Human papillomavirus testing versus repeat cytology for triage of minor cytological cervical lesions

Background: A typical squamous cells of undetermined significance (ASCUS) and low-grade squamous intra-epithelial lesions (LSIL) are minor lesions of the cervical epithelium, detectable by cytological examination of cells collected from the surface of the cervix of a woman. Usually, women with ASCUS and LSIL do not have cervical (pre-) cancer, however a substantial proportion of them do have underlying high-grade cervical intra-epithelial neoplasia (CIN, grade 2 or 3) and so are at increased risk for developing cervical cancer. Therefore, accurate triage of women with ASCUS or LSIL is required to identify those who need further management. This review evaluates two ways to triage women with ASCUS or LSIL: repeating the cytological test, and DNA testing for high-risk types of the human papillomavirus (hrHPV) - the main causal factor of cervical cancer. Objectives Main objective: To compare the accuracy of hrHPV testing with the Hybrid Capture 2 (HC2) assay against that of repeat cytology for detection of underlying cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) or grade 3 or worse (CIN3+) in women with ASCUS or LSIL. For the HC2 assay, a positive result was defined as proposed by the manufacturer. For repeat cytology, different cut-offs were used to define positivity: Atypical squamous cells of undetermined significance or worse (ASCUS+), low-grade squamous intra-epithelial lesions or worse (LSIL+) or high-grade squamous intra-epithelial lesions or worse (HSIL+). Secondary objective: To assess the accuracy of the HC2 assay to detect CIN2+ or CIN3+ in women with ASCUS or LSIL in a larger group of reports of studies that applied hrHPV testing and the reference standard (coloscopy and biopsy), irrespective whether or not repeat cytology was done. Search methods: We made a comprehensive literature search that included the Cochrane Register of Diagnostic Test Accuracy Studies; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE (through PubMed), and EMBASE (last search 6 January 2011). Selected journals likely to contain relevant papers were handsearched from 1992 to 2010 (December). We also searched CERVIX, the bibliographic database of the Unit of Cancer Epidemiology at the Scientific Institute of Public Health (Brussels, Belgium) which contains more than 20,000 references on cervical cancer. More recent searches, up to December 2012, targeted reports on the accuracy of triage of ASCUS or LSIL with other HPV DNA assays, or HPV RNA assays and other molecular markers. These searches will be used for new Cochrane reviews as well as for updates of the current review. Selection criteria: Studies eligible for inclusion in the review had to include: women presenting with a cervical cytology result of ASCUS or LSIL, who had undergone both HC2 testing and repeat cytology, or HC2 testing alone, and were subsequently subjected to reference standard verification with colposcopy and colposcopy-directed biopsies for histologic verification. Data collection and analysis: The review authors independently extracted data from the selected studies, and obtained additional data from report authors. Two groups of meta-analyses were performed: group I concerned triage of women with ASCUS, group II concerned women with LSIL. The bivariate model (METADAS-macro in SAS) was used to assess the absolute accuracy of the triage tests in both groups as well as the differences in accuracy between the triage tests. Main results: The pooled sensitivity of HC2 was significantly higher than that of repeat cytology at cut-off ASCUS+ to detect CIN2+ in both triage of ASCUS and LSIL (relative sensitivity of 1.27 (95% CI 1.16 to 1.39; P value < 0.0001) and 1.23 (95% CI 1.06 to 1.4; P value 0.007), respectively. In ASCUS triage, the pooled specificity of the triage methods did not differ significantly from each other (relative specificity: 0.99 (95% CI 0.97 to 1.03; P value 0.98)). However, the specificity of HC2 was substantially, and significantly, lower than that of repeat cytology in the triage of LSIL (relative specificity: 0.66 (95% CI 0.58 to 0.75) P value < 0.0001). Authors' conclusions: HPV-triage with HC2 can be recommended to triage women with ASCUS because it has higher accuracy (significantly higher sensitivity, and similar specificity) than repeat cytology. When triaging women with LSIL, an HC2 test yields a significantly higher sensitivity, but a significantly lower specificity, compared to a repeat cytology. Therefore, practice recommendations for management of women with LSIL should be balanced, taking local circumstances into account

2411. One Dose Vancomycin Prophylaxis for In-Hospital Clostridioides difficile - Associated Disease

Abstract Background Clostridioides difficile - associated disease (CDAD) is the most common cause of healthcare-associated diarrhea with increasing prevalence and mortality rates. Recent reports suggest that prophylactic administration of vancomycin or fidaxomicin might reduce in-hospital CDAD incidence. The aims of this study were to examine whether primary oral vancomycin prophylaxis (OVP) reduces the in-hospital incidence of CDAD in elderly patients treated with systemic antibiotics and its impact on 90-day readmission rate. Methods This single-center, retrospective cohort study included 484 patients ≥ 65 years who received antimicrobial therapy for ≥ 24 hours and were hospitalized for ≥ 72 hours during a 24-month period. Patients diagnosed with CDAD within the first 48 hours of hospitalization were excluded. OVP group received ≥ 1 dose of vancomycin 125 mg once per day. Results Patients within OVP group (122; 25.2%) had higher age adjusted Charlson comorbidity index (CCI) (8; IQR 6–10 vs. 6; 5–8), were more often hospitalized within 3 months (62; 50.8% vs. 121; 33.4%), more commonly received piperacillin/tazobactam (60; 49.2% vs. 81; 22.4%) and carbapenems (27; 22.1% vs. 43; 11.9%) with longer duration of antibiotic therapy (14; 10–20 vs 10; 10–14 days). CDAD was diagnosed in 3 (2.5%) patients in OVP, compared with 45 patients (12.4%, p = 0.0011) in control group. In logistic regression analysis CCI &gt; 6 (OR 3.54; 95% CI 1.79–6.87), OVP (0.19; 0.06–0.57), nursing home residency (4.10; 2.40–7.02), carbapenems (3.14; 1.60–6.15) and piperacillin/tazobactam (5.43; 2.87–10.14) were associated with CDAD. In this cohort, 28 (23.7%) patients from OVP and 69 (21.7%) patients from control group had 90-day readmission. 6 patients in OVP (4 new episodes) and 21 (14 new episodes) in control group were admitted for CDAD. Only CDAD during index hospitalization was associated with 90-day readmission (HR 4.60; 95% CI 1.93–10.96). Conclusion Primary OVP was highly effective in reducing the risk of in-hospital CDAD in elderly patients treated with systemic antimicrobial therapy. Prospective studies with follow-up are needed to define long-term efficacy and potential risks of this strategy. Disclosures All authors: No reported disclosures. </jats:sec

Adenoviral Pneumonia Outbreak in Immunocompetent Adults&mdash;A Missed Antimicrobial Stewardship Opportunity?

Background/Objectives: While the concept of viral community-acquired pneumonia (CAP) changed with COVID-19, the role of non-influenza viruses as a cause of CAP is less clear. The aim of this study was to describe the clinical course, risk factors, inflammatory profiles, antibiotic use, outcomes and complications of adenoviral (AdV) CAP. Methods: A prospective, non-interventional, observational cohort study included consecutively hospitalized immunocompetent adult patients with AdV CAP during an 18-month period. Clinical and laboratory data, including lymphocyte subpopulations and serum cytokine profiles were collected and correlated to clinical outcomes. Results: Fifty-eight patients with AdV CAP were included; 81% were males, with a median age of 33 (IQR 28&ndash;41) years and 62% without any comorbidities. All patients initially had high-grade fever for a median duration of 6 (5&ndash;7) days and respiratory symptoms. Increased CRP and procalcitonin, lymphopenia, mild thrombocytopenia and liver injury were frequent. Radiographic findings mimicked bacterial pneumonia (83% had unilateral involvement). Twenty-two patients (38%) had criteria for severe CAP, and these patients had higher procalcitonin, NLR, AST, ALT, LDH and CK, and lower T-lymphocyte CD4+ count. In comparison to influenza and bacterial CAP, patients with AdV had higher serum IL-2, IL-1&beta;, IL-8, IL-10, CXCL10 and MCP-1, and lower TGF-&beta;1 concentration. Thirteen patients required low-flow oxygen therapy, and 13 advanced respiratory support. Complications occurred in 29%, with one fatal outcome. While all patients received empirical antibiotic therapy, after AdV detection it was stopped in 21%, although only one patient had detected a possible bacterial coinfection. Conclusions: Since AdV CAP in immunocompetent patients is clinically and radiologically indistinguishable from bacterial CAP, it is associated with prolonged clinical course and lack of clinical response to antibiotics. This emphasizes the importance of AdV testing which could lead to more rational antimicrobial treatment