Melioidosis in New Caledonia: a dominant strain in a transmission hotspot.

Melioidosis is an infectious disease caused by Burkholderia pseudomallei, a bacterium endemic in Southeast Asia and northern Australia. In New Caledonia, sporadic cases were first described in 2005; since then, more cases have been identified. To improve our understanding of melioidosis epidemiology in New Caledonia, we compared the local cases and B. pseudomallei isolates with those from endemic areas. Nineteen melioidosis cases have been diagnosed in New Caledonia since 1999, mostly severe and with frequent bacteraemia, leading to three (16%) fatalities. All but one occurred in the North Province. Besides sporadic cases caused by non-clonal strains, we also identified a hotspot of transmission related to a clonal group of B. pseudomallei that is phylogenetically related to Australian strains.

Severity markers in severe leptospirosis: a cohort study.

We aimed to evaluate parameters for their value as severity markers in hospitalized leptospirosis patients. We recruited 47 informed adult consenting patients and assessed a number of clinical, hematological, biochemical, and biological variables. Patients were sorted according to severity based on fatality or the requirement of mechanical ventilation or dialysis; the parameters studied were compared between groups on inclusion and the next day. Beside septic shock presentation or a high severity score (Simplified Acute Physiology Score; SAPS II), increased lactate, total bilirubin, lipase, and AST/ALT ratio or a decreased cytokines IL-10/TNF-α ratio were all significantly associated with severity. The gene expression of the IL-1 receptor antagonist IL-1ra, IL-1α, and the long pentraxin PTX-3 were also transcribed at higher levels in most severe cases. Patients could rapidly improve or deteriorate, highlighting the need for a new assessment the next day. Our results add to the limited body of knowledge about severity markers in leptospirosis. They also suggest that patients should be reassessed the next day before being possibly discharged from the hospital. Further studies are needed in order to confirm relevant and reliable prognostic parameters in leptospirosis that would be helpful for the purpose of triage.

Acute osteomyelitis in children: the pathogenesis revisited?

PURPOSE OF THE STUDY: The present study reviews our experience of acute hematogenous osteomyelitis in 450 children over a period of 20 years from 1985 to 2004 at the Nouméa Territorial Hospital in New Caledonia. The objective was to formulate a new theory of the pathogenesis of this affection and to report our research on the disparity in the pathology between temperate countries and our own tropical Pacific area. PATIENT AND METHODS: Only children with an initially normal X-ray and showing symptoms for less than one week were included in the study. Subacute osteomyelitis, infant osteoarthritis and spinal and sacroiliac joint infections were all excluded. All children were treated according to a preestablished protocol including: clinical examination; blood tests; ultrasound, to determine the presence and size of the periosteal elevation and to exclude soft tissue abscess and frequent pyomyositis. Ultrasound was used in the decision to treat with antibiotics alone or with surgery. Computed Tomography was used for deep structures assessment and medical therapy guidance Surgery was limited to open drainage of the subperiosteal abscess only. Regular follow-up of outpatients was continued until normal blood test and X-ray results were achieved. RESULTS AND DISCUSSION: Four hundred and fifty children with a diagnosis of acute hematogenous osteomyelitis were identified, giving an average incidence of 22 new cases per year (range, 12-35). This incidence was two to five times as high as found in Europe. Fifty-three percent of our cases required surgical drainage (vs. 20 % in Europe). Ethnically, 60 % of the children were Melanesian and 20 % Polynesian (both represented less than 50 % of the local population). A similar incidence, about four times as high as in the population of European descent, was reported in Polynesians by our neighbors in New Zealand. The limbs were affected in 90 % of cases, and specifically lower limbs in 70 %. Multiple osseous lesions and systemic infection were recorded in 43 children (9.5 %). Blood cultures and surgical samples were positive in 80 % of cases, and otherwise negative. All the children were successfully treated, without chronic evolution or sequelae needing secondary surgery. The predominant microorganisms isolated were Staphylococcus aureus, in 81 % of cases, none of which were methicillin-resistant, and group A Streptococcus in 7.5 % of cases. A previous study of soft-tissue S. aureus infection showed the presence of Panton-Valentine Leukocidin (PVL) genes in 89 % of cases. These very infrequent genes are responsible for leukotoxic apoptosis, producing leukocidin, causing local acute aggressiveness. A parallel study, in progress for more than a year, is focusing on detecting PVL genes in S. aureus isolated from acute osteomyelitis: in the first nine children analyzed, PVL genes were likewise detected in 89 % of the S. aureus isolated, with no methicillin resistance. Ultrasonography allowed positive diagnosis in 64 % of cases on the day of admission and 84 % by the second day. Because of this very early presence of subperiosteal abscess at the beginning of the disease, and several other issues raised in the present study, we believe that Trueta's theory of acute osteomyelitis pathogenesis does not provide any logical explanation for our anatomoclinical observations. We believe that the primary focus of infection is in the osteoperiosteal area rather than under the growth plate in the metaphyseal bone. The term of Acute Osteo-Periostitis would therefore be much more suitable. A history of blunt trauma was found in 63 % of cases in the present series, and often reported in the literature. We speculate that two forms of infection fixation may develop: a local form, where bacteria carried by the blood stream reach a subperiosteal edema or hematoma secondary to blunt trauma, which is in our opinion the most frequent cause; and a general form, where fixation occurs as single or multifocal osteoperiostitis, and multivisceral locations in severe forms of septicemia. The disparity in this pathology between temperate countries and our own tropical Pacific area is certainly due to PVL-positive S. aureus and ethnic factors. The high prevalence of Melanesian and Polynesian patients confirms that they are at high risk of musculoskeletal infection in New Caledonia as in other Pacific countries, and it is possible that these ethnic groups are genetically susceptible to PVL-positive strains. LEVEL OF EVIDENCE: Level IV. Retrospective case series.

Clinical and microbial characteristics of invasive Streptococcus pyogenes disease in New Caledonia, a region in Oceania with a high incidence of acute rheumatic fever.

New Caledonia is an archipelago in the South Pacific with a high prevalence of acute rheumatic fever and rheumatic heart disease. Conducted in 2006, this study aimed at characterizing clinical manifestations and microbial features of isolates obtained from invasive Streptococcus pyogenes disease. Clinical and demographic data were collected prospectively. Isolates were biotyped, T typed, emm sequenced, and tested for antibiotic susceptibility. Detection of the speA, speB, speC, and ssa genes was also carried out. The estimated annual incidence of invasive S. pyogenes disease in 2006 was high at 38 cases/100,000 inhabitants in New Caledonia. Invasive isolates were obtained from 90 patients with necrotizing fasciitis (41 cases), bacteremia with no identified focus (12 cases), myositis (10 cases), septic arthritis (9 cases), erysipelas (8 cases), postpartum infection (4 cases), myelitis and osteomyelitis (3 cases), severe pneumonia (2 cases), and endocarditis (1 case). The most frequent associated comorbidities were skin lesions (71%) and obesity (29%). Thirty-one different emm types were identified, and the following six accounted for 54% of the isolates: emm15 (15.5%), emm92 (12.2%), emm106 (8.9%), emm74 (6.7%), emm89 (5.6%), and emm109 (5.6%). The speA, speC, and ssa genes were expressed at different frequencies in the various emm types. The first epidemiological study of invasive S. pyogenes disease in New Caledonia highlights that emm type distribution is particular and should be taken into account in the development of an appropriate vaccine. These findings support the prevention of pyoderma and other cutaneous lesions in order to limit the development of both invasive disease and poststreptococcal sequelae in the South Pacific.

Molecular epidemiology of carbapenem-resistant Acinetobacter baumannii in New Caledonia.

Carbapenem-resistant Acinetobacter baumannii (CR-Ab) ranked third, with a frequency of 24.8%, among 202 strains of multidrug-resistant bacteria isolated from clinical samples in the main hospital of New Caledonia in 2004. All CR-Ab isolates were analysed by isoelectric focusing, conjugation, pulsed-field gel electrophoresis and PCR for the presence of carbapenemase genes. Fifty CR-Ab isolates produced carbapenemase OXA-23. The isolates belonged to a single clone presenting several subtypes, suggesting an endemic situation. This study further illustrates the widespread prevalence of carbapenemase OXA-23-producing CR-Ab isolates in the South Pacific.

[Septicemia, bilateral community acquired pneumonia and empyema due to Burkholderia pseudomallei (mellioidosis) with a favorable outcome following prolonged specific antibiotic therapy]. / Septicémie, pneumopathie bilatérale et pleurésie purulente à Burkholderia pseudomallei (mélioïdose) d'évolution favorable sous antibiothérapie adaptée, prolongée.

INTRODUCTION: Melioidosis is an infectious disease due to Burkholderia pseudomallei (Bp). It is regarded as endemic in southeast Asia and northern Australia. The septicaemic form is a severe illness with a high mortality. The tsunami in 2004 has renewed its current importance. CASE REPORT: A 57 year old man was admitted to hospital with a 2 week history of fever, productive cough and progressive weight loss. On admission he was in septic shock and respiratory failures secondary to a left lower lobe community acquired pneumonia. This progressed to a left sided empyema. Bp was isolated from blood cultures and the pleural pus. Initial intensive therapy with ceftazidime and cotrimoxazole for 4 weeks, followed by cotrimoxazole alone for 20 weeks, led to complete recovery with little residual radiological abnormality. Follow up gave no evidence of relapse but revealed an operable, squamous cell, bronchial carcinoma. CONCLUSION: Melliodosis seems to be an emerging disease in New Caledonia with 10 cases identified since 1999. A favourable climate and possibly an animal reservoir might explain sporadic cases in this region. It is important for the medical profession to be aware of this disease in order to ensure the rapid and correct management of patients whose life is at risk.

Adjunction of rituximab to steroids and immunosuppressants for refractory/relapsing Wegener's granulomatosis: a study on 8 patients.

OBJECTIVE: Rituximab, an anti-CD20 biotherapy, has been effective against refractory and/or relapsing Wegener's granulomatosis (WG). But the frequency of and time to responses to rituximab, and its effects on various clinical WG manifestations remain to be thoroughly evaluated. METHODS: Retrospective study of 8 patients with refractory/relapsing WG. In addition to their ongoing therapy, 7 patients received rituximab (375 mg/m2 weekly for 4 weeks) and another received 2 rituximab infusions (1 g on days 1 and 15). Disease activity was assessed using BVAS 2003 before and 6 months after the first rituximab infusion. RESULTS: The median BVAS before rituximab was 14.3 (range 4-30). At 6 months, 5/8 patients had BVAS=0; 3/8 were in complete remission; 3/8 in partial remission (lung nodules persisted in 2 patients, scored 0 in BVAS); 2/8 did not respond. One patient relapsed 1 year after stopping rituximab and responded successfully to a second cycle. Dissociated responses of constitutional and 'vasculitis' symptoms, as opposed to granulomatous manifestations, were observed: the former regressed within days or weeks, while the latter regressed more slowly, over several months. Tolerance was good for 7 patients but 1 developed an urticarial rash during the last 3 infusions. Corticosteroids could be tapered in all patients. CONCLUSION: Rituximab, when prescribed in conjunction with corticosteroids and immunosuppressants to treat refractory/relapsing WG, was able to improve clinical outcome. But the dissociation of response times in patients with predominantly granulomatous manifestations, as opposed to vasculitis symptoms, merits further study before an optimal rituximab regimen can be defined.

Factors of severity at admission during an epidemic of dengue 1 in New Caledonia (South Pacific) in 2003.

We report a retrospective study of an epidemic of dengue in New-Caledonia (South Pacific) in 2003 among adult inpatients. The aim was to establish clinical and biological criteria for the severity of the infection at the time of admission. During 7 months, all inpatients older than 15 y having a laboratory-confirmed diagnosis of dengue fever (IgM or PCR) were included (n=170). Two groups were defined: severe cases (death and/or transfer to intensive care unit, n=24) and benign cases (n=146). Data were analysed using Epi-Info software. Univariate analysis showed that shock, haemorrhage and neurological complications were significantly more frequent in serious cases, respectively 37.5% vs 0.7%, 62.5% vs 32.2%, 25% vs 9.6% (p<0.05). Relevant biological criteria were: creatinine > 140 micromol/l (OR 12 (95% CI 3.93-37.44)), free bilirubin > 18 micromol/l (OR 12.69 ( 95% CI 2.88-59.5)), amylase > 220 UI/l (OR 27.34 (95% CI 4.57-210)) and platelets < 45,000/mm3 (OR 4.35 (95% CI 1.43-14.2)) with p<0.005 (VPP = 100% for association of 3 criteria). We suggest this combination of 4 biological criteria inclines to severity.

[Peritoneal tuberculosis simulating advanced ovarian carcinoma: a case report]. / Tuberculose péritonéale disséminée simulant un cancer ovarien: à propos d'un cas.

Disseminated peritoneal tuberculosis accounts for 1-3% of tuberculosis disease, represented by high frequency of lung defects in endemic countries. The authors report one case in a 43-year-old woman, the initial interpretation of which, based on pleural and peritoneal exudate, showed suspected latero-uterine mass and significant elevated serum CA 125 level, mimicking disseminated ovarian carcinoma. Only after exploring laparotomy with biopsy was disseminated peritoneal tuberculosis identified, thus correcting the diagnosis. Symptomatology, X-ray defect, and cynetic of serum CA 125 level were left in totality after 3 months of antituberculosis multidrugs. This is a diagnostic trap, which presents a new interest for such pathology as tuberculosis, which is on the increase again in the West.

[Probable Miller Fisher syndrome during Dengue fever type 2]. / Probable syndrome de Miller Fisher au cours d'une dengue de type 2.

A 57 year-old-man developed a left ophthalmoplegia associated with ataxia and areflexia while he had fever (39 degrees C) for two days. Dengue fever (DF) was diagnosed by definite criteria, i.e.: IgM seroconversion, positive culture from serum and positive PCR both from serum and CSF. Within one week, he fully and spontaneously recovered. To our knowledge, this neurological picture has never been reported in DF. Considering the immune-mediated nature of this condition, its pathogenesis in DF is proposed in reviewing the literature.

Use of corticosteroids in glomerulonephritis related to infective endocarditis: three cases and review.

We report the cases of three patients treated for infective endocarditis (IE) for whom corticosteroids were added to the antibiotic treatment. They all had clinical and biological evidence of immune-mediated glomerulonephritis. The microorganisms responsible for IE were Coxiella burnetii, Streptococcus bovis, and Cardiobacterium hominis. Median duration of IE before antimicrobial therapy was 7 months. In all patients, renal function deteriorated despite appropriate antimicrobial treatment for a mean duration of 16 days, but it improved after addition of corticosteroid therapy. All patients were cured of IE. A literature review revealed four additional cases of IE-related glomerulonephritis in which adjunctive immunosuppressive therapy was considered to be effective. Although corticosteroid therapy is generally not recommended for IE, it should be considered for patients whose renal dysfunction secondary to glomerulonephritis does not improve with appropriate antimicrobial treatment, especially if the duration of the illness is long.

Low rate of Clostridium difficile colonization in ambulatory and hospitalized HIV-infected patients in a hospital unit: a prospective survey.

OBJECTIVE: To determine the frequency of Clostridium difficile carriage in HIV-infected in- and out-patients, and to assess the role of this carriage in nosocomial transmission of C. difficile. PATIENTS AND METHODS: Prospective study in a university hospital. Forty-five consecutive HIV-infected out-patients and 120 hospitalized patients (52 HIV and 68 non HIV-infected-patients) were studied. During the period of hospitalization, 44 patients (24 HIV and 20 non-HIV-infected patients) with a negative culture within 48 h of admission were followed weekly for fecal carriage. Clostridium difficile culture and latex agglutination were performed on the fecal samples of each patient. In the case of positive culture and/or latex agglutination, C. difficile toxin assays were performed by microtitre cytotoxicity method. RESULTS: Out-patients: one patient was a carrier and one patient with diarrhoea was infected with a toxigenic strain (2/45, 4.5%, 95% CI = 1-17). Eighty percent of the HIV-infected out-patients had received antimicrobial agents previously. In-patients: in the first 48 h, five asymptomatic patients were carriers (three non-HIV and two HIV-infected patients). Among 20 patients who complained of diarrhoea, one HIV-infected patient had only a positive latex agglutination and one HIV-infected patient was infected with a toxigenic strain. Overall, 7/120 (5.8%, 95% CI = 2-10) patients were infected or colonized with C. difficile. During the hospitalization (743 patient-days), none of the 44 patients acquired C. difficile. CONCLUSION: This study suggests that in this given unit, C. difficile carriage is low, at least with single room accommodation, and in the absence of clusters of cases. This carriage is not different in HIV and non-HIV infected patients despite treatment with multiple antibiotics, and is not different in patients managed in different care environments. The systematic identification of C. difficile carriers for isolation and prophylactic treatment is not useful under these circumstances.

Response to fluconazole by 23 patients with human immunodeficiency virus infection and oral candidiasis: pharmacological and mycological factors.

The MICs of fluconazole for strains of Candida species and the levels of fluconazole in serum were determined at day 0 and day 14 for 23 human immunodeficiency virus-infected patients with oral candidiasis who were treated orally with 100 mg of fluconazole per day for 14 days. Among the 23 patients, 11 (48%) were not clinically cured and had persistent isolation of Candidiasis albicans (n = 10) and/or presence of non-C. albicans (n = 6). Clinical response could be predicted by the susceptibility of the strain to fluconazole determined at day 0. All 12 patients who were cured were infected with a strain for which the MIC was < 0.78 mg/liter. All four patients who were infected with a strain for which the MIC was > 3.12 mg/liter experienced clinical failure. These data suggest that a C. albicans strain could be defined as being susceptible when the MIC of fluconazole is < 0.78 mg/liter and as being resistant when the MIC is > 3.12 mg/liter.

Herpes simplex esophagitis in patients with AIDS: report of 34 cases. The Cooperative Study Group on Herpetic Esophagitis in HIV Infection.

Herpetic esophagitis (HE) associated with human immunodeficiency virus (HIV) is a rare condition mainly reported as isolated cases. We thus decided to study this association and analyze the possible predisposing factors, clinical and endoscopic presentations, and clinical response to treatment. Thirty-four HIV-1-infected patients were identified: 27 had histologically or virologically confirmed HE and seven had probable HE, a retrospective diagnosis based on the efficacy of acyclovir given alone. The median CD4 cell count was 15/mm3. Recent predisposing factors (such as nasogastric procedures, steroid therapy, and anticancer therapy) were noted with regard to 16 of the 34 patients (47%). Odynophagia and/or chest pain occurred in 30 patients (88%). At the time of diagnosis of HE, extraesophageal herpes was found in only 13 patients (38%). Superficial ulcers of the distal third of the esophagus were present in 17 (50%). Among 20 of the 27 patients with confirmed HE that could be evaluated, therapy with acyclovir led to complete resolution in 16 and partial response in 3; 1 patient died of HE. Five patients (15%) suffered confirmed or possible relapses. The mean interval between the diagnosis of HE and death was 8.8 months. Herpes simplex virus may be responsible for ulcerated esophagitis that occurs in the advanced stages of AIDS and that can be safely treated with acyclovir before a definitive diagnosis is made.

Comparison of infective endocarditis in patients with and without previously recognized heart disease.

In a consecutive series of patients with infective endocarditis, we compared the charts of 123 nonaddicted patients without previously known heart disease with those of 174 patients with native valve disease. The 2 groups were similar in age, sex, clinical findings, and mortality rates, but infective endocarditis was more often located on the aortic valve, more often due to Streptococcus bovis and enterococci in patients without previously known heart disease.

Procedures associated with infective endocarditis in adults. A case control study.

OBJECT: To assess the relative risk of infective endocarditis associated with various procedures and the protective efficacy of antibiotic prophylaxis by a case-control study. BACKGROUND: Recommendations for the prevention of infective endocarditis are based on the hypothesis of a relationship between procedures and infective endocarditis which is supported by anecdotal reports and data from experimental models. METHODS: Cases met the Von Reyn's diagnostic criteria modified with echocardiographic and macroscopic findings Controls were recruited from cardiology or medicinal wards. Cases (n = 171) and controls were matched as regards sex, age and underlying cardiac condition. They were requested to indicate all the medical, surgical or dental procedures within the previous 3 months. Among potential confounding factors, infectious episodes and skin wounds in the previous 3 months were reported. Antibiotic prophylaxis administration was documented for type, dosage, duration and administration schedule. RESULTS: Cases significantly more frequently than controls had undergone at least one procedure (matched odds ratio, 1.6; 95% confidence interval, 1.01 to 2.53). Dental procedures considered as a whole were not associated with an increased risk, although scaling and root canal treatment showed a trend towards a higher risk of infective endocarditis (P = 0.065). Among non-dental procedures, only surgery appeared to be at risk (matched odds ratio, 4.7; 95% confidence interval, 1.02 to 22). Considering all procedures, the risk of infective endocarditis increased significantly with the number of procedures. While general co-morbid conditions did not differ between the two groups, cases significantly more frequently than controls had experienced an infectious episode or a skin wound. In multivariate analysis, only infectious episodes and skin wounds significantly increased the risk of infective endocarditis. Scaling was the only independent risk factor for viridans streptococcal infective endocarditis. The 46% protective efficacy of antibiotic prophylaxis was not significant. CONCLUSIONS: Procedures do increase the risk of infective endocarditis. The interpretation of the apparent low risk associated with dental procedures may be as a result of the current practice of antibiotic prophylaxis. Our data suggest that surgery should be more clearly mentioned in future guidelines, and reemphasize that a rigorous treatment of any focal infection in cardiac patients is mandatory. From the efficacy rate of antibiotic prophylaxis,it can be estimated that the overall incidence of infective endocarditis might be reduced by 5 to 10% in France by appropriate use of antibiotic prophylaxis in cardiac patients.

RP 59500 prophylaxis of experimental endocarditis due to erythromycin-susceptible and -resistant isogenic pairs of viridans group streptococci.

RP 59500 is a new injectable streptogramin composed of two synergistic components (quinupristin and dalfopristin) which are active against a number of erythromycin-susceptible and -resistant gram-positive bacteria. The following experiments investigate the ability of RP 59500 to prevent experimental endocarditis due to either of two erythromycin-susceptible streptococcal isolates or their constitutively erythromycin-resistant Tn916 delta E transconjugants. RP 59500 had low MICs (0.125 to 0.5 mg/liter) for all four test organisms and was substantially bactericidal in vitro. Rats with catheter-induced aortic vegetations were given single-dose antibiotic prophylaxis 30 to 60 min before bacterial inoculation through a computerized pump system which permitted the simulation of drug kinetics for humans produced by either 7 mg of RP 59500 per kg of body weight or 1 g of vancomycin. Single-dose RP 59500 prophylaxis successfully prevented endocarditis due to both the erythromycin-susceptible parent strains and their erythromycin-resistant derivatives in rats challenged with the minimal inoculum infecting 90% of controls. In addition, RP 59500 also prevented infection in animals challenged with fivefold-larger inocula of the erythromycin-susceptible parent strains. Vancomycin successfully prevented endocarditis due to any of the four test organisms. These results underline the in vivo efficacy of RP 59500 against both erythromycin-susceptible and -resistant streptococci. Such good results against the resistant strains would not be expected with erythromycin or clindamycin, which are the standard macrolidelincosamide-streptogramin antibiotics used for endocarditis prophylaxis in humans. An oral form of RP 59500 which might advantageously replace some of the older prophylactic regimens is currently being developed.