Risk Factors for Complications during Outpatient Parenteral Antimicrobial Therapy for Adult Orthopedic and Neurosurgical Infections.

OBJECTIVES: Outpatient parenteral antimicrobial therapy (OPAT) is an effective way of treating infections, but complications are common. We identified patient characteristics and OPAT treatment factors associated with increased risk of OPAT-related complications. METHODS: We used a retrospective cohort design that assessed 337 adult patients treated with OPAT for orthopedic and neurosurgical infections between August 1, 2008 and May 30, 2010. Independent variables included demographics, infection characteristics, lead time factors, OPAT treatment factors, and comorbid conditions. Multivariable log-binomial regression was used to estimate the risk of OPAT complications. RESULTS: The mean patient age was 55 years (range 19-87), 86% had an orthopedic infection, and 44% were treated with intravenous vancomycin. OPAT complications were seen in 45% (152/337) of the cohort. Risk ratios for OPAT complications were 1.9 (95% confidence interval 1.4-2.5) in patients having no primary care provider, 1.7 (95% confidence interval 1.3-2.1) for those treated with vancomycin. CONCLUSIONS: Identifying specific patient characteristics and OPAT treatment factors could facilitate OPAT process improvements to reduce the risk of OPAT complications for vulnerable patients.

Best practices for centers of excellence in addressing periprosthetic joint infection.

Periprosthetic joint infection is a rare and devastating complication. Management of this complication often requires a multidisciplinary approach similar to that used for the care of patients with cancer. Several studies have reported better outcomes following total joint arthroplasties performed at specialized hospitals than those performed at general hospitals. Specialized institutions use care pathways that aid the multidisciplinary team in decision making. During the recent Musculoskeletal Infection symposium, specific issues were discussed with regard to the treatment of periprosthetic joint infection, including medical optimization, systematic approaches to infection management, and the importance of establishing registries to aid in the creation of Centers of Excellence. A Center of Excellence in periprosthetic infection could provide better overall outcomes with lower financial, physical, and emotional costs to patients.

Incidence of Pneumocystis jirovecii pneumonia after temozolomide for CNS malignancies without prophylaxis.

AIMS: Prophylaxis against Pneumocystis jiroveci pneumonia (PJP) is currently recommended for patients receiving chemoradiation with temozolomide for newly diagnosed glioblastoma multiforme. At our institution, PJP prophylaxis during temozolomide treatment has not been routinely given because of the paucity of supporting data. We investigated the rate of PJP infections in our patients. PATIENTS & METHODS: We conducted a retrospective chart review of 240 brain tumor patients treated between 1999 and 2012 with temozolomide and no PJP prophylaxis, 127 of which received concurrent chemoradiation. RESULTS: One in 240 patients (0.4%; 95% CI: 0.01-2.00; median total dose: 7375 mg/m(2); interquartile range: 1300) were diagnosed with PJP. CONCLUSION: There was a <1% rate of PJP for brain tumor patients treated with temozolomide until progression without PJP prophylaxis.

Posterior fixation without debridement for vertebral body osteomyelitis and discitis.

OBJECT: The authors evaluated the efficacy of posterior instrumentation for the management of spontaneous spinal infections. Standard surgical management of spontaneous spinal infection is based on debridement of the infected tissue. However, this can be very challenging as most of these patients are medically debilitated and the surgical debridement requires a more aggressive approach to the spine either anteriorly or via an expanded posterior approach. The authors present their results using an alternative treatment method of posterior-only neuro-decompression and stabilization without formal debridement of anterior tissue for treating spontaneous spinal infection. METHODS: Fifteen consecutive patients were treated surgically by 2 of the authors. All patients had osteomyelitis and discitis and were treated postoperatively with intravenous antibiotics for at least 6 weeks. The indications for surgery were failed medical management, progressive deformity with ongoing persistent spinal infection, or neurological deficit. Patients with simple epidural abscess without bony instability were treated with laminectomy and were not included in this series. Fourteen patients were treated with posterior-only decompression and long-segment rigid fixation, without formal debridement of the infected area. One patient was treated with staged anterior and posterior surgery due to delay in treatment related to medical comorbidities. The authors examined as their outcome the ambulatory status and recurrence of deep infection requiring additional surgery or medical treatment. RESULTS: Of the initial 15 patients, 10 (66%) had a minimum 2-year follow-up and 14 patients had at least 1 year of followup. There were no recurrent spinal infections. There were 3 unplanned reoperations (1 for loss of fixation, 1 for early superficial wound infection, and 1 for epidural hematoma). Nine (60%) of 15 patients were nonambulatory at presentation. At final followup, 8 of 15 patients were independently ambulatory, 6 required an assistive device, and 1 remained nonambulatory. CONCLUSIONS: Long-segment fixation, without formal debridement, resulted in resolution of spinal infection in all cases and in significant neurological recovery in almost all cases. This surgical technique, when combined with aggressive antibiotic therapy and a multidisciplinary team approach, is an effective way of managing serious spinal infections in a challenging patient population.

The Base Excision Repair system of Salmonella enterica serovar typhimurium counteracts DNA damage by host nitric oxide.

Intracellular pathogens must withstand nitric oxide (NO.) generated by host phagocytes. Salmonella enterica serovar Typhimurium interferes with intracellular trafficking of inducible nitric oxide synthase (iNOS) and possesses multiple systems to detoxify NO.. Consequently, the level of NO. stress encountered by S. Typhimurium during infection in vivo has been unknown. The Base Excision Repair (BER) system recognizes and repairs damaged DNA bases including cytosine and guanine residues modified by reactive nitrogen species. Apurinic/apyrimidinic (AP) sites generated by BER glycosylases require subsequent processing by AP endonucleases. S. Typhimurium xth nfo mutants lacking AP endonuclease activity exhibit increased NO. sensitivity resulting from chromosomal fragmentation at unprocessed AP sites. BER mutant strains were thus used to probe the nature and extent of nitrosative damage sustained by intracellular bacteria during infection. Here we show that an xth nfo S. Typhimurium mutant is attenuated for virulence in C3H/HeN mice, and virulence can be completely restored by the iNOS inhibitor L-NIL. Inactivation of the ung or fpg glycosylase genes partially restores virulence to xth nfo mutant S. Typhimurium, demonstrating that NO. fluxes in vivo are sufficient to modify cytosine and guanine bases, respectively. Mutants lacking ung or fpg exhibit NO.-dependent hypermutability during infection, underscoring the importance of BER in protecting Salmonella from the genotoxic effects of host NO.. These observations demonstrate that host-derived NO. damages Salmonella DNA in vivo, and the BER system is required to maintain bacterial genomic integrity.

Risks, diagnosis and outcomes of invasive fungal infections in haematopoietic stem cell transplant recipients.

Invasive fungal infections (IFIs) continue to cause considerable morbidity and mortality in haematopoietic stem cell transplant (HSCT) recipients. This review focuses on the risks for, and diagnosis of, IFIs (candidiasis, aspergillosis and other mould infections), and factors that affect current outcomes. Diagnosis of IFI is difficult, with the sensitivity of the gold standard tests (culture and histopathology) often <50%. Therefore, physicians rely on a constellation of clinical signs, radiography, culture, histopathology and adjunctive tests to establish diagnosis. HSCT recipients often have multiple co-morbidities, and understanding the current outcomes and prognostic variables is therefore important for overall management. This paper reviews historical trends and current data.

Aspergillosis: spectrum of disease, diagnosis, and treatment.

Infections by Aspergillus species present a particular challenge. The organism, which is ubiquitous in the environment, causes allergic disease in otherwise healthy individuals and devastating disease in the immunosuppressed. This article examines the range of infections caused by Aspergillus species, the challenges of diagnosis, and current treatment options.

Yersinia pseudotuberculosis disseminates directly from a replicating bacterial pool in the intestine.

Dissemination of Yersinia pseudotuberculosis within mice after oral inoculation was analyzed. Y. pseudotuberculosis translocated to organs such as the liver and spleen shortly after oral inoculation, but was quickly cleared. In contrast, a second temporally distinct bacterial translocation event resulted in successful hepatosplenic replication of the bacteria. Replicating pools of bacteria could be established in these organs in mouse mutants that lacked Peyer's patches. These animals frequently had sterile mesenteric lymph nodes, a finding consistent with translocation taking place independently of regional lymph node colonization. In further contradiction to accepted models for dissemination of enteropathogens, clonal analysis revealed that bacteria causing disease in the spleen and liver of C57BL/6J mice were derived from populations located outside the intestinal lymph nodes. Replication of bacteria in the intestine before translocation appeared critical for dissemination, as transient selective suppression by streptomycin of bacterial growth in the intestine delayed dissemination of Y. pseudotuberculosis. These results collectively indicate that hepatosplenic colonization appears intimately connected with the ability of Y. pseudotuberculosis to successfully establish replication in the intestinal lumen and does not result from ordered spread leading from the intestine to regional lymph nodes before dissemination.