Publications by authors named "Lionel Koch"

8 Publications

  • Page 1 of 1

Genomic and RT-qPCR analysis of trimethoprim-sulfamethoxazole and meropenem resistance in Burkholderia pseudomallei clinical isolates.

PLoS Negl Trop Dis 2021 02 16;15(2):e0008913. Epub 2021 Feb 16.

Bacteriology Unit, UMR-MD1 INSERM 1261, French Armed Biomedical Research Institut, Brétigny-sur-Orge, France.

Background: Melioidosis is an endemic disease in southeast Asia and northern Australia caused by the saprophytic bacteria Burkholderia pseudomallei, with a high mortality rate. The clinical presentation is multifaceted, with symptoms ranging from acute septicemia to multiple chronic abscesses. Here, we report a chronic case of melioidosis in a patient who lived in Malaysia in the 70s and was suspected of contracting tuberculosis. Approximately 40 years later, in 2014, he was diagnosed with pauci-symptomatic melioidosis during a routine examination. Four strains were isolated from a single sample. They showed divergent morphotypes and divergent antibiotic susceptibility, with some strains showing resistance to trimethoprim-sulfamethoxazole and fluoroquinolones. In 2016, clinical samples were still positive for B. pseudomallei, and only one type of strain, showing atypical resistance to meropenem, was isolated.

Principal Findings: We performed whole genome sequencing and RT-qPCR analysis on the strains isolated during this study to gain further insights into their differences. We thus identified two types of resistance mechanisms in these clinical strains. The first one was an adaptive and transient mechanism that disappeared during the course of laboratory sub-cultures; the second was a mutation in the efflux pump regulator amrR, associated with the overexpression of the related transporter.

Conclusion: The development of such mechanisms may have a clinical impact on antibiotic treatment. Indeed, their transient nature could lead to an undiagnosed resistance. Efflux overexpression due to mutation leads to an important multiple resistance, reducing the effectiveness of antibiotics during treatment.
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http://dx.doi.org/10.1371/journal.pntd.0008913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909661PMC
February 2021

Collective aeromedical transport of COVID-19 critically ill patients in Europe: A retrospective study.

Anaesth Crit Care Pain Med 2021 Feb 21;40(1):100786. Epub 2020 Nov 21.

Military Teaching Hospital Percy, Intensive Care Unit and Anaesthesiology Department, Clamart, France.

Background: In early 2020, the coronavirus disease 2019 (COVID-19) pandemic outbreak has posed the risk of critical care resources overload in every affected country. Collective interhospital transport of critically ill COVID-19 patients as a way to mitigate the localised pressure from overloaded intensive care units at a national or international level has not been reported yet. The aim of this study was to provide descriptive data about the first six collective aeromedical evacuation (MEDEVAC) of COVID-19 patients performed within Europe.

Methods: This retrospective study included all adult patients transported by the first six collective MEDEVAC missions for COVID-19 patients performed within Europe on the 18, 21, 24, 27, 31 of March and the 3 of April 2020.

Results: Thirty-six patients with acute respiratory distress syndrome (ARDS) were transported aboard six MEDEVAC missions. The median duration of mechanical ventilation in ICU before transportation was 4 days (3-5.25). The median PaO/FiO ratio obtained before, during the flight and at day 1 after the transport was 180 mmHg (156-202,5), 143 mmHg (118,75-184,75) and 174 mmHg (129,5-205,5), respectively, with no significant difference. The median norepinephrine infusion rate observed before, during the flight and at day 1 after the transport was 0,08 µg/kg. min (0,00-0,20), 0,08 (0,00-0,25), and 0,07 (0,03-0,18), respectively, with no significant difference. No life-threatening event was reported.

Conclusion: Collective aero-MEDEVAC of COVID-19 critically ill patients could provide a reliable solution to help control the burden of the disease at a national or international level.
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http://dx.doi.org/10.1016/j.accpm.2020.11.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680057PMC
February 2021

Oxygen Management During Collective Aeromedical Evacuation of 36 COVID-19 Patients With ARDS.

Mil Med 2020 Nov 19. Epub 2020 Nov 19.

Intensive Care Unit and Anesthesiology Department, Military Teaching Hospital Desgenettes, Lyon 69003, France.

Objective: The ongoing coronavirus disease-2019 pandemic leads to the saturation of critical care facilities worldwide. Collective aeromedical evacuations (MEDEVACS) might help rebalance the demand and supply of health care. If interhospital transport of patients suffering from ARDS is relatively common, little is known about the specific challenges of collective medevac. Oxygen management in such context is crucial. We describe our experience with a focus on this resource.

Methods: We retrospectively analyzed the first six collective medevac performed during the coronavirus disease-2019 pandemic by the French Military Health Service from March 17 to April 3, 2020. Oxygen management was compliant with international guidelines as well as aeronautical constraints and monitored throughout the flights. Presumed high O2 consumers were scheduled to board the last and disembark the first.

Results: Thirty-six mechanically ventilated patients were successfully transported within Europe. The duration of onboard ventilation was 185 minutes (145-198.5 minutes), including the flight, the boarding and disembarking periods. Oxygen intake was 1,650 L per patient per flight (1,350-1,950 L patient per flight) and 564 L per patient per hour (482-675 L per patient-1 per hour) and surpassed our anticipation. As anticipated, presumed high O2 consumers had a reduced ventilation duration onboard. The estimations of oxygen consumptions were frequently overshot, and only two hypoxemia episodes occurred.

Conclusion: Oxygen consumption was higher than expected, despite anticipation and predefined oxygen management measures, and encourages to a great caution in the processing of such collective medevac missions.
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http://dx.doi.org/10.1093/milmed/usaa512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717260PMC
November 2020

Natural outbreaks and bioterrorism: How to deal with the two sides of the same coin?

J Glob Health 2020 Dec;10(2):020317

Bacteriology Unit, French Armed Forces Biomedical Research Institute (IRBA), Bretigny sur Orge, France.

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http://dx.doi.org/10.7189/jogh.10.020317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7535343PMC
December 2020

Modeling the Inactivation of Viruses from the Family in Response to Temperature and Relative Humidity in Suspensions or on Surfaces.

Appl Environ Microbiol 2020 09 1;86(18). Epub 2020 Sep 1.

Risk Assessment Department, French Agency for Food, Environmental and Occupational Health and Safety, Maisons-Alfort, France.

Temperature and relative humidity are major factors determining virus inactivation in the environment. This article reviews inactivation data regarding coronaviruses on surfaces and in liquids from published studies and develops secondary models to predict coronaviruses inactivation as a function of temperature and relative humidity. A total of 102 values (i.e., the time to obtain a log reduction of virus infectivity), including values for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), were collected from 26 published studies. The values obtained from the different coronaviruses and studies were found to be generally consistent. Five different models were fitted to the global data set of values. The most appropriate model considered temperature and relative humidity. A spreadsheet predicting the inactivation of coronaviruses and the associated uncertainty is presented and can be used to predict virus inactivation for untested temperatures, time points, or any coronavirus strains belonging to and genera. The prediction of the persistence of SARS-CoV-2 on fomites is essential in investigating the importance of contact transmission. This study collects available information on inactivation kinetics of coronaviruses in both solid and liquid fomites and creates a mathematical model for the impact of temperature and relative humidity on virus persistence. The predictions of the model can support more robust decision-making and could be useful in various public health contexts. A calculator for the natural clearance of SARS-CoV-2 depending on temperature and relative humidity could be a valuable operational tool for public authorities.
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http://dx.doi.org/10.1128/AEM.01244-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480392PMC
September 2020

Nutrient depletion may trigger the Yersinia pestis OmpR-EnvZ regulatory system to promote flea-borne plague transmission.

Mol Microbiol 2019 11 13;112(5):1471-1482. Epub 2019 Sep 13.

University of Lille, INSERM, CNRS, CHU Lille, Institut Pasteur de Lille, U1019-UMR8204, CIIL-Center for Infection and Immunity of Lille, F-59000, Lille, France.

The flea's lumen gut is a poorly documented environment where the agent of flea-borne plague, Yersinia pestis, must replicate to produce a transmissible infection. Here, we report that both the acidic pH and osmolarity of the lumen's contents display simple harmonic oscillations with different periods. Since an acidic pH and osmolarity are two of three known stimuli of the OmpR-EnvZ two-component system in bacteria, we investigated the role and function of this Y. pestis system in fleas. By monitoring the in vivo expression pattern of three OmpR-EnvZ-regulated genes, we concluded that the flea gut environment triggers OmpR-EnvZ. This activation was not, however, correlated with changes in pH and osmolarity but matched the pattern of nutrient depletion (the third known stimulus for OmpR-EnvZ). Lastly, we found that the OmpR-EnvZ and the OmpF porin are needed to produce the biofilm that ultimately obstructs the flea's gut and thus hastens the flea-borne transmission of plague. Taken as a whole, our data suggest that the flea gut is a complex, fluctuating environment in which Y. pestis senses nutrient depletion via OmpR-EnvZ. Once activated, the latter triggers a molecular program (including at least OmpF) that produces the biofilm required for efficient plague transmission.
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http://dx.doi.org/10.1111/mmi.14372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842400PMC
November 2019

A review of melioidosis cases imported into Europe.

Eur J Clin Microbiol Infect Dis 2019 Aug 4;38(8):1395-1408. Epub 2019 Apr 4.

Laboratoire de Pharmaco-Chimie Radicalaire, Aix Marseille Univ, CNRS, ICR, Marseille, France, Marseille, France.

Melioidosis is a tropical bacterial infection, rarely encountered, and poorly known by clinicians. In non-endemic areas, a misdiagnosis can lead to a fatal outcome. This study aims to identify the main characteristics of imported and diagnosed melioidosis cases in Europe to increase clinician's awareness of this diagnosis. A literature review of imported and diagnosed human melioidosis cases in Europe was performed. PubMed and Web of Science search engines were used for retrieving articles from 2000 to November 2018. Seventy-seven cases of imported melioidosis into Europe described in the literature were identified. More than half of the cases were acquired in Thailand (53%) by men (73%). Patients were usually exposed to Burkholderia pseudomallei during a holiday stay (58%) of less than 1 month (23%) and were hospitalized during the month following their return to Europe (58%). Among travelers, melioidosis is less often associated with risk factor (16%), diabetes being the most frequently comorbidity related (19%). The clinical presentation was multifaceted, pneumonia being the most common symptom (52%), followed by cardiovascular form (45%) and skin and soft tissues damages (35%). The diagnosis was obtained by culture (92%), often supplemented by morphological, biochemical, and molecular identification (23%). Misdiagnoses were common (21%). Over half of the patients received a complete and adapted treatment (56%). Mortality is lower for returning traveler (6%). Imported melioidosis cases into Europe have their own characteristics. This possibility should be considered in patients with pneumonia, fever, and/or abscess returning from endemic areas even years after.
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http://dx.doi.org/10.1007/s10096-019-03548-5DOI Listing
August 2019

Transcriptomic studies and assessment of Yersinia pestis reference genes in various conditions.

Sci Rep 2019 02 21;9(1):2501. Epub 2019 Feb 21.

Institut de Recherche Biomédicale des Armées (IRBA), Brétigny-sur-Orge, France.

Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) is a very sensitive widespread technique considered as the gold standard to explore transcriptional variations. While a particular methodology has to be followed to provide accurate results many published studies are likely to misinterpret results due to lack of minimal quality requirements. Yersinia pestis is a highly pathogenic bacterium responsible for plague. It has been used to propose a ready-to-use and complete approach to mitigate the risk of technical biases in transcriptomic studies. The selection of suitable reference genes (RGs) among 29 candidates was performed using four different methods (GeNorm, NormFinder, BestKeeper and the Delta-Ct method). An overall comprehensive ranking revealed that 12 following candidate RGs are suitable for accurate normalization: gmk, proC, fabD, rpoD, nadB, rho, thrA, ribD, mutL, rpoB, adk and tmk. Some frequently used genes like 16S RNA had even been found as unsuitable to study Y. pestis. This methodology allowed us to demonstrate, under different temperatures and states of growth, significant transcriptional changes of six efflux pumps genes involved in physiological aspects as antimicrobial resistance or virulence. Previous transcriptomic studies done under comparable conditions had not been able to highlight these transcriptional modifications. These results highlight the importance of validating RGs prior to the normalization of transcriptional expression levels of targeted genes. This accurate methodology can be extended to any gene of interest in Y. pestis. More generally, the same workflow can be applied to identify and validate appropriate RGs in other bacteria to study transcriptional variations.
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http://dx.doi.org/10.1038/s41598-019-39072-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6385181PMC
February 2019