Safety and Efficacy of Prolonged Use of Dalbavancin in Bone and Joint Infections

ABSTRACT Dalbavancin is a lipoglycopeptide with potent activity against Gram-positive microorganisms, a long half-life, a favorable safety profile, and a high concentration in bone, which makes it an interesting alternative for treatment of osteoarticular infections. We performed a multicentric retrospective study of all patients with an osteoarticular infection (septic arthritis, spondylodiscitis, osteomyelitis, or orthopedic implant-related infection) treated with at least one dose of dalbavancin between 2016 and 2017 in 30 institutions in Spain. In order to evaluate the response, patients with or without an orthopedic implant were separated. A total of 64 patients were included. Staphylococcus epidermidis and Staphylococcus aureus were the most frequent microorganisms. The reasons for switching to dalbavancin were simplification (53.1%), adverse events (25%), or failure (21.9%). There were 7 adverse events, and no patient had to discontinue dalbavancin. In 45 cases, infection was related to an orthopedic implant. The implant material was retained in 23 cases, including that in 15 (65.2%) patients that were classified as cured and 8 (34.8%) that presented improvement. In 21 cases, the implants were removed, including those in 16 (76.2%) cases that were considered successes, 4 (19%) cases were considered improved, and 1 (4.8%) case that was considered a failure. Among the 19 cases without implants, 14 (73.7%) were considered cured, 3 (15.8%) were considered improved, and 2 (10.5%) were considered failures. The results show that dalbavancin is a well-tolerated antibiotic, even when >2 doses are administered, and is associated with a high cure rate. These are preliminary data with a short follow-up; therefore, it is necessary to gain more experience and, in the future, to establish the most appropriate dose and frequency.

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Per-oral endoscopic dual myotomy for the treatment of achalasia

Esophagus ◽

10.1007/s10388-021-00863-9 ◽

2021 ◽

Author(s):

Xianglei Yuan ◽

Zhe Feng ◽

Yanshi Zhao ◽

Xianhui Zeng ◽

Liansong Ye ◽

...

Keyword(s):

Adverse Events ◽

Clinical Success ◽

Mucosal Injury ◽

Single Session ◽

Eckardt Score ◽

Endoscopic Myotomy ◽

Favorable Safety ◽

Per Oral ◽

Disease Questionnaire

Abstract Background Repeat per-oral endoscopic myotomy is occasionally performed for persistent/recurrent symptoms in patients with achalasia, and yields favorable outcomes. We investigated a novel technique, per-oral endoscopic dual myotomy (dual-POEM), where a second myotomy was performed during a single session to augment the efficacy and avoid repeat interventions. The aim of this study was to evaluate its feasibility, safety and efficacy. Methods Consecutive patients diagnosed with achalasia who underwent dual-POEM (1/2018–5/2019) were prospectively collected and retrospectively analyzed. Patients with baseline Eckardt score ≥ 9, ≥ 10 years of symptoms, and/or having prior interventions other than myotomy received dual-POEM. The primary outcome was clinical success (Eckardt score ≤ 3). Secondary outcomes were procedure-related adverse events, change in lower esophageal sphincter (LES) pressure, and reflux complications. Results Seventeen patients received dual-POEM. Procedure-related adverse events were observed in 2 (11.8%) patients (mucosal injury and pneumonitis). Both were minor in severity. During a median follow-up of 33 months (interquartile range, IQR [31,35]; range, 19–36), clinical success was achieved in 16 (94.1%) patients. The median Eckardt score decreased from 9 (IQR [8, 11.5]; range 7–12) to 1 (IQR [1, 2]; range 0–4) (P < 0.001), and LES pressure decreased from 25.8 mmHg (IQR [21.7, 33.5]; range 17.7–46.3) to 7.4 mmHg (IQR [6.3, 10.4]; range 2.2–12.6) (P < 0.001). Seven (41.2%) patients developed postprocedural reflux either by gastroesophageal reflux disease questionnaire or esophagitis endoscopically, all successfully treated with proton pump inhibitors. Conclusion Dual-POEM preliminarily demonstrated high efficacy with a favorable safety profile in patients with achalasia with predictors of treatment failure.

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Resorbable polymer implants in unilateral transforaminal lumbar interbody fusion

Journal of Neurosurgery Spine ◽

10.3171/spi.2002.97.4.0464 ◽

2002 ◽

Vol 97 (4) ◽

pp. 464-467 ◽

Cited By ~ 5

Author(s):

Thomas G. Lowe ◽

Jeffrey D. Coe

Keyword(s):

Adverse Events ◽

Biodegradable Polymers ◽

Clinical Studies ◽

Interbody Fusion ◽

Transforaminal Lumbar Interbody Fusion ◽

Degenerative Disease ◽

Lumbar Interbody Fusion ◽

Content Type ◽

Fine Print

Object. Sixty patients underwent instrumentation-assisted posterior transforaminal lumbar interbody fusion (TLIF) with resorbable polymer cages and autograft bone for degenerative disease. This article discusses the technique of TLIF and its early outcomes. Methods. Although the follow-up period is short and results are preliminary, no adverse events or complications were attributed to the resorbable polymer. Conclusions. Further multicenter clinical studies are underway with a minimum 2-year follow-up period chosen as an endpoint to provide insight as to the future of biodegradable polymers as spinal interbody devices.

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Salvage retreatment after failure of radiosurgery in patients with arteriovenous malformations

Journal of Neurosurgery ◽

10.3171/jns.2003.98.2.0337 ◽

2003 ◽

Vol 98 (2) ◽

pp. 337-341 ◽

Cited By ~ 51

Author(s):

Kelly D. Foote ◽

William A. Friedman ◽

Thomas L. Ellis ◽

Frank J. Bova ◽

John M. Buatti ◽

...

Keyword(s):

Treatment Failure ◽

Initial Treatment ◽

Primary Treatment ◽

Size Reduction ◽

Cure Rate ◽

Mr Images ◽

Content Type ◽

The Mean ◽

Fine Print

Object. The goal of this study was to evaluate the outcomes of patients who underwent repeated radiosurgery to treat a residual intracranial arteriovenous malformation (AVM) after an initial radiosurgical treatment failure. Methods. The authors reviewed the cases of 52 patients who underwent repeated radiosurgery for residual AVM at the University of Florida between December 1991 and June 1998. In each case, residual arteriovenous shunting persisted longer than 36 months after the initial treatment; the mean interval between the first and second treatment was 41 months. Each AVM nidus was measured at the time of the original treatment and again at the time of retreatment, and the dosimetric parameters of the two treatments were compared. After retreatment, patients were followed up and their outcomes were evaluated according to a standard posttreatment protocol for radiosurgery for AVMs. The mean original lesion volume was 13.8 cm3 and the mean volume at retreatment was 4.7 cm3, for an average volume reduction of 66% after the initial treatment failure. Only two AVMs (3.8%) failed to demonstrate size reduction after the primary treatment. The median doses on initial and repeated treatment were 12.5 and 15 Gy, respectively. Five patients were lost to follow up and five refused neuroimaging follow up. One patient died of a hemorrhage shortly after retreatment. Of the remaining 41 patients, 24 had evidence of cure, 15 on angiographic studies and nine on magnetic resonance (MR) images. Seventeen had evidence of treatment failure, 10 on angiographic studies and seven on MR images. By angiographic criteria alone, the cure rate after retreatment was 60%, whereas according to angiographic and MR imaging results, the cure rate was 59%. Conclusions. Although initial radiosurgical treatment failed to obliterate the AVM in these 52 patients, it did produce a substantial therapeutic effect (volume reduction). This size reduction commonly allowed higher doses to be delivered during radiosurgical retreatment. The results show rates of angiographically confirmed cure comparable to primary treatment and a low incidence of complications, indicating that salvage radiosurgical retreatment is a safe and effective therapy in cases of failed AVM radiosurgery.

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Acute symptoms after gamma knife radiosurgery

Journal of Neurosurgery ◽

10.3171/jns.2002.97.supplement_5.0631 ◽

2002 ◽

Vol 97 ◽

pp. 631-634 ◽

Cited By ~ 17

Author(s):

E. J. St. George ◽

J. Kudhail ◽

J. Perks ◽

P. N. Plowman

Keyword(s):

Adverse Events ◽

Gamma Knife ◽

Gamma Knife Radiosurgery ◽

Neurological Dysfunction ◽

Content Type ◽

Lesion Type ◽

Patient Groups ◽

Pin Site ◽

Fine Print

Object. The purpose of this study was to examine the widely held assumption that early-onset symptoms after gamma knife radiosurgery (GKS) are uncommon. The study was designed to include all types of morbidity and not just those that lead to neurological dysfunction. It was hoped that the results of the study could lead to a more rational follow-up protocol. Methods. Data regarding adverse events were collected prospectively (within 2–3 weeks post-GKS) by telephone interview from 47 of the first 65 patients who could be reached. Immediate adverse events were defined as any new or unexpected symptom developing within 2 weeks of treatment and were graded as mild, moderate, or severe. Two thirds of all patients complained of new adverse symptoms; three patients required prolonged hospitalization, although in one case this was not related to the radiosurgery. The majority of symptomatic patients (91%) experienced mild or moderate complications. More than 50% of patients had headache. One third described pin site—related complications and one fifth suffered from nausea/vomiting or marked tiredness. Patients with moderate symptoms had a larger mean tumor volume and higher radiation dose than other patient groups. Prior radiation therapy, lesion type, or the posttreatment administration of steroid agents did not significantly influence the development of acute symptoms. Conclusions. Acute adverse events following GKS are not uncommon if all types of morbidity are considered. An increased appreciation of these other complications may improve posttreatment care.

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Improved treatment strategies can result in better outcomes following one-stage exchange surgery for MRSA periprosthetic joint infection

Journal of Medical Microbiology ◽

10.1099/jmm.0.001229 ◽

2020 ◽

Vol 69 (8) ◽

pp. 1100-1104

Author(s):

Malte Ohlmeier ◽

Sergei Filitarin ◽

Giorgio Delgado ◽

Jannik Frings ◽

Hussein Abdelaziz ◽

...

Keyword(s):

Revision Rate ◽

Joint Infection ◽

Treatment Strategies ◽

Content Type ◽

One Stage ◽

Joint Infections ◽

The Mean ◽

The One ◽

Final Cohort

Introduction. Periprosthetic joint infections caused by methicillin-resistant Staphylococcus aureus (MRSA-PJIs) are rare, with only a few studies reporting the treatment outcomes and even fewer reporting outcomes with one-stage exchange. Aim. This study aims to analyse the outcomes of one-stage exchange in the management of MRSA-PJIs. Methodology. Patients with MRSA-PJI of the hip and knee, who were treated with a one-stage exchange between 2001 and 2018 were enrolled in this study. The final cohort comprised of 29 patients, which included 23 hips and six knees. The mean follow-up was 5.3 years (1–9 years). Reinfection and complications rates after the one-stage exchange were analysed. Results. Overall infection control could be achieved in 93.1 % (27 out of 29 patients). The overall revision rate was 31.0% (9 patients), with three patients requiring an in-hospital revision (10.3 %). Six patients had to be revised after hospital discharge (20.7 %). Of the two reinfections, one had a growth of MRSA while the other was of methicillin-sensitive Staphyloccocus epidermidis. Conclusion. One-stage exchange surgery using current techniques could improve surgical outcomes with excellent results in the management of MRSA-PJIs.

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Safety and Efficacy of Moxifloxacin Monotherapy for Treatment of Orthopedic Implant-Related Staphylococcal Infections

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00027-10 ◽

2010 ◽

Vol 54 (12) ◽

pp. 5161-5166 ◽

Cited By ~ 22

Author(s):

Rafael San Juan ◽

Ana Garcia-Reyne ◽

Pedro Caba ◽

Fernando Chaves ◽

Carlos Resines ◽

...

Keyword(s):

Acute Onset ◽

Term Therapy ◽

Orthopedic Implant ◽

Cure Rate ◽

Chronic Infections ◽

Staphylococcal Infections ◽

Management Protocol ◽

Long Term Treatment

ABSTRACT The rifampin-ciprofloxacin combination is recommended for treatment of orthopedic implant-related staphylococcal infections to avoid the emergence of ciprofloxacin resistance; however, the efficacy of this combination is limited by the tolerability problems associated with the use of rifampin. Moxifloxacin is a quinolone up to 10 times more active against staphylococci than ciprofloxacin and the risk of resistance development during monotherapy against staphylococci is theoretically lower for moxifloxacin, but information regarding its use in bone infections is lacking. The aim of the present study was to evaluate the safety and clinical efficacy of moxifloxacin monotherapy in patients with orthopedic implant-related staphylococcal infections. From June 2006 to April 2009, all patients with culture-proven infection by quinolone-sensitive staphylococcal strains associated with orthopedic implants at our institution were included in a management protocol that mostly included specific surgery, 1 to 2 weeks of an intravenous course of cloxacillin-cefazolin or vancomycin, and long-term therapy with moxifloxacin (400 mg/day for 3 months). Cure was defined as (i) a lack of clinical signs and symptoms of infection, (ii) a C-reactive protein level less than 5 mg/liter, and (iii) absence of radiological signs of loosening or infection at the latest follow-up visit. Failure was defined as (i) persisting clinical and/or laboratory signs of infection or (ii) persisting or new isolation of the initial microorganism. A total of 48 patients with a median follow-up of 716 days (range, 102 to 1,613 days) were included in the study. Complete drug compliance was achieved in all but two patients (4.2%), who required drug discontinuation because of side effects (diarrhea and dizziness). No moxifloxacin-induced arrhythmia was reported. Twenty patients had joint prosthesis infections (5 acute-onset infections and 15 chronic infections), and 28 patients had osteosynthesis material infections (4 acute-onset infections and 24 chronic infections). The etiologies were methicillin-sensitive Staphylococcus aureus in 33 patients and a coagulase-negative staphylococcus (CoNS) in 15. Surgical management was performed for the majority of patients (37/48; 77%), and the implant was retained in 21 patients (43.8%). The global cure rate was 38/46 (82.6%), and the cure rate for patients with implant retention was 15/21 (71.4%). The global cure rate for the 32 patients with a minimum follow-up of 2 years was 80%. Of the eight cases of relapse, we obtained microbiological confirmation in six cases, and all bacteria recovered were quinolone susceptible. Monotherapy with moxifloxacin seems to be an effective, safe, and easy alternative for the long-term treatment of orthopedic implant-related staphylococcal infections by quinolone-sensitive strains. Comparative studies with rifampin-containing regimens are warranted.

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Antimicrobial-Related Severe Adverse Events during Treatment of Bone and Joint Infection Due to Methicillin-Susceptible Staphylococcus aureus

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02032-13 ◽

2013 ◽

Vol 58 (2) ◽

pp. 746-755 ◽

Cited By ~ 32

Author(s):

Florent Valour ◽

Judith Karsenty ◽

Anissa Bouaziz ◽

Florence Ader ◽

Michel Tod ◽

...

Keyword(s):

Risk Factors ◽

Staphylococcus Aureus ◽

Adverse Events ◽

Joint Infection ◽

Binary Logistic Regression ◽

Chronic Arthritis ◽

High Rate ◽

Content Type ◽

Joint Infections ◽

Severe Adverse Events

ABSTRACTProlonged antimicrobial therapy is recommended for methicillin-susceptibleStaphylococcus aureus(MSSA) bone and joint infections (BJI), but its safety profile and risk factors for severe adverse events (SAE) in clinical practice are unknown. We addressed these issues in a retrospective cohort study (2001 to 2011) analyzing antimicrobial-related SAE (defined according to the Common Terminology Criteria for Adverse Events) in 200 patients (male, 62%; median age, 60.8 years [interquartile range {IQR}, 45.5 to 74.2 years]) with MSSA BJI admitted to a reference regional center with acute (66%) or chronic arthritis (7.5%), osteomyelitis (9.5%), spondylodiscitis (16%), or orthopedic device-related infections (67%). These patients received antistaphylococcal therapy for a median of 26.6 weeks (IQR, 16.8 to 37.8 weeks). Thirty-eight SAE occurred in 30 patients (15%), with a median time delay of 34 days (IQR, 14.75 to 60.5 days), including 10 patients with hematologic reactions, 9 with cutaneomucosal reactions, 6 with acute renal injuries, 4 with hypokalemia, and 4 with cholestatic hepatitis. The most frequently implicated antimicrobials were antistaphylococcal penicillins (ASP) (13 SAE/145 patients), fluoroquinolones (12 SAE/187 patients), glycopeptides (9 SAE/101 patients), and rifampin (7 SAE/107 patients). Kaplan-Meier curves and stepwise binary logistic regression analyses were used to determine the risk factors for the occurrence of antimicrobial-related SAE. Age (odds ratio [OR], 1.479 for 10-year increase; 95% confidence interval [CI], 1.116 to 1.960;P= 0.006) appeared to be the only independent risk factor for SAE. In patients receiving ASP or rifampin, daily dose (OR, 1.028; 95% CI, 1.006 to 1.051;P= 0.014) and obesity (OR, 8.991; 95% CI, 1.453 to 55.627;P= 0.018) were associated with the occurrence of SAE. The high rate of SAE and their determinants highlighted the importance of the management and follow-up of BJI, with particular attention to be paid to older persons, especially for ASP dosage, and to rifampin dose adjustment in obese patients.

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Treatment of Pemphigus with Rituximab: Real-Life Experience in a Cohort of 117 Patients in Israel

Dermatology ◽

10.1159/000513515 ◽

2021 ◽

pp. 1-7

Author(s):

Adi Nosrati ◽

Emmilia Hodak ◽

Tomer Mimouni ◽

Meital Oren-Shabtai ◽

Assi Levi ◽

...

Keyword(s):

Adverse Events ◽

Life Experience ◽

Remission Rate ◽

Controlled Trial ◽

Real Life ◽

High Dose ◽

Efficacy Analysis ◽

Prospective Randomized Controlled Trial ◽

Favorable Safety

Background: A combined regimen of rituximab with corticosteroids for the treatment of pemphigus was effective in a prospective randomized controlled trial. Objective: To assess real-life response to rituximab in patients with pemphigus. Methods: A retrospective cohort of patients with pemphigus treated with ≥1 rituximab cycles (1,000 mg on days 0 and 14). The primary outcome was remission rate after 1 cycle. For efficacy analyses, a minimal 6-month follow-up was required. Adverse events were assessed in all patients. Results: The cohort included 117 patients for safety analysis, 108 for efficacy analysis (median follow-up of 33 months). All but one received concomitant corticosteroids, a third also received adjuvants. Overall, 80/108 patients (74%) achieved remission after the first rituximab cycle at a median of 5.5 months. Relapses occurred in 39 patients (49%) at a median of 18 months. Repeating treatment in relapsed patients increased remission rates to 75 and 88% after the second and third cycles, respectively. Adverse events were similar to those of previous publications. Two elderly patients died of infections attributable to rituximab combined with high-dose corticosteroids. Conclusion: In a large real-life long-term cohort, rituximab with corticosteroids ± adjuvants induced remission in most patients with pemphigus, with relatively favorable safety. Repeating treatment following relapse or remission failure was beneficial.

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Period of risk for recurrence in medulloblastoma

Journal of Neurosurgery ◽

10.3171/jns.1978.48.2.0159 ◽

1978 ◽

Vol 48 (2) ◽

pp. 159-163 ◽

Cited By ~ 48

Author(s):

Donald O. Quest ◽

Ronald Brisman ◽

Joao L. Antunes ◽

Edgar M. Housepian

Keyword(s):

Survival Rate ◽

Older Patients ◽

Survival Rates ◽

Cure Rate ◽

Content Type ◽

Congenital Tumor ◽

Factors Influencing ◽

Initial Surgery ◽

Embryonic Origin

✓ Ninety-nine patients with medulloblastoma who received surgery and radiotherapy, and had a statistically sufficient follow-up period were analyzed for factors influencing survival and the relevance of the “period of risk for recurrence” hypothesis. This postulate states that the period of risk for recurrence of a congenital tumor is equal to the age at presentation of illness plus 9 months' gestational time. The assumption is made that a tumor of embryonic origin will become manifest after a period of time determined by its inherent rate of growth and that tumor cells surviving treatment will multiply and present with recurrence in an equal period of time. Ten of 43 patients survived the period of risk, a presumed cure rate of 23%. None of these patients has subsequently developed evidence of tumor recurrence. Older patients at initial surgery had a somewhat greater survival rate for the first 5 years after treatment (10 of 26 older patients (38%) versus 15 of 54 younger patients (28%)), but by 10 years there was no appreciable difference in survival rates between those over 16 years of age and those younger. The beneficial effect of total neuraxis megavoltage radiotherapy is indicated by the improved 5-year survival rate from 9 of 41 patients (22%) to 16 of 39 patients (41%) with the newer techniques.

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Effectiveness of miltefosine in cutaneous leishmaniasis caused by Leishmania tropica in Pakistan after antimonial treatment failure or contraindications to first line therapy—A retrospective analysis

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0008988 ◽

2021 ◽

Vol 15 (1) ◽

pp. e0008988

Author(s):

Suzette Kämink ◽

Boota Masih ◽

Noor Ali ◽

Aman Ullah ◽

Syed Juma Khan ◽

...

Keyword(s):

Adverse Events ◽

Treatment Failure ◽

Cutaneous Leishmaniasis ◽

Treatment Options ◽

Previous Treatment ◽

Standard Of Care ◽

Initial Response ◽

Cure Rate ◽

Stomach Pain

Background Cutaneous leishmaniasis (CL) is a neglected tropical skin disease, caused by Leishmania protozoa. In Pakistan, where CL caused by L. tropica is highly endemic, therapy with pentavalent antimonials is the standard of care, but has significant toxicity when used in systemic therapy, while are no evidence-based safer alternative treatment options for L. tropica. The efficacy of oral miltefosine has not been studied in CL caused by L. tropica. We evaluated effectiveness and tolerability of miltefosine in patients with previous treatment failure or with contraindications to systemic antimonial treatment. Methods A retrospective review was conducted of a cohort of CL patients who were treated with a 28-day course of miltefosine between December 2017 and August 2019, in urban Quetta, Pakistan, an area endemic for L. tropica. Descriptive analyses were performed, and effectiveness was assessed by initial response after treatment, and final cure at routine follow up visits, six weeks to three months post-treatment. Tolerability was assessed by routinely reported adverse events. Results Of the 76 CL patients in the cohort, 42 (55%) had contraindications to systemic antimonial treatment, and 34 (45%) had failure or relapse after antimonial treatment. Twelve patients defaulted during treatment and 12 patients were lost to follow up. In the remaining 52 patients, final cure rate was 77% (40/52). In those with contraindications to systemic antimonial treatment the final cure rate was 83% (24/29) and in the failure and relapse group 70% (16/23). Twenty-eight patients (40.0%) reported 39 mild to moderate adverse events with the main complaints being nausea (41.0%), general malaise (25.6%), and stomach pain (12.8%). Conclusion Results indicate that miltefosine is an effective second line treatment in CL in areas endemic for L. tropica. Prospective studies with systematic follow up are needed to obtain definitive evidence of effectiveness and tolerability, including identification of risk factors for miltefosine treatment failure.

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