ESCMID Publications

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Clinical Microbiology and Infection (CMI)

CMI aims to publish original research and reviews that will assist physicians and clinical microbiologists in their management of patients, in the prevention of infectious diseases, and in developing and assessing innovative diagnostic approaches. CMI should help researchers to communicate as well as further their research. We aim to promote good methods in basic and clinical research, clear reporting, and to publish interesting and thought-provoking material. CMI is committed to the mission of European Society of Clinical Microbiology and Infection (ESCMID) ‘…to improve the diagnosis, treatment and prevention of infection-related diseases. This is achieved by promoting and supporting research, education, training and good medical practice.’

To be able to maintain CMI's level of excellence, we need your help. We would like to hear what you expect from CMI, what topics are of interest to you, and any suggestion or contribution you could make. Please send any new ideas you would like to share to the Editor-in-Chief: Leonard Leibovici leibovic[at]

More information can be found on the journal's home page.

Editor's selection of recent papers published in CMI

Researchers in France assessed the occurrence of infections related to implantable left ventricular assist device (LVAD), which are used in patients with end-stage heart failure. As the use of LVAD is expanding, infectious complications are emerging with limited data available to guide management. According to the study more than one in five patients had at least one infectious complication. The main bacteria isolated were Staphylococcus aureus, coagulase-negative staphylococci, Enterobacteriaceae, Pseudomonas aeruginosa and Corynebacterium sp. LVAD could be retained in all patients with the use of prolonged antibacterial treatment. The authors concluded that LVAD-related infections are common after implantation, and that they can be controlled with antibiotics.

Members of ESCMID Study Group for Infections in Critically Ill Patients (ESGCIP) have reviewed the current evidence around the use of aerosolized antibiotics to treat pneumonia in mechanically ventilated patients. Their efforts resulted in four technical requirements that should be followed to minimize treatment failure and adverse events in these patients.

Using next-generation sequencing (NGS), researchers in Australia identified single nucleotide polymorphisms (SNPs) in genes known to be linked to multi-antifungal drug resistance, in 12 clinical samples of Candida glabrata. While SNPs in FKS1, FKS2, CgCDR1, CgPDR1, FCY2, ERG9 and CgFLR1 genes increased the minimum inhibitory concentration (MIC) to echinocandins, azole and/or 5-cytosine compounds, SNPs in EPA6, PWP2, PWP5 were not associated with higher drug MICs. The results of the study suggest that using NGS to identify mutational patterns in resistance genes of C. glabrata is feasible. 

Researchers in the U.K. collected interviews and observational data from notes of six surgical teams at a teaching hospital to investigate antibiotic decision making during surgical ward rounds. The data indicated that surgeons’ antibiotic decisions come secondary to the surgical management of patients. Due to unclear responsibilities, lack of continuity and disjointed information, such decisions are often delegated, leading to sub-optimal antimicrobial management. In the face of increasing antibiotic resistance, the authors propose a position for a clinician who is specifically responsible for perioperative antibiotic management. (The paper is open access.)

Researchers in Spain assessed how levofloxacin, azithromycin or clarithromycin treatment affected the outcomes of patients with Legionella pneumonia (LP) requiring hospitalization. The primary endpoint of the study was 30-day mortality. Secondary endpoints included time to defervescence, time to achieve clinical stability, length of intravenous (IV) therapy, length of hospital stay, and early mortality (i.e. death from any cause within 48 hours of hospitalization). Overall, no significant differences between levofloxacin and azithromycin treatment were found for most outcomes. Compared to levofloxacin, patients treated with clarithromycin received longer IV antibiotic treatment and had a longer hospital stay.

Researchers in the United Kingdom evaluated clinical decision support systems (CDSS) for antimicrobial management. They included 58 original articles describing 38 independent CDSS. Most systems are platforms integrated with electronic medical records, which target antimicrobial prescribing and have rules based infrastructure providing decision support. CDSS studies fail to report consideration of the non-expert, end-user workflow, and tend to focus on antimicrobial selection. The authors recommend to include factors that drive non-expert decision making when designing CDSS interventions. They conclude that future work must aim to expand the systems beyond simply selecting appropriate antimicrobials, with clear and systematic reporting frameworks for interventions developed to address current gaps identified in the reporting of evidence.

Researchers from the United States wanted to give an overview of universal influenza virus vaccines and therapeutic antibodies in pre-clinical and clinical development. They identified universal influenza virus vaccines that target conserved regions of the influenza virus including the hemagglutinin stalk domain, the ectodomain of the M2 ion channel or the internal matrix and nucleoproteins that are in late pre-clinical and clinical development. These vaccines could confer broad protection against all influenza A and B viruses including drift variants and thereby abolish the need for annual re-formulation and re-administration of influenza virus vaccines, they stated. In addition, these novel vaccines would enhance our preparedness against emerging influenza virus pandemics. Finally, novel therapeutic antibodies against the same conserved targets are in clinical development and could become valuable tools in the fight against influenza virus infection. The authors conclude that both universal influenza virus vaccines and therapeutic antibodies are potential future options for the control of human influenza infections.

Researchers from France evaluated if screening for primary immunodeficiencies (PIDs) should be performed after the first invasive infection in young adults. In adults screening is recommended after two severe bacterial infections. The researchers included patients who had experienced an invasive infection with encapsulated bacteria commonly encountered in PIDs such as Streptococcus pneumoniae, Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae or group A Streptococcus. About one in five was diagnosed with PID. The researchers conclude that PID screening should be considered after a first unexplained invasive encapsulated bacterial infection in young adults.

Researchers from Belgium review tight blood glucose control and early macronutrient restriction as strategies to reduce nosocomial infections and sepsis in the critically ill. Although the optimal blood glucose target remains to be defined and many controversies are waiting to be solved, common sense supports preventing severe hyperglycaemia in all critically ill patients. When adequate monitoring tools and expertise are available, targeting strict normoglycaemia is preferable for ICU patients. However, when these conditions are not fulfilled in clinical practice, an intermediate target is advisable for safety reasons. Whether early macronutrient restriction renders moderate hyperglycaemia less harmful remains to be further explored. Future research that dares to challenge the classical dogmas will pave the way for clinical progress in this complex area of medicine.

Researchers in Sweden assessed the clinical effect of empirical treatment with narrow-spectrum beta-lactam monotherapy (NSBM) versus broad-spectrum beta-lactam monotherapy (BSBM) in non-severe community-acquired pneumonia (CAP). They observed no significant differences in 30-day and 90-day mortality between NSBM and BSBM. Patients who received BSBM were more often treated in an intensive care unit and had longer length of stay. Empirical NSBM appears to be effective in the majority of hospitalized immunocompetent adults with non-severe CAP and should be further evaluated in randomized trials, the authors concluded.

Researchers from the Netherlands and the United Kingdom investigated genetic variations of Listeria monocytogenes, a food-borne pathogen, and their potential to cause meningitis. They identified a bacteriophage, co-occurring with a novel plasmid associated with unfavourable outcome in patients. The plasmid carries the emrC gene, which confers decreased susceptibility to disinfectants used in the food-processing industry. Isolates harbouring emrC were growth-inhibited at higher levels of benzalkonium chloride, and had higher MICs for amoxicillin and gentamicin compared with isolates without emrC. The results show that the novel plasmid, carrying the efflux transporter emrC, is associated with increased incidence of certain types of listerial meningitis. Suggesting increased disease severity, the findings warrant consideration of disinfectants used in the food-processing industry that select for resistance mechanisms and may, inadvertently, lead to increased risk of poor disease outcome, the researchers conclude.

ESCMID’s journal Clinical Microbiology and Infection is inviting authors to submit papers for the theme issues that are planned for September – December 2017. The topics of the theme issues are New antibiotics and issues surrounding their development, approval and access; Acquired resistance in fungi: how large is the problem?; Antibiotic stewardship; and Nutrition and infection. You may submit articles in any CMI format: original research as full articles or as research notes; narrative or systematic reviews; commentaries or letters to the editor.

Immunocompromised patients in some countries are prescribed marijuana to control nausea or pain. But there is little data available on the infectious risks of medical marijuana. Researchers in the U.S. assessed the microbiome of twenty cannabis samples from different dispensaries in northern California. They found evidence for the presence of numerous Gram-negative bacilli and fungal pathogens. The authors conclude that it would be prudent to advise immunocompromised patients against the use of vaporized or inhaled marijuana because it places them at an increased risk for acquisition of severe infections.

Ève Dubé from the National Health Institute of Quebec in a comment discusses a study describing discrepancies between GPs’ vaccination recommendations for their patients and practices for their own children published in CMI. Dubé concludes that it is of critical importance to identify providers who are vaccine-hesitant to understand the causes of their hesitancies and to develop tailored strategies if we wish to maintain vaccination programs successes. As within the population, vaccine hesitancy in healthcare providers is highly context-specific and varies between different vaccines, professions and in time. There are important gaps in our understanding of the complex mix of factors leading to vaccine hesitancy among healthcare providers, which are key to design effective targeted interventions. Read a Healio article about vaccine hesitancy citing the original paper as well as an expert comment by ESCMID's vaccines study group EVASG. And read Dubé's paper in CMI.

The sepsis-3 definitions generated controversies regarding the general applicability of its recommendation defining organ dysfunction as 2-point increase in the sequential organ failure assessment (SOFA) score. Researchers of the Hellenic sepsis study group validated the recommendations with an emphasis on the quick SOFA (qSOFA) score. They studied 3,346 infections outside the ICU and 1,058 infections within the ICU. Their analysis positively validated the use of the SOFA score to predict unfavourable outcome and to limit misclassification into lower severity. However, the analysis also showed that the qSOFA score had inadequate sensitivity for early risk assessment.

The European Committee on Antimicrobial Susceptibility Testing (EUCAST) reviewed the use of whole-genome sequencing (WGS) for antimicrobial susceptibility testing (AST). The EUCAST experts concluded that for most bacterial species there is currently insufficient evidence to support the use of WGS-inferred AST to guide clinical decision making. They state that WGS-AST should be a funding priority if it is to become a rival to phenotypic AST. The major limitations to widespread adoption for WGS-based AST in clinical labs remain the current high-cost and limited speed of inferring antimicrobial susceptibility from WGS data as well as the dependency on prior culture since analysis directly on specimens remains challenging.

Researchers in Chile studied the efficacy and safety of withholding antimicrobials in children with cancer, fever and neutropenia (FN) with a demonstrated respiratory viral infection. The authors conclude that it is safe to reduce antimicrobial treatment in children with FN and respiratory viral infections. Physicians should favour the adoption of evidence-based management strategies, based on clinical and microbiological/molecular diagnostic criteria.

Researchers in Norway compared treating febrile neutropenia (FN) with benzylpenicillin plus an aminoglycoside vs the broad-spectrum beta-lactam antibiotic meropenem in neutropenic patients with lymphoma or leukaemia, and a suspected bacterial infection. Clinical success was significantly more frequent in patients randomized to the meropenem arm, and they also had fewer fatal outcomes than patients randomized to the benzylpenicillin plus an aminoglycoside regimen, the researchers found. Balancing the need for adequate antimicrobial therapy in each patient, and avoiding unnecessary use of broad-spectrum-beta-lactams to reduce antibiotic resistance in the interest of future patients, make this trial and future research important, the researchers conclude.

Researchers investigated the response to a pentavalent childhood vaccine (diphtheria, tetanus, whole cell pertussis, hepatitis B, Haemophilus influenzae type b) in Laos, a country where the high burden of vaccine-preventable diseases was thought to be due to low vaccine coverage. After a full documented course of vaccination, seroprotective rates were unusually low and disparate against components of the vaccine: only 38% of children were protected against hepatitis B, 56% against diphtheria and 85% against tetanus. Time since vaccination, age, home-birth and malnutrition only partially explained the poor vaccine responses. The study demonstrates an urgent need to monitor the serological response to vaccination, in particular in resource-poor countries, the researchers concluded.

An international research group led by the University of Queensland in Australia defined standardized endpoints to aid the design of trials that compare antibiotic therapies for bloodstream infection (BSI), including Staphylococcus aureus and Gram-negative BSI. They defined different primary and secondary endpoints for small-scale pilot studies designed to evaluate protocol design, feasibility and implementation as well as larger-scale trials designed to test hypotheses and influence clinical practice. These new endpoints provide a framework to aid future trial design, the authors conclude. Further work will be required to validate them with respect to patient-centred clinical outcomes. The paper is important because randomized controlled trials are the basis of evidence-based management of patients. The findings will help investigators choose endpoints that improve the management of patients.

 A group of German researchers showed that travel through airports does have the potential to introduce antibiotic-resistant bacteria onto surfaces at airports, which may pose a public health risk. International travellers can acquire antimicrobial-resistant bacteria while travelling and spread it in their home countries after returning from abroad. While the study is limited by its small sample size, time delays between sampling and culture and a lack of hygiene information, it also shows that a joint strategy by low, middle and high income countries is required to successfully fight antimicrobial resistance, the authors conclude. ESCMID will send out a press release on the paper 2 November.

Researchers at the Imperial College performed an economic evaluation of the cost associated with an outbreak of carbapenemase-producing Enterobacteriaceae (CPE) at hospitals in London. The outbreak cost €1.1 million over 10 months, comprising €312,000 of actual expenditure (drugs, laboratory costs, contact precautions, decontamination, monitoring and costs of bay closures), and €822,000 in opportunity cost (lost bed days, missed revenue, staff time). Reduced capacity to perform elective surgical procedures related to bed closures (€349,000) represented the greatest cost. An additional €153,000 was spent on estates renovations prompted by the outbreak. The authors conclude that CPE outbreaks are highly costly.

ESCMID’s Parity Commission explored the social, cultural, psychological, and organizational factors associated with inequality in the workplace among clinical microbiologists (CM) and infectious disease (ID) specialists at European hospitals. The study shows that discrimination occurs at all institutions in all the countries, though it is generally not explicit and uses disrespectful micro-behaviours that are hard to respond to when they occur. Inequality for example affects loans, distribution of research funds and gender and country representation in boards and conference faculty. Parenthood has a major impact on women’s careers, as women are still mainly responsible for family care. Responses to discrimination range from reactive to surrender strategies. The authors present an effective model for diagnosing discriminatory behaviours in a medical professional setting. The identification of inequality drivers may help national ID/CM societies to further reduce discrimination.

Researchers led by a team at the Imperial College London studied the impact of migration on multidrug-resistant tuberculosis (MDR-TB) in low-incidence countries in Europe. The study showed that a significant proportion of MDR-TB cases in migrants result from reactivation of latent infection. Screening, however, is highly problematic since current tests cannot distinguish latent MDR-TB. Although there is a human rights obligation to improve the diagnosis, treatment, and prevention of MDR-TB in migrants, refugees experience significant barriers to testing and treatment, exacerbated by increasingly restrictive health systems. The researchers call for further studies into the impact of screening on detection or prevention, and the potential consequences of failing to treat and prevent MDR-TB among migrants in Europe. An evidence-based guidance for treatment of latent infection and effective approaches for MDR-TB management are urgently needed, the researchers conclude.

Researchers in Hungary studied the efficacy of tigecycline compared to standard therapy with oral vancomycin plus intravenous metronidazole in adults treated for severe Clostridium difficile infection (sCDI). Patients treated with tigecycline had significantly better outcomes of clinical cure, less complicated disease courses and less CDI sepsis compared to patients receiving standard therapy. Tigecycline usage was not associated with adverse drug reactions or need for colectomy. Rates of ileus, toxic megacolon, mortality and relapse were similar between the two groups, the study showed. The researchers concluded that the favourable outcomes suggest that tigecycline should be considered as a potential candidate for therapeutic usage in cases of sCDI refractory to standard treatment.

Researchers in France investigated if general practitioners’ vaccination recommendations for their patients differ from their practices for their own children. The study showed that most reported that their own children were vaccinated, but that they did not always recommend the same vaccines to their patients. Nearly half, for example, reported that their children were vaccinated against hepatitis B but that they did not always recommend that vaccine to patients. Discrepancies were also observed with vaccines against measles-mumps-rubella, meningococcal bacteria and human papillomavirus. The researchers suggest that the reasons behind these discrepancies, including vaccine hesitancy, should be investigated.

Researchers in Australia investigated the prevalence and risk factors for asymptomatic toxigenic (TCD) and non-toxigenic C. difficile (NTCD)-colonisation in a broad cross-section of the general hospital population over a three-year period. TCD colonisation was associated with gastro-oesophageal reflux disease, a higher number of admissions in the previous year, and antimicrobial exposure during the current admission, while NTCD colonisation was associated with chronic obstructive pulmonary disease and chronic kidney failure. The researchers conclude that risk factors differ between patients with asymptomatic colonisation by toxigenic and non-toxigenic strains. Given that morbidity is largely driven by toxigenic strains, this novel finding has important implications for disease control and prevention.

Researchers from Marseille University investigated the challenges associated with pre-exposure prophylaxis (PrEP) with daily administration of doxycycline as a means to reduce the transmission of bacterial sexually transmitted infections (STIs) in men who have sex with men. The researchers discuss questions raised by this creative initiative as well as the challenges to improve the control of STIs through the use of PrEP. They conclude that relevant information should be drawn from available epidemiologic data to identify those who could benefit from such prophylactic treatment. They stress that the choice of antimicrobial agents is crucial, as antimicrobial susceptibility of STI agents is heterogeneous.

Researchers at the Department of Dental Medicine at the Karolinska Institute in Sweden investigated the effects a single dose of the antibiotic amoxicillin as prophylaxis has on the normal oral microflora. Six of the 29 healthy volunteers already carried resistant viridans streptococci in the saliva before receiving 2g of amoxicillin. Amoxicillin reduced the streptococci, while the proportion of those with reduced susceptibility increased significantly on days 2 and 5. The researchers conclude that a single dose of amoxicillin can cause an ecological disturbance and induce selection of resistant strains in the oral microflora.

Researchers from Switzerland, Austria and Israel reviewed point-of-care randomization and informed consent in clinical trials. For low-risk trials whose purpose is to evaluate non-experimental therapies or other measures toward which the medical community is in a state of equipoise, ethics committees should play a more active role in a more standardized fashion, the authors write. Patients in the clinic are continually subject to spontaneous “pseudo-randomizations” based on local dogma and the anecdotal experience of their physicians. Stronger ethics oversight would allow point-of-care trials to structure these spontaneous randomizations, using widely available informatics tools, in combination with opt-out informed consent where deemed appropriate.

Researchers in Switzerland and Australia conducted a clinical trial to find out if a fast molecular resistance test of Gram-positive cocci would allow physicians to initiate a targeted therapy with beta-lactams more quickly instead of starting with an empiric therapy with vancomycin. The researchers conclude that rapid determination of methicillin resistance in staphylococcal bacteraemia is accurate and significantly reduces the time to targeted antibiotic therapy in the subgroup of S. aureus, thereby avoiding unnecessary exposure to vancomycin. The study was published in ESCMID’s journal Clinical Microbiology and Infection.

Researchers in Lyon studied the incidence and prevalence of hepatitis B virus (HBV) infection in a large sentinel cohort to evaluate the epidemiology of HBV during vaccination policy changes. The HBV incidence fluctuated between 5 and 8 per 1,000 person-years in pre-1986 birth-cohorts, decreased to 2.1 in birth-cohorts 1986 to 1991 and rebounded to 5 in post-1991 birth-cohorts. The authors of the study concluded that the HBV incidence was ‘remarkably high’ in young adults with noticeable variations concomitantly to vaccination policy changes. A dramatic decline in immunization rate was temporally associated with a sharp rebound of infection after withdrawal of systematic adolescent vaccination in 1998, the researchers wrote in their paper published in CMI

Researchers at the Rambam Medical Center in Haifa, Israel, assessed the pros and cons of circumcision. Adult circumcision decreases the rate of HIV acquisition among men in settings with a high incidence of HIV and therefore indirectly reduces women’s risk of exposure. Deciding whether to perform the procedure is easier for people residing in areas with high prevalence of STIs, including HIV, and for those who choose to be circumcised or have their children circumcised on religious, social, or cultural grounds. For many others, a definite pro or con recommendation, based on a risk-benefit ratio, cannot be made. 

Last update: 03 January 2017

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