Clinical Microbiology & Infectious Diseases

Comparison of in vitro activity of the nitroimidazoles delamanid and pretomanid against multidrug-resistant and extensively drug-resistant tuberculosis Abstract Delamanid exhibited greater in vitro potency than pretomanid against multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) isolates. The pretomanid minimum inhibitory concentration (MIC) values of four MDR-TB isolates were found to be resistant to delamanid ranging from 0.031 to 0.063 mg/L. A novel nonsynonymous mutation within the fbiA gene (Glu249Lys) may be contributing to high-level resistance to delamanid and pretomanid in Mycobacterium tuberculosis.

Factors associated with blood culture positivity in patients with complicated skin and skin structure infection—a population-based study Abstract Skin and skin structure infection (SSSI) is classified as complicated (cSSSI) if it involves deep subcutaneous tissue or requires surgery. Factors associated with blood culture sampling and bacteremia have not been established in patients with cSSSI. Moreover, the benefit of information acquired from positive blood culture is unknown. The aim of this study was to address these important issues. In this retrospective population-based study from two Nordic cities, a total of 460 patients with cSSSI were included. Blood cultures were drawn from 258 (56.1%) patients and they were positive in 61 (23.6%) of them. Factors found to be associated with more blood culture sampling in multivariate analysis were diabetes, duration of symptoms shorter than 2 days and higher C-reactive protein (CRP) level. Whereas factors associated with less frequent blood culture sampling were peripheral vascular disease and a surgical wound infection. In patients from whom blood cultures were taken, alcohol abuse was the only factor associated with culture positivity, as CRP level was not. Patients with a positive blood culture had antibiotic streamlining more often than non-bacteremic patients. A high rate of blood culture positivity in patients with cSSSI was observed. Factors related to more frequent blood culture sampling were different from those associated with a positive culture.

Evaluation of risk factors associated to detection of Blastocystis sp. in fecal samples in population from Barcelona, Spain: a case-control study Abstract Blastocystis sp. is the most common intestinal parasite isolated in humans. The aim of the study was to describe the risk factors associated to Blastocystis sp. detection. A case-control retrospective study was carried out at Vall d’Hebron University Hospital (Barcelona, Spain), which receives all fecal samples collected in Barcelona at primary care level. Eligible patients were patients older than 18 years in whom three consecutive stool samples were examined for parasitic diagnosis from January to December 2017. Positive patients for Blastocystis sp. were assigned as cases whereas negative patients were assigned as controls. Overall, 4174 patients were eligible for the study, from whom 724 (17.3%) had Blastocystis sp. detection. From these, 170 cases (Blastocystis sp. positive) and 170 controls (Blastocystis sp. negative) were randomly selected for inclusion. One hundred and twenty-six (37.1%) of them were immigrants, and 171 (50.3%) patients had traveled out of Spain the year before. The majority of individuals had jobs with no direct contact with other people (health personnel, teachers, and caregivers) (85.6%), and 29.4% were in usual contact with animals. Regarding clinical information, 68.2% of patients presented digestive symptoms, 3.5% presented an immunosuppressant condition, and 6.5% were infected by other intestinal parasites. Variables associated to Blastocystis sp. detection were being born in Africa, having traveled abroad, and working in direct contact with other people. Having other intestinal parasitic infections had a protective value. Our study provides new insights into the epidemiology of Blastocystis sp. in industrialized countries.

Prediction of methicillin-resistant Staphylococcus aureus bloodstream infection: do we need rapid diagnostic tests? Abstract Staphylococcus aureus (SA) is the leading cause of bloodstream infection (BSI). The incidence of methicillin-resistant SA (MRSA) has decreased in France and Europe since one decade. Early and precise prediction of methicillin susceptibility is needed to improve probabilistic antibiotic therapy of MRSA-BSI. The aim of this study was to identify MRSA-BSI risk factors at admission and evaluate which patients need costly rapid diagnostic tests. A single-center retrospective descriptive study of all diagnosed SA-BSI was conducted in a French University Hospital between January 2015 and December 2016. All medical charts were reviewed. Univariate and multivariate analyses by a logistic regression model were performed on the data. We then build a prediction score of MRSA-BSI by assigning one point for each of the risk factor identified. During the study period, 151 SA-BSI were identified including 32 (21%) MRSA-BSI. In multivariate analysis, three factors were associated with MRSA-BSI: coming from long-term care facility, known previous MRSA colonization and/or infection, and chronic renal disease. Among our population, respectively, 5% and 100% had a MRSA-BSI when no or three risk factors were identified. Therefore, among the PCR performed, 43 (96%) could be avoided according to our clinical score. In our study, methicillin-susceptible SA and MRSA-BSI can be predictable by counting MRSA risk factors. This prediction rule could avoid the use of expensive rapid diagnostic tests. Prospective studies and prediction rules could help physicians to predict SA-BSI susceptibility to improve appropriate empiric therapy choice.

Potential false-positive urine Legionella enzyme immunoassay test results Abstract The objective of this study was to identify potential false-positive urine Legionella pneumophila (Legionella) enzyme immunoassay test results. A total of 107 consecutive patients with positive EIA tests were retrospectively analyzed over a 34-month period. Concurrent blood, urine, and sputum cultures, as well as chest radiographic findings, were reviewed in these patients. Twenty patients (19%) had no radiographic evidence of pulmonary disease despite a positive EIA test. In those 20 patients, 14 also had growth of non-Legionella bacteria. Of patients with an infiltrate or opacity on chest imaging, only 27 had Legionella sputum cultures obtained, with Legionella culture growth occurring in 7 (26%). Nine other patients had negative Legionella sputum cultures but the growth of another pathogenic organism in blood, sputum, and/or urine cultures. Pseudomonas aeruginosawas the most common organism isolated, found in 20% of patients in the entire cohort. Twenty-five patients (23%) were characterized as having probable false-positive Legionella urinary antigen EIA testing, and an additional 17 patients (16%) were characterized as having possible false-positive Legionella EIA tests. Our findings suggest that urine Legionella EIA tests may lead to a substantial number of cases being misdiagnosed as Legionaries’ disease in patients with non-Legionella bacterial colonization or infection.

Perceived differences between intensivists and infectious diseases consultants facing antimicrobial resistance: a global cross-sectional survey Abstract To identify differences in perception on multi-drug-resistant (MDR) organisms and their management at intensive care units (ICU). A cross-sectional survey was conducted. A proposal addressing a pathogen priority list (PPL) for ICU, arising from the TOTEM study, was compared with a sample of global experts in infections in critically ill patients. The survey was responded by 129 experts. Globally, ESBL Enterobacteriaceae, followed by carbapenem-resistant Acinetobacter baumannii and carbapenem-resistant Klebsiella pneumoniae, were the main concerns. Some differences in opinion were identified between 63 (49%) ICU physicians (ICU/anesthesiology) and 43 (33%) infectious disease consultants (ID physicians/microbiologists). The pathogens most concerning in the ICU for intensivists were ESBL Enterobacteriaceae (38%) versus carbapenem-resistant A. baumannii (48.3%) for ID consultants, (p < 0.05). Increasing number of ID consultants over intensivists (26% vs 14%) reported difficulty in choosing initial therapy for carbapenem-resistant A. baumannii. For intensivists, the urgent measures to limit development of antibiotic resistance were headed by cohort measures (26.3%) versus increasing nurse/patient ratio (32.5%) for ID consultants, (p < 0.05). Regarding effectiveness to prevent MDR development and spread, education programs (42.4%) were the priority for intensivists versus external consultation (35.7%) for ID consultants. Finally, both groups agreed that carbapenem resistance was the most pressing concern (> 70%) regarding emerging resistance. Differences in priorities regarding organisms, infection control practices, and educational priorities were visualized between ID/clinical microbiologists and ICU/anesthesiologists. Multi-disciplinary collaboration is required to achieve best care for ICU patients with severe infections.

Target attainment of cefotaxime in critically ill children with meningococcal septic shock as a model for cefotaxime dosing in severe pediatric sepsis Abstract Reduced target attainment of β-lactam antibiotics is reported in critically ill patients. However, as target attainment of cefotaxime in severely ill pediatric sepsis patients may differ from adults due to age-related variation in pharmacokinetics, we aimed to assess target attainment of cefotaxime in this pilot study using meningococcal septic shock patients as a model for severe sepsis. Secondary analysis of prospectively collected data from a randomized controlled trial. Children with meningococcal septic shock (1 month to 18 years) included in this study received cefotaxime 100–150 mg/kg/day as antibiotic treatment. Left-over plasma samples were analyzed using LC-MS/MS to determine cefotaxime concentrations. MIC values from EUCAST were used to determine target attainment of cefotaxime for Neisseria meningitidis (0.125 mg/l), but also for Streptococcus pneumoniae(0.5 mg/l), Enterobacteriaceae (1 mg/l), and Staphylococcus aureus (4 mg/l). Target attainment was adequate when all samples exceeded MIC or fourfold MIC values. One thirty-six plasma samples of 37 severe septic shock patients were analyzed for cefotaxime concentrations. Median age was 2 years with a median PRISM-score of 24 and mortality of 24.8%. The median unbound cefotaxime concentration was 4.8 mg/l (range 0–48.7). Target attainment ranged from 94.6% for the MIC of N. meningitidis to 16.2% for fourfold the MIC S. aureus. Creatinine levels were significantly correlated with cefotaxime levels. Target attainment of cefotaxime with current dosing guidelines seems to be adequate for N. meningitidis but seems to fail for more frequently encountered pathogens in severely ill children.

The clinical value of aquaporin-4 in children with hand, foot, and mouth disease and the effect of magnesium sulfate on its expression: a prospective randomized clinical trial Abstract To evaluate the clinical value of aquaporin-4 (AQP-4) in hand, foot, and mouth disease (HFMD) and to evaluate therapeutic efficacy of magnesium sulfate (MgSO4) and its effect on AQP-4 expression. Children with HFMD were divided into a common group, a severe group and a critical group according to Chinese guidelines; children in the critical group were further divided into two subgroups: routine treatment group and MgSO4 group. Outcome measures included systolic blood pressure (SBP), Heart rate (HR), the levels of AQP-4, interleukin-6 (IL-6), norepinephrine (NE), and neuron-specific enolase (NSE). Serum AQP-4, IL-6, NE, and NSE levels varied significantly among the critical, severe, and common groups before and after treatment. There were no significant differences in AQP-4 levels in cerebrospinal fluid (CSF) between the critical and severe groups before and after treatment; however, CSF AQP-4 levels in these two groups were higher than those in the common group before treatment. Serum and CSF AQP-4 levels in convalescence decreased significantly in the critical and severe groups. SBP, HR and serum AQP-4, IL-6, NE, NSE levels, but not CSF AQP-4 levels, were significantly lower in MgSO4 group than in the routine treatment group. AQP-4 in serum, but not in CSF, is a candidate biomarker for evaluating the severity and prognosis of HFMD; MgSO4 can provide protection on children with critical HFMD.

Monomicrobial bone and joint infection due to Corynebacterium striatum: literature review and amoxicillin-rifampin combination as treatment perspective Abstract Corynebacterium striatum is a ubiquitous colonizer of human skin and mucous membranes. It is increasingly involved in infections, especially with prosthetic devices or in immunocompromised individuals. Microbiological diagnosis is challenging and bacterial resistance is a major concern. We performed a retrospective study of monomicrobial bone and joint infections (BJI) due to C. striatum in two referral centers from April 2012 to July 2017. We collected the patients’ clinical and microbiological characteristics and outcomes. We also performed a literature review of BJI due to C. striatum. We identified 12 cases (nine prosthetic joint infections, one osteosynthetic device infection, one non-union, and one arthritis) in 11 patients, five of which were immunocompromised. Microbiological diagnosis was performed with prolonged culture media. Ten out of 12 strains were susceptible to aminopenicillin, a drug class not recommended for testing by the EUCAST/CASFM guidelines, and 8/12 patients were treated with amoxicillin-rifampicin. The cure rate was 8/12, after a median follow-up period of 487.5 days (IQR 140.3–1348.5). Twelve cases of BJI due to C. striatum were previously reported. Among them, 5/12 patients were immunocompromised, 3/12 cases were acute BJI, and 2/12 were device-related infections. The diagnosis was performed by PCR in one case, and 10/12 patients were treated with glycolipopeptides, with a cure rate of 11/12. We report the largest cohort of monomicrobial BJI with C. striatum. Determination of aminopenicillin susceptibility is essential since it is frequently active in our experience, even in BJI. The cure rate of this infection seems high.

Comparison of microbiological results obtained from per-wound bone biopsies versus transcutaneous bone biopsies in diabetic foot osteomyelitis: a prospective cohort study Abstract Transcutaneous bone biopsy (TCB) is the gold standard for taking microbiological specimens in diabetic foot osteomyelitis (DFO), but this technique is not widely used in diabetic foot care centers. We aimed to evaluate the reliability of per-wound bone biopsy (PWB) cultures by comparing them with concomitant TCB cultures obtained through healthy skin. This is a prospective monocentric study including patients seen in consultation for clinical and radiological diabetic foot osteomyelitis with positive probe-bone tests between April 2015 and May 2018. Two bone biopsies were performed on each consenting patient: TCB through a cutaneous incision in healthy skin, and PWB, after careful debridement of the wound. A total of 46 paired cultures were available from 43 eligible patients. Overall, 16 (42%) of the PWB and TCB pairs had identical culture results, but the TCB cultures were sterile in 8 (17%) cases. For 38 paired cultures with positive TCB, the correlation between PWB results and TCB results was 58.4%. PWB revealed all microorganisms found in the transcutaneous specimen in 26/38 samples (68.5%). In patients with DFO, the culture results of specimens taken by per-wound biopsies did not correlate well with those obtained by TCB. PWB should be reserved for cases where the transcutaneous biopsy is sterile or not feasible.