Sandra B. Nelson

Comparative Evaluation of the Tolerability of Cefazolin and Nafcillin for Treatment of Methicillin-Susceptible Staphylococcus aureus Infections in the Outpatient Setting

BACKGROUND Nafcillin and cefazolin are considered first-line therapy for most infections with methicillin-susceptible Staphylococcus aureus (MSSA), and recent studies have suggested similar clinical efficacy. Limited data are available on the comparative tolerability of these agents. METHODS In this retrospective cohort analysis of patients treated with either nafcillin or cefazolin for MSSA infection in the outpatient parenteral antimicrobial therapy clinic at Massachusetts General Hospital from 2007 to 2011, the frequency of premature antimicrobial discontinuation (PAD) and drug-emergent events (DEEs) was calculated. RESULTS Three hundred sixty-six and 119 patients were treated with nafcillin or cefazolin, respectively. The median anticipated duration of therapy was comparable at 28 (interquartile range [IQR], 16-37) and 29 (IQR, 24-39) days, respectively, for those treated with nafcillin and cefazolin. Fewer patients completed the prespecified treatment course with nafcillin than with cefazolin (PAD rate, 33.8% vs 6.7%; P < .0001). The hazard ratio for PAD in the nafcillin vs cefazolin groups was 2.81 (95% confidence interval [CI], 1.26-3.68). More patients in the nafcillin group developed rash (13.9% vs 4.2%; P = .002), renal dysfunction (11.4% vs 3.3%; P = .006), and liver function abnormalities (8.1% vs 1.6%; P = .01). Overall rates of DEEs per 1000 patient-days were 16.9 (95% CI, 10.4-27.3) and 4.8 (95% CI, 1.1-10.2), respectively. In 9 cases of nafcillin discontinuation, treatment was changed to cefazolin; all 9 completed treatment with no further observed DEEs. CONCLUSIONS Nafcillin treatment was associated with higher rates of both PAD as well as DEEs compared with cefazolin treatment. This difference in tolerability, in addition to efficacy and cost, should be considered when decisions for outpatient parenteral MSSA treatment are made.

Periprosthetic Joint Infection with Negative Culture Results: Clinical Characteristics and Treatment Outcome

Negative culture result is frequently encountered in periprosthetic joint infection, but its clinical feature has not been well studied. In this study, clinical characteristics and treatment outcome were compared in two patient groups: (1) 40 periprosthetic joint infections with negative culture results (culture-negative group) and (2) 135 patients with positive culture results (culture-positive group). In comparison of two groups, the culture-negative group showed significantly higher incidence of prior antibiotic use (p=0.005), higher incidence of prior resection surgery (p<0.001) and lower ESR (p=0.02) than the culture-positive group. The success rate of infection control was higher in the culture-negative group (p=0.006), which suggests that culture negativity may not necessarily be a negative prognostic factor for periprosthetic joint infection.

What’s New in Musculoskeletal Infection: Update on Biofilms

Infections involving orthopaedic surgical implants present unique challenges when compared with infections that do not involve implants. Microorganisms have a high affinity for adhering to foreign materials commonly used in orthopaedics, including cobalt-chromium, titanium, polyethylene, and polymethylmethacrylate (PMMA) cement. When bacteria adhere to these surfaces, they can form a complex structure surrounded by a self-generated extracellular polymeric substance (EPS) matrix formed by multiplex agents of biopolymers consisting of proteins, polysaccharides, lipids, nucleic acids, and humic substances1-3. The term “biofilm” is commonly used to describe this network of microorganisms, a term popularized by Dr. J. William Costerton et al. in 19784. Biofilms are formed by a confluence of bacteria commonly encountered in orthopaedic infections. Up to 65% of bacterial infections are caused by biofilm-producing organisms5. Staphylococci, specifically Staphylococcus aureus ( S. aureus ) and Staphylococcus epidermidis ( S. epidermidis ), are the most common biofilm-forming bacteria found in orthopaedics, and, when combined with Pseudomonas aeruginosa ( P. aeruginosa ), they represent nearly 75% of biofilm infections observed in medical devices6. Propionibacterium acnes ( P. acnes ), an organism commonly found in shoulder infections, has also been shown to form biofilm. Biofilms can be composed of a single organism or can be polymicrobial; polymicrobial biofilms are more difficult to eradicate7. Once bacteria adhere to the surface of implants, they may replicate and may form a complex network of microorganisms that communicate with one another via cell-to-cell signaling that facilitates the participation of bacteria in quorum sensing7. Quorum sensing serves as an elementary endocrine system whereby bacteria sense the local cell population density and regulate gene expression by releasing extracellular molecules to facilitate synchronized changes in the bacteria within the biofilm. These transcriptional changes can occur with the exchange of plasmids between bacteria, which can confer genes …

Peripheral blood eosinophilia and hypersensitivity reactions among patients receiving outpatient parenteral antibiotics.

BACKGROUND Although drug-induced peripheral eosinophilia complicates antimicrobial therapy, little is known about its frequency and implications. OBJECTIVE We aimed to determine the frequency and predictors of antibiotic-induced eosinophilia and subsequent hypersensitivity reactions (HSRs). METHODS We evaluated a prospective cohort of former inpatients receiving intravenous antibiotic therapy as outpatients with at least 1 differential blood count. We used multivariate Cox proportional hazards models with time-varying antibiotic treatment indicators to assess the effect of demographic data and antibiotic exposures on eosinophilia and subsequent HSRs, including documented rash, renal injury, and liver injury. Possible drug rash with eosinophilia and systemic symptoms (DRESS) syndrome cases were identified and manually validated. RESULTS Of 824 patients (60% male; median age, 60 years; median therapy duration, 41 days), 210 (25%) had eosinophilia, with median peak absolute eosinophil counts of 726/mL (interquartile range, 594-990/mL). Use of vancomycin, penicillin, rifampin, and linezolid was associated with a higher hazard of having eosinophilia. There was a subsequent HSR in 64 (30%) of 210 patients with eosinophilia, including rash (n = 32), renal injury (n = 31), and liver injury (n = 13). Patients with eosinophilia were significantly more likely to have rash (hazard ratio [HR], 4.16; 95% CI, 2.54-6.83; P < .0001) and renal injury (HR, 2.13; 95% CI, 1.36-3.33; P = .0009) but not liver injury (HR, 1.75; 95% CI, 0.92-3.33; P = .09). Possible DRESS syndrome occurred in 7 (0.8%) of 824 patients; 4 (57%) were receiving vancomycin. CONCLUSIONS Drug-induced eosinophilia is common with parenteral antibiotics. Although most patients with eosinophilia do not have an HSR, eosinophilia increases the hazard rate of having rash and renal injury. DRESS syndrome was more common than previously described.

Is Biopsying the Paravertebral Soft Tissue as Effective as Biopsying the Disk or Vertebral Endplate? 10-Year Retrospective Review of CT-Guided Biopsy of Diskitis-Osteomyelitis

OBJECTIVE The purpose of this study was to determine whether there is a difference in biopsying bone (endplate), disk, or paravertebral soft tissue to culture the pathogenic organism causing diskitis-osteomyelitis. MATERIALS AND METHODS A retrospective review was conducted of 111 spinal biopsies performed between 2002 and 2011. Pathologic examination was used as the reference standard for detecting diskitis-osteomyelitis. Microbiologic yield, sensitivity, and specificity were calculated. The yields for different groups were compared by use of Fisher exact test. The analysis was repeated with biopsy samples from patients not being treated with antibiotics at the time of biopsy. RESULTS A total of 122 biopsy specimens were obtained from 111 spinal biopsy procedures on 102 patients. Overall, 27 (22%) biopsies were performed on the endplate-disk, 61 (50%) on the disk only, and 34 (28%) on paravertebral soft tissue only. The microbiologic yield was 36% for all biopsies, 19% for endplate-disk biopsies, 39% for disk-only biopsies, and 44% for soft-tissue biopsies. The sensitivity and specificity of the microbiologic results for all specimens were 57% and 89%; endplate-disk, 38% and 86%; disk only, 57% and 89%; and paravertebral soft tissue, 68% and 92%. There was no statistically significant difference between the yields of the endplate-disk, disk-only, and paravertebral soft-tissue biopsies. CONCLUSION Paravertebral soft-tissue changes, when present, may be considered a viable target for biopsy in cases of diskitis-osteomyelitis, even in the absence of a paravertebral abscess.

Management of Fungal or Atypical Periprosthetic Joint Infections

ConsensusA fungal or atypical PJI is an infection of a jointarthroplasty caused by fungi or atypical bacteria.Delegate VoteAgree: 89%, Disagree: 7%, Abstain: 4% (Strong Con-sensus)JustificationGenerally a fungal or atypical PJI is believed to existwhen fungal organisms or atypical bacteria are isolat-ed from the joint fluid or intraoperative tissue samplesand these organisms are believed to be the dominantinfecting agents in the prosthetic joint.Fungi may be moulds/molds, yeasts, or dimorphicfungi. Moulds are fungi that grow in the form ofmulticellular filaments called hyphae. The vast majori-ty were Candida infections (which represent morethan 80% of PJIs). In contrast, fungi that can adopt asingle celled growth habit are called yeasts. Dimorphicfungi can exist as mold forms or as yeast. Atypicalbacteria are bacteria that have deviations of one ormore of the following characteristics of a typicalbacterium: cell wall (containing peptidoglycan), cellmembrane, no nuclear membrane, reproduction by cellfission, and susceptibility to antibiotics but not toantifungal agents.

Tolerability of Cefazolin after Immune-Mediated Hypersensitivity Reactions to Nafcillin in the Outpatient Setting

ABSTRACT The objective of the present study was to assess the safety and tolerability of cefazolin therapy among patients with methicillin-sensitive Gram-positive bacterial infections who develop non-IgE-mediated hypersensitivity reactions (HSRs) to nafcillin. In this retrospective cohort analysis of the Outpatient Parenteral Antimicrobial Therapy program at the Massachusetts General Hospital from 2007 through 2013, we identified patients switched from nafcillin to cefazolin after an immune-mediated HSR. We reviewed patient demographics, details about the original HSR, and outcomes after the switch to cefazolin therapy. HSRs were classified by reaction type and likely mechanism. There were 467 patients treated with nafcillin, of which 60 (12.8%) were switched to cefazolin during their prescribed course. Of the 60 patients who transitioned to cefazolin, 17 (28.3%) were switched because of non-IgE-mediated HSRs. HSRs included maculopapular rash (n = 10), immune-mediated nephritis (n = 3), isolated eosinophilia (n = 2), immune-mediated hepatitis (n = 1), and a serum sickness-like reaction (n = 1). All but one patient (94.1%) who switched to cefazolin tolerated the drug with resolution of the HSR and completed their therapy with cefazolin. No patient experienced worsening of their rash or progressive organ dysfunction. With appropriate monitoring, therapy with cefazolin after non-IgE-mediated HSRs to nafcillin appears to be safe.

Mycobacterial Musculoskeletal Infections

Although less common as causes of musculoskeletal infection than pyogenic bacteria, both Mycobacterium tuberculosis and nontuberculous mycobacteria can infect bones and joints. Although tuberculous arthritis and osteomyelitis have been recognized for millennia, infections caused by nontuberculous mycobacteria are being identified more often, likely because of a more susceptible host population and improvements in diagnostic capabilities. Despite advances in modern medicine, mycobacterial infections of the musculoskeletal system remain particularly challenging to diagnose and manage. This article discusses clinical manifestations of musculoskeletal infections caused by Mycobacterium tuberculosis and nontuberculous mycobacteria. Pathogenesis, unique risk factors, and diagnostic and therapeutic approaches are reviewed.

Prognostic Factors for Failure of Antibiotic Treatment in Patients With Osteomyelitis of the Spine

Study Design. Retrospective cohort study. Objective. The aim of this study was to identify factors independently associated with antibiotic treatment failure in patients with spinal osteomyelitis. Summary of Background Data. There are few studies that have identified risk factors for antibiotic treatment failure in medically managed spinal osteomyelitis. Identifying such factors could help to identify patients who can be treated solely with antibiotics. Methods. All patients who underwent antibiotic treatment for spinal osteomyelitis in one of our institutions between January 1, 2001 and January 1, 2015 were identified. Patients who underwent surgery before the start of the antibiotic treatment were excluded. Results. We included 215 patients with a mean age of 58 years; 63 (29%) patients had failure of antibiotic treatment. Diabetes (hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.03–2.79, P = 0.037), fever (HR 1.61, 95% CI 0.93–2.79, P = 0.088), osteomyelitis at an additional site (HR 5.17, 95% CI 2.63–27.9, P = 0.001), and the presence of an epidural abscess (HR 1.91, 95% CI 1.05–3.45, P = 0.033) were associated with failure of antibiotic treatment. In the multivariate Cox regression analysis, diabetes (HR 1.69, 95% CI 1.03–2.79, P = 0.019), osteomyelitis at an additional site (HR 8.26, 95% CI 2.51–27.2, P = 0.001), fever (HR 1.77, 95% CI 1.00–3.12, P = 0.050), and the presence of an epidural abscess (HR 1.82, 95% CI 1.06–3.13, P = 0.030) were independently associated with failure of antibiotic treatment. Conclusion. Antibiotic treatment failed in 29% of patients; diabetes, current other osteomyelitis, and having an epidural abscess were independently associated with failure of antibiotic treatment. Level of Evidence: 3

Fungal spinal epidural abscess: a case series of nine patients

BACKGROUND CONTEXT Fungal spinal epidural abscess (FSEA) is a rare entity with high morbidity and mortality. Reports describing the clinical features, diagnosis, treatment, and outcomes of FSEA are scarce in the literature. PURPOSE This study aimed to describe the clinical features, diagnosis, treatment, and outcomes of FSEA. STUDY DESIGN This study is designed as a retrospective clinical case series. PATIENT SAMPLE A continuous series of patients with the diagnosis of FSEA who presented at our institution from 1993 to 2016. METHODS We reviewed the electronic medical records of patients with SEA who were treated within our hospital system from 1993 to 2016. We only included SEA cases that were due to fungi. We also reviewed FSEA cases in the English language literature from 1952 to 2017 to analyze the features of FSEA. RESULTS From a database of 1,053 SEA patients, we identified 9 patients with FSEA. Aspergillus fumigatus was isolated from 2 (22%) patients, and Candida species were isolated from 7 (78%). Focal spine pain, neurologic deficit, and fever were demonstrated in 89%, 50%, and 44% of FSEA cases, respectively. Five of nine cases involved the thoracic spine, and eight were located anterior to the thecal sac. Three cases had fungemia, six had long symptom duration (>2 weeks) prior to presentation, seven had concurrent immunosuppression, and eight had vertebral osteomyelitis. Additionally, one case had residual motor deficit at last follow-up, one had S1 sensory radicular symptoms, two suffered recurrent FSEA, two died within hospitalization, and two died within 90 days after discharge. CONCLUSIONS In summary, the classic diagnostic triad (focal spine pain, neurologic deficit, and fever) is not of great clinical utility for FSEA. Biopsy, intraoperative tissue culture, and blood culture can be used to diagnose FSEA. The most common pathogens of FSEA are Aspergillus and Candida species. Therefore, empiric treatment for FSEA should cover these species while definitive identification is pending. FSEA is found in patients with poor baseline health status, which is the essential reason for its high mortality.