Persistence of antimicrobial resistance in respiratory streptococci.

OBJECTIVES: To assess whether persistence of antimicrobial resistance (i.e. non-susceptible resistance status) after treatment with penicillins or cephalosporins versus macrolides or tetracyclines differs and to compare the results obtained using routinely collected data with findings reported in prospective studies. METHODS: Routinely collected microbiological data from 14 voluntary participating laboratories (2005) containing information on resistance status and individual antimicrobial consumption patterns (mid 2004-2005) were analysed using a generalised estimating equation (GEE) approach. The link function was adjusted to acknowledge that the proportion of resistant isolates in the population not treated with antibiotics [baseline resistance (BR)] is not necessarily zero. To optimise the comparability of this study with prospective studies, the analysis was repeated after removal of 14 isolates from patients who did not survive 2005. RESULTS: BR estimates were unstable and their confidence intervals were wide, which called for a sensitivity analysis using an adjusted GEE model with three different BR estimates. All models indicated that the proportion of susceptible isolates differed by treatment group and increased significantly over time, with this increase being independent of treatment group. Persistence of resistance after exposure to macrolides or tetracyclines was approximately three times as long as after exposure to penicillins or cephalosporins. CONCLUSIONS: Resistance following treatment with macrolides or tetracyclines persists longer than following treatment with penicillins or cephalosporins, which confirms the findings from prospective studies and suggests the use of routinely collected data as a valuable alternative to determine such differences in persistence of resistance.

Viridans Group Streptococcal Infections in Children After Chemotherapy or Stem Cell Transplantation: A 10-year Review From a Tertiary Pediatric Hospital.

Viridans Group Streptococci (VGS) are associated with high mortality rates in febrile neutropenia; yet there are no recent European pediatric studies to inform antimicrobial therapy. The aim of this study was to describe the characteristics, outcome, and resistance patterns of children with VGS bacteremia (VGSB) undergoing treatment of malignancy or hematopoietic stem cell transplant. Patients aged 0 to 18 years, admitted to a tertiary pediatric hemato-oncology center with VGSB, from 2003 to 2013, were included in the study. All data were collected retrospectively from medical records. A total of 54 bacteremic episodes occurred in 46 patients. The most common underlying diagnosis was relapsed acute lymphoblastic leukemia. Streptococcus mitis was the most frequent organism. A total of 30% of isolates were resistant to penicillin and 100% sensitive to vancomycin. There were 8 episodes (14.8%) of Viridans Group Streptococcal Shock Syndrome; 6 resulted in admission to intensive care and 3 of these patients died of multiorgan failure. The potentially fatal nature of VGSB is confirmed. The high risk in relapsed acute lymphoblastic leukemia is of note. Research is needed to develop risk-stratification scores that identify children at risk of Viridans Group Streptococcal Shock Syndrome to guide empirical antimicrobial therapy in febrile neutropenia.

L-proline increases survival of tilapias infected by Streptococcus agalactiae in higher water temperature.

Streptococcosis causes massive tilapia kills, which results in heavy economic losses of tilapia farming industry. Out of the Streptococcosis, Streptococcus agalactiae is the major pathogen. The bacterium causes higher mortality of tilapias in higher than lower temperatures. However, effect of temperature on metabolic regulation which is related to the mortality is largely unknown. The present study showed 50% and 70% mortality of tilapias cultured in 25 °C and 30 °C, respectively, in comparison with no death in 20 °C following infection caused by S. agalactiae. Then, GC/MS based metabolomics was used to investigate a global metabolic response of tilapia liver to the two higher water temperatures compared to 20 °C. Thirty-six and forty-five varied abundance of metabolites were identified in livers of tilapias cultured at 25 °C and 30 °C, respectively. More decreasing abundance of amino acids and increasing abundance of carbohydrates were detected in 30 °C than 25 °C groups. On the other hand, out of the pathways enriched, the first five biggest impact pathways belong to amino acid metabolism. Decreasing abundance of l-proline was identified as a crucial biomarker for indexing higher water temperature and a potential modulator to reduce the high death. This was validated by engineering injection or oral addition of l-proline. Exogenous l-proline led to elevated amino acid metabolism, which contributes to the elevated survivals. Our findings provide a potential metabolic modulator for controlling the disease, and shed some light on host metabolic prevention to infectious diseases.

[Neurological complications of infective endocarditis in Burkina Faso. Clinical features, management and evolutionary profile]. / Les complications neurologiques des endocardites infectieuses au Burkina Faso. Caractéristiques cliniques, prise en charge et profil évolutif.

INTRODUCTION: Neurological complications are the most frequent extracardiac complications of infective endocarditis (IE). This study aimed to describe the epidemiological, clinical and paraclinical aspects, and outcome of neurological complications of infective endocarditis in three hospitals in the city of Ouagadougou in Burkina Faso. PATIENTS AND METHOD: From 1 January 2009 to 31 December 2012, we included all patients suffering from IE and selected those in whom a neurological complication was objectified. Neurological involvement was sought on clinical examination but especially CT brain (ischemic infarcts, hemorrhages, aneurysms and abscesses). Blood cultures were systematic. Echocardiography was done for vegetations and characteristics. RESULTS: Among 63 cases of IE, neurological complications were found in 14 patients (22.2%). The average age of patients with neurological complications was 37.4 ± 5.8 years. The sex ratio was 1.3 for women. Neurological damage consisted of nine cases of stroke (64.3%), three cases of hemorrhagic stroke (21.4%) and two cases of brain abscess (14.3%). Neurological complications had already occurred before hospitalization in 4 cases. Blood cultures were positive in 8 cases. Germs found were predominantly Staphylococcus aureus (5 cases) and Streptococcus a- viridans (2 cases). All cases of S. aureus were complicated by stroke. At echocardiography, vegetation was found in all cases. It was found on the mitral in 7 cases, the aorta in 3 cases, the mitral and aortic in 2 cases and the mitral and tricuspid in 2 cases also. The EI had occurred on a native valve in 11 cases, prosthesis in 4 cases (2 mitral and 2 aortic). The vegetations average diameter was 11.2 ± 2.1 mm (6.4 and 1 7.7 mm). Vegetations were mobile in 12 cases. The treatment consisted of antibiotics adapted to the antibiogram, neurological and cardiovascular monitoring. The evolution was marked by seven deaths (50%), including 5 deaths related to cerebral complication (71.4% of deaths). CONCLUSION: This study shows that neurological complications during infective endocarditis are frequent, dominated by stroke with a high mortality.

Early diagnosis and treatment of necrotizing fasciitis can improve survival: an observational intensive care unit cohort study.

BACKGROUND: The aim of this study was to describe the clinical characteristics, causative pathogens, clinical management and outcomes of patients presenting to a tertiary adult Australian intensive care unit (ICU) with a diagnosis of necrotizing fasciitis (NF). METHODS: This retrospective observational study was conducted in a 19-bed, level III, adult ICU in a 450-bed tertiary, regional hospital. Clinical databases were accessed for patients diagnosed with NF and admitted to The Geelong Hospital ICU between 1 February 2000 and 1 June 2011. Information on severity of sepsis, surgical procedures and microbiological results were collected. RESULTS: Twenty patients with NF were identified. The median age was 52.5 years and 38% were female. The overall mortality rate was 8.3%. Common co-morbidities were diabetes (21%) and heart failure (17%), although 50% of patients had no co-morbidities. Group A Streptococcus was the identified pathogen in 11 (46%) patients, and Streptococcus milleri group in 5 (21%) patients. Hyperbaric oxygen therapy was not used in the majority of patients. The initial antibiotics administered were active against subsequently cultured bacteria in 83% of patients. Median time to surgical debridement was 20 h. Diagnosis and management was delayed in the nosocomial group. CONCLUSIONS: This study reports physiological data, aetiology and therapeutic interventions in NF for an adult tertiary hospital. We demonstrate one of the lowest reported mortality rates, with early surgical debridement being achieved in the majority of patients. The main delay was found to be in the diagnosis of NF.

Decreased mortality of weaned pigs with Streptococcus suis with the use of in-water potassium penicillin G.

This study evaluated the efficacy of potassium penicillin G in drinking water of weaned pigs to reduce mortality and spread of infection caused by Streptococcus suis. A total of 896 18-day-old weaned pigs were randomly assigned to either treatment with potassium penicillin G in-water (Treated), or no treatment (Control). The outcomes analyzed were total mortality, mortality due to S. suis, and overall counts of S. suis colonies. The risk of mortality due to S. suis and total mortality were significantly increased in the Control group compared with Treated pigs (P < 0.05). Bacterial culture of posterior pharyngeal swabs indicated that Control pigs were significantly more likely to have ≥ 1000 colonies of S. suis per plate than were Treated pigs (P < 0.05). This study demonstrates that potassium penicillin G administered in drinking water is effective in reducing mortality associated with S. suis infection and reducing tonsillar carriage of S. suis.

Dried leaves of Rosmarinus officinalis as a treatment for streptococcosis in tilapia.

Dietary application of dried Rosmarinus officinalis (rosemary) leaves as a treatment for streptococcal infection was studied in tilapia, Oreochromis sp. Feeding with dried rosemary leaves significantly reduced mortality following infection with Streptococcus iniae: 44% mortality in the group fed 8% rosemary, similar to oxytetracycline treatment (43% mortality), and significantly lower than the control (65%). Dietary administration of 16% rosemary significantly reduced mortality because of Streptococcus agalactiae infection in 44 g fish (62% and 76% in 16% rosemary and control, respectively), but not in a similar experiment conducted with 5.5 g fish. The antibacterial effect of rosemary on S. iniae was studied. Activity of rosemary cultivar Israel was reduced during the winter, but there was no significant change in cultivars Oranit and Star. Storage of powdered rosemary leaves at 50 degrees C resulted in fourfold and eightfold higher MIC(24 h) values after 3 and 4.5 months, respectively. Storage at -20 degrees C, 4 degrees C and 25 degrees C and autoclaving (120 degrees C) each resulted in a twofold increase in MIC(24 h). Repeated exposures of S. iniae to rosemary did not affect minimal inhibitory concentration, suggesting no development of resistance to rosemary.

[Complicated skin and soft tissue infections]. / Komplizierte Haut- und Weichgewebsinfektionen.

Skin and soft tissue infections are common diseases. The spectrum ranges from slight furuncles to severe necrotizing soft tissue infections. Grampositive bacteria account for 70-80 % of cases as causative organisms. Diagnostics include rapid evaluation of locally limited or diffuse spreading extent of the disease. In complicated skin and soft tissue infections, surgical intervention with debridement and necronectomy is indicated. Necrotizing skin and soft tissue infections call for programmed redebridement. If systemic signs of inflammation are present (fever > 38 degrees C, leukocytosis, CRP elevation) or significant comorbidity exists, application of antibiotics is indicated. The prognosis in operatively treated patients is dependent on the time of surgical intervention.

The fatty acid composition of maternal diet affects lung prostaglandin E2 levels and survival from group B streptococcal sepsis in neonatal rat pups.

Dietary fatty acid effects upon the immune system may be mediated in part by effects upon the synthesis of proinflammatory mediators. The effects of maternal dietary fatty acid composition upon lung prostaglandin (PG) E2 levels and survival from group B streptococcal (GBS) infection were investigated in neonatal rat pups. Beginning on d 2 of gestation and throughout lactation, pregnant dams were fed a purified diet whose fat source (22% of energy) was either corn oil or menhaden fish oil. On postnatal d 3, pups were randomly cross-fostered to dams of the same diet group to minimize litter effects; litters were then culled to 10 pups per dam. On postnatal d 7, pups were either injected with 1 x 10(7.5) GBS organisms or were killed for determination of lung tissue levels of PGE2 and lung and erythrocyte fatty acid composition. Arachidonic acid and PGE2 levels were significantly higher in the lungs of pups in the corn oil group compared with the fish oil group. Forty-nine percent of pups in the corn oil group survived the GBS challenge compared with 79% of pups in the fish oil group (P = 0.0005). These data suggest that the fatty acid composition of pre- and/or postnatal diet affects the neonatal response to immune challenge, which may be due in part to effects upon the synthesis of pro-inflammatory mediators.

Evaluation of penicillin G in the prevention of streptococcal septicaemia in patients with acute myeloid leukaemia undergoing cytotoxic chemotherapy.

The efficacy of penicillin G was evaluated in the prevention of infections caused by streptococci in patients receiving remission induction or intensive consolidation treatment for acute myeloid leukaemia. Between 1980 and 1988, 29 episodes of streptococcal septicaemia occurred in 139 treatment events. All patients received as prophylaxis regimen ciprofloxacin (n = 38) or a combination of polymyxin B with nalidixic acid (n = 42) or neomycin (n = 59). Six patients died of streptococcal septicaemia despite adequate antibiotic treatment. The high incidence of streptococcal septicaemia lead to the administration of penicillin G in addition to ciprofloxacin as prophylaxis regimen during the 14 days immediately following cytotoxic chemotherapy. Only two episodes of streptococcal septicaemia were documented after addition of penicillin G to the prophylaxis regimen (n = 76, p < 0.001). Both patients had an uneventful recovery after treatment with vancomycin. Patients receiving penicillin G prophylaxis experienced fever during 17% of the time and received antimicrobial therapy during 20% of the time per treatment event compared with 27% and 32% respectively of this time in patients receiving no streptococcal prophylaxis (p < 0.001). Penicillin G prophylaxis was associated with an increased incidence of fever of unknown origin and more frequent isolation of aerobic gram-negative bacteria in surveillance cultures. Penicillin G in combination with ciprofloxacin proved to be highly successful in preventing infections caused by streptococci and in reducing infection-related mortality and morbidity.

Observations on the role of tumor necrosis factor-alpha in a murine model of shock due to Streptococcus pyogenes.

OBJECTIVE: To examine the effect of a monoclonal antibody to tumor necrosis factor-alpha (TNF-alpha) in a murine model of shock due to Streptococcus pyogenes. DESIGN: Prospective, multiexperimental, randomized, controlled trial. SETTING: University hospital research laboratory. INTERVENTIONS: An LD90 murine model of Gram-positive shock using S. pyogenes, associated with the presence of significant concentrations of TNF-alpha in the circulation. Prophylactic administration of antibody with concomitant saline controls. A 500-micrograms TN3-19.12 (hamster monoclonal antibody to recombinant murine TNF), or saline, by intravenous injection was administered. MEASUREMENTS AND MAIN RESULTS: Administration of 0.3 mL of 6 x 10(8) colony-forming units/mL of S. pyogenes H250 to mice resulted in 90% to 100% mortality rates in 72 hrs. Serum TNF-alpha concentrations peaked at 2 hrs after bacterial challenge and were 67.7 +/- 18.6 ng/mL. Treatment with anti-TNF-alpha monoclonal antibody abolished the serum TNF-alpha concentrations but did not affect the mortality rate. Serum endotoxin concentrations were < 50 pg/mL before challenge and at 0.5, 1, 2, 5, and 24 hrs after challenge. CONCLUSIONS: Pretreatment with an anti-TNF monoclonal antibody was not protective in this model of S. pyogenes sepsis, despite the presence of significant amounts of TNF in the circulation. These data suggest that TNF-alpha may not play such a crucial role in the pathogenesis of shock due to S. pyogenes.

Treatment of streptococcal infective endocarditis.

Patients with infective endocarditis caused by penicillin-sensitive streptococci (minimal inhibitory concentration for penicillin of 0.1 microgram/ml or less) may be treated successfully with one of the following regimens: aqueous penicillin G administered intravenously for four weeks, intravenous aqueous penicillin G for four weeks combined with streptomycin for the first two weeks of therapy, or parenterally administered penicillin plus streptomycin for two weeks. A cure rate of at least 98 percent may be anticipated with each of these regimens. During a 12-year period among 142 patients treated for two weeks with penicillin and streptomycin, one (0.7 percent) had relapse and four (3 percent) had vestibular toxicity. The major advantage of the two-week regimen is that it is more cost-effective than the four-week regimens. The major disadvantage of the use of streptomycin is the relatively low risk of vestibular toxicity. Patients with enterococcal endocarditis were treated initially for four weeks with aqueous penicillin G together with either streptomycin (streptomycin-susceptible enterococci, 36 patients) or gentamicin (streptomycin-resistant enterococci, 20 patients). Compared with patients who had symptoms for less than three months, patients with symptoms for longer than three months had a higher relapse rate (0 percent versus 44 percent; p less than 0.001) and mortality (2.5 percent versus 25 percent; p less than 0.001). Patients with mitral valve endocarditis had a significantly higher relapse rate (25 percent) than patients with aortic valve infection (0 percent; p less than 0.01]. Gentamicin-associated nephrotoxicity was more frequent (p less than 0.001) among patients treated with more than 3 mg/kg per day of gentamicin than among those treated with 3 mg/kg per day or less (100 percent versus 20 percent). Relapse and mortality rates did not differ significantly between patients treated with low-dose or high-dose gentamicin regimens. Patients who have had symptoms of enterococcal endocarditis for longer than three months or perhaps patients with mitral valve infection should receive at least six weeks of penicillin therapy together with an aminoglycoside; patients without either high-risk factor may be treated successfully for four weeks.

Influence of the developmental state of valvular lesions on the antimicrobial activity of cefotaxime in experimental enterococcal infections.

Cefotaxime has little antimicrobial activity in vitro against most strains of enterococci, as measured by conventional MICs and MBCs. However, the MICs of cefotaxime against many enterococci are markedly reduced by the addition of serum to the test medium. To assess the relevance of this observation in vivo, we examined the efficacy of cefotaxime in experimental Streptococcus faecalis endocarditis. Since response to antimicrobial agents may vary with the degree of vegetation development, therapeutic efficacy was assessed both in rabbits with newly formed vegetations and in rabbits with well-developed endocardial lesions. Peak serum levels of cefotaxime (50.1 +/- 20.0 micrograms/ml) exceeded the MIC in medium supplemented with serum (4 micrograms/ml), but not in Mueller-Hinton broth alone (greater than 64 micrograms/ml). After 4 days of therapy, animals with newly formed lesions (therapy initiated 1 h after infection, transvalvular catheters removed) had lower mean vegetation bacterial titers than did untreated controls. Among animals with mature vegetations (therapy initiated 12 h after infection, catheters indwelling), the rate of mortality was significantly reduced by cefotaxime therapy. However, no difference in vegetation titers was observed. Thus, cefotaxime demonstrated antienterococcal activity within newly formed vegetations, but did not inhibit bacterial proliferation within well-established vegetations.