In the region of Piedmont, in Northern Italy, formal monitoring of antimicrobial stewardship (AMS) programs has been in place since 2012. The objective of our study was to provide an updated ...assessment of AMS programs operating in our region, and to assess the impact of the COVID-19 pandemic on stewardship activities.
A retrospective observational study was conducted to investigate AMS programs implemented in acute-care trusts participating in a broader healthcare-associated infections and antimicrobial resistance (AMR) prevention and control program, promoted by the regional health department. Within this program, structure, process, and outcome indicators of AMS programs were investigated, using a previously developed scoring system. Differences between scores prior to (2019) and during the pandemic (2021) were assessed. Linear regression was used to assess whether the 5-year trends (2017-2021) in outcome measures in relation to structure and process scores were statistically significant. Compound annual growth rates (CAGR) for each outcome were calculated to illustrate changes in outcome rates over time.
All public trusts in the Region (20) and a small number of private institutions (3) provided data for this study. A modest, non-significant improvement was found for 2021 structure, process, and total scores compared to respective 2019 scores. A significant improvement was found concerning the definition of a formal mission statement, whereas significantly less trusts included monitoring adherence to antimicrobial policy or treatment guidelines in their programs. Overall consumption of antibiotics for systemic use saw an increase in 2021, with 2021 recording the highest median overall consumption compared to all previous years considered in this study. Methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant enterobacteria (CRE) rates decreased over the 5-year period. Significant downwards trends in MRSA rates were identified for high-outlier structure and process groups.
Results of this study suggest AMS programs in Piedmont were not set back following the pandemic. This outcome was possible thanks to well-established programs, coordinated within a regional framework. Continued efforts should be dedicated to supporting AMS programs and contrasting AMR, even when the focus is shifted towards other public health emergencies.
In November 2022, Italy participated in the third edition of the European Centre for disease prevention and control (ECDC) point prevalence survey (PPS) of healthcare-associated infections (HAIs) in ...acute-care hospitals. A questionnaire based on the WHO infection prevention and control assessment framework (IPCAF) was included, which aims to investigate multimodal strategies for the implementation of IPC interventions.
A PPS was conducted using the ECDC PPS protocol version 6.0. The Regional health authority of the region of Piedmont, in north-western Italy, chose to enlist all public acute-care hospitals. Data were collected within one day per each ward, within 3 weeks in each hospital, at hospital, ward and patient level. A score between 0-1 or 0-2 was assigned to each of the 9 items in the IPCAF questionnaire, with 14 points representing the best possible score. HAI prevalence was calculated at the hospital-level as the percentage of patients with at least one HAI over all included patients. Relations between HAI prevalence, IPCAF score, and other hospital-level variables were assessed using Spearman's Rho coefficient.
In total, 42 acute-care hospitals of the region of Piedmont were involved, with a total of 6865 included patients. All participant hospitals reported they employed multimodal strategies to implement IPC interventions. The median IPCAF overall score was 11/14 (interquartile range, IQR: 9.25-12). The multimodal strategy with the highest level of adherence was education and training, followed by communication and reminders. Strategies with the lowest level of adherence were safety climate and culture of change, and system change. Overall HAI prevalence was 8.06%. A weak to moderate inverse relation was found between IPCAF score and HAI prevalence (Spearman's Rho -0.340, p 0.034). No other significant correlation was found.
This study found a high self-reported overall level of implementation of multimodal strategies for IPC in the region. Results of this study suggest the relevance of the multimodal approach and the validity of the IPCAF score in measuring IPC programs, in terms of effectiveness of preventing HAI transmission.
Summary Objectives A main determinant of clinical response to antibiotic treatment is drug concentration at the infected site. Data on ceftriaxone (CFX) bone penetration are lacking. We measured CFX ...concentrations in infected bone to verify their relationship with pharmacodynamic microbiological markers. Methods Eleven patients undergoing debridement for septic non-union of the tibia and receiving intravenous CFX were studied. Plasma and bone specimens were collected intraoperatively at a variable interval after CFX administration. Drug concentrations were measured by high-performance liquid chromatography with ultraviolet detection (HPLC-UV) method. Results Bone samples were extracted at a mean of 3.3 h (range 1.5–8.0 h) since the start of CFX infusion. The mean ± standard deviation intraoperative CFX plasma concentration was 128.4 ± 30.8 mg/l; the corresponding bone concentrations were 9.6 ± 3.4 mg/l (7.8%) in the cortical compartment and 30.8 ± 8.6 mg/l (24.3%) in the cancellous compartment. The mean 24-h area under the concentration–time curve (AUC24 ) values were 176.8 ± 62.2 h*mg/l in cortical bone and 461.5 ± 106.8 h*mg/l in cancellous bone. The time above the minimum inhibitory concentration (T>MIC) was 24 h in all compartments. The estimated mean free AUC/MIC ratios and T>MIC were 140 and 24.4 h, respectively, in cancellous bone and 42.4 and 21 h, respectively, in cortical bone. Conclusions CFX bone penetration was poor (<15%) in the cortical compartment and satisfactory in the more vascularized cancellous bone. The T>MIC and AUC/MIC ratios suggest that CFX achieves a satisfactory pharmacokinetic exposure in cancellous bone as far as pathogens with a MIC of <0.5 are concerned. However, considering free drug concentrations, pharmacokinetic/pharmacodynamic targets may not be fully achieved in cortical bone. As antibiotic exposure can be suboptimal in the infected cortical compartment, and drug penetration may be impaired into necrotic bone and sequesters, a radical surgical removal of purulent and necrotic tissues appears essential to shorten treatment duration and to prevent treatment failures.
In the treatment of bone infections, a major determinant of the clinical response is the active drug concentration at the infected site. Because of the high prevalence of meticillin ...(methicillin)-resistant staphylococci and enterococci, glycopeptides are widely used for the treatment of bone and joint infections, but data on their penetration into human bone are lacking. The aim of our study was to measure vancomycin and teicoplanin concentrations in infected human bone under steady-state conditions and verify their relationship with inflammatory markers, patient demographic characteristics and pharmacodynamic microbiological markers.
Twenty-seven adult orthopaedic patients undergoing surgical debridement for septic pseudoarthrosis of the tibia and receiving either intravenous vancomycin (Vancocina) 1 g twice daily) or teicoplanin (Targosid) 10 mg/kg/day) were studied from January 2004 to January 2008. Plasma and bone specimens were simultaneously collected during surgery for pharmacokinetic and microbiological assays at a variable interval after antimicrobial administration. Bone samples were dissected into cortical and cancellous bone, cleaned of soft tissues, crushed and eluted into phosphate buffer. Necrotic samples and sequestra were not analysed.Plasma and bone antimicrobial concentrations were measured by a validated method of high-performance liquid chromatography with UV detection, and bone/plasma concentration ratios were calculated. Cortical and cancellous bone area under the concentration-time curve (AUC) over 24 hours (AUC(24)) values were measured by the linear-log trapezoidal rule, using WinNonlin) software, and were compared with the minimum inhibitory concentrations (MICs) of the infecting agents.
For vancomycin, the mean +/- SD concentrations were 2.66 +/- 1.2 mg/L in cortical bone and 11.53 +/- 7.8 mg/L in cancellous bone (corresponding to 20.67% and 89.39% of intraoperative plasma concentrations), and the mean +/- SD tissue AUC(24) values were 55.15 +/- 25.26 h . mg/L for cortical bone and 299.16 +/- 299.54 h . mg/L for cancellous bone. For teicoplanin, the mean +/- SD concentrations were 2.01 +/- 1.7 and 7.51 +/- 7.0 mg/L in cortical and cancellous bone, respectively (12.35% and 48.6% of intraoperative plasma concentrations), and the mean +/- SD teicoplanin tissue AUC(24) values were 34.08 +/- 23.6 h . mg/L and 155.17 +/- 132.8 h . mg/L for cortical bone and cancellous bone, respectively. The mean vancomycin AUC(24)/MIC ratios were 215.02 for plasma, 47.14 for cortical bone and 268.95 for cancellous bone. The mean teicoplanin AUC(24)/MIC ratios were 336.48, 36.27 and 197.21 for plasma, cortical bone and cancellous bone, respectively.
Bone penetration of both glycopeptides ranged from poor (<15%) to satisfactory (15-30%) in the cortical compartment, while it was far higher into the highly vascularized cancellous tissue. Vancomycin bone penetration was slightly higher than with teicoplanin, but the difference was not statistically significant. Higher bone concentrations were observed with higher inflammatory markers, possibly as a result of increased vascularization and vascular permeability under inflammatory conditions. Bone concentrations over the MIC and AUC/MIC ratios suggested that both glycopeptides achieve a satisfactory pharmacokinetic exposure in the cancellous bone, as far as Gram-positive pathogens are concerned. On the other hand, cortical bone exposure was suboptimal in most patients. Furthermore, as antimicrobial penetration may be affected by impaired blood supply, the role of radical surgical removal of purulent and necrotic tissues appears to be essential in order to shorten treatment duration and to reduce the risk of treatment failure.
The aim of this study was to evaluate the diagnostic value, in suspected infectious prostheses, of (99m)Tc-labeled hexamethylpropyleneamine oxime ((99m)Tc-HMPAO) leukocyte scintigraphy interpreted ...with the addition of a semiquantitative analysis.
By means of a retrospective review, we included a group of 78 consecutive patients with suspected hip or knee prosthesis infection. We performed 91 (99m)Tc-HMPAO-leukocyte scintigraphies and examined 95 localizations that were suspect. Images were acquired at 3 different time points after the injection of the labeled leukocytes: 50 min (early images), 4 h, and 24 h (late images). The scintigraphic examinations were independently evaluated by 3 observers; qualitative and semiquantitative analyses were performed. The final diagnosis of infection was based on surgical, histologic, and bacteriologic data and follow-up.
On qualitative analysis, sensitivity, specificity, and accuracy were 80.4%-87%, 65.3%-71.4%, and 75.8%-77.9%, respectively. On semiquantitative analysis, sensitivity, specificity, and accuracy were 95.6%, 95.8%, and 95.8%, respectively. The analysis of 95% confidential intervals showed statistically significant differences in specificity and accuracy between semiquantitative and qualitative analyses.
In those patients who underwent (99m)Tc-HMPAO-leukocyte scintigraphy for suspected hip or knee prosthesis infection, the addition of a semiquantitative evaluation to the qualitative analysis of early and late images leads to a significant improvement in both specificity and accuracy.
We studied a cohort of 299 HIV-positive individuals with known date of seroconversion to evaluate the role of Cytomegalovirus (CMV) in the natural history of HIV. The study population consisted of ...236 initially CMV-positive patients, 55 CMV-negative subjects and 8 CMV seroconverters. The study endpoints were the decline to CD4 + < 200 × 106 cells/l, AIDS, and death. The cumulative risk of CMV disease and the survival after CMV disease were also investigated. At intake, there was no inter-group difference in sex, age, risk behaviours, history of hairy leucoplakia or herpes zoster and antiretroviral treatment. During the follow-up, 108 patients fell below 200 CD4+ x 106 cells/l, 72 developed AIDS and 63 died. Twenty-one subjects had CMV disease. The cumulative incidence of CMV disease in the cohort was 18.9% and 23.3% within 8 and 9 years for the initially CMV-positive patients and 33.3% and 66.7% for the CMV seroconverters (log-rank test: p = 0.101). The median survival after CMV disease was 153 days (range: 28-855, interquartile range: 261), with a cumulative survival of 45.1%, 16.9% and 4.3% within 6, 12 and 18 months, respectively. On Cox's regression, the acute HIV seroconversion was an independent predictor of each endpoint, history of hairy leucoplakia or herpes zoster being associated only with CD4 + cell decline. Baseline CMV seropositivity was related to short survival (p = 0.037) and 2x2 inter-group comparison showed that older individuals with sexually acquired HIV who seroconverted to CMV had higher rates of progression to the study endpoints. Our data suggest that CMV infection influences the natural history of HIV disease and that CMV disease strongly affects the survival of the HIV-positive patients.
PDF
