Association of history of cerebrovascular disease with severity of COVID-19.

OBJECTIVE: To determine whether a history of cerebrovascular disease (CVD) increases risk of severe coronavirus disease 2019 (COVID-19). METHODS: In a retrospective multicenter study, we retrieved individual data from in-patients treated March 1 to April 15, 2020 from COVID-19 registries of three hospitals in Saxony, Germany. We also performed a systematic review and meta-analysis following PRISMA recommendations using PubMed, EMBASE, Cochrane Library databases and bibliographies of identified papers (last search on April 11, 2020) and pooled data with those deriving from our multicenter study. Of 3762 records identified, 11 eligible observational studies of laboratory-confirmed COVID-19 patients were included in quantitative data synthesis. Risk ratios (RR) of severe COVID-19 according to history of CVD were pooled using DerSimonian and Laird random effects model. Between-study heterogeneity was assessed using Cochran's Q and I2-statistics. Severity of COVID-19 according to definitions applied in included studies was the main outcome. Sensitivity analyses were conducted for clusters of studies with equal definitions of severity. RESULTS: Pooled analysis included data from 1906 laboratory-confirmed COVID-19 patients (43.9% females, median age ranging from 39 to 76 years). Patients with previous CVD had higher risk of severe COVID-19 than those without [RR 2.07, 95% confidence interval (CI) 1.52-2.81; p < 0.0001]. This association was also observed in clusters of studies that defined severe manifestation of the disease by clinical parameters (RR 1.44, 95% CI 1.22-1.71; p < 0.0001), necessity of intensive care (RR 2.79, 95% CI 1.83-4.24; p < 0.0001) and in-hospital death (RR 2.18, 95% CI 1.75-2.7; p < 0.0001). CONCLUSION: A history of CVD might constitute an important risk factor of unfavorable clinical course of COVID-19  suggesting a need of tailored infection prevention and clinical management strategies for this population at risk.

Detection of Robinsoniella peoriensis in multiple bone samples of a trauma patient.

We report a case of a 58-year-old male patient who underwent several surgeries following an accident. The bacterium Robinsoniella peoriensis was detected independently in multiple samples from both the right talus and tibia. The bacterium could only be identified using 16S rRNA gene sequencing.

Cerebral Abscess by Fonsecaea monophora-The First Case Reported in Germany.

We report the first case of cerebral Fonsecaea monophora infection in a German woman without immunodeficiency or travel history. F. monophora infection is a rare differential diagnosis of cerebral tumors; it was previously considered a tropical fungus. This case adds to the scarce reports in nontropical regions.

Serum vancomycin concentrations after oral and intracolonic vancomycin administration in a patient with colonic discontinuity and severe Clostridium difficile infection.

PURPOSE: A case of detectable systemic vancomycin levels after oral vancomycin administration but not after intracolonic administration in a patient with colonic discontinuity and severe Clostridium difficile infection (CDI) is reported. SUMMARY: A 63-year-old woman who had recently undergone pancreas-kidney transplantation developed severe CDI after 13 days of meropenem therapy for presumed urosepsis. Meropenem was stopped immediately, and treatment with oral vancomycin (250 mg every 6 hours) was started. Due to fulminant C. difficile colitis with signs of toxic megacolon and abdominal compartment syndrome, an emergency left hemicolectomy (Hartmann's procedure) was performed. Ten days after initiation of oral vancomycin therapy, the serum vancomycin concentration was 16.7 mg/L. After oral dose reduction to 125 mg every 6 hours, the measured serum vancomycin concentrations stayed above 10 mg/L. CDI therapy was terminated after 16 days. Eight days later, as sigmoidoscopy of the Hartmann rectal stump still showed pseudomembranes, intracolonic vancomycin application in the Hartmann rectal stump was started; 7-9 days after initiation of intracolonic therapy, the serum vancomycin concentration remained undetectable. The observed patterns of vancomycin exposure and absorption in this case suggest that the sigmoid colon is not the site of resorption of intracolonically applied vancomycin. CONCLUSION: A patient with severe CDI and Hartmann rectal stump after hemicolectomy was treated with vancomycin. After oral vancomycin therapy, significant enteral absorption was observed, while levels stayed undetectable during intracolonic administration alone.

The 2017 Update of the German Clinical Guideline on Epidemiology, Diagnostics, Therapy, Prevention, and Management of Uncomplicated Urinary Tract Infections in Adult Patients. Part II: Therapy and Prevention.

BACKGROUND: We aimed to update the 2010 evidence- and consensus-based national clinical guideline on the diagnosis and management of uncomplicated urinary tract infections (UTIs) in adult patients. Results are published in 2 parts. Part 1 covers methods, the definition of patient groups, and diagnostics. This second publication focuses on treatment of acute episodes of cystitis and pyelonephritis as well as on prophylaxis of recurrent UTIs. MATERIALS AND METHODS: An interdisciplinary group consisting of 17 representatives of 12 medical societies and a patient representative was formed. Systematic literature searches were conducted in MEDLINE, EMBASE, and the Cochrane Library to identify literature published in 2010-2015. RESULTS: For the treatment of acute uncomplicated cystitis (AUC), fosfomycin-trometamol, nitrofurantoin, nitroxoline, pivmecillinam, and trimethoprim (depending on the local rate of resistance) are all equally recommended. Cotrimoxazole, fluoroquinolones, and cephalosporins are not recommended as antibiotics of first choice, for concern of an unfavorable impact on the microbiome. Mild to moderate uncomplicated pyelonephritis should be treated with oral cefpodoxime, ceftibuten, ciprofloxacin, or levofloxacin. For AUC with mild to moderate symptoms, instead of antibiotics symptomatic treatment alone may be considered depending on patient preference after discussing adverse events and outcomes. Primarily non-antibiotic options are recommended for prophylaxis of recurrent urinary tract infection. CONCLUSION: In accordance with the global antibiotic stewardship initiative and considering new insights in scientific research, we updated our German clinical UTI guideline to promote a responsible antibiotic use and to give clear hands-on recommendations for the diagnosis and management of UTIs in adults in Germany for healthcare providers and patients.

The 2017 Update of the German Clinical Guideline on Epidemiology, Diagnostics, Therapy, Prevention, and Management of Uncomplicated Urinary Tract Infections in Adult Patients: Part 1.

OBJECTIVES: We aimed to update the 2010 evidence- and consensus-based national clinical guideline on the diagnosis and management of uncomplicated urinary tract infections (UTIs) in adult patients. MATERIALS AND METHODS: An interdisciplinary group consisting of 17 representatives of 12 medical societies and a patient representative was formed. Systematic literature searches were conducted in MEDLINE, -EMBASE, and the Cochrane Library to identify literature published in 2010-2015. RESULTS: We provide 75 recommendations and 68 statements in the updated evidence- and consensus-based national clinical guideline. The diagnostics part covers practical recommendations on cystitis and pyelonephritis for each defined patient group. Clinical examinations, as well as laboratory testing and microbiological pathogen assessment, are addressed. CONCLUSION: In accordance with the global antibiotic stewardship initiative and considering new insights in scientific research, we updated our German clinical UTI guideline to promote a responsible antibiotic use and to give clear hands-on recommendations for the diagnosis and management of UTIs in adults in Germany for healthcare providers and patients.

The revival of old antibiotics for treatment of uncomplicated urinary tract infections in the era of antibiotic stewardship.

PURPOSE OF REVIEW: In the era of increasing antibiotic resistance worldwide, this review highlights the advantages of revival of old antibiotics for treatment of uncomplicated urinary tract infections (uUTIs). RECENT FINDINGS: Recent studies have shown that these four oral old antibiotics, fosfomycin trometamol, nitrofurantoin, nitroxoline and pivmecillinam, show no increasing antibiotic resistance against uropathogens causing uUTI, are still effective for the treatment of uUTI and exhibit only minimal or no collateral damage as compared with fluoroquinolones or third-generation cephalosporines. SUMMARY: According to the principles of antibiotic stewardship, the prudent use of antibiotics is needed. Therefore, recent international and national guidelines already favour these old oral antibiotics as first-choice treatment of uUTI. Unfortunately, implementation of these guidelines is still suboptimal.

The complexity of diagnosing latent tuberculosis infection in older adults in long-term care facilities.

OBJECTIVES: In the USA, tuberculosis disease rates are highest in older adults. Diagnostic testing for latent tuberculosis infection (LTBI) has not been evaluated carefully in this group. The aim of this study was to define the relationship between tuberculin skin test (TST) results, T-SPOT.TB results, and T-cell responses to Mycobacterium tuberculosis antigens. METHODS: Long-term care facility residents with known prior TST results (positive or negative) were retested with TSTs and T-SPOT.TB. Prior exposure to M. tuberculosis was assessed by quantifying T-cell activation to mycobacterial antigens in vitro. RESULTS: The median age of the 37 participants was 77 years (range 57-98 years). Among 18 participants with a prior positive TST, three (16.7%) had a negative TST when retested (TST reversion); two had a negative T-SPOT.TB. Of the 15 who were historically and currently TST-positive, four (26.7%) had a negative T-SPOT.TB and one (6.7%) had a borderline result. Percentages of CD4+ T-cells responding to mycobacterial antigens were higher in participants with positive TST and T-SPOT.TB (18.2%) compared to those with a positive TST but negative T-SPOT.TB (6.4%, p=0.16) and negative TST and T-SPOT.TB (5.9%, p<0.001). CONCLUSIONS: LTBI testing in older adults is complicated by TST reversion and TST-positive/T-SPOT.TB-negative discordance, which may reflect clearance of infection or waning immunity.

B cell responses in older adults with latent tuberculosis: Considerations for vaccine development.

Reactivation of latent tuberculosis (LTBI) is more common among the aging population and may contribute to increased transmission in long-term health care facilities. Difficulties in detecting LTBI due to potential blunting of the tuberculin skin test (TST), and the lowered ability of the elderly to tolerate the course of antibiotics, underscore the need for an effective vaccine. Immuno-senescence reduces the capacity of vaccines to induce sufficient levels of protective immunity against many pathogens, further increasing the susceptibility of the elderly to infectious diseases. We sought to evaluate the response of B cells to Mycobacterium tuberculosis (Mtb) in residents of long-term care facilities to determine the feasibility of using a vaccine to control infection and transmission from reactivated LTBI. Our results demonstrate that although B cell responses were higher in subjects with LTBI, Mtb antigens could stimulate B cell activation and differentiation in vitro in TST negative subjects. B cells from elderly subjects expressed high basal levels of Toll-like receptor (TLR)2 and TLR4 and responded strongly to Mtb ligands with some activation pathways dependent on TLR2. B cells derived from blood, tonsil and spleen from younger subjects responded similarly and to the same magnitude. These results suggest that B cell responses are robust in the elderly and modifications to a TB vaccine, such as TLR2 ligand-based adjuvants, may help increase immune responses to a protective level.

Silicone-induced granuloma after injection for cosmetic purposes: a rare entity of calcitriol-mediated hypercalcemia.

Hypercalcemia is often a clue to the presence of unsuspected illness. We present an interesting case of an HIV-positive transgender female with a rare cause of silicone-induced granulomatous hypercalcemia. Although there have been a few case reports of silicone injections in dialysis patients causing hypercalcemia, this metabolic derangement secondary to silicone granulomas continues to be a unique entity with an unclear pathophysiology. We present a 45-year-old transgender HIV-positive female, with extensive silicone injections, who presented with symptomatic hypercalcemia. Workup for malignancy and hyperparathyroidism was negative. 1,25-Dihydroxyvitamin D level and 24-hour urine calcium level were elevated. CT scan showed extensive high-density reticulonodular densities in the buttocks and gluteal muscle fascia extending upwards to the lumbar region, along with prominent external iliac and inguinal lymph nodes. Nuclear imaging showed diffuse heterogeneity and increased uptake in the buttocks, most consistent with granuloma calcifications, and an inguinal lymph node biopsy confirmed a foreign body giant cell reaction. The patient was started on prednisone and this resulted in decrease in serum and urinary calcium levels. Physicians should have a high index of suspicion for silicone-induced hypercalcemia considering the growing prevalence of body contour enhancement with injections, implants, and fillers using this material.