Michèle Gerard

Rapid emergence and spread of OXA-48-producing carbapenem-resistant Enterobacteriaceae isolates in Belgian hospitals

During a polymerase chain reaction (PCR)-based surveillance study of β-lactam resistance, 19 OXA-48-positive enterobacterial isolates were detected at nine Belgian hospitals from January 2010 to April 2011. Most cases were presumed to have been locally acquired and were detected in patients who had not travelled abroad. Clonally related outbreaks occurred in two different cities. The majority of isolates co-produced several β-lactamases as well as non-β-lactam resistance genes. This report highlights the rapid emergence and spread of OXA-48-producing Enterobacteriaceae in Belgium.

Impact of rapid microbial identification directly from positive blood cultures using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry on patient management

For septic patients, delaying the initiation of antimicrobial therapy or choosing an inappropriate antibiotic can considerably worsen their prognosis. This study evaluated the impact of rapid microbial identification (RMI) from positive blood cultures on the management of patients with suspected sepsis. During a 6-month period, RMI by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was performed for all new episodes of bacteraemia. For each patient, the infectious disease specialist was contacted and questioned about his therapeutic decisions made based on the Gram staining and the RMI. This information was collected to evaluate the number of RMIs that led to a therapeutic change or to a modification of the patients general management (e.g. fast removal of infected catheters). During the study period, 277 new episodes of bacteraemia were recorded. In 71.12% of the cases, MALDI-TOF MS resulted in a successful RMI (197/277). For adult and paediatric patients, 13.38% (21/157) and 2.50% (1/40) of the RMIs, respectively, resulted in modification of the treatment regimen, according to the survey. In many other cases, the MALDI-TOF MS was a helpful tool for infectious disease specialists because it confirmed suspected cases of contamination, especially in the paediatric population (15/40 RMIs, 37.50%), or suggested complementary diagnostic testing. This study emphasizes the benefits of RMI from positive blood cultures. Although the use of this technique represents an extra cost for the laboratory, RMI using MALDI-TOF MS has been implemented in our daily practice.

Effectiveness of antiretroviral therapy initiated before the age of 2 months in infants vertically infected with human immunodeficiency virus type 1

Abstract The effectiveness and tolerance of antiretroviral therapy with a combination of three reverse transcriptase inhibitors starting at the time of diagnosis (before 2 months of age) was evaluated in four infants with vertically acquired HIV-1 infection. Plasma HIV-1 RNA levels ranged from 230,000 to 1,000,000 copies/ml before onset of triple therapy and fell below 50 copies/ml at 12 to 33 weeks of life in three of the infants. These three children, currently aged 158, 105 and 72 weeks, are asymptomatic, have normal lymphocyte subsets and no hypergammaglobulinaemia. Two children experienced a profound reduction in the amount of proviral DNA detected in blood and have become HIV-1 seronegative, although one of them has had HIV-1 RNA detectable on a single occasion at 114 weeks of life (303 copies/ml). Transient interruption of therapy resulted in a rapid but reversible increase in HIV-1 RNA levels in the third child and was associated with the production of HIV-specific antibodies. The fourth child whose parents were not compliant to treatment and follow-up had a poor virological response. Conclusion Early treatment of vertically acquired human immunodeficiency virus type 1 infection with three reverse transcriptase inhibitors is well tolerated and can result in such suppression of viral replication that specific antibodies are not produced, that proviral DNA falls to the lower limit of quantitation in blood and that all clinical and immunological manifestations of infection are avoided. Parental adhesion is crucial to the effectiveness of therapy.

Pancreatic disturbances and typhoid fever

During an 8-year period, 14 adult patients were hospitalized with typhoid fever confirmed by positive blood cultures for Salmonella typhi. Among these patients, we have retrospectively (n = 7) and prospectively (n = 7) evaluated pancreatic disturbance by serum amylase and lipase measurements at the time of admission. In 7 (50%) biological signs of pancreatitis were noted: mean amylase level 81 IU (range 30-201 IU, normal value less than 40 IU), mean lipase level 949 IU (range 468-2,000 IU, normal value less than 300 IU). Clinical signs of pancreatitis were observed in 4 cases, one of whom had a concomitant salmonella biliary tract infection and gall stones demonstrated by laparotomy and the others a normal biliary ultrasonographic examination with a swelling of the pancreas. No alcohol or drug use or other infection were noted before admission. This study suggests that biological or clinical pancreatitis should be considered as a frequent complication of typhoid fever. S. typhi should therefore be added to the list of pathogens implicated in the pathogenesis of non-alcoholic or non-lithiasic pancreatitis.

Risk of Misinterpretation of Ebola Virus PCR Results After rVSV ZEBOV–GP Vaccination

TO THE EDITOR—We would like to report on a recent false-positive Ebola polymerase chain reaction (PCR) result after postexposure prophylaxis (PEP) with the recombinant vesicular stomatitis virus (rVSV) Zaire Ebola virus–glycoprotein (ZEBOV–GP) vaccine. We believe this observation is important in light of ongoing vaccine and diagnostic developments sparked by the recent Ebola virus disease (EVD) epidemic. A physician working for Médecins Sans Frontières (MSF) was evacuated from Monrovia, Liberia, to Belgium on 4 December 2014. Two days earlier, she had accidentally pricked herself with an unused needle through 2 gloves that had been in contact with the skin of a patient confirmedwithEVD.Upon arrival inBrussels, she was asymptomatic but nonetheless immediately hospitalized at the SaintPierre University Hospital. The MSFOperational Center Brussels occupational physicians and the Belgian clinical Ebola expert team performed a risk assessment. Considering the limited options available for PEP in humans, the experience with post-exposure vaccination using a live-attenuated rVSV ZEBOV–GP in nonhuman primates [1], and a single report of PEP with this vaccine in a human [2], it was decided that a single dose (titer ≥1 × 10 pfu/mL) of the rVSV ZEBOV–GP vaccine (NewLink Genetics, Canada) would be administered. The next morning, the patient developed fever. Although the fever was likely attributable to an adverse reaction to the vaccine, the expert group agreed to immediately performmolecular testing for EVD. Blood samples collected immediately prior to and 16 hours after vaccination were sent to the Belgian National Reference Laboratory for Infectious and Tropical Diseases (Institute of Tropical Medicine, Antwerp) for analysis using 2 real-time (RT)-PCRs targeting different EBOV genes, according to the European guidelines [3]. An in-house RT-PCR (adapted from [4]), targeting EBOV–GP, and the commercially available RealStar filovirus RT-PCR (Altona Diagnostics GmbH, Hamburg, Germany), targeting the large polymerase gene, were used [5].The commercial PCR test was negative in both samples, while the in-house test was positive in the sample after vaccination (Figure 1A). Based on these results, the patient was considered as not infected. The patient fully recovered the following day. Subsequent PCR testing revealed that the in-house RT-PCR remained positive for up to 5 days after vaccination, which is longer than the 2 days previously reported [2] and most likely the result of the higher vaccine dose given. At day 6

A multicenter quasi-experimental study: impact of a central line infection control program using auditing and performance feedback in five Belgian intensive care units.

BackgroundWe analyzed the impact associated with an intervention based on process control and performance feedback to decrease central line-associated bloodstream infection (CLABSI) rates.This study was conducted from March 2011 to September 2012 in five adult intensive care units (ICU) located in two Belgian tertiary hospitals A and B, with a total of 53 beds.MethodsThis study was divided in three phases: P1 (baseline), P2 (intervention) and P3 (post intervention).During P2, external monitoring of five central venous catheters (CVC) care critical processes and monthly reporting (meetings and feedbacks reports posted) of performance indicators (CLABSI rate, CVC utilization ratio, compliance rate with each care process, and insertion site) to ICU workers were performed. The external monitoring of process measures was assessed by the same trained research nurse.A Poisson regression analysis was used to compare CLABSI incidence density rate per phase. Statistical significance was achieved with 2-sided p- value of < 0.05. For the analysis, we separated the five ICU in hospital A and B when appropriate.ResultsSignificantly improved total mean compliance was achieved for hand hygiene, CVC handling and CVC dressing. CLABSI rate declined from 4.00 (95% confidence interval (CI): 1.94-6.06) to 1.81 (0.46-3.17) per 1,000 CVC-days in P2 with an incidence rate ratio (IRR) of 0.49 (0.24-0.98, p = 0.043). A better response was observed in hospital A where the nurse participation at the monthly meeting was significantly higher than in hospital B (p < 0.001) as the percentage of feedbacks reports posted in ICU (p < 0.001). The decline in the CLABSI rate observed during P2 in comparison with P1 was independent of the insertion site (femoral or non-femoral; p = 0.054). The overall CLABSI rate increased to 2.73 (1.17-4.29) per 1,000 CVC-days with IRR of 0.67 (0.36-1.26, p = 0.212) in P3 compared to P1, but a high nursing turnover was observed in both hospitals.ConclusionsOur intervention focused on external auditing and performance feedback resulted in significant reduction in rates of CLABSI. Investigation continues regarding the most effective way to sustain CLABSI prevention practices and to improve the culture of safety in healthcare.

Hepatic Candidosis in a Patient with Acute Leukemia Leber-Candidose bei einem Patienten mit akuter Leukämie

Summary: Isolated hepatic candidosis has been described more frequently in patients with leukemia and consists in a particular clinical entity which remains difficult to control. We report here the case of a patient treated for acute nonlymphoblastic who developed hepatic candidosis two months after the end of intensive consolidation therapy.

Variations in catheter-related bloodstream infections rates based on local practices

BackgroundCatheter-related bloodstream infection (CRBSI) surveillance serves as a quality improvement measure that is often used to assess performance. We reviewed the total number of microbiological samples collected in three Belgian intensive care units (ICU) in 2009–2010, and we described variations in CRBSI rates based on two factors: microbiological documentation rate and CRBSI definition which includes clinical criterion for coagulase-negative Staphylococcus (CNS) episode.FindingsCRBSI rates were 2.95, 1.13 and 1.26 per 1,000 estimated catheter-days in ICUs A, B and C, respectively. ICU B cultured fewer microbiological samples and reported the lowest CRBSI rate. ICU C had the highest documentation rate but was assisted by support available from the laboratory for processing single CNS positive blood cultures. With the exclusion of clinical criterion, CRBSI rates would be reduced by 19%, 45% and 0% in ICUs A, B and C, respectively.ConclusionCRBSI rates may be biased by differences of blood culture sampling and CRBSI definition. These observations suggest that comparisons of CRBSI rates in different ICUs remain difficult to interpret without knowledge of local practices.

Acceptance of HIV-infected patients in assisted reproductive technique protocols

OBJECTIVE To assess the adequacy of a multidisciplinary approach providing information to couples affected by HIV before ART. DESIGN Prospective observational study. SETTING RT centre and infectious disease clinic, public university hospital. PATIENTS 50 couples with at least one HIV-infected partner. INTERVENTIONS Multidisciplinary approach towards ART by various intervening physicians (specialist in fertility, infectious diseases, paediatrics, obstetrics, psychiatry). MAIN OUTCOME MEASURED We analysed specifically the cases in which the staff did not accept and the patients compliance to the counselling procedures. RESULTS Among the 150 couples, 30 did not complete the procedure and were lost to follow-up. The remaining 120 couples were evaluated: 89 couples were accepted, 5 were temporarily refused and 26 were refused definitively. The major reasons for refusal were medical reasons (n=13). CONCLUSION Because of the high refusal rate and the drop of rate, a multidisciplinary approach is mandatory before initiating ART in seropositive couples.

Effectiveness of rescue antiretroviral therapy including intravenously administered zidovudine and foscarnet in a child with HIV-1 enteropathy.

As impaired absorption of oral drugs has been considered as a possible cause of antiretroviral therapy failure in human immunodeficiency virus type 1 disease, we report the potential role of intravenous agents to induce initial viral suppression in an infected child with chronic diarrhoea and severe wasting. This child, born in August 1993 to a black African mother, acquired in utero human immunodeficiency virus type 1 (HIV-1) infection after a full term pregnancy. Despite zidovudine monotherapy started at 1 month of life, CD4+ cells count declined markedly within the first 4 months of life (Fig. 1). At 16 months, she developed chronic diarrhoea without any identified enteric pathogen. A jejunal biopsy demonstrated severe grade 3 atrophy. She developed profound failure to thrive and progressive microcephaly (Fig. 1). At 29 months of age, nocturnal feedings with a semi-elementary diet and parenteral nutrition were alternated and were unsuccessful in interrupting the wasting syndrome. She developed repeated opportunistic infections including bacterial pneumonia, Candida oesophagitis, and recurrent herpes zoster. Repeated oropharyngeal, blood and urine cultures were negative for cytomegalovirus and the child remained seronegative for this pathogen. The child was treated with zidovudine until 1 year of age, then with didanosine. In January 1997, lamivudine and ritonavir were added to didanosine. This protease inhibitor-containing regimen did not result in any virological, immunological or physical improvement. In November 1997, after 3 months of parenteral nutrition, the chronic diarrhoea did not improve nor was there any weight gain, the child was started on a rescue therapy including two intravenously administered drugs (zidovudine 180 mg/m b.i.d. and foscarnet 90 mg/kg b.i.d.), and two oral drugs (nelfinavir 30 mg/kg t.i.d. and nevirapine 120 mg/m once a day for 2 weeks and then 180 mg/m b.i.d.). The rationale for intravenous administration of antiretroviral agents was the concern that oral drugs could be poorly absorbed because of the enteropathy. Foscarnet, a pyrophosphate analogue, inhibits the reverse transcriptase of HIV-1 and has been shown to decrease HIV-1 replication in vitro [3, 4] and in vivo in adults [1, 2]. However, its use in clinical practice is limited by a lack of oral bioavailability and nephrotoxicity. The co-administration of zidovudine and foscarnet is warranted by their pattern of resistance: concurrent administration of zidovudine could hinder the development of foscarnet resistant HIV-1 in vivo [5] and most of the mutations that reduce susceptibility to foscarnet can phenotypically reverse zidovudine resistance [6]. Retrospective analysis of genotypic resistance mutations on stored plasma samples showed high level resistance to zidovudine, and decreased susceptibility to didanosine, stavudine and nelfinavir, emphasising the role of foscarnet in induction therapy. Plasma HIV-1 RNA dropped to <400 copies/ml and chronic diarrhoea ceased within 4 weeks. Then, intravenously administered drugs were discontinued and oral didanosine (180 mg/m q.d) and stavudine (1 mg/kg b.i.d.) were initiated. Quadruple therapy with nelfinavir, nevirapine, didanosine and stavudine maintained the inhibition of viral replication over the following 4 years. Eur J Pediatr (2003) 162: 528–529 DOI 10.1007/s00431-003-1224-9