ESCMID Publications

ESCMID Panorama

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]post.tau.ac.il.

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

 

Portraits of some top CMI reviewers:

Onya Opota, Institute of Microbiology, University Hospital of Lausanne

Jean-Yves Madec, Agence Nationale de Sécurité Sanitaire (Anses), Lyon, France

Werner Zimmerli, Interdisciplinary Unit for Orthopaedic Infections, KS Liestal, Switzerland

Editor's selection of recent papers published in CMI

Short-term adjunctive treatment with aminoglycosides in critically ill patients is advocated in guidelines for the empirical treatment of sepsis, despite a lack of evidence from randomized trials. A large observational study recently reported more nephrotoxicity and a trend towards worse patient outcome in critically ill patients receiving aminoglycosides added to beta-lactam antibiotics. In this commentary published in CMI researchers from the Netherlands and the U.K. discuss if a randomized controlled trial (RCT) to obtain a more definite answer is justified and how it could be performed. The authors call for a large, pragmatic, multi-centre RCT with a careful design that ensures optimal treatment during the trial and a pro-active Data Safety Monitoring Board that monitors harm and benefit and can recommend trial termination for safety reasons. “For too long our specialty has sat on its hands over this and similar questions, thereby failing to embrace evidence-based medicine and the need for RCTs to address our common clinical questions,” the authors conclude.

Unemo et al investigated the increasing resistance of Mycoplasma genitalium (MG) to current first- and second-line treatment (azithromycin and moxifloxacin resp.) and estimated the prevalence of MG, Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) in 5,269 patients located in Denmark, Sweden and Norway. First, they compared the sensitivity and specificity of the new Aptima CE/IVD AMG test, with that of the MG Alt TMA-1 test and mgpB qPCR for pathogen detection. Sensitivity ranged between 99.13-100%, 99.13-100% and 73.24-82.60% respectively; the specificity ranged between 99.57-99.96%, 100% and 99.69-100% respectively. Second, they found the prevalence of MG infection was 7.2% (382/5269); that of azithromycin and moxifloxacin resistance-associated gene mutations was 41.4% (120/290; 17.7%-56.6%) and 6.6% (18/274; 4.1-10.2%) resp. The prevalence of CT and NG over the entire patient group was not given. The authors emphasized the importance of using validated and quality-assured molecular tests for MG detection, routine testing of MG-positive samples as well as surveillance of antimicrobial resistance.

Researchers in the U.S. compared newer glycopeptide antibiotics active against methicillin-resistant Staphylococcus aureus (MRSA) – telavancin, dalbavancin and oritavancin – to each other and standard care for the treatment of complicated skin and soft tissue infections (cSSTIs). Head-to-head comparisons showed no difference in clinical response between oritavancin, dalbavancin and telavancin. Telavancin had a higher incidence of overall adverse events compared to standard care, and compared to dalbavancin and oritavancin. Cost analyses demonstrated that dalbavancin and oritavancin were less costly compared to standard care. The use of dalbavancin could save third-party payers $1,442 to $4,803 per cSSTI, while oritavancin could save $3,571 to $6,932 per cSSTI. The researchers concluded that dalbavancin and oritavancin demonstrate efficacy and safety comparable to standard care and result in cost savings when standard care is treatment that covers MRSA.

Researchers systematically reviewed publicly available information on the scientific impact of the Ebola epidemic. They conclude that the Ebola outbreak had a significant scientific impact and resulted in high impact factor numbers. The main impact could be measured in the Americas and Europe, and was directly related to funding. African researchers were only marginally involved in the scientific processing (86.6% of all researchers were not African), perhaps due to the fact that major research centres are located in America and Europe. This emphasizes the importance of promoting closer cooperation between regions.

The ESCMID group for Lyme borreliosis, ESGBOR, published a position paper on the diagnosis of the tick-borne infection caused by Borrelia burgdorferi sensu lato. The most frequent clinical manifestations Lyme borreliosis (LB) are erythema migrans and Lyme neuroborreliosis. Currently, a large volume of diagnostic testing for Lyme borreliosis is reported, whereas the incidence of clinically relevant disease manifestations is low. This indicates overuse of diagnostic testing for LB with implications for patient care and cost effective health management. The recommendations provided in this review are intended to support both the clinical diagnosis and initiatives for a more rational use of laboratory testing in patients with clinically suspected Lyme borreliosis.

The main recommendations according to current European case definitions for Lyme borreliosis are as follows: Typical erythema migrans should be diagnosed clinically and does not require laboratory testing, the diagnosis of Lyme neuroborreliosis requires laboratory investigation of the spinal fluid including intrathecal antibody production for, and the remaining disease manifestations require testing for antibodies to Borrelia burgdorferi. Testing individuals with non-specific subjective symptoms is not recommended because of a low positive predictive value.

Researchers in France characterized prophage sequences in 14 isolates, representative of the major lineages, from a collection of 275 human group B Streptococcus isolates. PCR-based detection of prophages revealed the presence of at least one prophage in 72.4% of the 275 isolates and a significant association between neonatal infecting isolates and prophages C, and between adult infecting isolates and prophages A. The results suggest that prophages (possibly animal-associated) have conditioned bacterial adaptation and ability to cause infections in neonates and adults, and support a role of lysogeny with the emergence of GBS as a pathogen in human, the researchers concluded.

Despite the increase in software solutions for metagenomics, integration of metagenomics in clinical care, which requires method standardization and validation, is lacking. Motro and Moran-Gilad developed a novel computer module, microbial metagenomics mock scenario-based sample simulation (M3S3). The module was tested by generating virtual shotgun metagenomic samples for ten challenging infectious disease scenarios. For all scenarios, the 80 generated samples showed sequence compositions as predicted from user input. Spiked pathogen sequences were identified with most of the replicates and exhibited acceptable abundance, with slight differences between software tools. The authors conclude that the M3S3 tool can support the development and validation of standardized metagenomics applications in diagnostic workflows of clinical microbiology laboratories.

In a multi-centre observational cohort study (US and Canada), 1,832 hospitalized patients with Gram-negative bloodstream infections were evaluated to assess the utility of using prior microbiologic results to guide empiric treatment. The study found that 28% (504/1,832) of the patients had a documented prior Gram-negative organism from a non-screening culture within the previous 12 months. Antibiotic resistance of that organism was strongly predictive of the current organism’s resistance to the same antibiotic. The test attained an overall specificity of 0.92 (95% CI; 0.91-0.93; range 0.77 to 0.98) and a positive predictive value of 0.66 (95% CI;0.61-0.70; range 0.43 to 0.78) for predicting antibiotic resistance.
The authors conclude that in patients with a Gram-negative bloodstream infection, the most-recent prior Gram-negative organism resistant to a drug of interest (within the last 12 months) is highly specific for resistance and should preclude use of that antibiotic.

Due to the lack of clarity, EUCAST proposes to change the definition and usefulness of the susceptibility category “intermediate”. The proposed 2017 definition is formulated as follows: A microorganism is categorized as intermediate when there is a high likelihood of therapeutic success because exposure is enhanced (1) by adjusting the dosing regimen or (2) because the antimicrobial agent is concentrated at the site of infection. The proposal for the new definition is open for feedback from the public. Using this form, comments (with supporting data or references) can be sent to John Turnidge until 15 September 2017. For further information, please refer to the EUCAST website.

Members of EPI-NET, COMBACTE-NET and the EUCIC group for SUSPIRE published a systematic review, which evaluated healthcare-associated infections (HAIs) and antimicrobial resistance (AMR) indicators of 56 surveillance systems in 20 countries across Europe. Of these surveillance systems, 33 (58.9%) targeted HAIs, 45 (80.3%) AMR and 22 targeted both. The most frequent indicator of AMR was the proportion of resistant isolates (27/34 providing information; 79.42%); incidence rates were included in 18 (52.9%) systems. For HAIs in ICUs, 22 (100%) systems included data on central line-associated bloodstream infections, 19 (86.3%) included information on ventilator-associated pneumonia and catheter-associated urinary tract infections. Incidence density was the most frequent indicator in these types of infections. Regarding surgical site infections, the most frequent procedures included were hip prosthesis, colon surgery and caesarean section (21/22 systems; 95.5% of the systems). The authors conclude that publicly available information about the methods and indicators of surveillance systems is still frequently lacking and that there is a wide heterogeneity in procedures and indicators reported.

Bartoletti et al. investigated the epidemiology of bloodstream infections (BSI), predictors of 30-day mortality and risk factors for antibiotic resistance (multi-drug resistant organisms, [MDRO]) in patients with liver cirrhosis. BSI were caused by Gram-negative bacteria (53%), Gram-positive bacteria (47%) and Candida spp. (7%). Cox-regression analysis revealed that the 30-day mortality rate (25%) associated independently with delayed antibiotic treatment, inadequate empirical therapy and the CLIF-SOAF score. Independent risk factors (31% of BSIs) included previous antimicrobial exposure and previous invasive procedures. Spontaneous bacterial peritonitis as BSI source was associated with lower odds of MDRO infections. The authors urge to improve prevention and treatment strategies for MDRO in liver cirrhosis patients, as such infections account for nearly one third of all BSI in these patients and often result in delayed or inadequate empirical antimicrobial therapy and increased mortality rates.

A recent review by Morel et al assessed the potential contribution of a health economic analysis to a sustainable use of antibiotics. The authors found incomplete and short-term economic considerations, underpinning current antibiotic strategies, which contribute to suboptimal use. In addition, the study stresses that current incentives driving antibiotic sales and inappropriate prescribing practices should be disentangled to make way for sustainable use policies. Payment structures can be used to re-align incentives and promote optimal prescribing and sustainable use in general. Specifically, eliminating or altering reimbursement differentials will help to steer clinical practice more deliberately towards the minimization of selection pressure and corresponding levels of antibiotic resistance. Overall, this work highlights the need for appropriately designed cost-effectiveness analyses, incentives analyses and novel remuneration systems to underpin sustainable use policies both within and beyond the health sector.

Pegylated interferon (PEG-IFN) is used to induce a sustained off-treatment response and clear hepatitis B surface antigens (HBsAg) in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). Chuaypen et al. investigated the role of serum hepatitis B core-related antigen (HBcrAg) kinetics in predicting the outcome of PEG-IFN based therapy in HBeAg-negative CHB patients. Persistent virological remission (PVR) and HBsAg clearance at 3-year post-treatment was 29% (35/121) and 9% (11/121) respectively. Baseline HBcrAg correlated with HBV DNA and cccDNA, but not with HBsAg. Baseline HBsAg, and a decline in HBsAg and HBcrAg were associated with PVR, while a decline in HBsAg was predictive of HBsAg clearance. High baseline antigen levels (HBsAg ≥3.4 log10 IU/mL plus HBcrAg ≥3.7 log10 IU/mL) yielded high negative predictive values (NPV) of PVR (45/50; 90%) and HBsAg clearance (50/50, 100%). At week 12, declines of HBsAg, HBcrAg and combined both antigen levels <0.5 log10 yielded NPVs for PVR of 90% (71/79), 82% (61/74) and 96 (48/50), respectively. These results suggest that HBcrAg levels are associated with cccDNA and that HBcrAg and that the amounts of HBs Ag, could help identify patients with low probability of PVR and HBsAg clearance during long-term follow-up.

Preoperative screening and treatment of asymptomatic bacteriuria in periprosthetic joint infection after primary knee or hip replacement seems not required as a retrospective study by the Tampere University Hospital shows. Meeri Honkanen et al. identified patients who had undergone a primary hip or knee replacement between September 2002 and December 2013 from the hospital database (23 171 joint replacements, 10 200 hips, and 12 971 knees). Patients with subsequent PJI or superficial wound infection in a one-year follow-up period were identified based on prospective infection surveillance. The association between bacteriuria and PJI was examined using a multivariable logistic regression model. The incidence of PJI was 0.68% (n=158). Preoperative bacteriuria was not associated with an increased risk of PJI either in the univariate (0.51% vs. 0.71%, OR 0.72, 95% CI 0.34 – 1.54) or in the multivariable (OR 0.82, 95% CI 0.38 – 1.77) analysis. There were no cases where PJI was caused by a pathogen identified in the preoperative urine culture. During the study, the influence of possible confounding factors, especially chronic diseases, was taken into account extensively.

An ESGAP expert commentary in Clinical Microbiology and Infection discussed the urgent need to plan and fund teams of specialist health workers to promote appropriate antibiotics use. Ideally, such teams should consist of ID specialists, microbiologists, nurses and pharmacists. Together, their collaborative effort can improve diagnosis and treatment of infections as well as prevent the rise of drug-resistant bacteria. 

Link to the full press release  and the expert opinion piece

In 2012, the pneumococcal conjugated vaccine 10 was introduced into the national immunization schedule in Fiji. As part of an annual cross-sectional S. pneumoniae carriage survey, researchers in Australia and the UK detected 106 samples serotyped as ‘11F-like’ by microarray. Genomic DNA extraction and subsequent sequencing of these samples revealed a phylogenetic divergence in the wcwC and wcrL genes of the 11F-like cps locus and single nucleotide insertions within a homopolymeric region of the gct gene. These changes affected the antigenic properties of the capsule such that 11F-like isolates were serotyped as 11A by Quellung and latex agglutination. The authors propose that these isolates are a novel genetic variant of the S. pneumonia serotype 11A. Their findings have implications for invasive pneumococcal disease surveillance and studies investigating vaccine impact.

Zika virus (ZIKV) transmission through semen donation has never been reported but the risk is supported by the detection of ZIKV in semen and the demonstration of sexual transmission. Researchers of the Recipient Epidemiology and Donor Evaluation Study (REDS-III) ZIKV Study Group tested longitudinally collected semen samples provided by asymptomatic blood donors who tested positive for ZIKV RNA in plasma during ZIKV outbreaks in Puerto Rico and Florida in 2016. They concluded that a high percentage of detection of ZIKV RNA in the semen of asymptomatic men confirm that ZIKV is a new threat for reproductive medicine and should have important implications for assisted reproductive technology. They recommend that semen donations from men at risk for ZIKV infection should be tested for ZIKV RNA, regardless of symptoms of ZIKV infection.

Ursula Theuretzbacher urges the scientific community to use the term ‘innovation’ in a narrower sense in the context of research and development into novel antibiotics. The term is traditionally used in a broader sense to describe any novel class of drugs, target or mode of action. Regarding antimicrobials, however, she proposes to restrict the term to drugs that possess the potential to tackle resistance, i.e. compounds that are unlikely to be impacted by cross-resistance with existing therapies and that have a low potential for high-frequency high-level single-step resistance. An independent international expert panel should agree on the most predictive tests and detailed scientific criteria to define all biological aspects of ‘innovation’.

Researchers investigated the origin and the molecular basis for the success of ST235, the most prevalent Pseudomonas aeruginosa clone, which is frequently associated with epidemics where multidrug resistance complicates treatment. The results of the study suggest that P. aeruginosa ST235 has become prevalent across the globe potentially due to the selective pressure of fluoroquinolones. The researchers also found that the ST235 clone readily became resistant to aminoglycosides, beta-lactams, and carbapenems through mutation and acquisition of resistance elements among local populations.

The ESCMID Study Group for Infections in Compromised Hosts (ESGICH) contributed to a multinational study assessing the risk factors for the development of late-onset invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT). The researchers showed that more than half of IPA cases after KT occur beyond the sixth month, with some of them presenting very late. Late IPA entails a poor prognosis. They identified some risk factors (post-transplant immunosuppression-related events such as serious/opportunistic infection or de novo malignancy) that could help the clinician to delimit the subgroup of KT recipients at the highest risk for late IPA.

Vancomycin is currently the primary option treatment for methicillin-resistant Staphylococcus aureus (MRSA). However, an increasing number of MRSA isolates with high minimum inhibitory concentrations (MICs) within the susceptible range (vancomycin MIC creep), are being reported worldwide. The researchers at the University of Aveiro in Portugal conducted a meta-analysis to assess the evidence of vancomycin MIC creep, but they could not find any evidence of the MIC creep phenomenon.

Routine testing for pyrazinamide (PZA) resistance in tuberculosis cases is currently not performed due to drug stability and test-related handling issues and is further complicated by (highly diverse) mutations scattered along the length of the pncA gene, not all equally associated with PZA resistance. The performance of a new line probe assay (LPA), targeting a 700 bp fragment covering the entire pncA gene and part of its promoter region, was compared to a composite reference standard using a panel of 97 Mycobacterium tuberculosis isolates from various sources. For survey isolates, the test reached an overall agreement with the composite reference standard of 97.6% (80/82) excluding or 94.3% (82/87) including heteroresistant isolates. The test failed on 8.5% (5/9) of the clinical samples, but among valid results, 100% (14/14) sensitivity and 100% (7/7) specificity was attained compared to pncA Sanger sequencing. The authors conclude that the new test offers a valid molecular alternative for rapid and indirect PZA susceptibility testing, but requires further evaluation to assess the clinical risk of missing heteroresistance and falsely detecting lineage-specific, silent and non-associated mutations.

Two recent reports investigating human cases of psittacosis in Australia have uncovered a new role for Chlamydia psittaci, in equine reproductive disease and zoonoses. C. psittaci is traditionally an avian pathogen and cause of atypical pneumonia in humans associated with direct contact with infected birds. A cohort study of a cluster of human cases revealed that contact with the foetal membranes of a mare was the main risk factor. Subsequent molecular investigation revealed that the equine tissue was infected with a highly pathogenic avian strain of C. psittaci associated with infections in parrots throughout the world and serious zoonoses. Like other wildlife-borne diseases in Australia such as Hendra, this study reveals that chlamydial pathogen spill-over to horses is possible and that human contact with infected horses is a public health threat that needs to be considered by veterinarians and human physicians alike. [For access to the article you need to be a member/subscriber.]

Researchers working for the Infection Control Programme at the Geneva university hospitals assessed the quality of evidence provided by studies investigating antimicrobial stewardship (AMS) interventions. The authors conclude that future studies assessing the impact of new AMS strategies should produce compelling evidence by opting for cluster randomized clinical trials or controlled interrupted time series including a control arm. Furthermore, a holistic view of intended and unintended consequences should be reported, and a detailed process evaluation should be provided to adequately inform implementation of successful AMS strategies to battle the rising burden of antimicrobial resistance.

Currently there are no European and/or international recommendations regarding the legislative aspects of Faecal Microbiota Transplantation (FMT) products to treat recurrent Clostridium difficile infections (CDI). Researchers in the Netherlands published a review describing how they established the Netherlands Donor Feces Bank (NDFB) for standardised FMT products. They describe NDFB protocols for donor recruitment, donor selection, donor screening, as well as production, preparation, storage, distribution and transfers of the faecal suspension between various countries and institutions.

Researchers in China assessed the current working conditions and problems faced by ID professionals in their country. Almost all hospitals had ID wards and 9 out of 10 provided outpatient consultations. Specialised training was available 4 out of 5, and ID research was performed in about 70% of departments. The ratio of patient beds to doctors was 5:1, and of patient beds to nurses 5:1.85. The main service provided by ID physicians was the management of legally notifiable communicable diseases. Most of the physicians surveyed earned less than $15,000. Four out of five felt high or very high pressure in their work, and less than half were satisfied or very satisfied with their jobs. The limited medical service provided by ID physicians is poorly aligned with current healthcare demands, the authors concluded. Moreover, the heavy workloads, high stress, poor compensation, and limited career prospects for ID physicians in China impede the continued development of specialists and put them into a career dilemma. ID physicians should work to develop and diversify the field and to enhance their capacities by learning new technologies and collaborating with other disciplines.

ESCMID’s study group on antibiotic policies ESGAP published a paper on the access to older antibiotics in the journal Clinical Microbiology and Infection. The study showed that antibiotics used to treat a variety of common bacterial infections are becoming more difficult to access, mostly because the drugs are less profitable for manufacturers to produce and market. ESGAP conducted the study with researchers from Action on Antibiotic Resistance (ReAct), the International Society of Chemotherapy, the British Society for Antimicrobial Chemotherapy (BSAC) and the French Infectious Diseases society (SPILF). Have a look at the paper in CMI and the press release.

Researchers in Australia examined if men who have sex with men (MSM) without urethritis symptoms should be screened for urethral gonorrhoea. They used sensitive nucleic acid amplification testing to assess the rate of asymptomatic urethral gonorrhoea in MSM attending a sexual health centre for sexually transmitted infection screening. The study showed that about one in ten of those with positive urine tests reported no symptoms. The findings support guidelines that recommend screening asymptomatic MSM for urethral gonorrhoea.

Researchers from Japan compared the effectiveness and safety of empiric antipseudomonal beta-lactam monotherapy for febrile neutropenia. The meta-analysis of 50 studies with 10,872 patients showed that imipenem/cilastatin showed the highest odds of treatment success without modification and that ceftazidime in comparison was related to lower treatment success rate. Imipenem/cilastatin showed the lowest odds of all-cause death, while patients treated with cefepime in comparison had a higher risk for all-cause death. The authors concluded that imipenem/cilastatin, piperacillin/tazobactam, and meropenem are reasonable first-choice medications for empiric therapy of febrile neutropenia.

Researchers evaluated if experts followed international guidelines in the antibiotic treatment of infective endocarditis (IE). They found that global compliance with guidelines concerning antibiotic therapy was 58%, revealing the differences between theoretical ‘consensus’, local recommendations and actual practice. The adherence to guidelines was 100% when the protocol was simple, and decreased with the seriousness of the situation or in blood-culture-negative endocarditis that requires adaptation to clinical and epidemiological data. The authors conclude that experts in IE management do not follow international consensus guidelines regarding antibiotic use, although most of them were involved in the development of the guidelines.

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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