Machine learning for clinical decision support in infectious diseases: a narrative review of current applications

BackgroundMachine learning (ML) is a growing field in medicine. This narrative review describes the current body of literature on ML for clinical decision support in infectious diseases (ID).ObjectivesWe aim to inform clinicians about the use of ML for diagnosis, classification, outcome prediction and antimicrobial management in ID.SourcesReferences for this review were identified through searches of MEDLINE/PubMed, EMBASE, Google Scholar, biorXiv, ACM Digital Library, arXiV and IEEE Xplore Digital Library up to July 2019.ContentWe found 60 unique ML-clinical decision support systems (ML-CDSS) aiming to assist ID clinicians. Overall, 37 (62%) focused on bacterial infections, 10 (17%) on viral infections, nine (15%) on tuberculosis and four (7%) on any kind of infection. Among them, 20 (33%) addressed the diagnosis of infection, 18 (30%) the prediction, early detection or stratification of sepsis, 13 (22%) the prediction of treatment response, four (7%) the prediction of antibiotic resistance, three (5%) the choice of antibiotic regimen and two (3%) the choice of a combination antiretroviral therapy. The ML-CDSS were developed for intensive care units (n = 24, 40%), ID consultation (n = 15, 25%), medical or surgical wards (n = 13, 20%), emergency department (n = 4, 7%), primary care (n = 3, 5%) and antimicrobial stewardship (n = 1, 2%). Fifty-three ML-CDSS (88%) were developed using data from high-income countries and seven (12%) with data from low- and middle-income countries (LMIC). The evaluation of ML-CDSS was limited to measures of performance (e.g. sensitivity, specificity) for 57 ML-CDSS (95%) and included data in clinical practice for three (5%).ImplicationsConsidering comprehensive patient data from socioeconomically diverse healthcare settings, including primary care and LMICs, may improve the ability of ML-CDSS to suggest decisions adapted to various clinical contexts. Currents gaps identified in the evaluation of ML-CDSS must also be addressed in order to know the potential impact of such tools for clinicians and patients.     

Clinical characteristics of ambulatory and hospitalized patients with monkeypox virus infection: an observational cohort study

ObjectivesA global outbreak of monkeypox virus infections in human beings has been described since April 2022. The objectives of this study were to describe the clinical characteristics and complications of patients with a monkeypox infection.MethodsAll consecutive patients with a polymerase chain reaction (PCR)–confirmed monkeypox infection seen in a French referral centre were included.ResultsBetween 21 May and 5 July 2022, 264 patients had a PCR-confirmed monkeypox infection. Among them, 262 (262/264, 99%) were men, 245 (245/259, 95%) were men who have sex with men, and 90 (90/216, 42%) practiced chemsex in the last 3 months. Seventy-three (73/256, 29%) patients were living with human immunodeficiency virus infection, and 120 (120/169, 71%) patients were taking pre-exposure prophylaxis against human immunodeficiency virus infection. Overall, 112 (112/236, 47%) patients had contact with a confirmed monkeypox case; it was of sexual nature for 95% of the contacts (86/91). Monkeypox virus PCR was positive on the skin in 252 patients, on the oropharyngeal sample in 150 patients, and on blood in eight patients. The majority of patients presented with fever (171/253, 68%) and adenopathy (174/251, 69%). Skin lesions mostly affected the genital (135/252, 54%) and perianal (100/251, 40%) areas. Overall, 17 (17/264, 6%) patients were hospitalized; none of them were immunocompromised. Complications requiring hospitalization included cellulitis (n = 4), paronychia (n = 3), severe anal and digestive involvement (n = 4), non-cardia angina with dysphagia (n = 4), blepharitis (n = 1), and keratitis (n = 1). Surgical management was required in four patients.ConclusionThe current outbreak of monkeypox infections has specific characteristics: it occurs in the men who have sex with men community; known contact is mostly sexual; perineal and anal areas are frequently affected; and severe complications include superinfected skin lesions, paronychia, cellulitis, anal and digestive involvement, angina with dysphagia, and ocular involvement.     

Clinical and microbiological features of bacteraemia with Gram-positive anaerobic cocci: a population-based retrospective study

ObjectivesGram-positive, anaerobic cocci (GPAC) can cause infections in humans. Only a few cases of bacteraemia with GPAC have been reported. We describe the clinical and microbiological characteristics of GPAC bacteraemia.MethodsA retrospective population-based study of GPAC bacteraemia 2012–2016 in southern Sweden was performed. GPAC were identified using matrix-associated laser desorption ionization time-of-flight mass spectrometry or 16S rRNA gene sequencing. Etests were used to determine antibiotic susceptibilities. Data on patient and infection characteristics, treatment, and outcome were collected from the medical records.ResultsA total of 226 episodes of GPAC bacteraemia in adults were studied; this corresponds to an annual incidence of 3.4 cases per 100,000 persons per year. The bacteria identified were Anaerococcus spp. (n = 43), Atopobium spp. (n = 7), Blautia spp. (n = 1), Finegoldia spp. (n = 15), Parvimonas spp. (n = 100), Peptoniphilus spp. (n = 52), Peptostreptococcus spp. (n = 2), and Ruminococcus spp. (n = 9) of which 200 isolates were identified to the species level. Resistance to imipenem and piperacillin was not identified, whereas resistance among the 229 isolates to penicillin was detected in four, to metronidazole in six, and clindamycin in 16 isolates. The median age of patients was 73 years (55–83, IQR), 57% were male and comorbidities were common. Fifty-one per cent of infections were polymicrobial. In 60% of cases a focus of infection was identified. Forty per cent of patients had either organ dysfunction or shock. The 30-day mortality was 11%, and nosocomial infections were over-represented among the deceased.ConclusionsGPAC bacteraemia is much more common than previously reported. GPAC-bacteraemia is a condition with significant mortality mainly affecting elderly persons with comorbidities.     

Histopathological features of systemic sclerosis-associated myopathy: A scoping review

BackgroundScleromyositis (SM) is an emerging subset of myositis associated with features of systemic sclerosis (SSc) but it is currently not recognized as a distinct histopathological subset by the European NeuroMuscular Center (ENMC). Our aim was to review studies reporting muscle biopsies from SSc patients with myositis and to identify unique histopathological features of SM.MethodsA scoping review was conducted and included all studies reporting histopathological findings in SSc patients with myositis searching the following databases: PubMed, MEDLINE, EMBASE, CINAHL and EBM-Reviews. Clinical, serological, and histopathological data were extracted using a standardized protocol.ResultsOut of 371 citations, 77 studies that included 559 muscle biopsies were extracted. Fifty-seven percent (n = 227/400) had inflammatory infiltrates, predominantly T cells, which were endomysial (49%), perimysial (42%) and perivascular (41%). Few studies (18%, n = 8/44) evaluated the presence of B-cells. Myofiber atrophy was present in 48% (n = 104/218) of biopsies, and was predominantly perifascicular in 19% (n = 6/31), with necrosis reported in 56% (n = 162/290) of cases. Sarcolemmal MHC-I upregulation was found in 72% (n = 64/89) of biopsies. Non-specified C5b-9 deposition was described in 39% of muscle biopsies (n = 28/72). Neurogenic features were present in 23% (n = 44/191); endomysial fibrosis was reported in 35% (n = 120/340); and rimmed vacuoles were observed in 32% (n = 11/34) of biopsies. Capillaropathy, such as capillary dropout and/or ultrastructural endothelial abnormalities, was reported in 33% (n = 43/129) of cases. Reported ENMC categories were mainly polymyositis (21%), non-specific myositis (19%), immune-mediated necrotizing myopathy (16%), and dermatomyositis (8%). Histopathological features were analyzed according to serological subtypes in 28 studies, including anti-PM-Scl (n = 48), -Ku (n = 23) and -U1RNP (n = 90). Most of these biopsies demonstrated inflammatory infiltrates (range 49–85%) as well as MHC-I expression (range 63–81%). Necrosis was associated with anti-Ku (85%) and anti-U1RNP (73%), while anti-Ku was also associated with neurogenic features and rimmed vacuoles in 57% and 25% of cases, respectively.ConclusionOur review suggests that SM is characterized by heterogeneous pathological features using definitions included in current histopathological criteria. Whether a distinct histopathological signature exists in SM remains to be determined. SSc-specific and SSc-associated autoantibodies may help define more homogeneous histopathological subsets.     

Bacterial and fungal coinfection among hospitalized patients with COVID-19: a retrospective cohort study in a UK secondary-care setting

ObjectivesTo investigate the incidence of bacterial and fungal coinfection of hospitalized patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in this retrospective observational study across two London hospitals during the first UK wave of coronavirus disease 2019 (COVID-19).MethodsA retrospective case series of hospitalized patients with confirmed SARS-CoV-2 by PCR was analysed across two acute NHS hospitals (20 February–20 April 2020; each isolate reviewed independently in parallel). This was contrasted to a control group of influenza-positive patients admitted during the 2019–2020 flu season. Patient demographics, microbiology and clinical outcomes were analysed.ResultsA total of 836 patients with confirmed SARS-CoV-2 were included; 27 (3.2%) of 836 had early confirmed bacterial isolates identified (0–5 days after admission), rising to 51 (6.1%) of 836 throughout admission. Blood cultures, respiratory samples, pneumococcal or Legionella urinary antigens and respiratory viral PCR panels were obtained from 643 (77%), 110 (13%), 249 (30%), 246 (29%) and 250 (30%) COVID-19 patients, respectively. A positive blood culture was identified in 60 patients (7.1%), of which 39 were classified as contaminants. Bacteraemia resulting from respiratory infection was confirmed in two cases (one each community-acquired Klebsiella pneumoniae and ventilator-associated Enterobacter cloacae). Line-related bacteraemia was identified in six patients (three Candida, two Enterococcus spp. and one Pseudomonas aeruginosa). All other community-acquired bacteraemias (n = 16) were attributed to nonrespiratory infection. Zero concomitant pneumococcal, Legionella or influenza infection was detected. A low yield of positive respiratory cultures was identified; Staphylococcus aureus was the most common respiratory pathogen isolated in community-acquired coinfection (4/24; 16.7%), with pseudomonas and yeast identified in late-onset infection. Invasive fungal infections (n = 3) were attributed to line-related infections. Comparable rates of positive coinfection were identified in the control group of confirmed influenza infection; clinically relevant bacteraemias (2/141; 1.4%), respiratory cultures (10/38; 26.3%) and pneumococcal-positive antigens (1/19; 5.3%) were low.ConclusionsWe found a low frequency of bacterial coinfection in early COVID-19 hospital presentation, and no evidence of concomitant fungal infection, at least in the early phase of COVID-19.     

The association between antimicrobial resistance and HIV infection: a systematic review and meta-analysis

ObjectivesPeople living with HIV (PLWH) are at increased risk of infections with resistant organisms due to more frequent healthcare utilization. Our objective was to investigate the association between HIV and antimicrobial resistance (AMR).MethodsWe searched MEDLINE, EMBASE, Web of Science, LILACS and African Journals Online. Studies were eligible if they reported on AMR for colonization or infection with bacterial pathogens (excluding mycobacteria and bacteria causing sexually transmitted infections) and were stratified by HIV status, species and antimicrobials tested. Pooled odds ratios were used to evaluate the association between HIV and resistance.ResultsIn total, 92 studies published between 1995 and 2020 were identified. The studies included the following organisms: Staphylococcus aureus (n = 47), Streptococcus pneumoniae (n = 28), Escherichia coli (n = 6) and other Gram-negative bacteria. PLWH had a 2.12 (95%CI 1.36–3.30) higher odds for colonization and 1.90 (95%CI 1.45–2.48) higher odds for infection with methicillin-resistant S. aureus, a 2.28 (95%CI 1.75–2.97) higher odds of infection with S. pneumoniae with decreased penicillin susceptibility, and a 1.59 (95%CI 0.83-3.05) higher odds of resistance to third-generation cephalosporins in E. coli and Klebsiella pneumoniae.ConclusionThis review shows an increased risk of AMR in PLWH across a range of bacterial pathogens and multiple drug classes. The lack of laboratory capacity for identifying AMR, and limited access to alternative treatment options in countries with the highest burden of HIV, highlight the need for more research on AMR in PLWH. Overall, the quality of studies was moderate or low, which may impact the findings of this review.     

Origin and characteristics of haematogenous periprosthetic joint infection

ObjectivesRecognition of infectious origin of haematogenous periprosthetic joint infections (PJI) is crucial. We investigated the primary focus and characteristics of haematogenous PJI.MethodsConsecutive patients who presented with haematogenous PJI between 01/2010 and 01/2018 were retrospectively analysed. Haematogenous PJI was defined by diagnosis of infection ≥1 month after surgery, acute manifestation after a pain-free period and positive blood or prosthetic-site culture and/or evidence of distant infectious focus consistent with the pathogen. Fisher's exact, Student's t and Mann–Whitney U tests were used, as appropriate.ResultsA total of 106 episodes of PJI were included, involving 59 knee, 45 hip, one shoulder and one elbow prostheses. The median time from last surgery until haematogenous PJI was 47 months (range, 1–417 months). The pathogen was identified in 105 episodes (99%), including Staphylococcus aureus (n = 43), streptococci (n = 32), enterococci (n = 13), Gram-negative bacteria (n = 9) and coagulase-negative staphylococci (n = 8). Gram-negative bacteria were significantly more often found in hip joints than in knee joints. Blood cultures grew the pathogen in 43 of 70 episodes (61%). The primary infectious focus was identified in 72 episodes (68%) and included infections of intravascular devices or heart valves (22 episodes), skin and soft tissue (16 episodes), the oral cavity (12 episodes), urogenital (12 episodes) or gastrointestinal tract (seven episodes) and other sites (three episodes).ConclusionsIn acute PJI manifesting after a pain-free period, the haematogenous infection route should be considered and the primary infectious focus should be actively searched for. The cardiovascular system, skin and soft tissue, oral cavity, urogenital and gastrointestinal tracts were common origins of haematogenous PJI.     

Severe infections in patients with anti-neutrophil cytoplasmic antibody-associated vasculitides receiving rituximab: A meta-analysis

IntroductionThe efficacy of rituximab (RTX) for remission induction and maintenance in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) is now established, but the safety, particularly concerning severe infection risk, is not well known.ObjectiveThe purpose of this meta-analysis is to assess the prevalence and incidence of severe infections and the factors explaining heterogeneity in AAV patients treated with RTX.MethodsPubMed and Embase were searched up to December 2017. Prevalence and incidence was pooled using a random-effects model in case of significant heterogeneity (I² > 50%). Severe infection was defined as severe when it led to hospitalization, intravenous antibiotics therapy, and/or death. The heterogeneity was explored by subgroup analyses and meta-regression.ResultsThe included studies encompassed 1434 patients with a median age of 51.9 years. The overall prevalence and incidence of severe infections was 15.4% (95% CI [8.9; 23.3], I² = 90%, 33 studies) and 6.5 per 100 person-years (PY) (95% CI [2.9; 11.4], I² = 76%, 18 studies), respectively. The most common infections were bacterial (9.4%, 95% CI [5.1; 14.8]). The prevalence of opportunistic infection was 1.5% (95% CI [0.5; 3.1], I² = 58%) including pneumocytis jirovecii infections (0.2%, 95% CI [0.0; 0.6], I² = 0), irrespective of prophylaxis administration. Mortality related to infection was estimated at 0.7% (95% CI [0.2; 1.2], I² = 27%). The RTX cumulative dose was positively associated with prevalence of infections (13 studies, prevalence increase of 4% per 100 mg, p < .0001). The incidence of infection was negatively associated with duration of follow-up (8 studies, incidence decrease of 9% per year, p = .03).ConclusionPrevalence and incidence of severe infections, mainly bacterial ones, were high in AAV patients treated with RTX. This meta-analysis highlights the need for prospective studies to stratify infectious risk and validate cumulative RTX dose and duration of follow-up as modifying factors.     

Mycobacterial infections in adult recipients of allogeneic hematopoietic stem cell transplantation: A cohort study in a high endemic area

BackgroundMycobacterial infections are important and potentially life-threatening complications after organ transplantations. Notably, for the recipients of allogeneic hematopoietic stem cell transplantation (HSCT), there are a few supporting results to explore post-transplant mycobacterial infections. Taiwan is a high endemic area of the infection. We aim to investigate the incidence, risk factors, and survival of post-transplant mycobacterial infections, including mycobacterium tuberculosis (MTB) and non-tuberculous mycobacterium (NTM).MethodsWe included 422 adult patients undergoing allogeneic HSCT at an Asian tertiary medical center between January 2003 and December 2014. A total 26 subjects developed post-transplant mycobacterial infections. Risk factors, clinical features, and survival for post-transplant mycobacterial infections were collected and analyzed.ResultsPost-transplant mycobacterial infections occurred in 26 (6.2%) of 422 HSCT patients. Two-year cumulative incidences in MTB and NTM were 1.4% and 5.4%. In the multivariate analysis, being age >45 years (adjusted HR 2.21, 95% CI 1.01–4.83) and extensive chronic graft-versus-host disease (cGVHD) (adjusted HR 4.95, 95% CI 2.14–11.46) were identified as independent risk factors of infections. There was a trend as a risk factors in relapsed patients (P = 0.088). For patients with cGVHD, there was a significant difference of post-transplant survival between mycobacterial infections and none (P = 0.036). Pneumonia contributed most to mortality (n = 11, 42.3%).ConclusionMycobacterial infections are worth to note in a high endemic area. Once a high-risk group is identified, much effort is required to target new approaches for prevention, early detection and treatment of infections.     

Microbiology of hip and knee periprosthetic joint infections: a database study

ObjectivesKnowledge of the microbiological aetiology of periprosthetic joint infection (PJI) is essential to its management. Contemporary literature from the United States on this topic is lacking. This study aimed to identify the most common microorganisms associated with types of arthroplasty, the timing of infection, and clues to polymicrobial infection.MethodsWe performed an analytical cross-sectional study of patients 18 years of age or older with hip or knee PJI diagnosed at our institution between 2010 and 2019. PJI was defined using the criteria adapted from those of the Musculoskeletal Infection Society. Cases included PJI associated with primary or revision arthroplasty and arthroplasty performed at our institution or elsewhere.ResultsA total of 2067 episodes of PJI in 1651 patients were included. Monomicrobial infections represented 70% of episodes (n = 1448), with 25% being polymicrobial (n = 508) and the rest (5%, n = 111) culture-negative. The most common group causing PJI was coagulase-negative Staphylococcus species (other than S. ludgunensis) (37%, n = 761). The distribution of most common organisms was similar regardless of arthroplasty type. The S. aureus complex, Gram-negative bacteria, and anaerobic bacteria (other than Cutibacterium species) were more likely to be isolated than other organisms in the first year following index arthroplasty (OR 1.7, 95%CI 1.4–2.2; OR 1.5, 95%CI 1.1–2.0; and OR 1.5, 95%CI 1.0–2.2, respectively). The proportion of culture-negative PJIs was higher in primary than revision arthroplasty (6.5% versus 3%, p 0.0005). The presence of a sinus tract increased the probability of the isolation of more than one microorganism by almost three-fold (OR 2.6, 95%CI 2.0–3.3).ConclusionsJoint age, presence of a sinus tract, and revision arthroplasties influenced PJI microbiology.     

Identifying isoniazid resistance markers to guide inclusion of high-dose isoniazid in tuberculosis treatment regimens

ObjectivesEffective use of antibiotics is critical to control the global tuberculosis pandemic. High-dose isoniazid (INH) can be effective in the presence of low-level resistance. We performed a systematic literature review to improve our understanding of the differential impact of genomic Mycobacterium tuberculosis (Mtb) variants on the level of INH resistance. The following online databases were searched: PubMed, Web of Science and Embase. Articles reporting on clinical Mtb isolates with linked genotypic and phenotypic data and reporting INH resistance levels were eligible for inclusion.MethodsAll genomic regions reported in the eligible studies were included in the analysis, including: katG, inhA, ahpC, oxyR-ahpC, furA, fabG1, kasA, rv1592c, iniA, iniB, iniC, rv0340, rv2242 and nat. The level of INH resistance was determined by MIC: low-level resistance was defined as 0.1–0.4 μg/mL on liquid and 0.2–1.0 μg/mL on solid media, high-level resistance as >0.4μg/mL on liquid and >1.0 μg/mL on solid media.ResultsA total of 1212 records were retrieved of which 46 were included. These 46 studies reported 1697 isolates of which 21% (n = 362) were INH susceptible, 17% (n = 287) had low-level, and 62% (n = 1048) high-level INH resistance. Overall, 24% (n = 402) of isolates were reported as wild type and 76% (n = 1295) had ≥1 relevant genetic variant. Among 1295 isolates with ≥1 variant, 78% (n = 1011) had a mutation in the katG gene. Of the 867 isolates with a katG mutation in codon 315, 93% (n = 810) had high-level INH resistance. In contrast, only 50% (n = 72) of the 144 isolates with a katG variant not in the 315-position had high-level resistance. Of the 284 isolates with ≥1 relevant genetic variant and wild type katG gene, 40% (n = 114) had high-level INH resistance.ConclusionsPresence of a variant in the katG gene is a good marker of high-level INH resistance only if located in codon 315.     

Anti-herpesvirus prophylaxis,pre-emptive treatment or no treatment in adults undergoing allogeneic transplant for haematological disease: systematic review and meta-analysis

BackgroundHerpesviridae infections incur significant morbidity and indirect effects on mortality among allogeneic haematopoietic cell transplant (allo-HCT) recipients.ObjectivesTo study the effects of antiviral prevention strategies among haemato-oncological individuals undergoing allo-HCT.Data sourcesCochrane Central Register of Controlled Trials, MEDLINE, Embase and LILACS. We further searched for conference proceedings and trial registries.Study eligibility criteriaRandomized controlled trials (RCTs).ParticipantsAdults with haematological malignancy undergoing allo-HCT.InterventionsAntiviral prophylaxis versus no treatment/placebo or pre-emptive treatment and pre-emptive treatment versus prophylaxis with the same agent.MethodsRandom-effects meta-analysis was conducted computing pooled risk ratios (RR) with 95% CI and the inconsistency measure (I²). The certainty of the evidence was appraised by GRADE.ResultsWe included 22 RCTs. Antiviral prophylaxis reduced all-cause mortality (RR 0.83, 95% CI 0.7–0.99; 15 trials, I² = 0%), cytomegalovirus (CMV) disease (RR 0.54, 95% CI 0.34–0.85; n = 15, I² = 20%) and herpes simplex virus (HSV) disease (RR 0.29, 95% CI 0.2–0.43; n = 13, I² = 18%) compared with no treatment/placebo or pre-emptive treatment, all with high-certainty evidence. Furthermore, antivirals reduced HSV infection, CMV pneumonitis, CMV infection and varicella zoster virus disease. Anti-CMV prophylaxis (+/– pre-emptive treatment) compared with pre-emptive treatment alone reduced non-significantly all-cause mortality (RR 0.78, 95% CI 0.6–1.02; n = 8, I² = 0%), CMV disease (RR 0.47, 95% CI 0.23–0.97; n = 9, I² = 30%) and HSV disease (RR 0.41, 95% CI 0.24–0.67; n = 4, I² = 0%) with high-certainty evidence, as well as CMV and HSV infections. Antiviral prophylaxis did not result in increased adverse event rates overall or more discontinuation due to adverse events.ConclusionsAntiviral prophylaxis directed against herpesviruses is highly effective and safe, reducing mortality, HSV and CMV disease, as well as herpesvirus reactivations among allo-HCT recipients. Anti-CMV prophylaxis is more effective than pre-emptive treatment alone with respect to HSV and CMV disease and infection.     

Amoxicillin for acute lower respiratory tract infection in primary care: subgroup analysis by bacterial and viral aetiology

ObjectiveWe aimed to assess the effects of amoxicillin treatment in adult patients presenting to primary care with a lower respiratory tract infection (LRTI) who were infected with a potential bacterial, viral, or mixed bacterial/viral infection.MethodsThis multicentre randomized controlled trial focused on adults with LRTI not suspected for pneumonia. Patients were randomized to receive either antibiotic (amoxicillin 1 g) or placebo three times daily for 7 consecutive days using computer-generated random numbers (follow-up 28 days). In this secondary analysis of the trial, symptom duration (primary outcome), symptom severity (scored 0–6), and illness deterioration (reconsultation with new or worsening symptoms, or hospital admission) were analysed in pre-specified subgroups using regression models. Subgroups of interest were patients with a (strictly) bacterial, (strictly) viral, or combined infection, and patients with elevated values of procalcitonin, C-reactive protein, or blood urea nitrogen.Results2058 patients (amoxicillin n = 1036; placebo n = 1022) were randomized. Treatment did not affect symptom duration (n = 1793). Patients from whom a bacterial pathogen only was isolated (n = 207) benefited from amoxicillin in that symptom severity (n = 804) was reduced by 0.26 points (95% CI −0.48 to −0.03). The odds of illness deterioration (n = 2024) was 0.24 (95% CI 0.11 to 0.53) times lower from treatment with amoxicillin when both a bacterial and a viral pathogen were isolated (combined infection; n = 198).ConclusionsAmoxicillin may reduce the risk of illness deterioration in patients with a combined bacterial and viral infection. We found no clinically meaningful benefit from amoxicillin treatment in other subgroups.     

Listeria monocytogenes-associated respiratory infections: a study of 38 consecutive cases

ObjectivesListeria monocytogenes (Lm) is a foodborne human pathogen responsible for severe infections, including septicaemia, neurolisteriosis, and maternal–foetal and focal infections. Little is known about Lm-associated respiratory tract or lung infections.MethodsWe conducted a retrospective study of culture-proven cases of Lm pleural infections and pneumonia reported to the French National Reference Centre for Listeria from January 1993 to August 2016.ResultsThirty-eight consecutive patients with pleural infection (n = 32), pneumonia (n = 5), or both (n = 1) were studied; 71% of these were men. Median age was 72 (range 29–90). Two patients presented with concomitant neurolisteriosis. All patients but one reported at least one immunosuppressive condition (97%), with a median number of 2 (range 0–5), including 29% (8/28) with current exposure to immunosuppressive therapy and 50% (17/34) with ongoing neoplasia; 75% (21/28) reported previous pleural or pulmonary disease. Antibiotic therapy mostly consisted in amoxicillin (72%) associated with aminoglycoside in 32%. Chest-tube drainage was performed in 7/19 patients with empyema (37%); 25% of the patients (7/30) required intensive care management. In-hospital mortality reached 35% and occurred after a median time interval of 4 days (range 1–33 days). Three patients had recurrence of empyema (time interval of 1 week to 4 months after treatment completion). Altogether, only 13/31 patients (42%) diagnosed with Lm respiratory infection experienced an uneventful outcome at 2-year follow-up.ConclusionLm is a rare but severe cause of pneumonia and pleural infection in older immunocompromised patients, requiring prompt diagnosis and adequate management and follow-up.     

Estimating daily antibiotic harms: an umbrella review with individual study meta-analysis

BackgroundThere is growing evidence supporting the efficacy of shorter courses of antibiotic therapy for common infections. However, the risks of prolonged antibiotic duration are underappreciated.ObjectivesTo estimate the incremental daily risk of antibiotic-associated harms.MethodsWe searched three major databases to retrieve systematic reviews from 2000 to 30 July 2020 in any language.EligibilitySystematic reviews were required to evaluate shorter versus longer antibiotic therapy with fixed durations between 3 and 14 days. Randomized controlled trials included for meta-analysis were identified from the systematic reviews.ParticipantsAdult and paediatric patients from any setting.InterventionsPrimary outcomes were the proportion of patients experiencing adverse drug events, superinfections and antimicrobial resistance.Risk of bias assessmentEach randomized controlled trial was evaluated for quality by extracting the assessment reported by each systematic review.Data synthesisThe daily odds ratio (OR) of antibiotic harm was estimated and pooled using random effects meta-analysis.ResultsThirty-five systematic reviews encompassing 71 eligible randomized controlled trials were included. Studies most commonly evaluated duration of therapy for respiratory tract (n = 36, 51%) and urinary tract (n = 29, 41%) infections. Overall, 23 174 patients were evaluated for antibiotic-associated harms. Adverse events (n = 20 345), superinfections (n = 5776) and antimicrobial resistance (n = 2330) were identified in 19.9% (n = 4039), 4.8% (n = 280) and 10.6% (n = 246) of patients, respectively. Each day of antibiotic therapy was associated with 4% increased odds of experiencing an adverse event (OR 1.04, 95% CI 1.02–1.07). Daily odds of severe adverse effects also increased (OR 1.09, 95% CI 1.00–1.19). The daily incremental odds of superinfection and antimicrobial resistance were OR 0.98 (0.92–1.06) and OR 1.03 (0.98–1.07), respectively.ConclusionEach additional day of antibiotic therapy is associated with measurable antibiotic harm, particularly adverse events. These data may provide additional context for clinicians when weighing benefits versus risks of prolonged antibiotic therapy.     

Species distribution patterns and epidemiological characteristics of otomycosis in Southeastern Serbia

IntroductionOtomycosis, a superficial fungal infection of the external auditory canal (EAC), is a disease with exceptionally high prevalence.AimThe aim of this study was to determine the prevalence of otomycosis, the distribution of causative species and to evaluate epidemiological characteristics of these infections.MethodologyThe patients’ data were collected from record book and database of mycological examinations conducted at Public Health Institute Nis, Serbia. In the period from 2014 to 2018 samples of 1287 patients with symptoms and signs of EAC infection were investigated. Standard mycological methods were used for isolation and determination of fungi.ResultsHigh prevalence of otomycosis was determined in examined patients (22.7%). However, the prevalence rates did not differ significantly in the studied period (p = 0.931). The majority of patients were diagnosed with only unilateral EAC infection (82.9%). Considering all patients with otomycosis, mold infections caused by the genus Aspergillus (143/48.9%) were more frequent than Candida spp. ear infections (133/45.6%), with Aspergillus niger and Candida аlbicans being predominant causative agents. Mixed Aspergillus and Candida otomycosis was established in 16 (5.5%) patients. Otomycosis was more common in male subjects (26.8%, p = 0.003) who also suffered from Aspergillus otomycosis more frequently (17.5%, p < 0.001). The prevalence of these infections increases with age (p = 0.005), while they do not show seasonal pattern (p > 0.05).ConclusionNoted high prevalence of otomycosis, with both yeasts and non-dermatophyte molds acting as infectious agents which require different treatment, implies the necessity for further epidemiological monitoring of this form of superficial mycoses.     

The value of CMV IgG avidity and immunoblot for timing the onset of primary CMV infection in pregnancy

BackgroundPrimary CMV infections in pregnancy are usually asymptomatic and only detected by serology. Estimating the onset of infection is a major diagnostic goal, since primary infections around conception and in early gestation hold a higher risk for congenital disease than those in later pregnancy.ObjectivesTo assess the ability of serological supplementary CMV assays to date the onset of primary infection.Study designFrom our routine diagnosis we identified 61 pregnant women (n = 188 serum samples) with precisely determined onset of CMV primary infection either by IgG seroconversion (n = 24) or by significant IgG antibody rise (n = 37). One hundred and forty-seven sera were investigated using the VIDAS^® CMV IgG avidity EIA (BioMèrieux) and 83 sera using the recomBlot CMV IgG with avidity (Mikrogen).ResultsBoth assays proofed to be reliable in terms of timing the onset of CMV primary infection. An avidity index (AI) in the VIDAS avidity EIA of <40% indicated primary infection within the last 20 weeks (positive predictive value 93.4%; 99/106), whereas an intermediate AI excluded primary infection within the last 12 weeks (negative predictive value 88.2%; 15/17). The recomBlot showed high reliability (PPV 96.9%; 31/33) for timing the onset of infection within the last 14 weeks. Avidity testing by blot however could not be interpreted in 11 of 47 sera (23.4%).ConclusionFor timing the onset of infection (before or in early pregnancy) CMV avidity testing is most helpful if carried out within the first trimester up to the beginning of second trimester.