Genomic characterization of methicillin-susceptible Staphylococcus aureus carriage in patients on home parenteral nutrition and their caregivers.

In this prospective study, patients on home parenteral nutrition were twice as likely to be colonized with Staphylococcus aureus if their caregivers were also carriers. Among S. aureus-positive patients and their caregivers, molecular analysis showed 68% genetically related strains. Despite decolonization, genetically related strains reappeared in 70% of patients.

Oral antimicrobial agents in patients with short bowel syndrome: worth a try!

BACKGROUND: The use of oral antimicrobial agents in patients with short bowel syndrome (SBS) is challenging due to the changes in gastrointestinal anatomy that may result in diminished absorption and altered drug bioavailability. Prospective studies evaluating bioavailability of antimicrobial agents after oral administration in SBS patients are lacking. OBJECTIVES: To determine the bioavailability of orally administered antimicrobial agents commonly used for treatment in SBS patients to guide clinical decision making when faced with infections. METHODS: We performed an explorative, clinical study investigating the pharmacokinetics (PK) of clindamycin, ciprofloxacin, flucloxacillin and fluconazole in SBS patients with intestinal failure. Participants received a combination of two antimicrobial agents simultaneously. To determine the oral bioavailability, participants received a single oral and IV dose of both agents on two occasions, after which they underwent intensive PK sampling on six predefined time points up to 12 hours after administration. Primary outcome was the oral bioavailability of these antimicrobial agents. Secondary outcomes were intravenous PK characteristics following non-compartmental analysis. RESULTS: Eighteen SBS patients were included: the mean (SD) age was 59 (17) years and 61% of participants were female. The median observed (IQR) bioavailability of ciprofloxacin, clindamycin, flucloxacillin and fluconazole were 36% (24-50), 93% (56-106), 50% (32-76) and 98% (61-107), respectively. CONCLUSION: The bioavailability of selected antimicrobial agents in certain patients with SBS appeared to be better than expected, providing a feasible treatment option. Due to the large observed differences between patients, therapeutic drug monitoring should be part of the treatment to safeguard adequate exposure in all patients. TRIAL REGISTRATION: Registered in the Dutch Trial Register (NL7796) and EudraCT number 2019-002587-28.

Randomized clinical trial: Long-term Staphylococcus aureus decolonization in patients on home parenteral nutrition.

BACKGROUND & AIMS: Staphylococcus aureus decolonization has proven successful in prevention of S. aureus infections and is a key strategy to maintain venous access and avoid hospitalization in patients receiving home parenteral nutrition (HPN). We aimed to determine the most effective and safe long-term S. aureus decolonization regimen. METHODS: A randomized, open-label, multicenter clinical trial was conducted. Adult intestinal failure patients with HPN support and carrying S. aureus were randomly assigned to a 'continuous suppression' (CS) strategy, a repeated chronic topical antibiotic treatment or a 'search and destroy' (SD) strategy, a short and systemic antibiotic treatment. Primary outcome was the proportion of patients in whom S. aureus was totally eradicated during a 1-year period. Secondary outcomes included risk factors for decolonization failure and S. aureus infections, antimicrobial resistance, adverse events, patient compliance and cost-effectivity. RESULTS: 63 participants were included (CS 31; SD 32). The mean 1-year S. aureus decolonization rate was 61% (95% CI 44, 75) for the CS group and 39% (95% CI 25, 56) for the SD group with an OR of 2.38 (95% CI 0.92, 6.11, P = 0.07). More adverse effects occurred in the SD group (P = 0.01). Predictors for eradication failure were a S. aureus positive caregiver and presence of a (gastro)enterostomy. CONCLUSION: We did not demonstrate an increased efficacy of a short and systemic S. aureus decolonization strategy over a continuous topical suppression treatment. The latter may be the best option for HPN patients as it achieved a higher long-term decolonization rate and was well-tolerated (NCT03173053).

Catheter-related bloodstream infection management in patients receiving home parenteral nutrition: An observational cohort study.

BACKGROUND AND AIMS: Patients with intestinal failure receiving home parenteral nutrition (HPN) are susceptible to central-line associated bloodstream infections (CLABSIs), with crucial roles for adequate (empiric) antimicrobial therapy and effective catheter management strategies. Our aim was to link recent epidemiologic CLABSI data with clinical outcomes and to identify risk factors for therapeutic failure to decide on the safest and most accurate CLABSI management in patients receiving HPN. METHODS: A retrospective observational cohort study was conducted. All data on CLABSIs (period 2010-2020) in adult patients receiving HPN were retrieved. The efficacy of attempted catheter salvage and empiric antimicrobial treatment (ß-lactam antibiotics) in our center, with a low prevalence of methicillin-resistant staphylococci, was investigated. Multivariate cox-regression analysis was performed to identify risk factors for recurrent CLABSI. RESULTS: 389 CLABSIs occurred in 149 patients. The overall infection rate was 0.64 per 1000 central venous catheter (CVC) days. Most CLABSIs were caused by Coagulase-negative staphylococci (37%). Attempted CVC salvage was successful in 70% of the cases. Empiric antimicrobial therapy was found to be adequate in only 47% of cases, mainly because of insufficient Coagulase-negative staphylococci coverage. According to the Cox model, patients with a replaced CVC had a 50% lower risk of a new CLABSI than patients with a retained (salvaged) CVC during follow-up (HR 0.50; 95% CI 0.35-0.72, P < 0.001). CONCLUSIONS: CVC salvage can be achieved in most CLABSI cases but seems associated with a shorter CLABSI-free survival. Importantly, based on our findings, a glycopeptide containing antibiotic treatment regimen will increase the likelihood of adequate empiric coverage.

Individualizing the use of [18F]FDG-PET/CT in patients with complicated Staphylococcus aureus bacteremia: experiences from a tertiary care center.

PURPOSE: [18F]FDG-PET/CT scanning can help detect metastatic infectious foci and reduce mortality in patients with Staphylococcus aureus bacteremia (SAB), but it is unknown if patients with SAB and an indication for prolonged treatment because of possible endovascular, orthopaedic implant, or other metastatic infection still need [18F]FDG-PET/CT. METHODS: In a retrospective single-center cohort study, we included all consecutive adult patients with SAB between 2013 and 2020 if an [18F]FDG-PET/CT scan was performed and antibiotic treatment was planned for ≥ 6 weeks prior to [18F]FDG-PET/CT. We aimed to identify patients for whom treatment was adjusted due to the results of [18F]FDG-PET/CT, and assessed concordance of [18F]FDG-PET/CT and clinical diagnosis for infected prosthetic material. RESULTS: Among 132 patients included, the original treatment plan was changed after [18F]FDG-PET/CT in 22 patients (16.7%), in the majority (n = 20) due to diagnosing or rejecting endovascular (graft) infection. Antibiotic treatment modifications were shortening in 2, iv-oral switch in 3, extension in 13, and addition of rifampicin in 4 patients. Ninety additional metastatic foci based on [18F]FDG-PET/CT results were found in 69/132 patients (52.3%). [18F]FDG-PET/CT suggested vascular graft infection in 7/14 patients who lacked clinical signs of infection, but showed no infection of prosthetic joints or osteosynthesis material in eight patients who lacked clinical signs of such an infection. CONCLUSION: [18F]FDG-PET/CT can help refine treatment for SAB in patients with clinically suspected endovascular infection or vascular grafts, even if 6 weeks treatment is already indicated, but can be safely omitted in other patients who are clinically stable.

The diagnostic value of [18F]FDG-PET/CT in detecting septic thrombosis in patients with central venous catheter-related Staphylococcus aureus bacteremia.

PURPOSE: Septic thrombosis often complicates Staphylococcus aureus bacteremia (SAB) in patients with a central venous catheter. Currently there is no reference standard for diagnosis. We describe the diagnostic value of [18F]FDG-PET/CT imaging in a patient cohort and the potential contribution of quantitative measurements in detecting septic thrombosis. METHODS: We selected patients with catheter-related SAB from our institutional database (2013-2020). The contribution of [18F]FDG-PET/CT on clinical diagnosis of septic thrombosis was evaluated. Standardized Uptake Values (SUV) were measured and compared with a composite reference standard (clinical signs, initial [18F]FDG-PET/CT result, Multidisciplinary Team (MDT) meeting outcome) to identify a cut-off value for detecting septic thrombosis. RESULTS: We identified 93 patients with a catheter-related SAB. Quantitative measurements were possible for 43/56 patients in whom a [18F]FDG-PET/CT scan was performed. Septic thrombosis was clinically diagnosed in 30% (13/43) of the cases. In 85% of these cases, significant [18F]FDG-PET/CT uptake at the site of the thrombus was the deciding factor for diagnosis of septic thrombosis during the MDT meeting. All mean SUV's of thrombotic lesions were higher in patients with clinically proven septic thrombosis compared to patients in whom this diagnosis was rejected (p < 0.001). A SUVpeak thrombus/SUVmean blood ratio of 1.6 (AUC-ROC value 0.982) as cut-off to differentiate between septic thrombosis and non-septic thrombosis had a sensitivity of 92% (95% CI 64-100) and specificity of 89% (95% CI 65-99). An algorithm was designed to guide diagnosis of septic thrombosis. CONCLUSION: Quantitative [18F]FDG-PET/CT-derived parameters seem helpful to differentiate between septic and non-septic thrombosis in patients with catheter-related SAB.

Comparing success rates in central venous catheter salvage for catheter-related bloodstream infections in adult patients on home parenteral nutrition: a systematic review and meta-analysis.

BACKGROUND: Catheter-related bloodstream infection (CRBSI) is a life-threatening complication of parenteral nutrition. Therefore, optimal management, ideally with catheter salvage, is required to maintain long-term venous access. OBJECTIVES: We aimed to evaluate successful catheter salvage rates in patients on home parenteral nutrition (HPN). METHODS: Studies were retrieved from medical databases, conference proceedings, and article reference lists. Data were collected relating to clinical outcomes of 3 treatments: systemic antibiotics, antimicrobial lock therapy (ALT), and catheter exchange. ORs and 95% CIs were calculated from a mixed logistic effects model. RESULTS: From 10,036 identified publications, 28 met the inclusion criteria (22 cohort studies, 5 case-control studies, and 1 randomized clinical trial), resulting in a total of 4911 CRBSIs. To achieve successful catheter salvage, the addition of an antimicrobial lock solution was superior to systemic antibiotics alone (OR: 1.75; 95% CI: 1.21, 2.53; P = 0.003). Recurrence of infection was less common in studies that used ALT than in those that used systemic antibiotics alone (OR: 0.26; 95% CI: 0.11, 0.61; P = 0.002). The catheter exchange group was excluded from multilevel regression analysis because only 1 included study applied this treatment. Successful salvage rates were highest for coagulase-negative staphylococci, followed by Gram-negative rods and Staphylococcus aureus . CONCLUSIONS: The addition of an antimicrobial lock solution seems beneficial for successful catheter salvage in HPN-dependent patients with a CRBSI. Future prospective randomized studies should identify the most effective and pathogen-specific strategy.This review was registered at www.crd.york.ac.uk/PROSPERO as CRD42018102959.

Intravenous to Oral Switch in Complicated Staphylococcus aureus Bacteremia Without Endovascular Infection: A Retrospective Single-Center Cohort Study.

In this retrospective cohort study, selected patients with disseminated Staphylococcus aureus bacteremia, but without endovascular infection on echocardiography and 18F-FDG-PET/CT, were free of relapse after IV-oral switch. Mortality was low and similar to patients who received prolonged intravenous treatment. IV-oral switch was associated with a shorter length of hospital stay.

Eradication of Staphylococcus aureus colonization by chronic use of mupirocin in patients on home parenteral nutrition.

OBJECTIVES: Although in other groups Staphylococcus aureus eradication has proven to be an effective infection prevention measure, to our knowledge, no such studies have been performed in patients on home parenteral nutrition (HPN). The aim of this study was to investigate the efficacy of chronic nasal mupirocin use on S. aureus eradication and prevention of catheter related infections in patients on HPN. METHODS: This was a cohort study with data collected from adult patients on HPN who were screened for S. aureus carriage. In case of carriage, the patient was instructed to apply mupirocin nasal ointment monthly. Outcomes were the percentage of successful S. aureus eradication and the effect on the incidence of catheter-related infections and development of mupirocin resistance. RESULTS: S. aureus nasal carriage was found in 54% of the patients. Eradication was successful in 66% (70 of 106) of patients treated with mupirocin. Overall S. aureus catheter-related infection rates decreased by 50% (P = 0.02). The decrease was mostly due to a drop in central line-associated bloodstream infection (CLABSI) rates (0.26versus 0.1 per 1000 central venous catheter days; P = 0.04). The overall CLABSI rates decreased as well (incidence ratio rate, 0.43; 95% confidence interval. 0.24-0.76; P < 0.01). Low-level mupirocin resistance was observed in four patients. CONCLUSIONS: Findings from the present study highlighted the potential usefulness of mupirocin ointment prophylaxis to establish S. aureus eradication in patients on HPN. However, awareness for the development of mupirocin resistance is prudent. Further research needs to be carried out to validate these findings.

Clinical Characteristics and Outcomes of S. Aureus Bacteremia in Patients Receiving Total Parenteral Nutrition.

Background: Patients on total parenteral nutrition (TPN) are at risk of developing central line-associated infections. Specifically, Staphylococcus aureus bacteremia (SAB) is feared for its high complication rates. This prospective cohort study compares characteristics, clinical course and outcome of SAB in patients with and without TPN support. Methods: Clinical and microbiological data from all patients with positive blood cultures for S. aureus from two facilities, including our referral center for TPN support, were retrieved (period 2013-2020). Primary outcome was overall mortality, and included survival analysis using a multivariate Cox regression model. Secondary outcomes comprised a comparison of clinical characteristics and outcomes between both patient groups and analysis of factors associated with complicated outcome (e.g., endocarditis, deep-seated foci, relapse and death) in patients on TPN specifically. Results: A total of 620 SAB cases were analyzed, of which 53 cases received TPN at the moment the blood culture was taken. Patients in the TPN group were more frequently female, younger and had less comorbidity (p < 0.001). In-hospital death and overall mortality were significantly lower in TPN patients (4% vs. 18%, p = 0.004 and 10% vs. 34%, p < 0.001, respectively). Positive follow-up blood cultures, delayed onset of therapy and previous catheter problems were associated with a higher incidence of complicated SAB outcome in patients on TPN. Conclusion: Our data show that patients on TPN have a milder course of SAB with lower mortality rates compared to non-TPN SAB patients.

Long-term Staphylococcus aureus decolonization in patients on home parenteral nutrition: study protocol for a randomized multicenter trial.

BACKGROUND: Patients with long-term intestinal failure are usually treated by means of home parenteral nutrition (HPN) where they administer their nutritional formulation intravenously via a central venous access device (mostly a catheter). This implies that such patients are exposed to a lifelong risk of developing Staphylococcus aureus bacteremia (SAB). SAB poses a threat to both catheter and patient survival and may lead to frequent hospitalization and a permanent loss of vascular access. In other clinical settings, S. aureus carriage eradication has been proven effective in the prevention of S. aureus infections. Unfortunately, there is a complete lack of evidence in HPN support on the most effective and safe S. aureus decolonization strategy in S. aureus carriers. We hypothesized that long-term S. aureus decolonization in HPN patients can only be effective if it is aimed at the whole body (nasal and extra-nasal) and is given chronically or repeatedly on indication. Besides this, we believe that S. aureus carriage among caregivers, who are in close contact with the patient, are of great importance in the S. aureus transmission routes. METHODS/DESIGN: The CARRIER trial is a randomized, open-label, multicenter clinical trial in Dutch and Danish hospitals that treat patients on HPN. A total of 138 adult HPN patients carrying S. aureus will be randomly assigned to a search and destroy (SD) strategy, a quick and short, systemic antibiotic treatment, or a continuous suppression (CS) strategy, a repeated chronic topical antibiotic treatment. The primary outcome measure is the proportion of patients in whom S. aureus is totally eradicated during a 1-year period. Secondary outcomes are time to successful eradication, long-term antimicrobial resistance, adverse events, patient compliance, incidence of (S. aureus) infections, catheter removals, mortality rates, S. aureus transmission routes, quality of life, and health care costs. DISCUSSION: The CARRIER trial is designed to identify the most safe and effective long-term S. aureus carriage decolonization strategy in HPN patients. This will eventually lead to a better understanding of long-term S. aureus decolonization treatments in general. The results of this study will have a great impact on our daily clinical practice, which eventually may result in less S. aureus-related infections. TRIAL REGISTRATION: ClinicalTrials.gov; NCT03173053 . Registered on 1 June 2017.

An adult case with shigellosis-associated encephalopathy.

A 45-year-old man was presented at the emergency department with altered neurological status and a 1-day history of diarrhoea and fever. The patient's sexual history revealed multiple male partners. As bacterial meningitis or viral encephalitis was suspected, treatment was started accordingly. Cerebrospinal fluid investigations only showed a slight increase of leucocytes, and microbiological studies remained negative. Stool culture revealed Shigella flexneri, after which Shigella-associated encephalopathy was suspected. The patient recovered quickly with antibiotic treatment. The incidence of Shigella infections in the Western world is rising due to sexual transmission among men who have sex with men. Shigella-induced encephalopathy is a notorious complication among children with a severe form known as the Ekiri syndrome, though rarely seen in adults. This is the second report of encephalopathy in an adult with S. flexneri enteric infection.

Update on the Role of Infection and Biofilms in Wound Healing: Pathophysiology and Treatment.

BACKGROUND: Chronic wounds, and among these infected diabetic foot ulcers, are a worldwide problem. The poor treatment outcomes result in high healthcare costs, amputations, a decreased quality of life, and an increased mortality. These outcomes are influenced by several factors, including biofilm formation. A biofilm consists of pathogenic bacteria that are encased in an exopolysaccharide layer and communicate through secretion of signaling molecules. Bacteria that live in a biofilm are refractory to host responses and treatment. METHODS: We performed a nonsystematic review of the currently published to-date medical biofilm literature. The review summarizes the evidence of biofilm in chronic wounds, the role of biofilm in wound healing, detection of biofilm, and available antibiofilm treatments. Articles containing basic science and clinical research, as well as systematic reviews, are described and evaluated. The articles have variable levels of evidence. All articles have been peer reviewed and meet the standards of evidence-based medicine. RESULTS: Both animal and human studies have identified biofilm in chronic wounds and have suggested that healing might be influenced by its presence. A promising development in biofilm detection is rapid molecular diagnostics combined with direct microscopy. This technique, rather than classic culture, might support individualized treatment in the near future. A wide range of treatments for chronic wounds also influence biofilm formation. Several agents that specifically target biofilm are currently being researched. CONCLUSIONS: Biofilm formation has a substantial role in chronic wounds. Several diagnostic and therapeutic methods against biofilm are currently being developed.

18F-fluorodeoxyglucose positron emission tomography in elderly patients with an elevated erythrocyte sedimentation rate of unknown origin.

Patients with an elevated erythrocyte sedimentation rate (ESR) and non-specific symptoms often pose a diagnostic dilemma. PET/CT visualises infection, inflammation and malignancy, all of which may cause elevated ESR. The objective of this study was to determine the contribution of 18F-fluorodeoxglucose positron emission tomography (PET/CT) in the diagnostic work-up of referred patients with an elevated ESR, in whom initial routine evaluation did not reveal a diagnosis. We conducted a combined retrospective (A) and prospective (B) study in elderly (>50 years) patients with a significantly elevated ESR of ≥ 50 mm/h and non-specific complaints. In study A, 30 patients were included. Malignancy (8 patients), auto-inflammatory disease (8 patients, including 5 with large-vessel vasculitis) and infection (3 patients) were suggested by PET/CT. Two scans showed non-specific abnormalities and 9 scans were normal. Of the 21 abnormal PET/CT results, 12 diagnoses were independently confirmed and two alternative diagnosis were made. Two diagnoses were established in patients with a normal scan. In study B, 58 patients in whom a prior protocolised work-up was non-diagnostic, were included. Of these, 25 PET/CT-scans showed suspected auto-inflammatory disease, particularly large-vessel vasculitis (14 cases). Infection and malignancy was suspected in 5 and 3 cases, respectively. Seven scans demonstrated non-specific abnormalities, 20 were normal. Of the 40 abnormal PET/CT results, 22 diagnoses were confirmed, 3 alternative diagnoses were established. Only one diagnosis was established in the 20 patients with a normal scan. In both studies, the final diagnosis was based on histology, clinical follow-up, response to therapy or additional imaging. In conclusion, PET/CT may be of potential value in the diagnostic work-up of patients with elevated ESR if routine evaluation reveals no diagnosis. In particular, large-vessel vasculitis appears to be a common finding. A normal PET/CT scan in these patients suggests that it is safe to follow a wait-and-see policy.

Factors that influence treatment adherence of tuberculosis patients living in Java, Indonesia.

BACKGROUND AND OBJECTIVE: Due to nonadherence of tuberculosis (TB) patients to treatment, complications may arise and if remaining infectious, these patients may infect other people with TB. To obtain information about factors associated with nonadherence, we performed a study comparing adherent and nonadherent TB patients. METHODS: Adherent and nonadherent patients randomly selected from hospital records in one urban and two rural districts were interviewed using semi-structured questionnaires. Key informant interviews were done with TB nurses and doctors. RESULTS: The most frequently mentioned reason for nonadherence to treatment was feeling better. Although the drugs were given free of charge, many patients were nonadherent because of lack of money. Social support was considered very important for adherence. The study indicated that some patients had a negative image about the health care staff, treatment, and quality of medication. CONCLUSION: Treatment adherence of TB patients receiving treatment in hospitals in Central Java might be improved by providing health education about treatment duration and side effects, facilitating procedures for receiving treatment free of charge and reducing costs of transportation and consultation. Qualified friendly health care staff able to motivate patients might further improve adherence.