Real-world trough concentrations and effectiveness of long-acting cabotegravir and rilpivirine: a multicenter prospective observational study in Switzerland.

Background: The efficacy and tolerability of long-acting cabotegravir and rilpivirine were demonstrated in Phase III trials. However, low concentrations combined with other risk factors have been associated with an increased risk of virologic failure. This study aims to verify whether drug concentrations measured in a real-world setting are consistent with those previously reported. Methods: SHCS-879 is a nationwide observational study within the Swiss HIV Cohort Study for the monitoring of people with HIV (PWH) on long-acting cabotegravir plus rilpivirine. Samples were collected from March 2022 to March 2023. Findings: Overall, 725 samples were obtained from 186 PWH. Our data show a large inter-individual variability in cabotegravir and rilpivirine concentrations, with some individuals exhibiting repeatedly low concentrations. Rilpivirine trough concentrations were consistent with those from Phase III trials, while cabotegravir concentrations were lower. The first concentrations quartile was only slightly above the target of 664 ng/mL. Exploratory statistical analyses found 35% (p < 0·01) lower cabotegravir trough in males compared to females. Overall, 172 PWH (92%) remained suppressed and three experienced virologic failures (1·6%), of those, two had sub-optimal drug exposure. No association was found between low trough levels and detectable viral load. Interpretation: Real-world cabotegravir concentrations are substantially lower than previously reported. However, these concentrations appear sufficient to ensure sustained virological suppression in almost every PWH. These reassuring data challenge the rather conservative thresholds adopted to date, which may raise unnecessary concerns. Yet, our study reveals that some PWH have repeatedly very low drug levels, for reasons that remain to be elucidated. Funding: This work was funded by the Swiss National Science Foundation, grant number N◦ 324730_192449. This study received no support from pharmaceutical industries. This study was performed within the framework of the Swiss HIV Cohort Study, supported by the Swiss National Science Foundation (grant #201369), by SHCS project #879, and by the SHCS research foundation. The SHCS data were gathered by the Five Swiss University Hospitals, two Cantonal Hospitals, 15 affiliated hospitals and 36 private physicians (listed in http://www.shcs.ch/180-health-care-providers).

Vaccination willingness for COVID-19 among healthcare workers: a cross-sectional survey in a Swiss canton.

AIMS OF THE STUDY: Vaccination is regarded as the most promising response to the COVID-19 pandemic. We assessed opinions about COVID-19 vaccination, willingness to be vaccinated, and reasons for vaccination hesitancy among healthcare workers. METHODS: We conducted a cross-sectional, web-based survey among 3,793 healthcare workers in December 2020 in the Canton of Solothurn, Switzerland, before the start of the national COVID-19 vaccination campaign. RESULTS: Median age was 43 years (interquartile range [IQR] 31-53), 2,841 were female (74.9%). A total of 1,511 healthcare workers (39.8%) reported willingness to accept vaccination, whereas 1,114 (29.4%) were unsure and 1,168 (30.8%) would decline vaccination. Among medical doctors, 76.1% were willing, whereas only 27.8% of nurses expressed willingness. Among the 1,168 healthcare workers who would decline vaccination, 1,073 (91.9%) expressed concerns about vaccine safety and side effects. The willingness of healthcare workers to be vaccinated was associated with older age (adjusted odds ratio [aOR] 1.97, 95% confidence interval [Cl] 1.71-2.27) and having been vaccinated for influenza this year (aOR 2.70, 95% Cl 2.20-3.31). Healthcare workers who reported a lack of confidence in government were less likely to be willing to be vaccinated (aOR 0.58, 95% Cl 0.40-0.84), and women were less willing to be vaccinated than men (OR 0.33, 95% CI 0.28-0.38). CONCLUSION: Less than half of healthcare workers reported willingness to be vaccinated before the campaign start, but proportions varied greatly depending on profession and workplace. Strategies with clear and objective messages that particularly address the concerns of healthcare workers are needed if their willingness to be vaccinated against COVID-19 is to be further increased.

[Laparostoma-Avoidance and treatment of complications]. / Laparostoma ­ Vermeidung und Therapie von Komplikationen.

The open abdomen (OA) is an established concept for treating severe abdominal diseases. The most frequent reasons for placement of an open abdomen are abdominal sepsis (e.g. from intestinal perforation or anastomotic leakage), severe abdominal organ injury and abdominal compartment syndrome. The pathophysiology is much more complex than the surgeon's eye can see in an OA. The temporary closure of the abdominal wall ensures sufficient drainage of infected ascites, protection of the intestinal loops and conditioning of the abdominal wall in order to be able carry out definitive closure of the abdominal wall at the end of the surgical treatment. Negative peritoneal pressure therapy combined with fascia traction (with or without mesh) is well-established in the management of an open abdomen.

COVID-19 in a Patient with Accidental Drug-Induced Neutropenia.

BACKGROUND: Coronavirus disease 2019 (COVID-19) presents with a wide range of illness severity, from asymptomatic disease to severe acute respiratory distress syndrome (ARDS). Immunosuppression is considered a risk factor for severe COVID-19, but there are only few reports on disease progression in immunocompromised patients. CASE SUMMARY: We report the case of a 50-year-old patient with acute COVID-19 pneumonia, who had iatrogenic, clinically relevant bone marrow suppression due to accidental overdose with hydroxyurea, and decreased lung capacity due to a left-sided pneumonectomy 6 months earlier. Symptomatic treatment with oxygen supplementation and pulmonary physical therapy was initiated, and hydroxyurea was discontinued. Over 14 days, the patient's blood counts slowly recovered, and his clinical condition gradually improved, such that supplemental oxygen was no longer necessary and he could be discharged. DISCUSSION: A gradual increase in neutrophil and lymphocyte counts may be preferable to dampen a potentially detrimental immunological response triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Whether patients with severe COVID-19 benefit from immunosuppressive therapy should be further evaluated. LEARNING POINTS: Acute respiratory distress syndrome is a serious complication in COVID-19 and appears to be triggered by a proinflammatory cytokine storm.Immunosuppression may avoid an immune hyper-response triggered by SARS-CoV-2.

Transmission risk of SARS-CoV-2 to healthcare workers -observational results of a primary care hospital contact tracing.

BACKGROUND: The coronavirus disease (COVID)-19 epidemic is evolving rapidly. Healthcare workers are at increased risk for infection, and specific requirements for their protection are advisable to ensure the functioning of the basic healthcare system, including the availability of general practitioners (GPs). Understanding the transmission risk is particularly important for guiding evidence-based protective measures in the primary healthcare setting. METHODS: Healthcare worker contacts of an initially undiagnosed COVID-19 case, who were without personal protective equipment, in particular not wearing facemasks, were screened with nasopharyngeal swabs and polymerase chain reaction tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), irrespective of respiratory symptoms or fever seven days after initial contact. The details of exposure to the index case were obtained during routine contact investigation after unintentional pathogen exposure. RESULTS: Twenty-one healthcare workers reported contacts with the index case. Three healthcare workers reported respiratory symptoms (cough) or low-grade fever within 4 days. None of them tested positive for SARS-CoV-2 at the time of symptom onset. All 21 healthcare workers tested SARS-CoV-2 negative 7 days after initial index case contact, including the three healthcare workers with previous symptoms. Ten of the 21 healthcare workers reported a cumulative exposure time of >15 minutes. Longer cumulative contact times were associated with more individual contacts, reduced contact time per contact and activities with physical patient contact. The closest relative of the index patient tested SARS-CoV-2 positive 2 days after the index case presented at the hospital emergency department. CONCLUSION: We found a low risk of SARS-CoV-2 transmission in a primary care setting. These findings are compatible with previous reports of the highest transmission probability in household settings with prolonged close contacts. The current protective measures for healthcare workers, including strict adherence to basic standard hygiene and facemasks, offer considerable protection during short periods of contact with symptomatic COVID-19 cases by diminishing the risk of direct and indirect transmission.

Is there a role for procalcitonin in differentiating uncomplicated and complicated diverticulitis in order to reduce antibiotic therapy? A prospective diagnostic cohort study.

AIMS OF THE STUDY: While studies show that antibiotic treatment for uncomplicated diverticulitis seems to have no benefit, most experts advocate antimicrobial therapy for complicated diverticulitis. However, even for uncomplicated diverticulitis, most clinicians are very reluctant to withhold antibiotics. Biomarkers could help to guide antibiotic therapy as this approach has been shown to be effective for acute respiratory infections. In this diagnostic cohort study we evaluated whether procalcitonin could be a biomarker to distinguish complicated from uncomplicated cases of diverticulitis. METHODS: Complicated diverticulitis was defined as having abscess formation or perforation diagnosed by abdominal computed tomography (CT) scan. In all patients with suspected diverticulitis, procalcitonin values were measured at admission and on day 2. These values were blinded for clinicians, and treatment was carried out according to the physician's judgement. Two groups (complicated vs uncomplicated diverticulitis) were defined. Patients who had received antibiotic treatment before admission were excluded. Difference in procalcitonin values was calculated for both groups using the Mann-Whitney test. Receiver operating characteristics (ROC) were calculated to determine cut-off values for procalcitonin according to the gold standard (abdominal CT scans). RESULTS: 115 patients were included for analysis. 35 patients (30%) suffered from complicated diverticulitis. The median procalcitonin value for uncomplicated diverticulitis was significantly lower compared to complicated diverticulitis (median 0.05, interquartile range [IQR] 0.05-0.06 ng/l vs median 0.13, IQR 0.05-0.23 ng/l; p <0.0001). In the ROC analysis, the sensitivity and specificity were 81% and 91% when the highest procalcitonin value (days 1 and 2) was considered, with a cut-off value of 0.1 ng/l. CONCLUSION: Procalcitonin was able to differentiate with a high sensitivity and specificity between complicated and uncomplicated cases of diverticulitis when combined with abdominal CT scans. As most clinicians still treat uncomplicated diverticulitis with antibiotics, procalcitonin could be an interesting parameter for guiding therapy and decreasing antibiotic usage. This should be further evaluated in randomised trials.

Correction: A Cross-Sectional Study of Colonization Rates with Methicillin-Resistant Staphylococcus aureus (MRSA) and Extended-Spectrum Beta-Lactamase (ESBL) and Carbapenemase-Producing Enterobacteriaceae in Four Swiss Refugee Centres.

[This corrects the article DOI: 10.1371/journal.pone.0170251.].

A Cross-Sectional Study of Colonization Rates with Methicillin-Resistant Staphylococcus aureus (MRSA) and Extended-Spectrum Beta-Lactamase (ESBL) and Carbapenemase-Producing Enterobacteriaceae in Four Swiss Refugee Centres.

BACKGROUND: The recent crisis of refugees seeking asylum in European countries challenges public health on many levels. Most refugees currently arrive from Syria, Afghanistan, or Eritrea. Data about multidrug resistant bacteria (MDR) prevalence are not present for these countries. However, when entering the European heath care systems, data about colonisation rates regarding highly resistant bacterial pathogens are important. METHODS: We performed a cross-sectional screening in four Swiss refugee centres to determine the colonization rates for MRSA and ESBL- and carbapenemase-producing Enterobacteriaceae. We used pharyngeal, nasal, and inguinal swabs for MRSA and rectal swabs and urine for ESBL and carbapenemase screening using standard microbiological procedures. Whole genome sequencing (WGS) was used to determine the relatedness of MRSA isolates with high resolution due to a suspected outbreak. RESULTS: 41/261(15.7%) refugees were colonized with MRSA. No differences regarding the country of origin were observed. However, in a single centre significantly more were colonized, which was confirmed to be a recent local outbreak. 57/241 (23.7%) refugees were colonized with ESBL with significantly higher colonisation in persons originating from the Middle East (35.1%, p<0.001). No carbapenemase producers were detected. CONCLUSION: The colonisation rate of the refugees was about 10 times higher for MRSA and 2-5 times higher for ESBL compared to the Swiss population. Contact precaution is warranted for these persons if they enter medical care. In cases of infections, MRSA and ESBL-producing Enterobacteriaceae should be considered regarding antibiotic treatment choices.

Low sensitivity of needle aspiration cultures in patients with cellulitis/erysipelas.

PURPOSE: Cellulitis is normally treated without knowledge of the responsible pathogen. Blood cultures are positive in about 2-4 %, and superficial swabs are of no value. Needle aspiration has been proposed with identifying the likely pathogen in up to 29 %, but these studies are of older date and the technique is not widely used. METHODS: We prospectively evaluated the sensitivity of needle aspiration cultures in all patients with erysipelas/cellulitis. Diagnosis was made clinically by the treating physician. Needle aspiration was done with a 1 ml syringe and a 26G needle. The needle was removed and the syringe brought to the microbiological laboratory and analysed according to standard procedures. RESULTS: 95 Patients were seen during a period of 22 month. 4 Patients were excluded, as diagnosis was not confirmed. Cellulitis was present in 10/91 and erysipelas in 81/91 patients. In the first 25 patients with needle aspiration from the margin, none was positive. In 8/66 (12 %) patients where needle aspiration was done at the site of maximum inflammation, the pathogen was identified. 4/8 Cultures were positive for S. aureus, 2/8 for streptococci and 2/8 for other bacteria. In 11/66 (16.6 %) patients, skin colonisation flora was detected. In the subgroup of patients without prior antibiotic treatment and needle aspiration from the site of maximum inflammation, sensitivity was slightly better 8/55 (14.5 %; 95 % CI 7.5-25.8 %). CONCLUSIONS: Needle aspiration culture had a low sensitivity for detecting responsible pathogen in patients with cellulitis/erysipelas. No impact in antibiotic treatment could be observed.

Can we trust the guidelines? Comparison between the data presented and the recommendations of the International Antiviral Society-USA Panel.

INTRODUCTION: Clinicians often do not have the time and possibilities to read all scientific evidence necessary to maintain high quality patient care. They rely on guidelines made by experts to help them in their daily work. METHODS: We compared the 2012 recommendations and the arguments of the IAS-USA Panel with the data referenced and presented with the original data of the studies. Special topic was the timing of antiretroviral therapy. Only studies included in the guideline text were analyzed. RESULTS: There is a large discrepancy between the data and the recommendations concerning early antiviral therapy. The studies are either not designed to answer this question or the data is not sufficient to support the arguments. The authors highlight benefits without mention of side effects or other problems. Neither in transmission rates, nor mortality, AIDS events, co-morbidities (hepatitis B and C excluded) or decreasing the risk of malignancy, the data presented support early therapy. CONCLUSIONS: A large discrepancy between the underlining data and the recommendation made by the IAS-USA Panel exists concerning early antiviral therapy.

Per oral substitution with 300000 IU vitamin D (Cholecalciferol) reduces bone turnover markers in HIV-infected patients.

BACKGROUND: Osteoporosis and bone fractures seem to be higher in HIV-infected Patients compared to the general populations. Moreover, bone turnover markers are increased in patients on antiretroviral therapy and vitamin D deficiency is prevalent in HIV-infected patients. However, the influence of per oral cholecalciferol on bone metabolism in HIV infected patients is not well understood. METHODS: We measured the bone turnover markers in 96 HIV-infected patients: Bone specific alkaline phosphatase (BSAP), Pyridinoline (PYR), Desoxypyridinoline (DPD) and 25-OH vitamin D. If 25-OH vitamin D was below 75 nnol/L (87/96 patients), 300000 IU cholecalciferol was given per os. 25OH-vitamin D and bone turn over markers were determinded 3 month later. 25 OH-vitamin D was corrected for circannual rythm y'=y+17.875*sin2π/365*day+2.06, whereas bone turnover markers were not corrected. The paired students t-Test was used to compare the two periods. No calcium supplementation or biphosphonate therapy was given. RESULTS: Corrected 25OH-vitamin D levels increased significantly after supplementation (42.7 ± 26.61 vs. 52.85 ± 21.8 nmol/L, p < 0.001). After supplementation, bone turnover markers were significantly lower. The values decreased for BSAP from 21.31 ± 14.32 to 17.53 ± 8.17 µg/L (p < 0.001), PYR from 74.57 ± 36.83 to 54.82 ± 21.43 nmol/mmol creatinine (p < 0.001) and DPD from 15.17 ± 8.34 to 12.61 ± 5.02 nmol/mmol creatinine (p = 0.01). CONCLUSIONS: After per oral substitution with cholecalciferol, bone formation as well as bone resorption markers decreased significant. We postulate a protective effect on bone structure with cholecalciferol supplementation.

The routine use of urinary pneumococcal antigen test in hospitalised patients with community acquired pneumonia has limited impact for adjustment of antibiotic treatment.

BACKGROUND: The urinary pneumococcal antigen (PnAG) test is widely used in the setting of community acquired pneumonia (CAP). Data regarding the impact of the test on antibiotic prescriptions are lacking. METHOD: The study population consisted of patients with suspicion of CAP in whom PnAG testing was performed. From November 2007 until August 2008, all patients in whom pneumococcal antigen testing (Binax Now®, PnAG) was performed were evaluated. In a second period, from September 2008 until March 2009, we stopped PnAG testing in our institution. We compared the microbiological verification procedures, antibiotic prescription and the final diagnosis of CAP of the first period (n = 139) against the second period (n = 147). RESULTS: Only 139/188 patients in whom PnAG was performed had CAP. Of these, 22 (15%) were PnAG positive. In 11/22 patients, the diagnosis of pneumococcal pneumonia was additionally confirmed by positive blood and/or sputum culture. In only 6 of the remaining 11 patients, antibiotic treatment was changed as a consequence of the positive PnAG test. In cases of blood culture positive and in sputum positive pneumococcal pneumonia, only 8/13 (61%) and 3/15 (20%) were PnAG positive, respectively. The costs of the PnAG test were 188 × 42 CHF (in total 7,896 CHF) and no cost savings were observed. Neither with empiric nor with consequently prescribed antibiotic treatment was a difference found between the PnAG and control period. CONCLUSION: In our patient population, the routine Binax Now® PnAG testing did not lead to cost savings or narrowing of antibiotic prescriptions. Thus, PnAG testing should be limited to cases of diagnostic uncertainty where blood or sputum cultures are negative or not available.

Severe isoniazid related sideroblastic anemia.

Isoniazid induced sideroblastic anemia is a rare event. We report case of a 45 year old Caucasian women with development of severe anaemia 4 month after introduction of Isoniazid as part of Tuberculosis treatment. While haemoglobin fell to 47 g/L and erythrocyte count to 1.5 G/L, reticulocytes were very low (reticulocyte production index of 0.48), but bone marrow aspirate showed an accelerated erythropoiesis with ringsideroblasts. Anaemia rapidly resolved after cessation of Isoniazid. We postulate an Isoniazid induced inhibition of the δ-Amino-levulinat-synthase resulting in marked depletion of heam synthesis.

Markers of bone turnover are elevated in patients with antiretroviral treatment independent of the substance used.

OBJECTIVES: Osteoporosis and bone fractures are correlated to antiretroviral treatment. It is not clear whether some substances comprise greater risks of bone loss than others. METHODS: We measured pyridinoline, deoxypyridinoline crosslinks, and bone-specific alkaline phosphatase in 113 HIV-positive patients. We compared patients with and without antiretroviral treatment. We then compared patients with versus without tenofovir and patients with protease inhibitor versus nonnucleoside reverse transcriptase inhibitor use. RESULTS: Bone-specific alkaline phosphatase, pyridinoline, and deoxypyridinoline crosslinks were significantly higher in patients with antiretroviral treatment compared with patients without antiretroviral treatment: 24.5 versus 13.04 pg/L (P < 0.001), 82.73 versus 51.93 nmol/mmol (P < 0.001), and 16.56 versus 9.94 nmol/mmol (P < 0.001), respectively. In contrast, no difference was found between patients with and without tenofovir: 25.38 versus 20.02 pg/l (P = 0.1); 79.85 versus 83.95 nmol/mmol (P = 0.64), and 19.12 versus 14.00 nmol/mmol (P = 0.14), respectively. Comparison between patients with protease inhibitor versus nonnucleoside reverse transcriptase inhibitor yielded no difference either: 23.07 versus 27.18 pg/L (P = 0.24), 92.96 versus 80.73 nmol/mmol (P = 0.36), and 18.22 versus 16.39 nmol/mmol (P = 0.55). CONCLUSION: Markers for bone turnover are higher in treated compared with untreated patients. No difference concerning tenofovir use or protease inhibitor versus nonnucleoside reverse transcriptase inhibitor use could be found.