, can develop from infections, although trauma is a more common cause. Myoglobinuric acute kidney injury (AKI) is a potentially life-threatening complication of rhabdomyolysis. Reports of rhabdomyolysis and AKI induced by salmonella infection are rare in the Korean literature. This paper describes a case of salmonella enteritis complicated by rhabdomyolysis and AKI. A 58-year-old man presented to the hospital with a two day history of watery diarrhea, abdominal pain and high fever. Initial blood chemistry revealed a serum creatinine (Cr) level of 3.4 mg/dL, with elevations of serum creatine phosphokinase (CK, 5,635 IU/L) and serum myoglobin (>3,000 ng/mL). Intravenous hydration and empirical antibiotic treatment with ciprofloxacin were initiated. Blood and stool cultures grew salmonella group B, which was sensitive to ciprofloxacin, ampicillin, and ceftazidime. Parenteral ciprofloxacin was continued for 14 days. During the first week of hospitalization, peak levels of serum Cr and CK were 9.5 mg/dL and 89,155 IU/L, respectively. Thereafter clinical and biochemical parameters gradually improved without dialysis. The patient was discharged on the 20th hospital day with normal CK levels except for serum Cr. His renal function normalized (serum Cr 1.0 mg/dL) two months after discharge. Based on the results of this case, prompt fluid therapy and early administration of antibiotics should be performed in patients with salmonella infection complicated by rhabdomyolysis and AKI.

Hemorrhagic cystitis with massive bleeding from nontyphoidal Salmonella infection: A case report

Hemorrhagic cystitis is defined by lower urinary tract symptoms that include dysuria, hematuria, and hemorrhage and is caused by viral or bacterial infection or chemotherapeutic agents. Reports of hemorrhagic cystitis caused by non-typhoidal salmonella (NTS) are extremely rare. We report a case of a 41-year-old man with hemorrhagic cystitis from NTS that caused massive bleeding and shock. The patient was hospitalized for uncontrolled diabetes and obstructive uropathy related to severe cystitis. A urine culture was positive for group D NTS. This case demonstrated that hemorrhagic cystitis in a patient with a risk factor such as diabetes can be a manifestation of local extraintestinal NTS infection.

A Case of Septic Arthritis of the Knee Joint due to Group D Non-typhoidal Salmonella

Osteoarticular infections due to non-typhoidal Salmonella are rare, occurring with an incidence rate of 0.1-0.2%. An immunocompromised state and the existence of sickle cell anemia are known risk factors for development of septic arthritis due to Salmonella. In this report, we describe a patient with septic arthritis of the left knee caused by non-typhoidal Salmonella . An 82-year-old woman visited the emergency room presenting with left knee pain, fever and dyspnea. The patient had osteoarthritis and was treated with oral analgesics, but not with an intra-articular injection. Upon assessment of the patient's joint fluid and blood culture results, non-typhoidal Salmonella (Salmonella group D) was detected. Arthroscopy-guided irrigation and debridement, and administration of oral antibiotics (fluoroquinolone) over six weeks were required in order to achieve a full recovery from the infection.

Ill-defined Granulomas Demonstrated in Ulcers of the Terminal Ileum and Transverse Colon in a Patient with Typhoid Fever / 대한소화기내시경학회지

Typhoid fever, the most serious human salmonellosis, is a systemic infectious disease caused by Salmonella enterica serovar Typhi and is characterized by prolonged fever, bacteremia, and multiplication of the organism within mononuclear phagocytic cells of the liver, spleen, lymph nodes, and Peyer's patches. The characteristic lesion of typhoid fever is an ulceration of the small intestinal lymphoid tissue, particularly the Peyer's patches. The usual histological findings of typhoid ulcer are necrosis and histiocytic proliferation that phagocytizes erythrocytes and degenerated lymphocytes. A granuloma is an unusual histopathological presentation of a typhoid lesion. Even if granulomas have been reported in the bone marrow, liver, and spleen in cases of typhoid fever, granulomas in primary ulcers of the ileum and transverse colon have been reported very rarely. We experienced a case of typhoid fever in which ill-defined granulomas were seen in ulcers of the terminal ileum and transverse colon.

A Case of Neck Abscess Caused by Salmonella Serotype D in a Patient with Liver Cirrhosis

Non-typhoidal salmonellosis, which is increasing nowadays in Korea as well as in the developed countries, is manifested as enteritis in most cases, but it also encompasses bacteremia, intraabdominal infections, and bone, joint and soft tissue infections. These rare diseases are known to result from primary gastrointestinal infection and subsequent bacteremia with or without symptoms. We experienced a case of neck abscess caused by Salmonella serotype D, which is a rare but important differential diagnosis of neck abscess. We herein report it.

Salmonellosis in children: Analysis of 72 Salmonella-positive culture cases during the last 10 years / 소아과

PURPOSE: We aimed to investigate the clinical manifestations of and antibiotic resistance in culture-proven childhood salmonellosis. METHODS: Clinical manifestations and laboratory data of and antibiotic use in subjects with culture-proven childhood salmonellosis, who were treated at the Chonbuk National University Hospital between September 1998 and August 2008, were analyzed retrospectively. Patients with underlying diseases or concomitant illnesses were excluded. RESULTS: We assessed a total of 72 patients. There were 68 stool culture-positive cases, 7 blood culture-positive cases, and 3 both stool culture- and blood culture-positive cases. Salmonella group D was the most frequent pathogen in stool (63.9%) and blood (71.4%) cultures. Salmonella typhi was isolated in 1 case. Of the 72 patients, 45 (62.5%) were male children, of which 29 (40.3%) were aged 15,000/microliter) and leukopenia (leukocyte count, 5 mg/dL) and erythrocyte sedimentation rate (>20 mm/h) were observed in 88.9% and 58.3% of the patients, respectively. Fifty-two (85.2%) of 61 patients who had undergone antibiotic treatment received a third-generation cephalosporin as definitive antibiotic therapy. Multidrug resistance rate was 40.0% in the first 5 years of the study and 71.4% in the last 5 years. No fatalities occurred in this series. CONCLUSION: Children with culture-proven salmonellosis showed relatively benign clinical outcomes. Appropriate antibiotic treatment of <2 weeks is probably adequate for those without a suppurative focus of infection. The incidence of antibiotic resistant isolates was recently seen to increase.

A Case of Rhabdomyolysis and Acute Renal Insufficiency Associated with Gastroenteritis Caused by Salmonella Group C / 대한신장학회잡지

Rhabdomyolysis is a syndrome characterized by muscle necrosis and release of intracellular muscle constituents into the circulation. Rhabdomylosis can be precipitated by different causes, such as trauma, extraordinary physical exer- tion, metabolic disorder, drugs, toxins, infection, or endocrinopathy. Salmonellosis is another rare cause of rhabdomyolysis. We report a 62-year-old male who developed severe diarrhea and vomitting, one day after boiled pork & raw octopus ingestion. The diagnosis of rhabdomyolysis was established primarily by the elevated serum CPK and myoglobin level. There were no other traumatic, metabolic, toxic, or enzymatic causes for the rhabdomyolysis. Stool cultures received at the first day of hospitalization yielded Salmonella Group C. Salmonella sp. is suggested to cause muscle damage by direct bacterial invasion as well as by decreasing the oxidative and glycolytic enzyme activity of skeletal muscles and by activating lysosomal enzymes. We wish to draw attention to these serious complication of salmonella gastroenteritis, and to institute of prompt measures for preventing the development of ATN. We report a case of acute renal failure associated with rhabdomyolysis and gastroenteritis caused by salmonella Group C with review of literatures.

Salmonella osteomyelitis with osteonecrosis in a patient with systemic lupus erythematosus / 대한내과학회지

Although infectious diseases are frequent in systemic lupus erythematosus, salmonella osteomyelitis is rarely reported. We here report an unusual case of salmonella osteomyelitis with osteonecrosis in a patient with systemic lupus erythematosus. A 29-year old woman with systemic lupus erythematosus was admitted to our hospital because of a painful swelling of right knee joint. She had been taking steroid and cyclophosphamide for 4 months because of diffuse membranous proliferative lupus nephritis. MRI showed both osteonecrosis of the right distal femur and osteomyelitis of the right proximal tibia. The abscess culture demonstrated almonella species (non typhoidal). The infection was treated successfully by a combination of surgical drainage and intravenous ceftriaxone.

A Case of Salmonella-triggered Reactive Arthritis in a Child, Initially Presented as Juvenile Rheumatoid Arthritis / 소아알레르기및호흡기학회지

Salmonella-triggered reactive arthritis appears one to three weeks after the onset of salmonella infection and presents with asymmetric, usually migratory, oligo- or polyarthritis. The course is usually self-limiting and symptoms last two to six months. We experienced a 10-year-old male patient who presented to a local pediatric center with long-lasting fever and right ankle joint pain. The pain migrated to the left ankle joint, both wrists, and both knees and he was diagnosed as juvenile rheumatoid arthritis and was medicated with NSAIDs and corticosteroid. In the meantime, 20 days prior to the transfer to our hospital he was febrile with nausea and abdominal pain and the antibody titer of S. typhi O Ag by Widal test was 1 : 320, and an antibiotic therapy was followed. Soon after, the fever subsided but the migrating joint symptoms continued and he was transferred to our hospital. Widal tests were weekly checked and the antibody titers of S. typhi O Ag were 1 : 160, 1 : 320, 1 : 320, 1 : 160, 1 : 160, respectively. ESR was 55 mm/hr, CRP 9.18 mg/dl, HLA-B27 positive and his endoscopic findings of the colon showed mild lymphoid hyperplasia and mucosal nodularities in the cecum and ileocecal area. Stool cultures and duodenal juice culture for Salmonella and Shigella were all negative. He was treated with ibuprofen and bactrim and the joint symptoms were gradually mitigated. After discharge, he maintained mildly elevated CRP levels and antibody levels by Widal tests, but was free from symptoms except for several episodes of finger pains for 11 months.

Effect of Alcohol Administration on Production of Cytokines, Salmonella Infection and Penicillin V - Induced Anaphylaxis in Mice / 대한면역학회지

The present study was undertaken to investigate the effect of acute administration of ethanol on production of cytokines such as IL-1j3, IL-2, IL-6, IL-10 and TNF-a, induction of penicillin V-induced active fatal anaphylaxis, and resistence to Salmonel/a typhimurium infection in mice. Ethanol administration into mice was performed by intraperitoneal injection of 0.5 ml of 20 % ethanol for 3 consecutive days before induction of cytokines with lipopolysaccharide (LPS), Con A or Salmone/la injection. Serum levels of cytokines were measured by ELISA. It was found that ethanol administration significantly inhibited both the serum levels of all cytokines examined and the resistance of mice to S. typhimurium. However, ethanol administration failed to prevent penicillin-induced fatal anaphylaxis. Taken together, the present results may need new insights in the diagnosis and treatment of various immunologically-mediated diseases.

Salmonella infection in patients with plasmodium falciparum malaria.

Patients with P.falciparum malaria infection are unusually susceptible to a variety of infectious diseases. There is an increased incidence of salmonella infection and bacteremia in patients with malaria. The objective of the present study was to report 3 patients with P.falciparum malaria infection in association with salmonellosis. These patients presented with fever and their blood smears revealed P.falciparum. They were treated with anti-malarial drugs. The malarial parasites disappeared from the peripheral blood, however, the fever persisted or recurred within a few days. Blood cultures grew S.choleraesusis, S.enteritidis and S.paratyphi A, respectively. These patients were treated successfully with antibiotics. Blood cultures should therefore be performed in all patients with P.falciparum malaria whose fever persists after treatment with antimalarial drugs.