Influence of initial misdiagnosis on mortality in patients with bacteraemia: propensity score matching and propensity score weighting analyses.

BACKGROUND: The diagnostic process is a key element of medicine but it is complex and prone to errors. Infectious diseases are one of the three categories of diseases in which diagnostic errors can be most harmful to patients. In this study we aimed to estimate the effect of initial misdiagnosis of the source of infection in patients with bacteraemia on 14 day mortality using propensity score methods to adjust for confounding. METHODS: Data from a previously described longitudinal cohort of patients diagnosed with monobacterial bloodstream infection (BSI) at the Leiden University Medical Centre (LUMC) between 2013 and 2015 were used. Propensity score matching and inversed probability of treatment weighting (IPTW) were applied to correct for confounding. The average treatment effect on the treated (ATT), which in this study was the average effect of initial misdiagnosis on the misdiagnosed (AEMM), was estimated. Methodological issues that were encountered when applying propensity score methods were addressed by performing additional sensitivity analyses. Sensitivity analyses consisted of varying caliper in propensity score matching and using different truncated weights in inversed probability of treatment weighting. RESULTS: Data of 887 patients were included in the study. Propensity scores ranged between 0.015 and 0.999 and 80 patients (9.9%) had a propensity score > 0.95. In the matched analyses, 35 of the 171 misdiagnosed patients died within 14 days (20.5%), versus 10 of the 171 correctly diagnosed patients (5.8%), yielding a difference of 14.6% (7.6%; 21.6%). In the total group of patients, the observed percentage of patients with an incorrect initial diagnosis that died within 14 days was 19.8% while propensity score reweighting estimated that their probability of dying would have been 6.5%, if they had been correctly diagnosed (difference 13.3% (95% CI 6.9%;19.6%)). After adjustment for all variables that showed disbalance in the propensity score a difference of 13.7% (7.4%; 19.9%) was estimated. Sensitivity analyses yielded similar results. However, performing weighted analyses without truncation yielded unstable results. CONCLUSION: Thus, we observed a substantial increase of 14 day mortality in initially misdiagnosed patients. Furthermore, several patients received propensity scores extremely close to one and were almost sure to be initially misdiagnosed.

Treatment failure of Helicobacter Pylori in primary care.

BACKGROUND: Due to increasing antibiotic resistance, the worldwide efficacy of Helicobacter pylori (Hp) eradication treatment has decreased. AIM: To determine antimicrobial resistance of Hp in primary care. DESIGN & SETTING: Retrospective cohort study using real-world routine health care data from 80 general practices in the Netherlands. METHOD: Patients with ICPC-codes for gastric symptoms or ATC-code for acid inhibition in the period 2010-2020 were selected. Main outcomes were antimicrobial resistance of Hp, defined as the prescription of a second eradication treatment within 12 months, and clinical remission of gastric symptoms, defined as no usage of acid inhibition one year following eradication therapy. RESULTS: We identified 138,455 patients with gastric symptoms and/or acid inhibition use (mean age 57 years [SD 18.2], 43% male). A total of 5,224 (4%) patients received a Hp eradication treatment. A second treatment was prescribed to 416 (8%) of those patients. From these, 380 patients received amoxicillin-clarithromycin, 16 amoxicillin-metronidazole and 11 clarithromycin-metronidazole as first regimen and were considered antimicrobial resistant. We observed a 0.8% increment per year of patients requiring a second eradication treatment (P=0.003, 95% CI 0.33-1.22). After successful eradication, 2,329/4,808 (48%) patients used acid inhibition compared to 355/416 (85%) patients following treatment failure (P<0.001). CONCLUSION: Antimicrobial treatment is not successful in almost one-tenth of Hp infections in primary care after a first treatment containing clarithromycin and/or metronidazole. Although the treatment failure rate is not as high as reported in secondary care, the increasing trend is concerning and may require revision of the current guidelines.

Prospective and systematic screening for invasive aspergillosis in the ICU during the COVID-19 pandemic, a proof of principle for future pandemics.

The diagnostic performance of a prospective, systematic screening strategy for COVID-19 associated pulmonary aspergillosis (CAPA) during the COVID-19 pandemic was investigated. Patients with COVID-19 admitted to the ICU were screened for CAPA twice weekly by collection of tracheal aspirate (TA) for Aspergillus culture and PCR. Subsequently, bronchoalveolar lavage (BAL) sampling was performed in patients with positive screening results and clinical suspicion of infection. Patient data were collected from April 2020-February 2022. Patients were classified according to 2020 ECMM/ISHAM consensus criteria. In total, 126/370 (34%) patients were positive in screening and CAPA frequency was 52/370 (14%) (including 13 patients negative in screening). CAPA was confirmed in 32/43 (74%) screening positive patients who underwent BAL sampling. ICU mortality was 62% in patients with positive screening and confirmed CAPA, and 31% in CAPA cases who were screening negative. The sensitivity, specificity, positive and negative predictive value (PPV & NPV) of screening for CAPA were 0.71, 0.73, 0.27, and 0.95, respectively. The PPV was higher if screening was culture positive compared to PCR positive only, 0.42 and 0.12 respectively. CAPA was confirmed in 74% of screening positive patients, and culture of TA had a better diagnostic performance than PCR. Positive screening along with clinical manifestations appeared to be a good indication for BAL sampling since diagnosis of CAPA was confirmed in most of these patients. Prospective, systematic screening allowed to quickly gain insight into the epidemiology of fungal superinfections during the pandemic and could be applicable for future pandemics.

Female Sex and Mortality in Patients with Staphylococcus aureus Bacteremia: A Systematic Review and Meta-analysis.

Importance: Staphylococcus aureus is the leading cause of death due to bacterial bloodstream infection. Female sex has been identified as a risk factor for mortality in S aureus bacteremia (SAB) in some studies, but not in others. Objective: To determine whether female sex is associated with increased mortality risk in SAB. Data Sources: MEDLINE, Embase, and Web of Science were searched from inception to April 26, 2023. Study Selection: Included studies met the following criteria: (1) randomized or observational studies evaluating adults with SAB, (2) included 200 or more patients, (3) reported mortality at or before 90 days following SAB, and (4) reported mortality stratified by sex. Studies on specific subpopulations (eg, dialysis, intensive care units, cancer patients) and studies that included patients with bacteremia by various microorganisms that did not report SAB-specific data were excluded. Data Extraction and Synthesis: Data extraction and quality assessment were performed by 1 reviewer and verified by a second reviewer. Risk of bias and quality were assessed with the Newcastle-Ottawa Quality Assessment Scale. Mortality data were combined as odds ratios (ORs). Main Outcome and Measures: Mortality at or before 90-day following SAB, stratified by sex. Results: From 5339 studies retrieved, 89 were included (132 582 patients; 50 258 female [37.9%], 82 324 male [62.1%]). Unadjusted mortality data were available from 81 studies (109 828 patients) and showed increased mortality in female patients compared with male patients (pooled OR, 1.12; 95% CI, 1.06-1.18). Adjusted mortality data accounting for additional patient characteristics and treatment variables were available from 32 studies (95 469 patients) and revealed a similarly increased mortality risk in female relative to male patients (pooled adjusted OR, 1.18; 95% CI, 1.11-1.27). No evidence of publication bias was encountered. Conclusions and Relevance: In this systematic review and meta-analysis, female patients with SAB had higher mortality risk than males in both unadjusted and adjusted analyses. Further research is needed to study the potential underlying mechanisms.

Eradication of community-onset Methicillin-resistant Staphylococcus aureus carriage: a narrative review.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) colonization increases infection risk in both patients and healthy individuals. Decolonization therapy has been proven to reduce S. aureus infections, but data on the effectiveness of individual decolonization strategies in community-onset MRSA carriage are scarce. OBJECTIVES: The aim of this narrative review was to summarize the evidence on strategies for the elimination of MRSA colonization in community-onset MRSA carriers. SOURCES: PubMed database was searched for studies on MRSA eradication, from inception to July 2023. CONTENT: Topical therapy is proven to be effective in nasal-only carriage and in temporary load reduction. Mupirocin nasal ointment in combination with chlorhexidine body wash is highly effective in nasal-only MRSA carriers in the community as well. In patients with extra-nasal colonization, addition of orally administered antibiotics likely increases success rates compared with topical therapy alone. Studies on systemic treatment of extra-nasal MRSA decolonization are subject to a high heterogeneity of antimicrobial agents, treatment duration, and control groups. The majority of evidence supports the use of a combination of topical therapy with rifampin and another antimicrobial agent. Decolonization treatment with probiotics is a promising novel non-antibiotic strategy. However, achieving long-term decolonization is more likely in countries with low MRSA prevalence, given the risk of recolonization in a context of high MRSA prevalence. IMPLICATIONS: The decision to pursue community-onset MRSA eradication treatment in the individual patient should be based on the combination of the treatment objective (short-term bacterial load reduction in health care settings vs. long-term eradication in community settings), and the likelihood of successful decolonization. The latter is influenced by both individual risk factors for treatment failure, and the risk of recolonization. The addition of a combination of systemic antibiotics is rational for extra-nasal long-term decolonization. To determine the most effective systemic antimicrobial agents in MRSA decolonization, more research is needed.

Rapid Response to Remdesivir in Hospitalised COVID-19 Patients: A Propensity Score Weighted Multicentre Cohort Study.

INTRODUCTION: Remdesivir is a registered treatment for hospitalised patients with COVID-19 that has moderate clinical effectiveness. Anecdotally, some patients' respiratory insufficiency seemed to recover particularly rapidly after initiation of remdesivir. In this study, we investigated if this rapid improvement was caused by remdesivir, and which patient characteristics might predict a rapid clinical improvement in response to remdesivir. METHODS: This was a multicentre observational cohort study of hospitalised patients with COVID-19 who required supplemental oxygen and were treated with dexamethasone. Rapid clinical improvement in response to treatment was defined by a reduction of at least 1 L of supplemental oxygen per minute or discharge from the hospital within 72 h after admission. Inverse probability of treatment-weighted logistic regression modelling was used to assess the association between remdesivir and rapid clinical improvement. Secondary endpoints included in-hospital mortality, ICU admission rate and hospitalisation duration. RESULTS: Of 871 patients included, 445 were treated with remdesivir. There was no influence of remdesivir on the occurrence of rapid clinical improvement (62% vs 61% OR 1.05, 95% CI 0.79-1.40; p = 0.76). The in-hospital mortality was lower (14.7% vs 19.8% OR 0.70, 95% CI 0.48-1.02; p = 0.06) for the remdesivir-treated patients. Rapid clinical improvement occurred more often in patients with low C-reactive protein (≤ 75 mg/L) and short duration of symptoms prior to hospitalisation (< 7 days) (OR 2.84, 95% CI 1.07-7.56). CONCLUSION: Remdesivir generally does not increase the incidence of rapid clinical improvement in hospitalised patients with COVID-19, but it might have an effect in patients with short duration of symptoms and limited signs of systemic inflammation.

Osteomyelitis caused by Streptococcus intermedius in immunocompetent adults - a case report and systematic literature review.

Hematogenous osteomyelitis caused by Streptococcus intermedius is rare, particularly in immunocompetent adults. The aim of this paper is to provide an overview of the clinical presentation, prognosis as well as treatment of this disease, with the focus on immunocompetent adults. Six medical literature libraries were searched to identify studies reporting on Streptococcus intermedius induced hematogenous osteomyelitis in immunocompetent adults. In addition, we presented a case of a 44-year-old man from our institution that is illustrative for this disease. Four case reports describing four patients were identified by this systematic literature review. Hence, the data of five patients (including our case) were assessed. The most common presenting symptom was localised pain, followed by fever. Portal entries were found in two patients (general periodontitis and necrotic dentition). The localisations of osteomyelitis were diverse: femoral (two patients), lumbar spine (two patients), and the iliac bone (one patient). Treatment strategies varied strongly, but antibiotics (penicillins) were administered in each case, and two patients underwent surgical debridement. Follow-up ranged from 2 weeks to more than 6 months; one patient died from septic shock. Only a very limited number of immunocompetent adults with Streptococcus intermedius induced hematogenous osteomyelitis have been described. Based on the available data, we summarised the clinical presentation, prognosis as well as treatment of hematogenous osteomyelitis caused by Streptococcus intermedius in this patient population.

IgA antibody immunotherapy targeting GD2 is effective in preclinical neuroblastoma models.

BACKGROUND: Immunotherapy targeting GD2 is very effective against high-risk neuroblastoma, though administration of anti-GD2 antibodies induces severe and dose-limiting neuropathic pain by binding GD2-expressing sensory neurons. Previously, the IgG1 ch14.18 (dinutuximab) antibody was reformatted into the IgA1 isotype, which abolishes neuropathic pain and induces efficient neutrophil-mediated antibody-dependent cellular cytotoxicity (ADCC) via activation of the Fc alpha receptor (FcαRI/CD89). METHODS: To generate an antibody suitable for clinical application, we engineered an IgA molecule (named IgA3.0 ch14.18) with increased stability, mutated glycosylation sites and substituted free (reactive) cysteines. The following mutations were introduced: N45.2G and P124R (CH1 domain), C92S, N120T, I121L and T122S (CH2 domain) and a deletion of the tail piece P131-Y148 (CH3 domain). IgA3.0 ch14.18 was evaluated in binding assays and in ADCC and antibody-dependent cellular phagocytosis (ADCP) assays with human, neuroblastoma patient and non-human primate effector cells. We performed mass spectrometry analysis of N-glycans and evaluated the impact of altered glycosylation in IgA3.0 ch14.18 on antibody half-life by performing pharmacokinetic (PK) studies in mice injected intravenously with 5 mg/kg antibody solution. A dose escalation study was performed to determine in vivo efficacy of IgA3.0 ch14.18 in an intraperitoneal mouse model using 9464D-GD2 neuroblastoma cells as well as in a subcutaneous human xenograft model using IMR32 neuroblastoma cells. Binding assays and PK studies were compared with one-way analysis of variance (ANOVA), ADCC and ADCP assays and in vivo tumor outgrowth with two-way ANOVA followed by Tukey's post-hoc test. RESULTS: ADCC and ADCP assays showed that particularly neutrophils and macrophages from healthy donors, non-human primates and patients with neuroblastoma are able to kill neuroblastoma tumor cells efficiently with IgA3.0 ch14.18. IgA3.0 ch14.18 contains a more favorable glycosylation pattern, corresponding to an increased antibody half-life in mice compared with IgA1 and IgA2. Furthermore, IgA3.0 ch14.18 penetrates neuroblastoma tumors in vivo and halts tumor outgrowth in both 9464D-GD2 and IMR32 long-term tumor models. CONCLUSIONS: IgA3.0 ch14.18 is a promising new therapy for neuroblastoma, showing (1) increased half-life compared to natural IgA antibodies, (2) increased protein stability enabling effortless production and purification, (3) potent CD89-mediated tumor killing in vitro by healthy subjects and patients with neuroblastoma and (4) antitumor efficacy in long-term mouse neuroblastoma models.

Prolonged antibiotic prophylaxis after pancreatoduodenectomy: systematic review and meta-analysis.

BACKGROUND: Previous studies have reported conflicting results of prolonged antibiotic prophylaxis on infectious complications after pancreatoduodenectomy. This study evaluated the effect of prolonged antibiotics on surgical-site infections (SSIs) after pancreatoduodenectomy. METHODS: A systematic review and meta-analysis was undertaken of SSIs in patients with perioperative (within 24 h) versus prolonged antibiotic (over 24 h) prophylaxis after pancreatoduodenectomy. SSIs were classified as organ/space infections or superficial SSI within 30 days after surgery. ORs were calculated using a Mantel-Haenszel fixed-effect model. RESULTS: Ten studies were included in the qualitative analysis, of which 8 reporting on 1170 patients were included in the quantitative analysis. The duration of prolonged antibiotic prophylaxis varied between 2 and 10 days after surgery. Four studies reporting on 782 patients showed comparable organ/space infection rates in patients receiving perioperative and prolonged antibiotics (OR 1.35, 95 per cent c.i. 0.94 to 1.93). However, among patients with preoperative biliary drainage (5 studies reporting on 577 patients), organ/space infection rates were lower with prolonged compared with perioperative antibiotics (OR 2.09, 1.43 to 3.07). Three studies (633 patients) demonstrated comparable superficial SSI rates between patients receiving perioperative versus prolonged prophylaxis (OR 1.54, 0.97 to 2.44), as well as in patients with preoperative biliary drainage in 4 studies reporting on 431 patients (OR 1.60, 0.89 to 2.88). CONCLUSION: Prolonged antibiotic prophylaxis is associated with fewer organ/space infection in patients who undergo preoperative biliary drainage. However, the optimal duration of antibiotic prophylaxis after pancreatoduodenectomy remains to be determined and warrants confirmation in an RCT.

Almost 40 in 100 patients develop an infection after pancreatic surgery. This study collected research that studied the effect of prolonged antibiotics after pancreatic surgery on the number of infections after surgery. Research articles were selected if patients who received antibiotics only during surgery were compared with those who had prolonged antibiotics after surgery. Prolonged antibiotics means antibiotics for longer than 24 h after surgery. Comparing patients who had antibiotics during surgery and those who received prolonged antibiotics after surgery, this study focused on the number of abdominal infections and wound infections. Ten studies were selected, and these studies included 1170 patients in total. The duration of prolonged antibiotics ranged from 2 to 5 days after pancreatic surgery. Four studies (with 782 patients) showed comparable abdominal infections in patients who had antibiotics only during surgery and those who had prolonged antibiotics after surgery (OR 1.35, 95 per cent c.i. 0.94 to 1.93). However, for patients with a stent in the bile duct (5 studies on 577 patients), fewer abdominal infections were seen in patients who had prolonged antibiotics after surgery compared with patients who received antibiotics only during surgery (OR 2.09, 1.43 to 3.07). Three studies (633 patients) showed the same rate of wound infections in patients who had antibiotics only during surgery compared with those who received prolonged antibiotics after operation (OR 1.54, 0.97 to 2.44). The number of wound infections was also the same in patients with a stent in the bile duct (OR 1.60, 0.89 to 2.88). Prolonged antibiotics after pancreatic surgery seem to lower abdominal infections in patients who have a stent placed in the bile duct. However, the best duration of antibiotics is unclear; a decent study is needed.

Prolonged antibiotics after pancreatoduodenectomy reduce abdominal infections in patients with positive bile cultures: a dual-center cohort study.

BACKGROUND: Abdominal infections account for substantial morbidity after pancreatoduodenectomy. Contaminated bile is the presumed main risk factor, and prolonged antibiotic prophylaxis might prevent these complications. This study compared organ/space infection (OSIs) rates in patients receiving perioperative versus prolonged antibiotic prophylaxis after pancreatoduodenectomy. METHODS: Patients undergoing pancreatoduodenectomy in two Dutch centers between 2016 and 2019 were included. Perioperative prophylaxis was compared prolonged prophylaxis (cefuroxime and metronidazole for five days). The primary outcome was an isolated OSI: an abdominal infection without concurrent anastomotic leakage. Odds ratios (OR) were adjusted for surgical approach and pancreatic duct diameter. RESULTS: OSIs occurred in 137 out of 362 patients (37.8%): 93 patients with perioperative and 44 patients with prolonged prophylaxis (42.5% versus 30.8%, P = 0.025). Isolated OSIs occurred in 38 patients (10.5%): 28 patients with perioperative and 10 patients with prolonged prophylaxis (12.8% versus 7.0%, P = 0.079). Bile cultures were obtained in 198 patients (54.7%). Patients with positive bile cultures showed higher isolated OSI rates with perioperative compared to prolonged prophylaxis (18.2% versus 6.6%, OR 5.7, 95% CI: 1.3-23.9). CONCLUSION: Prolonged antibiotics after pancreatoduodenectomy are associated with fewer isolated OSIs in patients with contaminated bile and warrant confirmation in a randomised controlled trial (Clinicaltrials.gov NCT0578431).

Global Differences in the Management of Staphylococcus aureus Bacteremia: No International Standard of Care.

BACKGROUND: Despite being the leading cause of mortality from bloodstream infections worldwide, little is known about regional variation in treatment practices for Staphylococcus aureus bacteremia (SAB). The aim of this study was to identify global variation in management, diagnostics, and definitions of SAB. METHODS: During a 20-day period in 2022, physicians throughout the world were surveyed on SAB treatment practices. The survey was distributed through listservs, e-mails, and social media. RESULTS: In total, 2031 physicians from 71 different countries on 6 continents (North America [701, 35%], Europe [573, 28%], Asia [409, 20%], Oceania [182, 9%], South America [124, 6%], and Africa [42, 2%]) completed the survey. Management-based responses differed significantly by continent for preferred treatment of methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) bacteremia, use of adjunctive rifampin for prosthetic material infection, and use of oral antibiotics (P < .01 for all comparisons). The 18F-FDG PET/CT scans were most commonly used in Europe (94%) and least frequently used in Africa (13%) and North America (51%; P < .01). Although most respondents defined persistent SAB as 3-4 days of positive blood cultures, responses ranged from 2 days in 31% of European respondents to 7 days in 38% of Asian respondents (P < .01). CONCLUSIONS: Large practice variations for SAB exist throughout the world, reflecting the paucity of high-quality data and the absence of an international standard of care for the management of SAB.

The association of female sex with management and mortality in patients with Staphylococcus aureus bacteraemia.

OBJECTIVES: The association of biological female sex with outcome in patients with Staphylococcus aureus bacteraemia remains unresolved. The aim of this study was to determine the independent association of female sex with management and mortality in patients with S. aureus bacteraemia. METHODS: This is a post hoc analysis of prospectively collected data from the S. aureus Bacteraemia Group Prospective Cohort Study. Adult patients with monomicrobial S. aureus bacteraemia at Duke University Medical Center were enrolled from 1994 to 2020. Univariable and multivariable Cox regression analyses were performed to assess differences in management and mortality between females and males. RESULTS: Among 3384 patients with S. aureus bacteraemia, 1431 (42%) were women. Women were, as compared with men, more often Black (581/1431 [41%] vs. 620/1953 [32%], p < 0.001), haemodialysis dependent (309/1424 [22%] vs. 334/1940 [17%], p 0.001) and more likely to be infected with methicillin-resistant S. aureus (MRSA) (697/1410 [49%] MRSA in women vs. 840/1925 [44%] MRSA in men, p 0.001). Women received shorter durations of antimicrobial treatment (median 24 [interquartile range 14-42] vs. 28 [interquartile range 14-45] days, p 0.005), and were less likely to undergo transesophageal echocardiography as compared with men (495/1430 [35%] vs. 802/1952 [41%], p < 0.001). Despite these differences, female sex was not associated with 90-day mortality in either univariable (388/1431 [27%] in women vs. 491/1953 [25%] in men, p 0.204) or multivariable analysis (adjusted hazard ratio for women 0.98 [95% CI, 0.85-1.13]). DISCUSSION: Despite significant differences in patient characteristics, disease characteristics, and management, women and men with S. aureus bacteraemia have a similar mortality risk.

Influence of surface characteristics of implant materials on MRSA biofilm formation and effects of antimicrobial treatment.

Introduction: One of the main causes of treatment failure in bacterial prosthetic joint infections (PJI) is biofilm formation. The topography of the biofilm may be associated with susceptibility to antimicrobial treatment. The aims of this study were to assess differences in topography of biofilms on different implant materials and the correlation thereof with susceptibility to antimicrobial treatment. Methods: Methicillin-resistant Staphylococcus aureus (MRSA) 7-day mature biofilms were generated on disks made from titanium alloys (Ti-6Al-7Nb and Ti-6Al-4V), synthetic polymer and orthopedic bone cement, commonly used in implant surgery. The surface topography of these implant materials and the biofilms cultured on them was assessed using atomic force microscopy. This provided detailed images, as well as average roughness (Ra) and peak-to-valley roughness (Rt) values in nanometers, of the biofilm and the material surfaces. Bacterial counts within biofilms were assessed microbiologically. Antimicrobial treatment of biofilms was performed by 24-h exposure to the combination of rifampicin and ciprofloxacin in concentrations of 1-, 5- and 10-times the minimal bactericidal concentration (MBC). Finally, treatment-induced differences in bacterial loads and their correlation with biofilm surface parameters were assessed. Results: The biofilm surfaces on titanium alloys Ti-6Al-7Nb (Ra = 186 nm) and Ti-6Al-4V (Ra = 270 nm) were less rough than those of biofilms on silicone (Ra = 636 nm). The highest roughness was observed for biofilms on orthopedic bone cement with an Ra of 1,551 nm. Interestingly, the roughness parameters of the titanium alloys themselves were lower than the value for silicone, whereas the surface of the bone cement was the roughest. Treatment with 1- and 5-times the MBC of antibiotics resulted in inter-material differences in colony forming units (CFU) counts, ultimately showing comparable reductions of 2.4-3.0 log CFU/mL at the highest tested concentration. No significant differences in bacterial loads within MRSA biofilms were observed between the various implant materials, upon exposure to increasing concentrations of antibiotics. Discussion: The surface parameters of MRSA biofilms were determined by those of the implant materials on which they were formed. The antibiotic susceptibility of MRSA biofilms on the various tested implant materials did not differ, indicating that the efficacy of antibiotics was not affected by the roughness of the biofilm.

Determinants of inappropriate antibiotic prescription in primary care in developed countries with general practitioners as gatekeepers: a systematic review and construction of a framework.

OBJECTIVES: This study aimed to identify determinants of inappropriate antibiotic prescription in primary care in developed countries and to construct a framework with the determinants to help understand which actions can best be targeted to counteract development of antimicrobial resistance (AMR). DESIGN: A systematic review of peer-reviewed studies reporting determinants of inappropriate antibiotic prescription published through 9 September 2021 in PubMed, Embase, Web of Science and the Cochrane Library was performed. SETTING: All studies focusing on primary care in developed countries where general practitioners (GPs) act as gatekeepers for referral to medical specialists and hospital care were included. RESULTS: Seventeen studies fulfilled the inclusion criteria and were used for the analysis which identified 45 determinants of inappropriate antibiotic prescription. Important determinants for inappropriate antibiotic prescription were comorbidity, primary care not considered to be responsible for development of AMR and GP perception of patient desire for antibiotics. A framework was constructed with the determinants and provides a broad overview of several domains. The framework can be used to identify several reasons for inappropriate antibiotic prescription in a specific primary care setting and from there, choose the most suitable intervention(s) and assist in implementing them for combatting AMR. CONCLUSIONS: The type of infection, comorbidity and the GPs perception of a patient's desire for antibiotics are consistently identified as factors driving inappropriate antibiotic prescription in primary care. A framework with determinants of inappropriate antibiotic prescription may be useful after validation for effective implementation of interventions for decreasing these inappropriate prescriptions. PROSPERO REGISTRATION NUMBER: CRD42023396225.

Identifying and Predicting Postoperative Infections Based on Readily Available Electronic Health Record Data.

Identification of postoperative infections based on retrospective patient data is currently done using manual chart review. We used a validated, automated labelling method based on registrations and treatments to develop a high-quality prediction model (AUC 0.81) for postoperative infections.

Trends in antibiotic selection pressure generated in primary care and their association with sentinel antimicrobial resistance patterns in Europe.

OBJECTIVES: We studied trends in antibiotic prescribing by primary care and assessed the associations between generated antibiotic selection pressure (ASP) and the prevalence of sentinel drug-resistant microorganisms (SDRMs). METHODS: The volume of antibiotic prescribing in primary and hospital care expressed in DDD/1000 inhabitants per day and the prevalences of SDRMs in European countries where GPs act as gatekeepers were obtained from the European Centre for Disease Control ESAC-NET. Associations were tested between (i) DDD and (ii) the Antibiotic Spectrum Index (ASI) as a proxy indicator for ASP, and the prevalences of three SDRMs: MRSA, MDR Escherichia coli and Streptococcus pneumoniae resistant to macrolides. RESULTS: Fourteen European countries were included. Italy, Poland and Spain had the highest prevalence of SDRMs and prescribed the highest volume of antibiotics in primary care (average 17 DDD per 1000 inhabitants per day), approximately twice that of countries with the lowest volumes. Moreover, the ASIs of these high antibiotic volume countries were approximately three times higher than those of the low-volume countries. Cumulative ASI showed the strongest association with a country's prevalence of SDRMs. The cumulative ASI generated from primary care was about four to five times higher than the cumulative ASI generated by hospital care. CONCLUSIONS: Prevalences of SDRMs are associated with the volume of antimicrobial prescribing and in particular broad-spectrum antibiotics in European countries where GPs act as gatekeepers. The impact of ASP generated from primary care on increasing antimicrobial resistance may be much larger than currently assumed.

The Dutch Working Party on Antibiotic Policy (SWAB) guideline for the approach to suspected antibiotic allergy.

OBJECTIVES: Prudent handling of reported antibiotic allergies is an important aspect of antibiotic stewardship. The Dutch Working Party on Antibiotic Policy (SWAB) constituted a multidisciplinary expert committee to provide evidence-based recommendations for bedside decision-making in antibiotic therapy in patients that report an antibiotic allergy. METHODS: The guideline committee generated 12 key questions, most of which were population, intervention, comparison, and outcome questions relevant to both children and adults with suspected antibiotic allergies. For each question, a systematic literature search was performed and reviewed for the best available evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The quality of evidence was graded from very low to high, and recommendations were formulated in structured discussions as strong or weak. RESULTS: Sixty recommendations were provided for suspected allergy to ß-lactam antibiotics (BLAs) and non-ß-lactam antibiotics. Owing to the absence of randomized controlled trials in this field, the underlying evidence was predominantly graded as low or very low. Available data support that a detailed allergy history should always be performed and critically appraised. When cross-allergy between BLA groups is not to be expected due to the absence of molecular similarity of the side chains, the patient can be safely exposed to the alternative BLA. An exception to this rule is severe delayed-type reactions in which re-exposure to a BLA should only be considered after consultation with a multidisciplinary team. CONCLUSIONS: Accumulated scientific data now support a more liberal approach that better balances the benefits of treatment with first choice and usually smaller spectrum antibiotics with appropriate avoidance of antibiotics in case of a truly high risk of a (severe) allergic reaction. In The Netherlands, a formal guideline was developed that provides recommendations for the approach toward suspected allergy to BLA and frequently used non-ß-lactam antibiotics, thereby strongly supporting antimicrobial stewardship.

[What does excess mortality tell us?] / Covid-19: wat zegt oversterfte ons?

Excess mortality due to covid-19 is estimatedas actual mortality minus expected mortality in the covid-19 period. Excess mortality in 2020-2021 in the Netherlands is estimated to be 30,000 persons. Excess mortality should be divided in mortality as consequences of covid-19 infections (direct effects) and mortality due indirect effects of the pandemic. As excess mortality assesses mortality under one single scenario (the actual scenario including its specific measures), it cannot directly be used to know what the number of deaths would have been under different scenarios. In line, it cannot be used to determine whether actual measures in the covid-19 pandemic were optimal (or not). And obviously, excess mortality only assesses the impact on mortality, not the impact on other relevant health-related, sociological or economical areas.

[What does excess mortality tell us?] / Covid-19: wat zegt oversterfte ons?

Excess mortality due to covid-19 is estimatedas actual mortality minus expected mortality in the covid-19 period. Excess mortality in 2020-2021 in the Netherlands is estimated to be 30,000 persons. Excess mortality should be divided in mortality as consequences of covid-19 infections (direct effects) and mortality due indirect effects of the pandemic. As excess mortality assesses mortality under one single scenario (the actual scenario including its specific measures), it cannot directly be used to know what the number of deaths would have been under different scenarios. In line, it cannot be used to determine whether actual measures in the covid-19 pandemic were optimal (or not). And obviously, excess mortality only assesses the impact on mortality, not the impact on other relevant health-related, sociological or economical areas.