Prolongation Of Prophylaxis Research Articles

Pneumocystis Pneumonia After Allogeneic Hematopoietic Cell Transplantation: A Case-Control Study on Epidemiology and Risk Factors on Behalf of the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation

Pneumocystis pneumonia (PCP) is a life-threatening complication after allogeneic hematopoietic cell transplantation (allo-HCT). However, allo-HCT procedures have evolved toward older patients, unrelated donors, and reduced-intensity conditioning, possibly modifying the risks. Polymerase chain reaction (PCR), widely used nowadays, is more sensitive than microscopy diagnostic methods. This study aimed to assess the factors associated with PCP in allo-HCT recipients within 2 years of HCT and managed according to current procedures. This multicenter, nested case-control study included PCP cases diagnosed by PCR, cytology, or immunofluorescence on bronchoalveolar lavage fluid between 2016 and 2018. Two controls per case were selected from the ProMISe registry and matched for the center, transplant date, and underlying disease. Fifty-two cases and 104 controls were included among the 5452 patients who underwent allo-HCT in the participating centers. PCP occurred at a median of 11.5 months after transplantation. The mortality rate was 24% on day 30 after the PCP diagnosis and 37% on day 90. The clinical presentation and mortality rates of the 24 patients diagnosed using only PCR were not different from those diagnosed with microscopy methods. Our study demonstrates a substantial incidence of, and mortality from, PCP, after allogeneic HCT despite well-established prophylactic approaches. In our experience, PCP nowadays occurs later after transplant than previously reported, justifying the prolongation of prophylaxis after six months in many cases. Allo-HCT recipients diagnosed with PCR as the only PCP marker should benefit from specific treatment as for other patients.

PNEUMOCYSTIS PNEUMONIA OCCURRENCE AND PROPHYLAXIS DURATION IN KIDNEY TRANSPLANT RECIPIENTS ACCORDING TO PERIOPERATIVE TREATMENT WITH RITUXIMAB

Background: Pneumocystis pneumonia (PCP) is a life-threatening fungal infection that can occur in kidney transplantation (KT) recipients. A growing number of KT recipients are receiving perioperative treatment with rituximab, which is associated with prolonged B-cell depletion and possible risk of PCP occurrence; however, the optimal prophylaxis duration according to rituximab treatment is yet unknown. We compared the occurrence of PCP and the duration of prophylaxis in KT recipients according to rituximab treatment. Methods: We retrospectively analyzed 2110 patients who underwent KT between January 2009 and December 2016, who were divided into non-Rituximab group (n = 1588, 75.3%) and rituximab group (n = 522, 24.7%). Results: In the rituximab group, the estimated number needed to treat (NNT) for prophylaxis prolongation from 6 to 12 months was 29.0 with a relative risk reduction of 90.0%. In the non-rituximab group, the estimated NNT value was 133.3 and the relative risk reduction was 66.4%. Rituximab treatment (hazard ratio (HR) = 3.09; P < 0.01) and acute rejection (HR = 2.19; P = 0.03) were significant risk factors for PCP in multivariate analysis.Conclusion: Our results suggest that maintaining PCP prophylaxis for 12 months may be beneficial in KT recipients treated with rituximab for desensitization or acute rejection treatment.

Pneumocystis pneumonia occurrence and prophylaxis duration in kidney transplant recipients according to perioperative treatment with rituximab

BackgroundPneumocystis pneumonia (PCP) is a life-threatening fungal infection that can occur in kidney transplantation (KT) recipients. A growing number of KT recipients are receiving perioperative treatment with rituximab, which is associated with prolonged B-cell depletion and possible risk of PCP occurrence; however, the optimal prophylaxis duration according to rituximab treatment is yet unknown. We compared the occurrence of PCP and the duration of prophylaxis in KT recipients according to rituximab treatment.MethodsWe retrospectively analyzed 2110 patients who underwent KT between January 2009 and December 2016, who were divided into non-Rituximab group (n = 1588, 75.3%) and rituximab group (n = 522, 24.7%).ResultsIn the rituximab group, the estimated number needed to treat (NNT) for prophylaxis prolongation from 6 to 12 months was 29.0 with a relative risk reduction of 90.0%. In the non-rituximab group, the estimated NNT value was 133.3 and the relative risk reduction was 66.4%. Rituximab treatment (hazard ratio (HR) = 3.09; P < 0.01) and acute rejection (HR = 2.19; P = 0.03) were significant risk factors for PCP in multivariate analysis.ConclusionsOur results suggest that maintaining PCP prophylaxis for 12 months may be beneficial in KT recipients treated with rituximab for desensitization or acute rejection treatment.

Chinese guideline for the prevention of surgical site infection

Surgical site infection (SSI) is one of the most common health care-associated infections, which increases patients' financial burden, prolongs hospital days, and even raises mortality. Prevention of SSI requires the integration of a range of preventive measures before, during, and after surgery. This guideline is based on current evidence and clinical practice, and takes into account the balance between benefits and harms, the evidence quality level, cost and resource allocation, and patient values and preferences. We present in this guideline 22 recommendations suitable for Chinese conditions and specific to the preoperative, intraoperative and postoperative periods. Preventive measures including nutritional support, immunosuppressive agents, bathing, mechanical bowel preparation with oral antibiotics, hair removal, optimal timing for administration of surgical antibiotic prophylaxis, and surgical hand preparation, were involved in the preoperative period. During the intraoperative and postoperative period, preventive measures include normothermia, blood glucose control, fluid therapy, drapes and gowns, wound-protector devices, incisional wound irrigations, prophylactic vacuum suction therapy, antimicrobial-coated sutures, antimicrobial prophylaxis in the presence of a drainage, optimal timing for wound drain removal, wound dressing, and surgical antibiotic prophylaxis prolongation. It should be noted that when applying recommendations, surgeons should combine the conditions of their hospitals and patients' conditions. More researches are required to further investigate unsolved problems.

Responding to the Global Guidelines for the Prevention of Surgical Site Infection, 2018: A focus on surgical antibiotic prophylaxis prolongation.

Responding to the Global Guidelines for the Prevention of Surgical Site Infection, 2018: A focus on surgical antibiotic prophylaxis prolongation.

Invited Commentary

The burden of postoperative infection is felt broadly both in patient outcomes and in resource utilization. Over the past decade, the Nationwide Inpatient Sample and the National Surgical Quality Improvement Program have highlighted the full impact of these adverse events [1Rowell K.S. Turrentine F.E. Hutter M.M. Khuri S.F. Henderson W.G. Use of national surgical quality improvement program data as a catalyst for quality improvement.J Am Coll Surg. 2007; 204: 1293-1300Abstract Full Text Full Text PDF PubMed Scopus (191) Google Scholar, 2de Lissovoy G. Fraeman K. Hutchins V. Murphy D. Song D. Vaughn B.B. Surgical site infection: incidence and impact on hospital utilization and treatment costs.Am J Infect Control. 2009; 37: 387-397Abstract Full Text Full Text PDF PubMed Scopus (796) Google Scholar]. Although researchers are increasingly turning to national administrative databases to acquire patient samples, these sources are frequently marred by inconsistent or incomplete clinical data. In this issue of The Annals, Robich and colleagues [3Robich M.P. Sabik J.F. Houghtaling P.L. et al.Prolonged effect of postoperative infectious complications on survival after cardiac surgery.Ann Thorac Surg. 2015; 99: 1591-1600Google Scholar] harness their impressive single-institution operative volume to shed light on the long-term clinical impact of postoperative infections after cardiac operations. Performing propensity-matched analysis on a clinically focused dataset, the authors show that patients who experience postoperative infections and are successfully treated retain an increased risk of death after discharge that gradually decreases over time. In particular, the risk-adjusted survival for patients with septicemia, pneumonia, or harvest site infection is inferior to that in propensity-matched, noninfected control patients. Although the authors report a negative survival impact for as long as 1 year after discharge, a large portion of this excess risk is observed within the first 3 months. Notably, noninfected control patients in the matched group also had relatively poor 1-year survival, suggesting that patients who experience infectious adverse events tend to be sicker at baseline. The authors then identified numerous risk factors associated with postoperative infections, including age, immunosuppression, operative duration, diabetes, prolonged ventilation, and others. These results reinforce intuitive associations with valuable, objective evidence. The authors rightly acknowledged that, as with nearly all propensity-matching studies, there may be unaccounted confounders and imperfect matching. Nevertheless, this study and others carry important implications for both perioperative management and follow-up after discharge. The identification of a high-risk patient may suggest roles for antibiotic prophylaxis prolongation up to 48 hours [4Lador A. Nasir H. Mansur N. et al.Antibiotic prophylaxis in cardiac surgery: systematic review and meta-analysis.J Antimicrob Chemother. 2012; 67: 541-550Crossref PubMed Scopus (83) Google Scholar], fast-track extubation, early mobilization and urinary catheter removal, or surgical techniques aimed at preserving sternal blood supply [5Deo S.V. Shah I.K. Dunlay S.M. et al.Bilateral internal thoracic artery harvest and deep sternal wound infection in diabetic patients.Ann Thorac Surg. 2013; 95: 862-869Abstract Full Text Full Text PDF PubMed Scopus (127) Google Scholar]. After discharge, these patients should receive aggressive follow-up with a low threshold for readmission. Finally, this study’s results advocate for certain surgical quality indicators to extend beyond the short-term perioperative period, because it is becoming increasingly clear that adverse outcomes months or even years after an operation may nevertheless be associated with adverse events directly related to the operation. Prolonged Effect of Postoperative Infectious Complications on Survival After Cardiac SurgeryThe Annals of Thoracic SurgeryVol. 99Issue 5PreviewWhether patients having infections after cardiac surgery are at a survival disadvantage after hospital discharge is unclear. Our objectives were (1) to identify characteristics of such patients and (2) to determine whether this complication is associated with increased mortality beyond hospital discharge. Full-Text PDF

Evaluation of the Duration of the Antibiotic Prophylaxis in Paediatric Postoperative Heart Surgery Patients

The ideal duration of postoperative antibiotic prophylaxis in heart surgery is unknown. The most recent guidelines recommend a decrease in prophylaxis time to decrease the emergence of multiresistant germs. However, compliance with these recommendations is scant. Our aim was to determine whether a decrease in prophylaxis time entails an increase in the infection rate. A retrospective study was performed between September 2003 and March 2006, including all patients of ages between 1 day and 14 years who were admitted to the intensive care unit after heart surgery. Patients being treated for an infection at the time of surgery were excluded. The appearance of nosocomial infection, localisation, and the causative agent, if isolated, were included; demographic and clinical analytical variables, duration and type of antibiotic prophylaxis, and duration of other invasive devices were also included. Standard analysis and multivariable logistical regression were performed. 194 patients were included in the study. The median duration of antibiotic prophylaxis was 72 h (range 24 to 176), with the most-used prophylaxis regimen being second-generation cephalosporins plus aminoglycosides. The incidence of nosocomial infection, mainly bacteraemia, was 11.9%. The type of antibiotic therapy used for prophylaxis did not affect the incidence of infection. In the multivariable logistical regression, only prolongation of antibiotic prophylaxis >48 h, central venous access maintenance time, and intubation increased the infection rate. The suspension of antibiotic prophylaxis in the 48 h after surgery in pediatric patients undergoing heart surgery does not increase the incidence of nosocomial infection. According to our results, prolongation of prophylaxis >48 h increases the infection rate.

Profilaxis de la infección por citomegalovirus en el trasplante hepático

CMV prevention strategies in liver transplant recipients should be stratified according to serological status. In donor (D)-/recipient (R)- combinations, no prophylaxis or preemptive therapy is recommended. In the remaining combinations, the most widely used strategies are universal prophylaxis and preemptive therapy. Both strategies are effective compared with placebo but have not been compared with each other in well-designed clinical trials. Preemptive therapy is the preferred strategy in low-risk patients while prophylaxis is the most widely used option in those at high-risk. Delayed CMV disease is an adverse consequence of universal prophylaxis. Prolongation of prophylaxis from 100 to 200 days does not reduce the incidence of CMV disease. CMV-specific cell mediated immunity, facilitated by preemptive therapy and delayed by prophylaxis, has a therapeutic effect by reducing CMV replication. The drug of choice in both strategies is valganciclovir but the duration and dose differ. When preemptive therapy is used, viremia monitoring is required for the first 4 months. The technique of choice is quantitative polymerase chain reaction. Given the lack of conclusive data, the choice of one or other strategy in these patients should be individualized in each patient and center according to the available resources and possibilities of follow-up.

Antibiotic prophylaxis in cardiac surgery: systematic review and meta-analysis

Antibiotic prophylaxis is recommended in cardiac surgery. Current debate concerns the type of antibiotic(s), dosing and the duration of prophylaxis. Systematic review of randomized controlled trials comparing one antibiotic regimen versus another in cardiac surgery. We searched The Cochrane Library, PubMed, LILACS, conference proceedings and bibliographies. Two reviewers independently extracted the data. The primary outcome was deep sternal wound infections (DSWIs). Meta-analysis was performed using the Mantel-Haenszel fixed-effect method. Risk ratios (RRs) with 95% confidence intervals (95% CIs) are reported. Fifty-nine trials were included. There were no significant differences in DSWI or all other categories of surgical site infections (SSIs) for antibiotic prophylaxis with β-lactams comprising a Gram-negative spectrum of coverage versus prophylaxis targeting Gram-positive bacteria, but the former led to a significantly lower rate of post-operative pneumonia (RR 0.68, 95% CI 0.51-0.90) and all-cause mortality (RR 0.66, 95% CI 0.47-0.92). In trials comparing different antibiotic regimens for different durations, prophylaxis duration of ≤24 h post-operation led to higher rates of DSWI (RR 1.83, 95% CI 1.25-2.66), any sternal SSI, surgical interventions for SSI and endocarditis compared with longer duration prophylaxis. There was no advantage of regimens lasting >48 h post-operation. In the comparison of glycopeptides versus β-lactams, an advantage of glycopeptides was observed when comparators were given for similar duration and for β-lactams when given for a longer duration than the glycopeptides. There was no significant advantage of high antibiotic dosing. Evidence supports second- or third-generation cephalosporins for cardiac surgery prophylaxis and points at a possible advantage of prophylaxis prolongation up to 48 h post-operatively.

Preventing CMV Viremia and Disease 3–6 Months After Renal Transplantation

To the Editor: The letter by Mossad et al. raises some important issues regarding strategies for preventing CMV disease occurring after completion of antiviral prophylaxis (i.e. late-onset CMV). It is correct that in the IMPACT trial, for patients receiving 100 days of prophylaxis, the majority of late-onset disease occurred between month 3 and month 6 posttransplant (1). I agree that routine virologic monitoring after completing 100 days of prophylaxis (a hybrid prophylaxis/pre-emptive strategy) may be an alternative prevention approach (vs prolongation of prophylaxis). However, based on the current literature it is unclear what the comparative efficacy of this would be for the prevention of late-onset disease. In one study analyzing the potential value of such a strategy after completing of a 3 month course of antiviral prophylaxis, routine viral load monitoring would have predicted late-onset disease in only 24/64 (38%) cases (2). Since in vivo viral doubling time may be quite rapid in high-risk transplant patients (in the range of 1–2 days) (3), it may be that more intensive viral load monitoring (e.g. weekly) would be required in order to prove effective in preventing disease. Such intensive monitoring may be logistically difficult in some settings once patients are beyond 3 months posttransplant. Ideally a randomized trial comparing prolonged prophylaxis versus a hybrid prophylaxis/pre-emptive approach would help better define the best method for prevention of late-onset disease. Alternatively the use of better predictive tools such as cell mediated immunity assessments, may allow a more individually tailored approach for prophylaxis in the future. More simple measurements of immune response such as seroconversion in donor-seropositive/recipient-seronegative patients (D+/R–) do not appear to have significant clinical utility for prediction of late-onset CMV disease (4). However, assessment of CMV-specific CD4+ or CD8+ T-cell responses may be more useful for predicting late-onset disease. For example, detection of CMV-specific CD4+ T cells was associated with protection from subsequent viremia in a cohort of kidney transplant recipients (5). However, more data is needed on the predictive value of such assessments before they can be adopted into routine clinical practice. The author of this manuscript has conflicts of interest to disclose as described by the American Journal of Transplantation. Atul Humar has received grant support and/or honoraria from Roche, Astellas, Pfizer and CSL Behring.

Selective low-dose valganciclovir for prevention of cytomegalovirus disease following kidney transplantation

To assess the safety of a cytomegalovirus prophylaxis regimen using selective low-dose valganciclovir. Retrospective before-after comparison, including consecutive kidney transplant recipients between 2002 and 2004. Excluded were deaths or graft loss within one month after transplantation. During the first period, universal prophylaxis with oral ganciclovir was used. During the second period, selective prophylaxis with low-dose valganciclovir (450 mg/day) was given to patients at high-risk for CMV disease (D+/R- recipients and patients treated with anti-lymphocyte antibodies) and oral acyclovir to all other patients. We compared the incidence of CMV disease between the two periods. Two hundred and sixty-four patients underwent kidney transplantation of which 221 were included. The incidence of CMV disease was higher with selective low-dose valganciclovir compared to universal ganciclovir without statistical significance, by intention to treat (4.7% vs. 8.5%, respectively, OR 1.88, 95% CI 0.63-5.60) and among patients adhering to the prophylaxis protocol (3.1% vs. 6.8% respectively, OR 2.85, 95% CI 0.65-12.38). Only late-onset CMV was observed for compliant patients. On multivariate analysis, only recipients' serostatus remained significantly associated with CMV disease (OR 0.22, 95% CI 0.07-0.70). Selective low-dose valganciclovir may provide similar protection against CMV when compared to universal oral ganciclovir. Prolongation of prophylaxis beyond 100 days should be explored.

An evaluation of antimicrobial prophylaxis in paediatric surgery and its financial implication

To assess the appropriateness of use of antimicrobial prophylaxis in paediatric surgery in Singapore. A prospective evaluation of the use of antimicrobial prophylaxis in paediatric patients undergoing surgery in KK Hospital, Singapore was carried out from September and December 2001. Process measures for the study included adherence to local or international guidelines, choice and dose of antimicrobial agent and timing and duration of prophylaxis. Outcome measures included surgical site and other related infections. A cost analysis was also performed to look at the extra expenditure due to any excessive use of antimicrobials. A total of 171 patients with a mean age of 5.7 years (SD=4.5) were included in the study. Among the 117 (68.4%) elective and 54 (31.6%) emergency procedures, 22 cases (12.8%) were fully compliant with the guidelines. The most frequently encountered non-compliance types were unnecessary prolongation of prophylaxis (54.4%), inappropriate choice of antibiotics (42.7%) and overdose of antibiotics (26.3%). The estimated extra cost to patients for the study period was Sing$13,879.41 (US 8164.36). The results showed a significantly high level of inappropriate use of antimicrobial prophylaxis in paediatric surgery in Singapore. However, when the individual factors such as appropriate choice of antibiotics, appropriate timing and duration were considered, the situation was very similar to the results obtained from overseas studies.

Prophylaxis of Venous Thrombosis.

Mechanical measures such as graduated compression stockings and intermittent compression boots are available for venous thrombosis prophylaxis, but compliance may be limited. Plantar venous pneumatic compression devices have attained widespread acceptance by both patients and nurses because of their comfort and compact size, but their track record for efficacy is poor. Inferior vena cava filters prevent pulmonary embolism, but do not halt the thrombotic process or prevent venous thrombosis. Pharmacologic prophylaxis traditionally has relied upon minidose unfractionated heparin; however, re-examination is warranted in the face of increasingly ill and complex patients. My opinion is that small, fixed doses of once-daily low molecular weight heparin will eventually replace minidose unfractionated heparin as the standard pharmacologic prophylaxis regimen for most surgical and medical patients. Prolongation of prophylaxis after hospital discharge should receive increased emphasis. Most patients being transferred to a skilled nursing facility should receive venous thromboembolism prophylaxis. Similarly, most patients undergoing total hip or knee replacement should receive prolonged preventive regimens, with at least 1 month of anticoagulation. Despite advances, certain aspects of venous thrombosis prophylaxis remain problematic. First, a surprisingly high number of hospitalized patients develop venous thrombosis because of failed (rather than omitted) prophylaxis. Second, many patients in intensive care have a combination of peripheral vascular disease and active bleeding (usually gastrointestinal) that precludes mechanical or pharmacologic prophylaxis. Third, neurosurgical patients undergoing craniotomy for brain tumors suffer a high rate of venous thrombosis and major pulmonary embolism despite the routine use of combined mechanical and pharmacologic prophylaxis. My opinion is that these three areas, in addition to the hospital culture of prophylaxis, should receive increased attention in an effort to prevent venous thromboembolism.

Pseudomembranous colitis associated with antibiotic prophylaxis in orthopaedic surgery.

We report 16 orthopaedic patients who had antibiotic-associated diarrhoea (pseudomembranous colitis) after operation. There was an association with the use of cephradine and with the prolongation of prophylaxis for more than three peri-operative doses. Five cases occurred as a cluster, suggesting that the causative agent, Clostridium difficile, may be infectious in some situations.