Duration Of Systemic Antibiotic Therapy Research Articles

Moderate to Severe Soft Tissue Diabetic Foot Infections: A Randomized, Controlled, Pilot Trial of Post-debridement Antibiotic Treatment for 10 versus 20 days.

Background:The optimal duration of antibiotic therapy for soft-tissue infections of the diabetic foot remains unknown.Objective:We determine if antibiotic therapy after debridement for a short (10 days), compared with a long (20 days), duration for soft-tissue infections of the diabetic foot results in similar rates of clinical remission and adverse events (AE).Summary of Background Data:The optimal duration of systemic antibiotic therapy, after successful debridement, for soft tissue infections of diabetic patients is unknown. Because of the high recurrence risk, overuse is commonplace.Methods:This was a randomized, controlled, non-inferiority pilot trial of cases of diabetic foot infection (excluding osteomyelitis) with the primary outcome of “clinical remission at 2-months follow-up”.Results:Among 66 enrolled episodes (17% females; median age 71 years), we randomized 35 to the 10-day arm and 31 to the 20-day arm. The median duration of the parenteral antibiotic therapy was 1 day, with the remainder given orally. In the intention-to-treat population, we achieved clinical remission in 27 (77%) patients in the 10-day arm compared to 22 (71%) in the 20-days arm (P = 0.57). There were a similar proportion in each arm of AE (14/35 versus 11/31; P = 0.71), and remission in the per-protocol population (25/32 vs 18/27; P = 0.32). Overall, 8 soft tissue DFIs in the 10-day arm and 5 cases in the 20-day arm recurred as a new osteomyelitis [8/35 (23%) versus 5/31 (16%); P = 0.53]. Overall, the number of recurrences limited to the soft tissues was 4 (6%). By multivariate analysis, rates of remission (intention-to-treat population, hazard ratio 0.6, 95%CI 0.3-1.1; per-protocol population 0.8, 95%CI 0.4-1.5) and AE were not significantly different with a 10-day compared to 20-day course.Conclusions:In this randomized, controlled pilot trial, post-debridement antibiotic therapy for soft tissue DFI for 10 days gave similar (and non-inferior) rates of remission and AEs to 20 days. A larger confirmatory trial is under way.Trial registration:ClinicalTrials NCT03615807.

Combined antibiotic therapy spacers either commercial or handmade are superior to monotherapy - a microbiological analysis at the second stage of revision.

Background: Antibiotic-loaded spacers are often used during two-stage exchange for periprosthetic joint infections (PJIs) both for its mechanical properties and as a means of local antibiotic delivery. Purpose: The main goal of this study is to compare the efficacy of different options of antibiotic(s) in spacers concerning the rate of positive cultures at the second stage. Patients and Methods: We retrospectively evaluated two-stage exchange procedures for infected hip or knee arthroplasty performed between 2012 and 2018 in which adequate (at least four deep tissue samples) culture results in both stages were available. The type of spacer and antibiotics used, in addition to several other patient, infection and treatment-related variables, were registered and correlated to microbiological findings in the second stage. Results: Fifty-eight cases were included with a 19.0 % (11/58) overall rate of positive cultures during reimplantation. With a mean follow-up of 46 months, failure rate was significantly higher at 63.6 % (7/11) in cases with positive cultures at reimplantation compared to 4.3 % (2/47) for those with negative cultures during reimplantation ( 0.001). The need for additional surgeries was also significantly higher (odds ratio (OR) 122.67, confidence interval (CI) 95 % 11.30–1331.32, 0.001). Multivariable analysis revealed antibiotics in the spacers were the main independent prognostic risk factor associated with positive cultures at the second stage with an advantage for combined antibiotics. Monotherapy is associated with failure with an OR of 16.99. Longer time between surgeries did not have statistical significance ( 0.05), and previous surgical treatment for PJI, presence of difficult-to-treat microorganism(s), duration of systemic antibiotic therapy or even treatment within a dedicated septic team were not shown to be independent risk factors. Among combined antibiotic spacers, there were no significant differences between the rate of positive cultures during the second stage, comparing commercially available vancomycin/gentamicin spacers to hand-mixed vancomycin/meropenem manufactured spacers (8.3 % [2/24] vs. 15.0 % [3/20], 0.68). Conclusions: Results show that combined antibiotic therapy spacers are advantageous when compared to gentamicin monotherapy as they produce significantly lower rates of subsequent positive cultures during the second stage. Hand-mixed high-dose vancomycin/meropenem spacers seem to perform just as well as prefabricated commercially available vancomycin/gentamicin options. Level of Evidence: Therapeutic level III.

Short postsurgical antibiotic therapy for spinal infections: protocol of prospective, randomized, unblinded, noninferiority trials (SASI trials)

BackgroundThere are several open scientific questions regarding the optimal antibiotic treatment of spinal infections (SIs) with or without an implant. The duration of postsurgical antibiotic therapy is debated.MethodsWe will perform two unblinded randomized controlled trials (RCTs). We hypothesize that shorter durations of systemic antibiotic therapy after surgery for SI are noninferior (10% margin, 80% power, α = 5%) to existing (long) treatment durations. The RCTs allocate the participants to two arms of 2 × 59 episodes each: 3 vs. 6 weeks of targeted postsurgical systemic antibiotic therapy for implant-free SIs or 6 vs. 12 weeks for implant-related SIs. This equals a total of 236 adult SI episodes (randomization scheme 1:1) with a minimal follow-up of 12 months. All participants receive concomitant multidisciplinary surgical, re-educational, internist, and infectious disease care. We will perform three interim analyses that are evaluated, in a blinded analysis, by an independent study data monitoring committee. Besides the primary outcome of remission, we will also assess adverse events of antibiotic therapy, changes of the patient’s nutritional status, the influence of immune suppression, total costs, functional scores, and the timely evolution of the (surgical) wounds. We define infection as the presence of local signs of inflammation (pus, wound discharge, calor, and rubor) together with microbiological evidence of the same pathogen(s) in at least two intraoperative samples, and we define remission as the absence of clinical, laboratory, and/or radiological evidence of (former or new) infection.DiscussionProvided that there is adequate surgical debridement, both RCTs will potentially enable prescription of less antibiotics during the therapy of SI, with potentially less adverse events and reduced overall costs.Trial registrationClinicalTrials.gov, NCT04048304. Registered on 5 August 2019.Protocol version2, 5 July 2019.

Short or Long Antibiotic Regimes in Orthopaedics (SOLARIO): a randomised controlled open-label non-inferiority trial of duration of systemic antibiotics in adults with orthopaedic infection treated operatively with local antibiotic therapy

BackgroundOrthopaedic infections, such as osteomyelitis, diabetic foot infection and prosthetic joint infection, are most commonly treated by a combination of surgical debridement and a prolonged course of systemic antibiotics, usually for at least 4–6 weeks. Use of local antibiotics, implanted directly into the site of infection at the time of surgery, may improve antibiotic delivery and allow us to shorten the duration of systemic antibiotic therapy, thereby limiting the frequency of side effects, cost and selection pressure for antimicrobial resistance.MethodsSOLARIO is a multicentre open-label randomised controlled non-inferiority trial comparing short and long systemic antibiotic therapy alongside local antibiotic therapy. Adult patients with orthopaedic infection, who have given informed consent, will be eligible to participate in the study provided that no micro-organisms identified from deep tissue samples are resistant to locally implanted antibiotics. Participants will be randomised in a 1:1 ratio to receive either a short course (≤ 7 days) or currently recommended long course (≥ 4 weeks) of systemic antibiotics. The primary outcome will be treatment failure by 12 months after surgery, as ascertained by an independent Endpoint Committee blinded to treatment allocation. An absolute non-inferiority margin of 10% will be used for both per-protocol and intention-to-treat populations. Secondary outcomes will include probable and definite treatment failure, serious adverse events, treatment side effects, quality of life scores and cost analysis.DiscussionThis study aims to assess a treatment strategy that may enable the reduction of systemic antibiotic use for patients with orthopaedic infection. If this strategy is non-inferior, this will be to the advantage of patients and contribute to antimicrobial stewardship.Trial registrationClinicaltrials.gov, NCT03806166. Registered on 11 November 2019.

Adjunctive Nebulized Antibiotics: What Is Their Place in ICU Infections?

Inhaled antibiotics have been used as adjunctive therapy for patients with pneumonia, primarily caused by multidrug resistant (MDR) pathogens. Most studies have been in ventilated patients, although non-ventilated patients have also been included (but not discussed in this review), and most patients have had nosocomial pneumonia. Aerosolized antibiotics are generally added to systemic therapy, and have shown efficacy, primarily as salvage therapy for failing patients and as adjunctive therapy after an MDR gram-negative has been identified. An advantage to aerosolized antibiotics is that they can achieve high intra-pulmonary concentrations that are potentially effective, even for highly resistant pathogens, and because they are generally not well-absorbed systemically, it is possible to avoid some of the toxicities of systemic therapy. When using inhaled antibiotics, it is essential to choose the appropriate agent and the optimal delivery method. Animal and human studies have shown that aerosolized antibiotics reach higher concentrations in the lung than systemic antibiotics, but that areas of dense pneumonia may not receive as much antibiotic as less affected areas of lung. Optimal delivery in ventilated patients depends on device selection, generally with a preference for vibrating mesh nebulizers and with careful attention to where the device is placed in the ventilator circuit and how the delivery is coordinated with the ventilator cycle. Although some studies have shown a benefit for clinical cure, adjunctive therapy has not led to reduced mortality. In some studies, adjunctive aerosol therapy has reduced the duration of systemic antibiotic therapy, thus serving to promote antimicrobial stewardship. Two recent multicenter, randomized, double-blinded, placebo-controlled trials of adjunctive nebulized antibiotics for VAP patients with suspected MDR gram-negative pneumonia were negative for their primary endpoints. This may have been related to trial design and execution and the lessons learned from these studies need to be incorporated in any future trials. Currently, routine use of adjunctive aerosolized therapy cannot be supported by available data, and this therapy is only recommended to assist in the eradication of highly resistant pathogens and to be used as salvage therapy for patients failing systemic therapy.

THE EFFECTS OF GENTAMICIN-IMPREGNATED COLLAGEN SPONGE VERSUS GENTAMICIN-IMPREGNATED POLYMETHYLMETHACRYLATE BEADS IN PATIENTS WITH OSTEOMYELITIS

Objective: The usage of antibiotic-impregnated polymethylmethacrylate (PMMA) beads is regarded as the gold standard for local antibiotic delivery. However, the relatively new antibiotic-impregnated collagen sponge has multiple advantages over it. The objective of this study is to compare the measurable effects between gentamicin-impregnated collagen sponge and gentamicin-impregnated (PMMA) beads in patients with osteomyelitis.Methods: This is a case–control study which involved 60 patients who were diagnosed with osteomyelitis between January 2014 and June 2015, and underwent first surgical debridement with application of either gentamicin-impregnated collagen sponge (n=28) or gentamicin-impregnated PMMA beads (n=32). The numbers of debridement, trend of blood parameters, duration of hospitalization, and total duration of systemic antibiotic therapy needed to be completed were reviewed from the patients’ file.Results: A total of 53 patients of 60 were diagnosed with osteomyelitis of the lower limbs, while the remaining seven were involving the upper limbs. The gentamicin-impregnated collagen sponge group has significant lower reoperative rate (p<0.05) and also significant reduction of total white cell count in 6 weeks (p<0.05). The two groups showed no statistical difference in regard of duration of hospital admission, duration of systemic antibiotic therapy completed, and the reduction of C-reactive protein at 6 weeks post-debridement.Conclusion: This study reiterates the efficacy of gentamicin-impregnated collagen sponge that results in lower reoperative rate as compared to conventional gentamicin-impregnated PMMA beads.

Granulocyte-colony stimulating factors as adjunctive therapy for diabetic foot infections

Granulocyte-colony stimulating factor (G-CSF) increases the release of neutrophil endothelial progenitor cells from the bone marrow and improves neutrophil functions, which are often impaired in people with diabetes. To examine the effects of adjunctive G-CSF compared with placebo or no growth factor added to usual care on rates of infection, cure and wound healing in people with diabetes who have a foot infection. In March 2013, for this second update, we searched the Cochrane Wounds Group Specialised Register (searched 14 March 2013); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 2); Ovid MEDLINE (1948 to March Week 1 2013); Ovid EMBASE (1974 to 2013 March 13); Ovid MEDLINE (In-Process march 13,2013); and EBSCO CINAHL (1982 to 28 February 2013). Randomised controlled trials (RCTs) that evaluated the effect of adding G-CSF to usual care in people with a diabetic foot infection. Three review authors independently assessed trial eligibility, methodological quality and extracted data. We reported risk ratio (RR) or, for continuous outcomes, mean differences (MD), with 95% confidence intervals (CI). In the case of low or no heterogeneity we pooled studies using a fixed-effect model. We identified and included five eligible trials with a total of 167 patients. The investigators administered various G-CSF preparations, at different doses and for different durations of time. Adding G-CSF did not significantly affect the likelihood of resolution of infection or wound healing, but it was associated with a significantly reduced likelihood of lower extremity surgical interventions (RR 0.38; 95 % CI 0.21 to 0.70), including amputation (RR 0.41; 95 % CI 0.18 to 0.95). Moreover, providing G-CSF reduced the duration of hospital stay (MD -1.40 days; 95% CI -2.27 to -0.53 days), but did not significantly affect the duration of systemic antibiotic therapy (MD -0.27 days; 95% CI -1.30 to 0.77 days). The available evidence is limited, but suggests that adjunctive G-CSF treatment in people with a diabetic foot infection, including infected ulcers, does not appear to increase the likelihood of resolution of infection or healing of the foot ulcer. However, it does appear to reduce the need for surgical interventions, especially amputations, and the duration of hospitalisation. Clinicians might consider adding G-CSF to the usual treatment of diabetic foot infections, especially in patients with a limb-threatening infection, but it is not clear which patients might benefit.

Two-stage revision of infected hip arthroplasty using an antibiotic-loaded spacer: retrospective comparison between short-term and prolonged antibiotic therapy

The optimal duration of systemic antibiotic therapy in patients with prosthetic hip infection (PHI) undergoing staged exchange arthroplasty (SEA) has not been determined. We hypothesized that with an antibiotic-loaded cement spacer (ALCS), in the interim, short-term antibiotic therapy is as effective as a conventional prolonged treatment course. We reviewed 99 patients with PHI who were managed with SEA using an ALCS from February 2002 to October 2005. A standard (4-6 week) antibiotic treatment course was administered in the first 46 patients and a short-term (1 week) therapy was adopted in the subsequent 53 patients. Eight patients (four in each group) had persistent infection following the first attempt of surgery and antibiotic treatment; in three of them the infection was cured by additional debridement prior to re-implantation. Forty-two (91%) patients in the long-term group and 47 (89%) patients in the short-term group were free of infection (P = 0.67) at an average follow-up of 43 months (range, 24-60 months). Five (11%) patients developed complications related to prolonged antibiotic therapy. The short-term treatment resulted in a shorter hospital stay (18 versus 43 days, P < 0.001) and a lower direct medical cost (US$13 732 versus US$21 756, P < 0.001). Short-term antibiotic therapy was not associated with a higher rate of treatment failure. Given the higher costs and incidence of complications, protracted courses of antibiotic administration may not necessarily be routine practice in patients with PHI undergoing SEA, provided that an ALCS is used.

Failure of antibiotic therapy in Staphylococcus epidermidis infection of implantable venous access devices in patients with AIDS, as documented by molecular typing.

OBJECTIVE: To study the efficacy and safety of high-concentration antibiotic locks in association with systemic antibiotherapy in Staphylococcus epidermidis infections of totally implantable venous access devices (TIVADs) in patients with AIDS. METHODS: Thirty-one episodes of S. epidermidis TIVAD infection were observed in nine patients. Locks consisted of high concentrations of aminoglycosides or vancomycin according to antibiogram results (susceptibility results obtained with the disk diffusion technique). Genotyping of bacterial strains was performed by pulsed-field gel electrophoresis (PFGE) in 26 of the 31 infectious episodes. RESULTS: The infections occurred within a median period of 62 catheter-days. The median duration of systemic antibiotic therapy was 17.5 days in association with a median of three antibiotic locks. Failure as defined by the occurrence of a novel episode within 2 months was observed in 17 of the 31 infections (58%). According to the PFGE results, relapse with the same strain of S. epidermidis or reinfection with a different strain of S. epidermidis could be assigned to 10 episodes which failed to respond to therapy. Relapse was observed in six of 10 episodes. Four episodes were followed by the occurrence of a novel infection with a different S. epidermidis strain. In one patient, a relapse occurred despite TIVAD removal. CONCLUSION: Our observations further document the poor efficacy of associating antibiotic locks with systemic antibiotic therapy for the treatment of TIVAD infections in patients with AIDS.