Management of unexpected laboratory exposure to Burkholderia pseudomallei.

Burkholderia pseudomallei is a Gram-negative saprophytic bacillus that causes melioidosis. The infection is endemic in South-East of Asia and Northern Australia. B. pseudomallei has been designated as bioterrorism agent and its manipulation should be done in a biological safety level 3 capability. Workers in laboratories may be accidentally exposed to B. pseudomallei before its identification, with a risk of laboratory-acquired melioidosis. We want to describe a case of melioidosis occurred in our hospital and its management at laboratory. The objective of this article is to provide guidance to microbiologists confronted with a suspicious case of B. pseudomallei on the management of the exposition. We report here a couple of microbiological arguments that can usually guide microbiologists towards presumptive identification of B. pseudomallei. This case report shows the importance of MALDI-TOF MS accurate databases to ensure accurate microbial identification and antibiotic prophylaxis adapted to individuals who were exposed. We also want to underline the importance of developing an effective strategy of prevention against any accidental exposure that can occur in a microbiological laboratory.

Efficacy of vancomycin lock therapy for totally implantable venous access port-related infection due to coagulase-negative staphylococci in 100 patients with cancer.

OBJECTIVES: Data on the efficacy of vancomycin catheter lock therapy (VLT) for conservative treatment of totally implantable venous access port-related infections (TIVAP-RI) due to CoNS are scarce. The aim of this study was to evaluate the effectiveness of VLT in the treatment of TIVAP-RI due to CoNS in cancer patients. METHODS: This prospective, observational, multicentre study included adults with cancer treated with VLT for a TIVAP-RI due to CoNS. The primary endpoint was the success of VLT, defined as no TIVAP removal nor TIVAP-RI recurrence within 3 months after initiation of VLT. The secondary endpoint was 3 month mortality. Risk factors for VLT failure were also analysed. RESULTS: One hundred patients were included [men 53%, median age 63 years (IQR 53-72)]. Median duration of VLT was 12 days (IQR 9-14). Systemic antibiotic therapy was administered in 87 patients. VLT was successful in 44 patients. TIVAP could be reused after VLT in 51 patients. Recurrence of infection after completion of VLT occurred in 33 patients, among which TIVAP was removed in 27. Intermittent VLT (antibiotic solution left in place in the TIVAP lumen part of the time) was identified as a risk factor for TIVAP-RI recurrence. At 3 months, 26 deaths were reported; 1 (4%) was related to TIVAP-RI. CONCLUSIONS: At 3 months, success of VLT for TIVAP-RI due to CoNS was low. However, removing TIVAP was avoided in nearly half the patients. Continuous locks should be preferred to intermittent locks. Identifying factors of success is essential to select patients who may benefit from VLT.

A prospective, observational study of fidaxomicin use for Clostridioides difficile infection in France.

OBJECTIVE: To describe the characteristics, management and outcomes of hospitalised patients with Clostridioides difficile infection (CDI) treated with and without fidaxomicin. METHODS: This prospective, multicentre, observational study (DAFNE) enrolled hospitalised patients with CDI, including 294 patients treated with fidaxomicin (outcomes recorded over a 3-month period) and 150 patients treated with other CDI therapies during three 1-month periods. The primary endpoint was baseline and CDI characteristics of fidaxomicin-treated patients. RESULTS: At baseline, the fidaxomicin-treated population included immunocompromised patients (39.1%) and patients with severe (59.2%) and recurrent (36.4%) CDI. Fidaxomicin was associated with a high rate of clinical cure (92.2%) and low CDI recurrence (16.3% within 3 months). Clinical cure rates were ≥90% in patients aged ≥65 years, those receiving concomitant antibiotics and those with prior or severe CDI. There were 121/296 (40.9%) patients with adverse events (AEs), 5.4% with fidaxomicin-related AEs and 1.0% with serious fidaxomicin-related AEs. No fidaxomicin-related deaths were reported. CONCLUSIONS: Fidaxomicin is an effective and well-tolerated CDI treatment in a real-world setting in France, which included patients at high risk of adverse outcomes.Trial registration: Description of the use of fidaxomicin in hospitalised patients with documented Clostridium difficile infection and the management of these patients (DAFNE), NCT02214771, www.ClinicalTrials.gov.

Impact of the beta-lacta test on the management of urinary tract infections at the emergency department.

INTRODUCTION: Rapid detection of extended-spectrum ß-lactamases is essential. In this study, we evaluated the potential impact of ß-lacta test on both the times to appropriate antibiotic therapy and to the implementation of patient isolation measures. PATIENTS AND METHODS: We included prospectively all the patients admitted to the emergency department for clinical suspicion of urinary tract infection. Compared with physician's decision, we analysed the potential impact of ß-lacta test on the initial antibiotic therapy and on the implementation of hygiene measures. This study has been registered under number NCT02897609. RESULTS: We included 203 patients, 43% with acute pyelonephritis and 21% with acute prostatitis. The ß-lacta test had a 95.2% sensitivity and a 99.5% specificity to detect extended-spectrum ß-lactamases. Taking the ß-lacta test results into account would have decreased significantly both the times to appropriate therapy and to isolation measures from 54 to 2.7 h and from 55.2 to 2.6 h, respectively. CONCLUSION: The ß-lacta test could reduce significantly the times to appropriate therapy and implementation of isolations measures.

Clinical impact of rapid susceptibility testing on Mueller-Hinton Rapid-SIR directly from urine specimens.

Urinary tract infection diagnosis and management generally involves a 48-h microbiological delay to obtain the antibiotic susceptibility test (AST) results. In the context of multidrug resistance, reducing the time to obtain AST results is an essential factor, allowing for more timely appropriate treatment. We conducted a single-centre prospective study on urinary samples meeting two criteria: significant leukocyturia > 50/mm3 and exclusive presence of Gram-negative bacilli on direct examination. AST were performed by direct inoculation on Mueller-Hinton Rapid-SIR (MHR-SIR) agar. We evaluated the time to antibiotic adaptation by the antimicrobial stewardship team according to rapid AST results. Patients were subsequently excluded from the study if asymptomatic bacteria were confirmed, or in the absence of clinical data. Seventy patients were included. Mean age of patients was 68.8 years (± 21.3). Empirical antibiotic treatment were mainly based on third generation cephalosporins (n = 33), fluoroquinolones (n = 15), beta-lactamin/beta-lactamase inhibitors (n = 7), fosfomycin and nitrofurantoin (n = 5, each). The average time to obtain results was 7.2 h (± 1.6 h). Adaptation of therapy following MHR-SIR was performed for 29 patients (41%) with early switch to oral antibiotics, de-escalation or escalation in respectively 72.3%, 30%, and 11% of cases. Time saving of MHR-SIR compared with the standard technique was 42.6 (± 16.7) h. This study showed that rapid antibiotic susceptibility test results, using MHR-SIR method directly from urine, can be obtained 40 h earlier than conventional AST. The study also demonstrated significant clinical impact on the selection and reduction of the antibiotic therapy spectrum.

Evaluation of the Unyvero i60 ITI® multiplex PCR for infected chronic leg ulcers diagnosis.

OBJECTIVES: Unyvero i60 ITI multiplex PCR (mPCR) may identify a large panel of bacteria and antibiotic resistance genes. In this study, we compared results obtained by mPCR to standard bacteriology in chronic leg ulcer (CLU) infections. METHODS: A prospective study, part of the interventional-blinded randomized study "ulcerinfecte" (NCT02889926), was conducted at Saint Joseph Hospital in Paris. Fifty patients with a suspicion of infected CLU were included between February 2017 and September 2018. Conventional bacteriology and mPCR were performed simultaneously on deep skin biopsies. RESULTS: Staphylococcus aureus and Pseudomonas aeruginosa were the most detected pathogens. Regarding the global sensitivity, mPCR is not overcome to the standard culture. Anaerobes and slow growing bacteria were detected with a higher sensitivity rate by mPCR than standard culture. CONCLUSION: Unyvero i60 ITI multiplex PCR detected rapidly pathogenic bacteria in infected CLU especially anaerobes and slow growing bacteria and was particularly effective for patients previously treated with antibiotics.

Impact of a multiplex PCR assay (FilmArray®) on the management of patients with suspected central nervous system infections.

Microbiological diagnosis of central nervous system (CNS) infections is challenging due to limited access to CNS samples, overlap between meningitis and encephalitis, and the multiplicity of pathogens potentially involved. We aimed to estimate the impact of a commercial multiplex PCR assay (FilmArray® meningitis/encephalitis) on the management of patients with suspicion of meningitis or encephalitis, in terms of time to diagnosis, antimicrobial agents use, duration of hospitalization, and costs. This prospective observational study was conducted at Saint Joseph Hospital (Paris, France) from December 2016 to December 2017. All CSF samples sent to the microbiology laboratory for suspicion of meningitis and/or encephalitis, with CSF cells count > 5 cells/µL, were tested by meningitis/encephalitis multiplex PCR assay. One hundred thirty patients were included. The multiplex PCR assay was positive in 33 patients (25%). Main pathogens found were Enterovirus (n = 12), Varicella-Zoster virus (n = 7), Herpes simplex virus-2 (n = 6), and Listeria monocytogenes (n = 3) as main pathogens. The multiplex PCR assay reduced time to microbiological diagnosis by 3.3 ± 1.6 days and allowed an earlier discontinuation of empirical anti-infective drugs in 42 patients (32%) and an earlier hospital discharge in 23 patients (18%), with an estimated saving of 82 hospital days overall, and a management cost reduction of 26,242 € (201 €/patient). The systematic use of the FilmArray® meningitis/encephalitis multiplex PCR assay may allow earlier diagnosis, earlier discontinuation of empirical treatment, reduced duration of stay, and costs reduction.

Clinical impact of rapid susceptibility testing on MHR-SIR directly from blood cultures.

BACKGROUND: In a previous study, we demonstrated that rapid antibiotic susceptibility tests (ASTs) can be performed directly on blood culture samples tested on Mueller-Hinton Rapid agar (MHR-SIR) with a time delay of 6-8 h. OBJECTIVES: Using this rapid disc diffusion method, we analysed the clinical impact associated with rapid reporting of results in our hospital setting. METHODS: All patients with bloodstream infections (BSIs) related to Enterobacteriaceae or Staphylococcus aureus were prospectively included in the study. The rapid ASTs were performed by incubation of positive blood cultures on MHR-SIR for 6-8 h by direct inoculation according to BSAC recommendations. RESULTS: One hundred and sixty-seven patients with BSIs were included as MHR-guided adaptation therapy cases. Eighty percent had Enterobacteriaceae-related BSIs, of which 12 (9%) were ESBL producers and 20% were S. aureus-related BSIs. A urinary or intra-abdominal infection was observed in 44.3% and 19.8%, respectively, of Enterobacteriaceae-related infections. The most frequent sources of infections for S. aureus BSIs were cutaneous and endovascular, in 43% and 23% of cases, respectively. Forty-four percent of the patients benefited from therapeutic modification according to the results of the MHR-SIR AST. Thus, empirical antibiotic therapy was modified by using antibiotic therapy that had too wide a spectrum or was unsuitable in 26% and 18% of cases, respectively. Compared with the 24 h required for the reference method, the median length of time to provision of susceptibility test results by MHR-SIR was 7 h. CONCLUSIONS: This study showed a significant time saving (17 h) on the appropriateness of antibiotic prescription and demonstrated a significant impact regarding the choice and reduction of the spectrum of antibiotic therapy.

Prospective evaluation of rapid antimicrobial susceptibility testing by disk diffusion on Mueller-Hinton rapid-SIR directly on blood cultures.

BACKGROUND: With the worldwide spread of antibiotic resistance, delivering antibiotic susceptibility test (AST) results in a timely manner represents a major challenge. In cases of sepsis, rapid AST may facilitate early optimization of empiric antibiotic therapy. Disc diffusion is a well-standardized AST method, however 16 to 24 h are required to achieve an overall AST profile according to antimicrobial societies. METHODS: In this prospective pilot study, we evaluated the performance of Mueller-Hinton-Rapid-SIR (MHR-SIR) agar after 6-8 h of incubation in comparison with standard MH agar after 16 h of incubation directly on positive blood cultures caused by Enterobacteriaceae and Staphylococcus aureus from routine clinical microbiology. A total of 133 positive blood samples including 110 Enterobacteriaceae (83%) and 23 Staphylococcus aureus (17%) were tested in parallel by two direct AST methods, each using EUCAST breakpoints. For each combination bacterium and antibiotic, we compared the categorical agreement and the correlation between the diameters obtained by MHR-SIR and by standard MH. RESULTS: Our results showed 97.7% categorical agreement for Enterobacteriaceae, with 1.4% minor errors, 0.4% major errors and 0.5% very major errors. For S. aureus, we observed 97.8% categorical agreement, 1.9% minor errors, 0.3% major errors and no very major errors. CONCLUSION: Our results showed excellent categorical agreement and correlations between diameters for MHR-SIR and standard MH methods. MHRSIR can predict the result of overall AST profile within 6-8 h with reliable results. AST is obtained on the same day the blood culture becomes positive, with a very moderate cost.

Performance of rapid antimicrobial susceptibility testing by disk diffusion on MHR-SIR agar directly on urine specimens.

The standard method for the diagnosis of urinary tract infections is urine culture that requires 18-48 h for the identification of the bacteria and an additional 24 h until the results of antimicrobial susceptibility testing (AST) are available. We evaluated here a rapid AST method by disc diffusion performed directly on urine samples with a delay of 8 h. A total of 245 urine samples with monobacterial Gram negative observed on microscopy were tested in parallel by two AST methods. Rapid AST method was performed directly on urine samples using Rapid Mueller-Hinton (MHR-SIR) with 8-h incubation before reading and standard method was performed as usual. We compared the categorical agreement and the correlation between the diameters obtained by standard method and by MHR-SIR directly on urine samples. Over the 5285 tested combinations, we observed 5172 (97.9%) categorical agreement, 82 (1.5%) minor errors, 17 (0.3%) major errors, and 14 (0.3%) very major errors. Our results showed an excellent categorical agreement and correlations between diameters for MHR-SIR and standard methods. MHR-SIR performed directly on urine samples with monomicrobial Enterobacteriacae can predict the result of overall AST profile in 8 h with reliable results. The main advantage of MHR-SIR is that it offers the possibility of obtaining results 40 h earlier than conventional AST. The cost is estimated for less than 6 USD for 16 antibiotics, chosen by the microbiologist.

A case of daptomycin-induced immune thrombocytopenia.

We report a case of severe daptomycin-induced immune thrombocytopenia in a patient treated for methicillin-resistant Staphylococcus epidermidis and ampicillin-resistant Enterococcus faecalis bacteremia acquired in an intensive care unit. Serum antibodies bound to platelets in the presence of daptomycin on flow cytometry. There was no evidence of other causes of thrombocytopenia. The patient died of brain herniation complicating extensive cerebral hemorrhage. To our knowledge, this is the first described case of daptomycin-induced thrombocytopenia.

Cerebrovascular diseases in HIV-infected patients.

Cerebrovascular disease (CVD) has early been recognized in HIV-infected patients, including infectious arteritis, inflammatory vasculitis, aneurismal and small-vessel arteriopathy, to which adds now the premature atherosclerotic cerebral arteriopathy associated with the highly active antiretroviral therapy (HAART)-induced metabolic disorders. As a result of the increased life-expectancy associated with HAART, HIV patients grow older and are exposed to the combined vascular risk of antiviral-induced metabolic changes and advancing age. Several studies have documented subclinical cervical artery atherosclerosis, as assessed by intima-media thickness, ultrasound detection of carotid artery plaques and intracerebral small-vessel disease, all being associated with the induced metabolic changes. This suggests that vascular prevention should be performed on a long-term basis.

Efficacy of etravirine for treatment of acute HIV meningoencephalitis.

We describe a patient with human immunodeficiency virus (HIV) and hepatitis C virus coinfection who experienced recurrent episodes of acute HIV meningoencephalitis. The addition of etravirine to the therapeutic regimen completely resolved symptoms, and HIV was no longer detected in cerebrospinal spinal fluid specimens. Etravirine has a satisfactory safety profile and, in this case, was a durable alternative therapy for HIV meningoencephalitis.

HIV-associated vascular diseases: structural and functional changes, clinical implications.

After more than two decades of AIDS epidemic, the spectrum of HIV-associated vascular diseases has mainly evolved from infectious and inflammatory vasculitides to premature atherosclerosis, its related contributing conditions (metabolic syndrome, dyslipidemia, insulin resistance syndrome) and complications (acute coronary and cerebrovascular syndromes). Today, as the AIDS epidemic further progresses worldwide and as the life expectancy of HIV-infected patients treated with effective antiviral regimens has dramatically increased, more than 10% of patients experience cardiovascular manifestations. The complex interplay between viral infection, inflammatory and cytokines pathways, protease inhibitors-induced hyperlipidemia and direct effects on endothelial cells has not, by far, been integrated in a single comprehensive pathogenesis network. However, recognition of its main components has resulted in a broader appreciation of cardiovascular risk and risk factors in HIV-infected/treated patients. Cardiovascular prevention is required in more than one half of HIV-infected/treated patients to achieve a reliable effectiveness of modern antiretroviral therapy. As the prognosis of HIV patients improves continuously, this rate is also likely to increase in the future.

[The HIV-infected traveler: infectious risks and prevention]. / Le voyageur infecté par le VIH: risques infectieux et prévention.

Patients with human immunodeficient virus (HIV) must make special preparations before traveling. They have a higher risk of infection than the general population. They are more likely to develop malaria and the clinical episodes will be more severe, particularly in pregnant women. Prescriptions for malaria prophylaxis and treatment must take into account their interactions with antiretroviral drugs. Vaccination decisions require consideration of the risk and severity of the vaccine preventable diseases in the destination area, the nature of the vaccine, the patient's immune status, and the risk of virological rebound as a consequence of vaccination. Some countries have entry restriction for travelers with HIV. Special precautions may be necessary for transporting and storing antiretroviral medications.

Urolithiasis in HIV-positive patients treated with atazanavir.

Among protease inhibitors, atazanavir has not been associated with urolithiasis in clinical studies. We describe 11 cases of atazanavir-associated urolithiasis in patients with human immunodeficiency virus (HIV) infection. Patients with low water intake, high urinary pH, and a prior history of urinary stones may have a higher risk of atazanavir-associated urine crystallization.

Is pertussis being considered as a cause of persistent cough among adults?

A study was conducted to determine the 1124 French Sentinel network general practitioners ability to consider pertussis as a cause of persistent cough among adults. Pertussis was rarely considered in the differential diagnosis of cough (6%). Factors associated with pertussis being considered included younger age, shorter cough duration, world health organization clinical definition for pertussis, and muscular chest pain.