Severe odontogenic infections : epidemiological, microbiological and therapeutic factors

Objectives: A retrospective study is made of the odontogenic infections treated in La Paz University Hospital (Madrid, Spain) during 2007 and 2008, with an epidemiological and microbiological analysis of a large group of patients.Study Design: A retrospective descriptive study was made, involving the consecutive inclusion of all patients with odontogenic infection requiring admission to our hospital in the period between January 2007 and December 2008. Results: A total of 151 patients were included, with a mean age of 40.3 years and a balanced gender distribution. The most frequently affected teeth were those located in the posterior mandibular segments, caries being the main underlying cause. Most isolates comprised mixed flora, particularly viridans streptococci, different species of Prevotella, Micromonas micros, and different species of Actinomyces. Susceptibility analysis of the microbial isolates showed a high percentage resistance to clindamycin (42.8% of all isolates), particularly among viridans streptococci.Conclusions: The use of antibiotics in head and neck infections requires updated protocols based not only on the existing scientific evidence but also on the epidemiological reality of each center. On the other hand, identification is required of the surgical factors determining infection and how they influence morbidity associated with this type of pathology. © Medicina Oral

Meropenem heteroresistance in clinical isolates of OXA-48–producing Klebsiella pneumoniae

OXA-48–producing Klebsiella pneumoniae isolates often show growth of colonies within inhibition zones in carbapenem diffusion assays. The nature of these colonies was investigated in a series of clinical isolates of OXA-48–producing K. pneumoniae obtained in the context of a hospital outbreak, and they were found to be persistent colonies that reproduced again the same phenotype when they were collected and tested in diffusion assays again. The frequency of mutations conferring resistance to meropenem (8 µg/mL) was determined for the same isolates. The average mutation frequency was 5.47·10-6 (range: 2.59·10-8–5.87·10-5), and the analysis of several resistant mutants showed that all of them had mutations in the ompK36 porin gene. Heteroresistance was investigated using population analysis profiling. The profiles were compatible with mutation frequency assays, and all the colonies analyzed were resistant mutants. In OXA-48–producing K. pneumoniae, the growth of persisters seems to be specific of diffusion assays

Proof-of-concept trial of the combination of lactitol with Bifidobacterium bifidum and Lactobacillus acidophilus for the eradication of intestinal OXA-48-producing Enterobacteriaceae

Background: The major reservoir of carbapenemase-producing Enterobacteriaceae (CPE) is the gastrointestinal tract of colonized patients. Colonization is silent and may last for months, but the risk of infection by CPE in colonized patients is significant. Methods: Eight long-Term intestinal carriers of OXA-48-producing Enterobacteriaceae (OXA-PE) were treated during 3 weeks with daily oral lactitol (Emportal®), Bifidobacterium bifidum and Lactobacillus acidophilus (Infloran®). Weekly stool samples were collected during the treatment period and 6 weeks later. The presence of OXA-PE was investigated by microbiological cultures and qPCR. Results: At the end of treatment (EoT, secondary endpoint 1), four of the subjects had negative OXA-PE cultures. Three weeks later (secondary endpoint 2), six subjects were negative. Six weeks after the EoT (primary endpoint), three subjects had negative OXA-PE cultures. The relative intestinal load of OXA-PE decreased in all the patients during treatment. Conclusions: The combination of prebiotics and probiotics was well tolerated. A rapid reduction on the OXA-PE intestinal loads was observed. At the EoT, decolonization was achieved in three patients

Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections

IMPORTANCE The consumption of broad-spectrum drugs has increased as a consequence of the spread of multidrug-resistant (MDR) Escherichia coli. Finding alternatives for these infections is critical, for which some neglected drugs may be an option. OBJECTIVE To determine whether fosfomycin is noninferior to ceftriaxone or meropenem in the targeted treatment of bacteremic urinary tract infections (bUTIs) due to MDR E coli. DESIGN, SETTING, AND PARTICIPANTS This multicenter, randomized, pragmatic, open clinical trial was conducted at 22 Spanish hospitals from June 2014 to December 2018. Eligible participants were adult patients with bacteremic urinary tract infections due to MDR E coli; 161 of 1578 screened patients were randomized and followed up for 60 days. Data were analyzed in May 2021. INTERVENTIONS Patients were randomized 1 to 1 to receive intravenous fosfomycin disodium at 4 g every 6 hours (70 participants) or a comparator (ceftriaxone or meropenem if resistant; 73 participants) with the option to switch to oral fosfomycin trometamol for the fosfomycin group or an active oral drug or pa renteral ertapenem for the comparator group after 4 days. MAIN OUTCOMES AND MEASURES The primary outcome was clinical and microbiological cure (CMC) 5 to 7 days after finalization of treatment; a noninferiority margin of 7% was considered. RESULTS Among 143 patients in the modified intention-to-treat population (median [IQR] age, 72 [62-81] years; 73 [51.0%] women), 48 of 70 patients (68.6%) treated with fosfomycin and 57 of 73 patients (78.1%) treated with comparators reached CMC (risk difference, -9.4 percentage points; 1-sided 95% CI, -21.5 to infinity percentage points; P = .10). While clinical or microbiological failure occurred among 10 patients (14.3%) treated with fosfomycin and 14 patients (19.7%) treated with comparators (risk difference, -5.4 percentage points; 1-sided 95% CI. -infinity to 4.9; percentage points; P = .19), an increased rate of adverse event-related discontinuations occurred with fosfomycin vs comparators (6 discontinuations [8.5%] vs 0 discontinuations; P = .006). In an exploratory analysis among a subset of 38 patients who underwent rectal colonization studies, patients treated with fosfomycin acquired a new ceftriaxone-resistant or meropenem-resistant gram-negative bacteria at a decreased rate compared with patients treated with comparators (0 of 21 patients vs 4 of 17 patients [23.5%]; 1-sided P = .01). CONCLUSIONS AND RELEVANCE This study found that fosfomycin did not demonstrate noninferiority to comparators as targeted treatment of bUTI from MDR E coli; this was due to an increased rate of adverse event-related discontinuations. This finding suggests that fosfomycin may be considered for selected patients with these infections

Severe odontogenic infections : epidemiological, microbiological and therapeutic factors

Objectives: A retrospective study is made of the odontogenic infections treated in La Paz University Hospital (Madrid, Spain) during 2007 and 2008, with an epidemiological and microbiological analysis of a large group of patients.Study Design: A retrospective descriptive study was made, involving the consecutive inclusion of all patients with odontogenic infection requiring admission to our hospital in the period between January 2007 and December 2008. Results: A total of 151 patients were included, with a mean age of 40.3 years and a balanced gender distribution. The most frequently affected teeth were those located in the posterior mandibular segments, caries being the main underlying cause. Most isolates comprised mixed flora, particularly viridans streptococci, different species of Prevotella, Micromonas micros, and different species of Actinomyces. Susceptibility analysis of the microbial isolates showed a high percentage resistance to clindamycin (42.8% of all isolates), particularly among viridans streptococci.Conclusions: The use of antibiotics in head and neck infections requires updated protocols based not only on the existing scientific evidence but also on the epidemiological reality of each center. On the other hand, identification is required of the surgical factors determining infection and how they influence morbidity associated with this type of pathology. © Medicina Oral

How do physicians cope with controversial topics in existing guidelines for the management of infective endocarditis?:results of an international survey

International audienceInternational guidelines are available to help physicians prescribe appropriate antibiotic regimens to patients with infective endocarditis (IE). However some topics of these guidelines are controversial. We conducted an international survey to assess physicians' adherence to these guidelines, focusing on these controversial items. An invitation to participate to a 15-question online survey was sent in 2012-2013 to European Society of Clinical Microbiology and Infectious Diseases (ESCMID) members, scientific societies and corresponding authors of publications on IE mentioned in PubMed from 1990 to 2012, inclusive. Eight hundred thirty-seven physicians participated in the survey, and 625 (74.7%) completed it over the first question. The results showed great heterogeneity of practices. Claiming to follow guidelines was marginally associated with more guideline-based strategies. Gentamicin use depended on causative pathogens (p <0.001) and physician specialty (p 0.02). Eighty-six per cent of the physicians favoured vancomycin alone or in combination with gentamicin or rifampicin as a first-line treatment for left-sided native valve methicillin-resistant Staphylococcus aureus IE, 31% considered switching to oral therapy as a therapeutic option and 33% used the ampicillin and ceftriaxone combination for enterococcal IE as a first-line therapy. Physician specialty significantly affected the choice of a therapeutic strategy, while practicing in a university hospital or the number of years of practice had virtually no impact. Our survey, the largest on IE treatment, underscores important heterogeneity in practices for treatment of IE. Nonetheless, physicians who do not follow guidelines can have rational strategies that are based on the literature. These results could inform the revision of future guidelines and identify unmet needs for future studies

Clinical efficacy of ceftazidime/avibactam versus other active agents for the treatment of bacteremia due to carbapenemase-producing Enterobacteriaceae in hematologic patients

Objectives: The primary objective was to describe clinical features, treatment and outcomes in patients with carbapenemase-producing Enterobacteriaceae (CPE) bacteremia. Additionally, patients treated with ceftazidime/avibactam (study group) were compared to the rest of the patients (comparator group) to determine the influence of the treatment in both crude mortality and clinical cure. Methods: Multicenter and retrospective study that included patients with hematologic malignancies who had CPE bacteremia. A bivariate analysis was performed to compare the clinical variables between the study group and the control group. Results: 31 patients were included. Bacteremia was considered primary in 14 (45%) patients. Overall crude mortality at 30 days was 45.2% (n = 14). Mortality was more frequent when septic shock (78.6% vs 11.8%; p > 0.001) and higher Pitt score (6 + 14 vs 1.5 + 4; p < 0.01) were present. 8 patients (25.8%) received treatment with ceftazidime/avibactam. No significant differences in crude mortality were found between study and comparator groups (p = 0.19). In contrast, patients in study group had higher clinical cure rates than the comparator group within 14 days of initiating treatment (85.7% vs. 34.8%, respectively, p = 0.031). Conclusions: CPE bacteremia is associated with high mortality in patients with hematologic malignancies. Ceftazidime/avibactam may be an effective alternative for treating these patients

Opportunities to improve antimicrobial use in paediatric intensive care units: a nationwide survey in Spain.

Improving antimicrobial use is a complex process that requires an accurate assessment of ongoing problems and barriers. Paediatric intensive care units (PICU) have seldom been assessed from this perspective. Two Internet-based, self-administered surveys were conducted nationwide in Spain between January and February 2014. The first survey aimed to assess those characteristics of Spanish PICUs that could influence antimicrobial prescribing or antimicrobial stewardship. The second survey targeted Spanish PICU physicians and pursued to assess their attitudes and perceptions regarding antimicrobial resistance and antimicrobial use. Information about 29/39 contacted PICUs was obtained. A total of 114/206 (55.3%) paediatric intensivists responded. PICUs were heterogeneous regarding years since foundation, number of beds, type of patients admitted and staffing. Only 11 (37.9%) PICUs had available e-prescribing systems. Procalcitonin was available in 24 (89.1%) PICUs, but there were no procalcitonin-based protocols in 14 (60.9%) of them. Half of surveyed PICUs had implemented antimicrobial stewardship activities. Ninety-eight of the 114 PICU physicians (86%) who participated considered that antimicrobial resistance was a significantly relevant problem for their daily and that improving antimicrobial use in their PICU should be a priority (103; 90.4%). The main perceived problems regarding antimicrobial use were the excessive use of antimicrobials in patients with nonconfirmed infections and excessive use of broad-spectrum antimicrobials. The most valued antimicrobial stewardship interventions were the implementation of protocols to guide antimicrobial therapy. Spanish PICU doctors are aware of the relevance of the problem of antimicrobial resistance and the need to improve antimicrobial use. Targeted interventions should take into account their difficulties and preferences when feasible

Convalescent Plasma for COVID-19: A multicenter, randomized clinical trial

Background: Passive immunotherapy with convalescent plasma (CP) is a potential treatment for COVID-19 for which evidence from controlled clinical trials is lacking. Methods: We conducted a multi-center, randomized clinical trial in patients hospitalized for COVID-19. All patients received standard of care treatment, including off-label use of marketed medicines, and were randomized 1:1 to receive one dose (250-300 mL) of CP from donors with IgG anti-SARS-CoV-2. The primary endpoint was the proportion of patients in categories 5, 6 or 7 of the COVID-19 ordinal scale at day 15. Results: The trial was stopped after first interim analysis due to the fall in recruitment related to pandemic control. With 81 patients randomized, there were no patients progressing to mechanical ventilation or death among the 38 patients assigned to receive plasma (0%) versus 6 out of 43 patients (14%) progressing in control arm. Mortality rates were 0% vs 9.3% at days 15 and 29 for the active and control groups, respectively. No significant differences were found in secondary endpoints. At inclusion, patients had a median time of 8 days (IQR, 6-9) of symptoms and 49,4% of them were positive for anti-SARS-CoV-2 IgG antibodies. Conclusions: Convalescent plasma could be superior to standard of care in avoiding progression to mechanical ventilation or death in hospitalized patients with COVID-19. The strong dependence of results on a limited number of events in the control group prevents drawing firm conclusions about CP efficacy from this trial. (Funded by Instituto de Salud Carlos III; NCT04345523).This research is funded by the Government of Spain, Ministry of Science and Innovation, Instituto de Salud Carlos III, grant number COV20/00072 (Royal Decree-Law 8/2020, of 17 March, on urgent extraordinary measures to deal with the economic and social impact of COVID-19), co-financed by the European Regional Development Fund (FEDER) ‘‘A way to make Europe’’ and supported by SCReN (Spanish Clinical Research Network), ISCIII, project PT17/0017/0009. Clinical trial insurance coverage was kindly donated by MARCH RS Correduría de Seguros y Reaseguros. Mikel Mancheño-Losa holds a "Río Hortega" research contract (expte. CM19/00226N