Flucloxacillin and cefazolin for treatment of Staphylococcus aureus bloodstream infection.

PURPOSE: Antistaphylococcal penicillins and cefazolin have been used as first line therapy in Methicillin-susceptible Staphylococcus aureus bloodstream infection. While efficacy of both regimens seems to be similar, the compounds may differ with regard to tolerability. This study aims to describe the clinical use of cefazolin and flucloxacillin, focussing on discontinuation or change of anti-infective agent due to adverse events. METHODS: This observational prospective study was conducted at two German tertiary care centres with an internal recommendation of flucloxacillin for MSSA-BSI in one, and of cefazolin in the other centre. Adverse events were registered weekly under treatment and at a 90-day follow-up. Descriptive analysis was complemented by a propensity score analysis comparing adverse events (stratified rank-based test applied to the sum of Common Terminology Criteria for adverse events ratings per patient). RESULTS: Of 71 patients included, therapy was initiated with flucloxacillin in 56 (79%), and with cefazolin in 15 (21%). The propensity score analysis indicates a statistically significant difference concerning the severity of adverse events between the treatment groups in favour of cefazolin (p = 0.019). Adverse events led to discontinuation of flucloxacillin in 7 individuals (13% of all patients receiving flucloxacillin). Clinical outcome was not different among treatment groups. CONCLUSION: Using cefazolin rather than flucloxacillin as a first line agent for treatment of MSSA-BSI is supported by these clinical data.

Brain abscess with Ureaplasma parvum in a patient with granulomatosis with polyangiitis.

PURPOSE: Ureaplasma species are associated with urogenital infections, infertility and adverse pregnancy outcomes as well as neonatal infections. Involvement of the central nervous system in adults is extremely rare. We report an unusual case of a brain abscess secondary to otitis media with Ureaplasma parvum in a patient with granulomatosis with polyangiitis (GPA). METHODS: Imaging and laboratory findings, treatment decisions, and outcome of this case are explicated. RESULTS: A young adult with GPA presented with progredient earache after ambulant diagnosis of otitis media. Despite different courses of broad-spectrum antibiotic therapy, she developed meningoencephalitis due to mastoiditis following temporal abscess formation. Mastoidectomy and neurosurgical abscess removal were performed. Standard cultures of cerebrospinal fluid, blood and intracranial abscess material, as well as polymerase chain reaction (PCR) for common bacterial and viral meningitis pathogens remained negative. Only eubacterial PCR of intracranial abscess material returned positive for Ureaplasma parvum. The patient finally improved under antibiotic therapy with moxifloxacin and doxycycline. CONCLUSION: Ureaplasma species are rare causative pathogens in immunocompromised patients. They should be considered in patients with humoral immunodeficiencies with culture-negative infections failing standard therapy. Eubacterial PCR should be performed in early states of infection in these patients for immediate diagnosis and initiation of appropriate treatment to prevent adverse outcomes.

Chest X-ray Analysis With Deep Learning-Based Software as a Triage Test for Pulmonary Tuberculosis: An Individual Patient Data Meta-Analysis of Diagnostic Accuracy.

BACKGROUND: Automated radiologic analysis using computer-aided detection software (CAD) could facilitate chest X-ray (CXR) use in tuberculosis diagnosis. There is little to no evidence on the accuracy of commercially available deep learning-based CAD in different populations, including patients with smear-negative tuberculosis and people living with human immunodeficiency virus (HIV, PLWH). METHODS: We collected CXRs and individual patient data (IPD) from studies evaluating CAD in patients self-referring for tuberculosis symptoms with culture or nucleic acid amplification testing as the reference. We reanalyzed CXRs with three CAD programs (CAD4TB version (v) 6, Lunit v3.1.0.0, and qXR v2). We estimated sensitivity and specificity within each study and pooled using IPD meta-analysis. We used multivariable meta-regression to identify characteristics modifying accuracy. RESULTS: We included CXRs and IPD of 3727/3967 participants from 4/7 eligible studies. 17% (621/3727) were PLWH. 17% (645/3727) had microbiologically confirmed tuberculosis. Despite using the same threshold score for classifying CXR in every study, sensitivity and specificity varied from study to study. The software had similar unadjusted accuracy (at 90% pooled sensitivity, pooled specificities were: CAD4TBv6, 56.9% [95% confidence interval {CI}: 51.7-61.9]; Lunit, 54.1% [95% CI: 44.6-63.3]; qXRv2, 60.5% [95% CI: 51.7-68.6]). Adjusted absolute differences in pooled sensitivity between PLWH and HIV-uninfected participants were: CAD4TBv6, -13.4% [-21.1, -6.9]; Lunit, +2.2% [-3.6, +6.3]; qXRv2: -13.4% [-21.5, -6.6]; between smear-negative and smear-positive tuberculosis was: were CAD4TBv6, -12.3% [-19.5, -6.1]; Lunit, -17.2% [-24.6, -10.5]; qXRv2, -16.6% [-24.4, -9.9]. Accuracy was similar to human readers. CONCLUSIONS: For CAD CXR analysis to be implemented as a high-sensitivity tuberculosis rule-out test, users will need threshold scores identified from their own patient populations and stratified by HIV and smear status.

Vertebral Osteomyelitis After Spine Surgery: A Disease With Distinct Characteristics.

STUDY DESIGN: Prospective cohort study. OBJECTIVE: We aimed to determine the 2-year survival and to identify clinical and microbiological characteristics of patients with native vertebral osteomyelitis (VO) as compared to postoperative VO to find further strategies for improvement of the management of VO. SUMMARY OF BACKGROUND DATA: A relevant subgroup (20%-30%) of patients with VO has a history of spine surgery. Infection in these patients might be clinically different from native VO. However, clinical, microbiological, and outcome characteristics of this disease entity have not been well studied as most trials either excluded these patients or are limited by a small cohort and short observation period. METHODS: Between 2008 and 2013, patients who presented at a tertiary care center with symptoms and imaging findings suggestive of VO were reviewed by specialists in infectious diseases, clinical microbiology, and orthopedics to confirm the diagnosis and followed prospectively for a period of 2 years. Statistical analysis for group comparisons, survival analysis, and uni- and multivariable Cox regression models were performed. RESULTS: Thirty percent of the patients with VO (56/189) reported a history of spine surgery in the same segment. Patients with postoperative infection had a lower ASA score (American Society of Anesthesiologists) (P = 0.01) and were less likely to suffer from comorbidities compared to native cases (P = 0.003). Infections caused by coagulase-negative staphylococci (33.3 vs. 6.5%, P < 0.001) and other bacteria of the skin flora (15.2 vs. 0%, P = 0.002) were more prevalent in postoperative patients. Suffering from native VO increased the 2-year mortality risk 3-fold, also when adjusted for the remaining risk factors ASA score and number of comorbidities (hazard ratio 2.916 [95% confidence interval 1.215 -6.999], P = 0.017). CONCLUSION: Beside clear microbiological differences, the significant better 2-year survival supports the concept of postoperative VO presenting a distinct disease entity. The subtle disease presentation of patients with postoperative VO should not attenuate clinical suspicion of physicians. LEVEL OF EVIDENCE: 3.

Spondylodiscitis: Diagnosis and Treatment Options.

BACKGROUND: A recent population-based study from Denmark showed that the incidence of spondylodiscitis rose from 2.2 to 5.8 per 100 000 persons per year over the period 1995-2008; the age-standardized incidence in Germany has been estimated at 30 per 250 000 per year on the basis of data from the Federal Statistical Office (2015). The early diagnosis and treatment of this condition are essential to give the patient the best chance of a good outcome, but these are often delayed because it tends to present with nonspecific manifestations, and fever is often absent. METHODS: This article is based on a systematic search of Medline and the Cochrane Library for the period January 2009 to March 2017. Of the 788 articles identified, 30 publications were considered. RESULTS: The goals of treatment for spondylodiscitis are to eliminate infection, restore functionality of the spine, and relieve pain. Magnetic resonance imaging (MRI) remains the gold standard for the radiological demonstration of this condition, with 92% sensitivity and 96% specificity. It also enables visualization of the spatial extent of the infection and of abscess formation (if present). The most common bacterial cause of spondylodiscitis in Europe is Staphylococcus aureus, but tuberculous spondylodiscitis is the most common type worldwide. Antibiotic therapy is a pillar of treatment for spondylodiscitis and should be a part of the treatment in all cases. Neurologic deficits, sepsis, an intraspinal empyema, the failure of conservative treatment, and spinal instability are all indications for surgical treatment. CONCLUSION: The quality of life of patients who have been appropriately treated for spondylodiscitis has been found to be highly satisfactory in general, although back pain often persists. The risk of recurrence increases in the presence of accompanying illnesses such as diabetes mellitus, renal failure, or undrained epidural abscesses.

A novel multiple-instance learning-based approach to computer-aided detection of tuberculosis on chest X-rays.

To reach performance levels comparable to human experts, computer-aided detection (CAD) systems are typically optimized following a supervised learning approach that relies on large training databases comprising manually annotated lesions. However, manually outlining those lesions constitutes a difficult and time-consuming process that renders detailedly annotated data difficult to obtain. In this paper, we investigate an alternative approach, namely multiple-instance learning (MIL), that does not require detailed information for optimization. We have applied MIL to a CAD system for tuberculosis detection. Only the case condition (normal or abnormal) was required during training. Based upon the well-known miSVM technique, we propose an improved algorithm that overcomes miSVM's drawbacks related to positive instance underestimation and costly iteration. To show the advantages of our MIL-based approach as compared with a traditional supervised one, experiments with three X-ray databases were conducted. The area under the receiver operating characteristic curve was utilized as a performance measure. With the first database, for which training lesion annotations were available, our MIL-based method was comparable to the supervised system ( 0.86 versus 0.88 ). When evaluating the remaining databases, given their large difference with the previous image set, the most appealing strategy was to retrain the CAD systems. However, since only the case condition was available, only the MIL-based system could be retrained. This scenario, which is common in real-world applications, demonstrates the better adaptation capabilities of the proposed approach. After retraining, our MIL-based system significantly outperformed the supervised one ( 0.86 versus 0.79 and 0.91 versus 0.85 , and p=0.0002 , respectively).

Diagnostic accuracy of computer-aided detection of pulmonary tuberculosis in chest radiographs: a validation study from sub-Saharan Africa.

BACKGROUND: Chest radiography to diagnose and screen for pulmonary tuberculosis has limitations, especially due to inter-reader variability. Automating the interpretation has the potential to overcome this drawback and to deliver objective and reproducible results. The CAD4TB software is a computer-aided detection system that has shown promising preliminary findings. Evaluation studies in different settings are needed to assess diagnostic accuracy and practicability of use. METHODS: CAD4TB was evaluated on chest radiographs of patients with symptoms suggestive of pulmonary tuberculosis enrolled in two cohort studies in Tanzania. All patients were characterized by sputum smear microscopy and culture including subsequent antigen or molecular confirmation of Mycobacterium tuberculosis (M.tb) to determine the reference standard. Chest radiographs were read by the software and two human readers, one expert reader and one clinical officer. The sensitivity and specificity of CAD4TB was depicted using receiver operating characteristic (ROC) curves, the area under the curve calculated and the performance of the software compared to the results of human readers. RESULTS: Of 861 study participants, 194 (23%) were culture-positive for M.tb. The area under the ROC curve of CAD4TB for the detection of culture-positive pulmonary tuberculosis was 0.84 (95% CI 0.80-0.88). CAD4TB was significantly more accurate for the discrimination of smear-positive cases against non TB patients than for smear-negative cases (p-value<0.01). It differentiated better between TB cases and non TB patients among HIV-negative compared to HIV-positive individuals (p<0.01). CAD4TB significantly outperformed the clinical officer, but did not reach the accuracy of the expert reader (p = 0.02), for a tuberculosis specific reading threshold. CONCLUSION: CAD4TB accurately distinguished between the chest radiographs of culture-positive TB cases and controls. Further studies on cost-effectiveness, operational and ethical aspects should determine its place in diagnostic and screening algorithms.