Baseline iron status and presence of anaemia determine the course of systemic Salmonella infection following oral iron supplementation in mice.

BACKGROUND: Iron deficiency anaemia (IDA) is a major health concern. However, preventive iron supplementation in regions with high burden of infectious diseases resulted in an increase of infection related morbidity and mortality. METHODS: We fed male C57BL/6N mice with either an iron deficient or an iron adequate diet. Next, they received oral iron supplementation or placebo followed by intraperitoneal infection with Salmonella Typhimurium (S.Tm). FINDINGS: We found that mice with IDA had a poorer clinical outcome than mice on an iron adequate diet. Interestingly, iron supplementation of IDA mice resulted in higher bacterial burden in organs and shortened survival. Increased transferrin saturation and non-transferrin bound iron in the circulation together with low expression of ferroportin facilitated the access of the pathogen to iron and promoted bacterial growth. Anaemia, independent of iron supplementation, was correlated with reduced neutrophil counts and cytotoxic T cells. With iron supplementation, anaemia additionally correlated with increased splenic levels of the cytokine IL-10, which is suggestive for a weakened immune control to S.Tm infection. INTERPRETATION: Supplementing iron to anaemic mice worsens the clinical course of bacterial infection. This can be traced back to increased iron delivery to bacteria along with an impaired anti-microbial immune response. Our findings may have important implications for iron supplementation strategies in areas with high endemic burden of infections, putting those individuals, who potentially profit most from iron supplementation for anaemia, at the highest risk for infections. FUNDING: Financial support by the Christian Doppler Laboratory for Iron Metabolism and Anemia Research.

Mitracarpus frigidus (Rubiaceae) inhibits inflammatory and oxidative stress mediators in Salmonella sp. mouse infection.

OBJECTIVES: Evaluation of the in-vivo anti-inflammatory activity of the methanolic extract obtained from the aerial parts of Mitracarpus frigidus (MFM) in the infection caused by two Salmonella strains and its chemical fingerprint by UFLC-quadrupole time of flight-MS. METHODS: The efficacy of MFM was investigated in a classical in-vivo Salmonella infection mouse model. A Salmonella reference strain (ATCC 13311) and a clinical isolate were used to infect mice and then MFM was orally administered during 14 days. At the end of the treatment with MFM, the infection and inflammatory levels were assayed. KEY FINDINGS: MFM treatment showed a significant reduction in mice mortality by Salmonella infection and, also, did not cause alterations in the liver function. Inhibitions of inflammatory and oxidative stress mediators [malondialdehyde (MDA), catalase, and metalloproteinase] were possibly involved in the observed effects. Chlorogenic acid, clarinoside, quercetin-pentosylhexoside, rutin, kaempferol-3O-rutinoside, kaempferol-rhamnosylhexoside and 2-azaanthraquinone were identified in MFM. CONCLUSIONS: MFM was effective in some inflammatory parameters, in the experimental conditions that were used in the study. The results presented in this study and the previous in-vitro anti-Salmonella activity reported by our research group reinforce the importance of MFM studies to considerer it as an alternative treatment for salmonellosis.

PART I: FIGHTING CANCER WITH DEADLY BACTERIA.

A 200-year-old observation might provide a new way to eliminate tumors by infecting cancer patients with bacteria. Kristie Nybo explores a new approach that could transform cancer treatment.

PART II: BREAKTHROUGHS IN TUMOR-SEEKING BACTERIA.

Newly engineered bacterial strains propel an immune-mediated cancer therapy toward clinical applications. Hannah Martin Lawrenz reports on the latest developments.

Pyelonephritis in Japan caused by Salmonella enterica subspecies arizonae.

Salmonella enterica subsp. arizonae is a bacteria commonly found in the gut of reptiles. In humans, infections caused by this organism are rare. Most cases originate from southwestern United States, where rattlesnake products are often used in traditional medicine. In Asia, only a few cases have been described. This case report documents a case involving a 64-year-old woman with pyelonephritis caused by S. arizonae in Japan. She had no history of contact with reptiles or foreign travel. The likely route of transmission is unclear. She was treated with cephalosporins for 14 days and the pyelonephritis appeared to be resolved; however recurrence occurred twice -after two weeks and then after one month. Prolonged antibiotic therapy with amoxicillin resolved the infection. This case demonstrates that pyelonephritis associated with S. arizonae can be found outside of the typical geographic region and may not be associated with typical animal hosts.

Zhankuic acid A isolated from Taiwanofungus camphoratus is a novel selective TLR4/MD-2 antagonist with anti-inflammatory properties.

TLR4, a membrane receptor that functions in complex with its accessory protein myeloid differentiation factor-2 (MD-2), is a therapeutic target for bacterial infections. Taiwanofungus camphoratus is highly valued as a medicinal mushroom for cancer, hypertension, and inflammation in traditional medicine. Zhankuic acid A (ZAA) is the major pharmacologically active compound of T. camphoratus. The mechanism of action of T. camphoratus or ZAA has not been fully elucidated. We analyzed the structure of human TLR4/MD-2 complex with ZAA by X-score and HotLig modeling approaches. Two Abs against MD-2 were used to verify the MD-2/ZAA interaction. The inflammation and survival of the mice pretreated with ZAA and injected with LPS were monitored. The modeling structure shows that ZAA binds the MD-2 hydrophobic pocket exclusively via specific molecular recognition; the contact interface is dominated by hydrophobic interactions. Binding of ZAA to MD-2 reduced Ab recognition to native MD-2, similar to the effect of LPS binding. Furthermore, ZAA significantly ameliorated LPS-induced endotoxemia and Salmonella-induced diarrhea in mice. Our results suggest that ZAA, which can compete with LPS for binding to MD-2 as a TLR4/MD-2 antagonist, may be a potential therapeutic agent for gram-negative bacterial infections.

The iron link between malaria and invasive non-typhoid Salmonella infections.

Epidemiological studies have demonstrated an association between malaria and invasive non-typhoid Salmonella (NTS) infections, especially in children. We explore the role of iron as a possible cofactor in this association. Malarial disease, among others, is associated with enhanced erythrophagocytosis and inflammation, which increases the iron content of macrophages and thereby also the survival of Salmonella spp. within macrophages. Whether iron supplementation programs augment the risk of invasive NTS infections in malaria-endemic regions is an important global health issue that still needs to be determined.

An unusual dual infection with Salmonella bredeney, including bacteraemia, and enterohaemorrhagic Escherichia coli O157 that posed a therapeutic dilemma.

In this case report, we describe an unusual case of a patient who had a dual infection with Salmonella bredeney including bacteraemia and enterohaemorrhagic Escherichia coli O157 following travel to Cyprus. This posed a therapeutic dilemma. We delayed treatment of the Salmonella infection until signs of colitis had resolved.

Empiric antimicrobial therapy and infectious diarrhea. Do we need local guidelines?

BACKGROUND: In the management of acute diarrhea, administration of antibiotics may be indicated. Appropriate antimicrobial therapy can shorten illness, reduce morbidity and can be life-saving in invasive infections. Emergence of microbial strains resistant to commonly used antibiotics means that treatment failures may become common. Because of changing patterns of resistance, knowledge of recent local patterns of susceptibility can guide the initial choice of antibiotics. METHODS: A retrospective study was conducted to investigate the epidemiology of infective gastroenteritis in patients over 14years old in the region of Chania (Crete). We reviewed all positive stool cultures and susceptibilities of the pathogens recovered from patients with symptoms of acute diarrhea, from 2003 until October 2010. RESULTS: Out of 194 positive stool cultures, we observed 139 cases of Salmonella enterica and 48 cases of Campylobacter jejuni. During the last 3years of observation there was an increased incidence of C. jejuni, especially after the tap water outbreak that occurred in our region in 2009. DISCUSSION: In the vast majority of acute diarrhea in adults, antibiotics are of no benefit and overprescription may confer to side effects, costs and emergence of resistance. Antibiotics are initiated in cases of febrile diarrheas especially those believed to have moderate to severe disease. Considering the increased incidence of C. jejuni and the resistance of the great majority of isolated strains to quinolones as well as the sensitivity of Salmonella spp. to azithromycin, administration of azithromycin empirically for acute diarrhea, when indicated, could be appropriate in our region.

Quiste esplénico sobreinfectado en paciente inmunocompetente / Superinfected splenic cyst in immunocompetent patient

No disponible

Amelioratory effects of zinc supplementation on Salmonella-induced hepatic damage in the murine model.

Zinc (Zn) has been reported to influence the susceptibility of the host to a diverse range of infectious pathogens, including viruses, bacteria, fungi and protozoa. We report here an evaluation of the effects of Zn supplementation on Salmonella enterica serovar Typhimurium (S. typhimurium)-induced hepatic injury in the murine model. Zinc levels in the plasma and liver tissues were measured by atomic absorption spectroscopy. The effect of Zn supplementation was evaluated by assessing the bacterial load and levels of lipid peroxidation (LPO), antioxidants and monokines present in the hepatic tissue as well as by histopathological studies. Zinc supplementation reduced the bacterial load in the liver and reversed hepatic microscopic abnormalities. It also decreased the levels of LPO but increased the levels of reduced glutathione (GSH) as well as the activities of superoxide-dismutase (SOD) and catalase in the livers of infected mice supplemented with Zn compared to the livers of infected mice not supplemented with Zn. Zinc supplementation was also able to modulate the levels of monokines such as tumour necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1) and interleukin-6 (IL-6). Our results indicate a role for Zn in downregulating oxidative stress and upregulating antioxidant defense enzymes through the action of monokines, suggesting that supplementation with Zn has a protective function in Salmonella-induced liver injury.

Risk of recurrent nontyphoid Salmonella bacteremia in HIV-infected patients in the era of highly active antiretroviral therapy and an increasing trend of fluoroquinolone resistance.

BACKGROUND: Risk of recurrent nontyphoid Salmonella (NTS) bacteremia and trends of antimicrobial resistance of NTS remain unknown in human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART). METHODS: Ninety-three patients who received a diagnosis of NTS bacteremia from June 1994 through June 2006 were prospectively followed up. Incidence of recurrent NTS bacteremia was compared between the pre-HAART era (June 1994-March 1997) and the HAART era (April 1997-June 2006). Prevalence of antimicrobial resistance was compared among the NTS isolates obtained in the pre-HAART era, the early HAART era (April 1997-June 2002), and the late HAART era (July 2002-June 2006). RESULTS: Compared with patients enrolled in the pre-HAART era, patients who received HAART had an incidence of recurrent NTS bacteremia that was significantly reduced by 96%; the incidence of recurrent NTS bacteremia was 2.56 cases per 100 person-years in the HAART era, compared with 70.56 cases per 100 person-years in the pre-HAART era (rate ratio, 0.036; 95% confidence interval, 0.012-0.114; P<.001). In the HAART era, the incidence of recurrent NTS bacteremia did not increase among patients receiving fluoroquinolone prophylaxis for 30 days (3.95 cases per 100 person-years), with a rate ratio of 0.43 (95% confidence interval, 0.07-2.58). Although resistance to ampicillin, cotrimoxazole, and chloramphenicol decreased, the proportion of NTS isolates resistant to fluoroquinolones increased from 0% in the pre-HAART era to 6.2% in the early HAART era and 34.2% in the late HAART era (P=.002). CONCLUSIONS: The risk of recurrent NTS bacteremia decreased significantly in the HAART era, although NTS isolates obtained from HIV-infected patients were increasingly resistant to fluoroquinolones.

[Cholangitis with hepatic microabscesses caused by Salmonella enterica serovar choleraesuis]. / Cholangitis mit hepatischen Mikroabszessen durch Salmonella enterica Serovar Choleraesuis.

HISTORY AND ADMISSION FINDINGS: A 71-year-old man was admitted to the emergency unit of another hospital with a mild gastroenteritis and high fever. On admission g-GT and C-reactive protein (CRP) levels were markedly elevated. Under nonspecific antibiotic therapy with ampicillin/sulbactam the fever persisted and for the first time, on day 5, the patient complained of right-sided abdominal pain. An increase in the laboratory values indicated cholestasis. After changing the antibiotics to ceftriaxon and metronidazole, acute cholangitis being suspected, the fever subsided immediately and the CRP level decreased. The patient was discharged after seven days of antibiotic treatment. But he was once more admitted after four weeks to another hospital because of severely reduced general condition and mild fever. He was transferred to our unit after two weeks. INVESTIGATIONS AND DIAGNOSIS: The test values indicated cholestasis and CRP was markedly elevated, while aminotransferase activity was slightly increased and normocytic normochromic anemia developed. Viral hepatitis, autoimmune and metabolic liver diseases, toxic liver damage, extrahepatic cholestasis and an endocarditis were excluded. Bile was aspirated by endoscopic retrograde cholangiopancreatography and added to blood culture bottles. Salmonella enterica serovar choleraesuis var. Kunzendorf was isolated. TREATMENT AND FURTHER COURSE: The patient was treated with ciprofloxacin, 2 x 250 mg by mouth for a total of five weeks. After 17 days of treatment no Salmonella bacteria were grown from a newly aspirated bile sample and the patient became free of fever. CONCLUSION: Salmonella infections do not always present as gastroenteritis. Bacteremia should be considered in the differential diagnosis of such infections. If cholangitis persists, the aspiration of bile for microbiological tests can be a rational diagnostic step and facilitates treatment. Prolonged administration of antibiotics is necessary to avoid relapse. and follow-up is very important when treatment is finished.

Cefotaxime-ciprofloxacin combination therapy for nontyphoid Salmonella bacteremia and paravertebral abscess after failure of monotherapy.

Therapeutic failure of monotherapy with either a third-generation cephalosporin or a fluoroquinolone against nontyphoid salmonellae has been observed in clinical practice. Combination therapy with both agents is recommended in the literature for treating life-threatening infections. However, we know of no published case reports that indicate a therapeutic advantage of this combination therapy for nontyphoid salmonellae infections. We describe a 60-year-old man who had breakthrough bacteremia with vertebral osteomyelitis and paravertebral abscess caused by Salmonella enterica serotype Choleraesuis. This was not controlled with sequential monotherapy but was eventually cured with cefotaxime-ciprofloxacin combination therapy. The Etest showed that the strain was susceptible to cefotaxime and ciprofloxacin, but resistant to nalidixic acid. Cefotaxime and ciprofloxacin in combination may be considered as an option for difficult-to-treat salmonellosis.

Artritis séptica por Salmonella no typhi: presentación de un caso y revisión de la bibliografía / Non-typhi Salmonella septic arthritis: case report and review of the literature

La artritis séptica por Salmonella no typhi representa menos del 2 por ciento del total de las artritis sépticas1. El serotipo etiológico más frecuente es Salmonella enteritidis. Su clínica, precedida o no de una gastroenteritis, no difiere de otras artritis sépticas, y se presenta con fiebre y sinovitis monoarticular, habitualmente en rodilla, cadera y hombro. La inmunosupresión (terapéutica, virus de la inmunodeficiencia humana [VIH], lupus eritematoso sistémico [LES], etc.) es el principal factor de riesgo en su desarrollo. La drepanocitosis, la hemofilia, las neoplasias y las edades extremas de la vida también predisponen a su aparición. El diagnóstico se realiza por cultivo de líquido sinovial. El tratamiento está condicionado por las resistencias descritas a múltiples antibióticos, incluso a los más actuales, como son las fluoroquinolonas. Las complicaciones locales más frecuentes son la limitación residual funcional y la osteomielitis. El pronóstico, marcado por la enfermedad de base, presenta una elevada mortalidad (AU)

Persistent diarrhea, arthritis, and other complications of enteric infections: a pilot survey based on California FoodNet surveillance, 1998-1999.

Numerous complications of enteric infections have been described, including persistent diarrhea, reactive arthritis, and Guillain-Barre syndrome. We determined the frequency of self-reported complications of enteric infections in a pilot study in the California site of the Foodborne Diseases Active Surveillance Network. From 1 April 1998 through 31 March 1999, active surveillance identified 1454 infections in Alameda and San Francisco counties, of which 52% were Campylobacter infections, 22% were Salmonella infections, 15% were Shigella infections, 6% were Cryptosporidium infections, 2% were Escherichia coli O157:H7 infections, 2% were Yersinia infections, and 1% were Vibrio infections. We mailed surveys to 1331 eligible participants, and 571 (43%) were returned. A new health problem following infection was reported by 153 (27%) of the respondents: 12 (8%) reported new onset of joint pain and 53 (35%) reported new gastrointestinal symptoms, of whom 38 reported persistent diarrhea, including 2 who reported irritable bowel syndrome. Three respondents reported hair loss. The frequency, nature, and etiology of these complications merit further investigation.

Síndrome hemofagocítico reactivo a infección por "Salmonella typhi" / Reactive hemophagocytic síndrome caused by "salmonella typhi" infection

El síndrome hemafagocítico (SHF) o histiocitosis reactiva es un trastorno de la inmunorregulación en el que, de forma primaria o secundaria, se desencadena una activación y proliferación incontrolada, no maligna de linfocitos T y macrófagos, con intensa actividad fagocítica de células hematopoyéticas. Se asocia a un estado de hipercitocinemia responsable de la mayoría de los síntomas y su diagnóstico incluye un conjunto de datos clínicos, de laboratorio y hallazgos histológicos, con hemofagocitosis prominente. Se presenta el caso de un niño afectado por síndrome hemafagocítico reactivo (SHFR) a infección por Salmonella typhi (AU)

[Renal replacement therapy in acute infectious renal insufficiency]. / Zamestitel'naia terapiia pri infektsionnoi ostroi pochechnoi nedostatochnosti.

A modern view on renal failure in patients with infectious diseases is presented and possibilities of various methods of renal replacement therapy are evaluated. The authors emphasize the obligatory combination of etiotropic and pathogenetic therapy. A clinical case is presented: a patient with tropical and 3-day malaria was effectively treated by high-flow intermittent hemofiltration.