Background. Empirical antifungal therapy is the standard treatment for persistent or relapsing antibiotic-resistant neutropenic fever. However, overtreatment resulting in increased toxicity and ...treatment-related cost is a major shortcoming of such therapy. We assessed the feasibility of a "preemptive" approach based on the incorporation of sensitive, noninvasive diagnostic tests for consecutive high-risk neutropenic patients who had received fluconazole prophylaxis while avoiding empirical therapy. Methods. A total of 136 treatment episodes for persons who were at risk of acquiring invasive fungal infection (IFI) were screened for the presence of galactomannan with an enzyme immunoassay. A diagnostic evaluation, which included thoracic computed tomography scanning (HRCT) and bronchoscopy with lavage, was performed on the basis of well-defined clinical, radiological, and microbiological criteria. Only seropositive patients and patients with a positive microbiological test result plus supportive radiological findings received liposomal amphotericin B. Results. Neutropenic fever developed in 117 episodes, of which at least 41 episodes (35%) satisfied existing criteria for empirical antifungal therapy. However, our protocol-driven preemptive approach reduced the rate of antifungal use for these episodes from 35% to 7.7% (a 78% reduction) and led to the early initiation of antifungal therapy in 10 episodes (7.3%) that were clinically not suspected of being IFI. No undetected cases of invasive aspergillosis were identified; 1 case of zygomycosis was missed. Breakthrough candidemia was diagnosed by conventional culture techniques and was treated successfully. With use of a preemptive approach, the 12-week survival rate for patients with IFI was 63.6% (it was 63.1% for those with invasive aspergillosis). Conclusion. Preemptive therapy based on enzyme immunoassay and HRCT reduced the exposure to expensive and potentially toxic drugs and offered effective antifungal control, but it failed to detect non-Aspergillus IFI.
Summary Non-typeable Haemophilus influenzae (NTHi) is a major cause of mucosal infections such as otitis media, sinusitis, conjunctivitis, and exacerbations of chronic obstructive pulmonary disease. ...In some regions, a strong causal relation links this pathogen with infections of the lower respiratory tract. In the past 20 years, a steady but constant increase has occurred in invasive NTHi worldwide, with perinatal infants, young children, and elderly people most at risk. Individuals with underlying comorbidities are most susceptible and infection is associated with high mortality. β-lactamase production is the predominant mechanism of resistance. However, the emergence and spread of β-lactamase-negative ampicillin-resistant strains in many regions of the world is of substantial concern, potentially necessitating changes to antibiotic treatment guidelines for community-acquired infections of the upper and lower respiratory tract and potentially increasing morbidity associated with invasive NTHi infections. Standardised surveillance protocols and typing methodologies to monitor this emerging pathogen should be implemented. International scientific organisations need to raise the profile of NTHi and to document the pathobiology of this microbe.
Screening for galactomannan (GM) has been adopted by many European centers as part of the management plan for allogeneic stem cell transplant recipients. However, the temporal onset of GM antigenemia ...remains unknown. A series of allogeneic stem cell transplant recipients were monitored prospectively, and the relationship between antigenemia and other diagnostic triggers for initiation of antifungal therapy was analyzed. GM detection had a sensitivity of 94.4% and a specificity of 98.8%. Positive and negative predictive values were 94.4% and 98.8%, respectively. This statistical profile was better than that of other triggers, including unexplained fever, new pulmonary infiltrates, isolation of Aspergillus species, and abnormalities seen on computed tomography. Antigenemia preceded diagnosis on the basis of radiologic examination or Aspergillus isolation by 8 and 9 days in 80% and 88.8% of patients, respectively. Antigenemia preceded therapy in 83.3% of patients. Detection of GM was especially useful when patients were receiving steroid treatment or when coexisting conditions masked the diagnosis of invasive aspergillosis. Prospective screening for GM allows earlier diagnosis of aspergillosis than do conventional diagnostic criteria
Background.Prompt diagnosis of invasive pulmonary aspergillosis (IPA) remains a challenge. Galactomannan (GM) detection in bronchoalveolar lavage (BAL) fluid by the Platelia enzyme immunoassay aims ...to further improve upon the test's utility by applying it directly to specimens from the target organ. Methods.A retrospective analysis of the Platelia assay was performed on BAL samples from 99 evaluable high-risk hematology patients, including 58 with proven or probable IPA. Results.BAL GM demonstrated an improved sensitivity profile (91.3% with an optical density OD index cutoff of ⩾1.0) in comparison with culture and microscopy (50% and 53.3%, respectively). The diagnostic accuracy as given by the area under the receiver operating characteristic curve was 0.93 (95% confidence interval, 0.88–0.99); further decreasing the OD index cutoff to ⩾0.5 compromised specificity more than it improved sensitivity. Estimates of the positive and negative predictive value of the Platelia assay on BAL samples (OD index, ⩾1.0) were 76% and 96%, respectively. The mean BAL GM OD index was not different in neutropenic versus nonneutropenic case patients (3.9 and 4.5, respectively; P=.3); however, a trend toward decreased sensitivity in patients receiving mold-active prophylaxis was noted. Conclusion.BAL GM is a valuable adjunctive diagnostic tool to other conventional microbiologic and radiologic studies.
Background.Many health care centers worldwide use the Platelia Aspergillus enzyme immunoassay (PA-EIA; Bio-Rad Laboratories) for diagnosis of invasive aspergillosis (IA). A cutoff optical density ...(OD) index of 1.5 was originally recommended by the manufacturer, but in practice, most institutions use lower cutoff values. Moreover, a cutoff OD index of 0.5 was recently approved in the United States. In the present study, we set out to optimize the cutoff level by performing a retrospective analysis of PA-EIA values for samples that had been obtained prospectively from adult patients at risk for IA at 2 European health care centers. Methods.In total, 239 treatment episodes were included of which there were 19 episodes of proven IA and 19 episodes of probable IA. Per-episode and per-test analyses and receiver operating characteristic curves were used to determine the optimal cutoff value. Results.In the per-episode analysis, lowering the cutoff OD index for positivity from 1.5 to 0.5 increased the overall sensitivity by 21% (from 76.3% to 97.4%) but decreased the overall specificity by 7% (from 97.5% to 90.5%). Requiring 2 consecutive samples with an OD index ⩾0.5 resulted in the highest test accuracy, with an improved positive predictive value. At a cutoff OD index of 0.5, the antigen test result was positive during the week before conventional diagnosis in 65% of cases and during the week of diagnosis in 79.5% of cases. Conclusions.A cutoff OD index of 0.5—identical to the approved cutoff in the United States—improves the overall performance of the PA-EIA for adult hematology patients.
Background and Aims
Community‐acquired pneumonia (CAP) is a common infectious disease affecting children and adults of any age. Mycoplasma pneumoniae has emerged as leading causative agent of CAP in ...some region, and the abrupt increasing resistance to macrolide that widely used for management of M. pneumoniae has reached to the level that it often leads to treatment failures.
Objective
We aim to discuss the drivers for development of macrolide‐resistant M. pneumoniae, antimicrobial stewardship and also the potential treatment options for patients infected with macrolide‐resistant M. pneumonia.
Methods
The articles in English and Chinese published in Pubmed and in Asian medical journals were selected for the review.
Results
M. pneumoniae can develop macrolide resistance by point mutations in the 23S rRNA gene. Inappropriate and overuse of macrolides for respiratory tract infections may induce the resistance rapidly. A number of countries have introduced the stewardship program for restricting the use of macrolide. Tetracyclines and fluoroquinolones are highly effective for macrolide‐resistant strains, which may be the substitute in the region of high prevalence of macrolide‐resistant M. pneumoniae.
Conclusion
The problem of macrolide resistant M. pneumonia is emerging. Antibiotic stewardship is needed to inhibit the inappropriate use of macrolide and new antibiotics with a more acceptable safety profile for all ages need to be explored.
Actinomycosis is an opportunistic infection caused by bacteria of the
Actinomyces
spp., commonly
A. israelii
. These are non-pathogenic commensals in the mouth, gut, and female genital tract. An ...infection may arise following trauma or surgery, such as tooth extraction. More than half of cases of actinomycosis occur in the perimandibular area and are termed cervicofacial actinomycosis. Initially, the infection develops as a painful, rapidly progressive swelling. The lesion may then indurate and is often painless while the overlying skin discolors red to purple-blue. Prolonged treatment with antibiotics and surgery are often required for resolution, unless treatment is promptly started. However, diagnosis may be delayed or missed because of difficult bacterial culturing and frequent confusion with malignancy and other infections. This case study describes six patients who developed cervicofacial actinomycosis following third molar extraction. The purpose of this study is to inform clinicians on this stubborn and deceitful disease entity and to highlight the importance of clinical recognition for quick resolution with minimal morbidity.
Purpose
Evidence supports the implementation of outpatient parenteral antimicrobial therapy (OPAT) as standard of care. Until 2015 the overall experience with OPAT in Belgium remained limited. The ...aim of this study was to evaluate the efficacy and safety of a Belgian ‘OPAT at home’ program, which was implemented in University Hospitals Leuven starting from January 2017.
Methods
A mono-centric, prospective, observational study was carried out. All OPAT cases discharged between 10 January 2017 and 10 January 2019 were included in the study. Relevant demographic and clinical patient data were collected. The outcomes were clinical cure rate, OPAT related readmission rate, adverse event rate and patients’ satisfaction.
Results
Over the two-year study period, 152 OPAT episodes were started in 130 patients, resulting in 3153 avoided hospitalization days which corresponds to 5.4 freed hospital beds. Urinary tract infections accounted for 40.8% of OPAT courses and temocillin was the most frequently used antibiotic (24.3%). Cure was achieved in 97.9% of the OPAT episodes. During 22 (14.5%) OPAT episodes, patients experienced adverse events, including line related adverse events (7.9%) and adverse drug events (6.6%). An OPAT related readmission rate of 9.2% was observed, mostly related to line-associated adverse events. All patients who completed the satisfaction survey (
n
= 23) were very satisfied with their OPAT course.
Conclusion
The University Hospitals Leuven OPAT program is associated with a high level of clinical cure and low all-cause readmission and adverse event rates. Improvement actions are described to further reduce the readmission rate to less than 5.0%.
Summary An international group of multidisciplinary experts on middle-ear and paediatric infections met to explore where consensus exists on the management of acute otitis media. After informal ...discussions among several specialists of paediatric infectious disease, the group was expanded to include a larger spectrum of professionals with complementary expertise in middle-ear disease. Acute otitis media is a very common bacterial infection in children worldwide, leading to excessive antibiotic consumption in children in most countries and to a substantial burden of deafness and suppurative complications in developing countries. The group attempted to move beyond the existing controversies surrounding guidelines on acute otitis media, and to propose to clinicians and public health officials their views on the actions needed to be taken to reduce the disease burden caused by acute otitis media and the microbial antibiotic resistance from the resulting use of antibiotics. Definition of acute otitis media and diagnostic accuracy are crucial steps to identify children who will potentially benefit from treatment with antibiotics and to eliminate unnecessary prescribing. Although the group agreed that antibiotics are distributed indiscriminately, even to children who do not seem to have the disease, no consensus could be reached on whether antibiotics should be given to all appropriately diagnosed children, reflecting the wide range of practices and lack of convincing evidence from observational studies. The major unanimous concern was an urgent need to reduce unnecessary prescribing of antibiotics to prevent further increases in antibiotic resistance. Prevention of acute otitis media with existing and future viral and bacterial vaccines seems the most promising approach to affect disease burden and consequences, both in developed and developing countries.
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