National action plans for antimicrobial resistance and variations in surveillance data platforms.

Objective: To assess how national antimicrobial susceptibility data used to inform national action plans vary across surveillance platforms. Methods: We identified available open-access, supranational, interactive surveillance platforms and cross-checked their data in accordance with the World Health Organization's (WHO's) Data Quality Assurance: module 1. We compared platform usability and completeness of time-matched data on the antimicrobial susceptibilities of four blood isolate species: Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus and Streptococcus pneumoniae from WHO's Global Antimicrobial Resistance and Use Surveillance System, European Centre for Disease Control's (ECDC's) network and Pfizer's Antimicrobial Testing Leadership and Surveillance database. Using Bland-Altman analysis, paired t-tests, and Wilcoxon signed-rank tests, we assessed susceptibility data and number of isolate concordances between platforms. Findings: Of 71 countries actively submitting data to WHO, 28 also submit to Pfizer's database; 19 to ECDC; and 16 to all three platforms. Limits of agreement between WHO's and Pfizer's platforms for organism-country susceptibility data ranged from -26% to 35%. While mean susceptibilities of WHO's and ECDC's platforms did not differ (bias: 0%, 95% confidence interval: -2 to 2), concordance between organism-country susceptibility was low (limits of agreement -18% to 18%). Significant differences exist in isolate numbers reported between WHO-Pfizer (mean of difference: 674, P-value: < 0.001, and WHO-ECDC (mean of difference: 192, P-value: 0.04) platforms. Conclusion: The considerable heterogeneity of nationally submitted data to commonly used antimicrobial resistance surveillance platforms compromises their validity, thus undermining local and global antimicrobial resistance strategies. Hence, we need to understand and address surveillance platform variability and its underlying mechanisms.

A decade of Campylobacter and Campylobacter bacteraemias in a district general hospital and the surrounding London and South East region, England.

BACKGROUND: Campylobacter bacteraemia is a rare complication of the most common bacterial gastrointestinal infection but is associated with significant morbidity and mortality. There is limited data describing current trends in surveillance and antimicrobial resistance for the Campylobacter strains involved. At the Epsom and St Helier's University Hospital (ESTH), we noted a marked increase in Campylobacter bacteraemia infections in 2021. METHODS: We extracted Campylobacter reports using the UK Health Security Agency's (UKHSA) Second Generation Surveillance System (laboratory reporting system) between 1st January 2012 and 31st December 2021. We reviewed patient records of patients with Campylobacter bacteraemia for details including presentation, past medical history, duration of hospital stay, and antibiotic use. RESULTS: Between 2012 and 2021, ESTH reported a total of 34 cases of Campylobacter bacteraemia. In 2021, the estimated incidence was 6.8 cases per 100,000 population and in the surrounding area, the incidence was 0.4 per 100,000 population. The incidence rate of Campylobacter bacteraemia in London and the South East region was significantly lower than ESTH (RR = 0.17, p < 0.0001). Campylobacter bacteraemia cases at ESTH reported a high number of co-morbidities (average number of comorbidities = 2.3) and had a duration of stay in hospital of a median of 7 days (IQR = 4-10 days). Campylobacter jejuni was the most commonly reported species for stool and blood Campylobacter in ESTH, London, and South East England. CONCLUSION: Campylobacter bacteraemia reports at ESTH were significantly (p < 0.001) higher than the surrounding London and South East region. While no common cause for the exceedance of Campylobacter bacteraemia has been identified, common risk factors for Campylobacter bacteraemia infection include underlying health conditions, being older, and male.

Clinical, microbiological characteristics and predictors of mortality in patients with carbapenemase-producing Enterobacterales bloodstream infections: a multicentre study.

Objectives: To investigate the clinical, microbiological characteristics and outcomes of patients with bloodstream infections (BSI) due to carbapenemase-producing Enterobacterales (CPE). Methods: A multicentre retrospective observational study of patients with BSIs due to CPE admitted to six UK hospitals was conducted between 2011 and 2021. Multivariate analysis was used to identify factors predicting 30-day case fatality rate (CFR). Results: There were 84 episodes of CPE-BSIs, 37 (44%) due to OXA-48, 35 (42%) to metallo-betalactamases (MBL) and 12 (14%) to KPC. 63% of patients were male with a median age of 64 years. Common organisms included Klebsiella spp. (61%), Escherichia coli (20%) and Enterobacter spp. (13%). Urinary devices were more often involved in OXA-48 BSIs (12/37; 32%) compared to infections caused by MBL and KPC (4/35; 11% and 1/12; 8%; P = 0.046). In contrast, central venous catheters were more frequently present in KPC-BSIs (10/12; 92%) compared with OXA-48 and MBL (11/37; 30% and 20/35; 57%; P = 0.002). Effective definitive antimicrobials were received by 72/84 (86%) patients, comprising monotherapy (32/72; 44%) or combination therapy (40/72; 56%). 30-day case fatality rate (CFR) was 38%. Sepsis or septic shock was associated with death [OR 3.81 (CI 1.19-12.14), P = 0.024]. Conclusion: Strategies targeting high-risk patients and adherence to infection prevention bundles for urinary devices and central venous catheters can reduce OXA-48 and KPC-BSIs. Early recognition and management of severe sepsis, prompt initiation of appropriate antimicrobial therapy and development of novel antimicrobials are crucial to mitigate the high CFR associated with CPE-BSIs.

Integration of family planning services into health care for HIV-positive women in Botswana.

OBJECTIVE: To create and assess a clinic model to address the unmet need for effective contraception among women living with HIV in Botswana, where half of all pregnancies are unintended and 30% of women of reproductive age are living with HIV. METHODS: We introduced family planning services into an HIV clinic in Gaborone, Botswana. Our intervention gave HIV providers brief training on contraceptive counseling plus the option of immediate referral of interested patients to an on-site contraception provider. We administered a survey to patients and providers before and after intervention. Patients were female, aged 18-45 years and using antiretrovirals. RESULTS: At baseline, 6% of 141 patients discussed contraception with their HIV-care provider, compared with 61% of 107 post intervention (P < 0.001). At baseline, 6% of patients reported wanting to use long-acting reversible contraception (LARC). Post intervention, 45% of patients chose to meet with the contraception provider, and 29% wanted to use LARC (P < 0.001 versus baseline). All providers strongly agreed that they were better informed about contraception post intervention and were satisfied with their ability to counsel and refer women for contraception. CONCLUSIONS: Provision of on-site contraceptive services in this HIV clinic encouraged family planning discussions and increased interest in LARC.

Use of an allograft patch in repair of hypoplastic left heart syndrome may complicate future transplantation.

OBJECTIVE: Cryopreserved allograft tissue used in the Norwood procedure for infants with hypoplastic left heart syndrome (HLHS) has the potential to cause marked immunologic sensitization which may complicate potential future heart transplantation, if required. The purpose of this study was to assess the anti-HLA antibody response to allograft patches used in the initial repair of HLHS. METHODS: A prospective cohort study was conducted comparing the panel-reactive antibody levels (PRA) in 12 infants undergoing repair of HLHS with cryopreserved allograft patch to 10 infants undergoing arterial switch for transposition of the great arteries (no allograft tissue used). PRA for Class I (HLA-A, B, C) and Class II (HLA-DR, DQ) antibodies were assessed preoperatively and postoperatively using flow cytometry. RESULTS: The two groups were well matched at the time of surgery (age, weight, gender). Infants in both groups received blood from multiple donors; however, the allograft group received significantly more (12+/-10 vs. 5+/-1 units; P<0.001). By 4 months, most infants receiving allograft tissue had become highly sensitized for both Class I PRA (62+/-40 vs. 0; P=0.002) and Class II PRA (49+/-42 vs. 2+/-3; P=0.022). This response continued to increase at 12 months: Class I PRA (79+/-21 vs. 0; P=0.008) and Class II PRA (66+/-27 vs. 5+/-6; P=0.008). Specificity analysis confirmed antibodies were specific for the donor allograft HLA type. In addition, infants who were coincidently HLA-matched with their allograft did not develop an elevated PRA. CONCLUSIONS: Allograft tissue used in the repair of HLHS is associated with profound donor specific immunologic sensitization in the majority of recipients and may complicate or jeopardize future transplantation. Methods to reduce the immunogenicity of cryopreserved allograft tissue used for arch reconstruction requires further investigation.

Current understanding of the mechanisms for clearance of apoptotic cells-a fine balance.

Apoptosis is an important cell death mechanism by which multicellular organisms remove unwanted cells. It culminates in a rapid, controlled removal of cell corpses by neighboring or recruited viable cells. Whilst many of the molecular mechanisms that mediate corpse clearance are components of the innate immune system, clearance of apoptotic cells is an anti-inflammatory process. Control of cell death is dependent on competing pro-apoptotic and anti-apoptotic signals. Evidence now suggests a similar balance of competing signals is central to the effective removal of cells, through so called 'eat me' and 'don't eat me' signals. Competing signals are also important for the controlled recruitment of phagocytes to sites of cell death. Consequently recruitment of phagocytes to and from sites of cell death can underlie the resolution or inappropriate propagation of cell death and inflammation. This article highlights our understanding of mechanisms mediating clearance of dying cells and discusses those mechanisms controlling phagocyte migration and how inappropriate control may promote important pathologies.

Failure of prophylactic intravenous immunoglobulin to prevent sensitization to cryopreserved allograft tissue used in congenital cardiac surgery.

OBJECTIVE: Cryopreserved allograft tissue used in the Norwood procedure for infants with hypoplastic left heart syndrome causes profound immunologic sensitization, which may complicate future transplantation. Intravenous immunoglobulin has been shown to reduce sensitization after it has developed, allowing successful transplantation. The purpose of this pilot trial was to determine whether intravenous immunoglobulin given before and after the procedure could prevent sensitization to cryopreserved allograft patches used in the initial repair of hypoplastic left heart syndrome. METHODS: Intravenous immunoglobulin (2 g/kg) was given preoperatively, 3 weeks postoperatively, and 4 months postoperatively to 7 infants undergoing the Norwood procedure. Panel-reactive antibodies were measured with flow cytometry preoperatively and at 1, 4, 6, and 12 months postoperatively and compared with values from a contemporary cohort of 12 infants undergoing the Norwood procedure who did not receive intravenous immunoglobulin. RESULTS: The groups were well matched for length and weight at time of surgery. Control infants were somewhat younger than the cohort receiving intravenous immunoglobulin (8 +/- 5 vs 17 +/- 14 days, P = .021). There were no differences in transfusion requirements. There was no difference in the degree of sensitization between control and intravenous immunoglobulin groups at 1 month (class I panel-reactive antibodies 20% +/- 30% vs 4% +/- 9%, P = .443, class II panel-reactive antibodies 17% +/- 27% vs 20% +/- 17%, P = .400), 4 months (class I panel-reactive antibodies 62% +/- 40% vs 73% +/- 41%, P = .813, class II panel-reactive antibodies 49% +/- 42% vs 54% +/- 41%, P = .706), and 12 months (class I panel-reactive antibodies 49% +/- 42% vs 58% +/- 39%, P = .686, class II panel-reactive antibodies 44% +/- 36% vs 49% +/- 42%, P = .651). CONCLUSION: Despite studies showing intravenous immunoglobulin to reduce sensitization, we were unable to demonstrate that intravenous immunoglobulin prevented sensitization after exposure to allograft tissue in neonates undergoing congenital cardiac surgery.