A man with recurrent furunculosis.
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Biomedical subjects
Publications and source records attributed to John M Embil.
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We report a case of definite Lactococcus garvieae native-valve endocarditis. The diagnosis was suspected in a patient presenting with congestive heart failure and found to have Enterococcus hirae bacteremia, with a history of L. garvieae bacteremia 1 month prior. Diagnosis was confirmed by 16S rRNA gene sequencing of the 2 isolates and the demonstration of aortic valve vegetations.
Skin and soft tissue infections (SSTIs) span a broad spectrum of clinical entities from limited cellulitis to rapidly progressive necrotizing fasciitis, which may be associated with septic shock or a toxic shock-like syndrome. These infections may manifest initially as pyodermas that then progress; alternatively, they may arise from metastatic spread of microorganisms from a distant focus. Regardless of the source, SSTIs may lead to critical illness. The complex interplay of environment, host, and pathogen are important to consider when evaluating SSTIs and planning appropriate therapy. The keys to a successful outcome are early identification of risk factors for specific pathogens and early initiation of empiric antimicrobial therapy. For certain types of SSTIs, surgical intervention for diagnosis and/or therapy is also required.
BACKGROUND: In a multicenter, international, double-blind, randomized clinical trial involving hospitalized patients with complicated skin and skin-structure infections (cSSSIs), meropenem and imipenem/cilastatin (both administered 500 mg intravenously every 8 hours) were not significantly different in their efficacy and safety profiles. OBJECTIVE: The objective of the post hoc subgroup analysis discussed in the current article was to report the efficacy and tolerability of meropenem and imipenem/cilastatin for the treatment of cSSSIs in patients with or without underlying diabetes mellitus (DM). METHODS: Hospitalized patients aged > or =13 years with evidence of cSSSIs were eligible for inclusion. Patients were randomized to receive meropenem or imipenem/cilastatin, each 500 mg intravenously every 8 hours, for at least 3 days and up to a maximum of 14 days. Patients were analyzed according to the presence or absence of DM and by the pathogen(s) isolated from wound cultures at baseline, end of N treatment, and test-of-cure visits. The primary efficacy end point was clinical outcome at the posttreatment follow-up (test-of-cure) visit in the clinically evaluable and modified intent-to-treat (intent-to-treat [ITT] subjects who met all eligibility criteria) populations; this was defined as 7 to 14 days after final administration of antibiotics. The secondary efficacy end points included clinical response at the test-of-cure visit in the ITT population (ie, those who received >1 dose of study drug) and at the end of N treatment visit in the clinically evaluable and fully evaluable populations. At baseline, the end of N treatment, and the test-of-cure visits, specimens were obtained from the most extensive site of skin and skin-structure infection and were cultured for bacteria. Adverse events were monitored daily during treatment and for 30 days after the completion of all antibiotic treatment. RESULTS: Of the 1076 patients enrolled in the original study, 398 had DM. The mean ages of patients with and without DM were 55 and 45 years, respectively; 17.3% of patients with DM and 6.1% of patients without DM had impaired renal function at study entry. Complex abscess was the most common infection diagnosis in both groups (patients with DM, 30.0%; patients without DM, 48.8%). The other top infections per group (patients with and without DM, respectively) were as follows: cellulitis, 24.6% and 12.4%; and ischemic/diabetic ulcers, 20.9% and 1.9%. Gram-negative aerobic and anaerobic pathogens accounted for >40% of bacterial isolates from both groups, with polymicrobial infections reported in 44.2% of patients with DM and 34.0% of patients without DM. In the clinically evaluable population, the satisfactory clinical response rate was 85.6% for patients with DM receiving meropenem and 72.4% for those receiving imipenem/cilastatin; for patients without DM, those rates were 86.6% and 89.0%, respectively. Meropenem and imipenem/cilastatin were generally well tolerated. Reported adverse events were similar between groups. CONCLUSION: This subgroup analysis found that 500 mg every 8 hours intravenously of meropenem or imipenem/cilastatin appeared efficacious and well tolerated for the treatment of cSSSIs among these patients with and without DM.
EXECUTIVE SUMMARY: 1. Foot infections in patients with diabetes cause substantial morbidity and frequent visits to health care professionals and may lead to amputation of a lower extremity. 2. Diabetic foot infections require attention to local (foot) and systemic (metabolic) issues and coordinated management, preferably by a multidisciplinary foot-care team (A-II). The team managing these infections should include, or have ready access to, an infectious diseases specialist or a medical microbiologist (B-II). 3. The major predisposing factor to these infections is foot ulceration, which is usually related to peripheral neuropathy. Peripheral vascular disease and various immunological disturbances play a secondary role. 4. Aerobic Gram-positive cocci (especially Staphylococcus aureus) are the predominant pathogens in diabetic foot infections. Patients who have chronic wounds or who have recently received antibiotic therapy may also be infected with Gram-negative rods, and those with foot ischemia or gangrene may have obligate anaerobic pathogens. 5. Wound infections must be diagnosed clinically on the basis of local (and occasionally systemic) signs and symptoms of inflammation. Laboratory (including microbiological) investigations are of limited use for diagnosing infection, except in cases of osteomyelitis (B-II). 6. Send appropriately obtained specimens for culture before starting empirical antibiotic therapy in all cases of infection, except perhaps those that are mild and previously untreated (B-III). Tissue specimens obtained by biopsy, ulcer curettage, or aspiration are preferable to wound swab specimens (A-I). 7. Imaging studies may help diagnose or better define deep, soft-tissue purulent collections and are usually needed to detect pathological findings in bone. Plain radiography may be adequate in many cases, but MRI (in preference to isotope scanning) is more sensitive and specific, especially for detection of soft-tissue lesions (A-I). 8. Infections should be categorized by their severity on the basis of readily assessable clinical and laboratory features (B-II). Most important among these are the specific tissues involved, the adequacy of arterial perfusion, and the presence of systemic toxicity or metabolic instability. Categorization helps determine the degree of risk to the patient and the limb and, thus, the urgency and venue of management. 9. Available evidence does not support treating clinically uninfected ulcers with antibiotic therapy (D-III). Antibiotic therapy is necessary for virtually all infected wounds, but it is often insufficient without appropriate wound care. 10. Select an empirical antibiotic regimen on the basis of the severity of the infection and the likely etiologic agent(s) (B-II). Therapy aimed solely at aerobic Gram-positive cocci may be sufficient for mild-to-moderate infections in patients who have not recently received antibiotic therapy (A-II). Broad-spectrum empirical therapy is not routinely required but is indicated for severe infections, pending culture results and antibiotic susceptibility data (B-III). Take into consideration any recent antibiotic therapy and local antibiotic susceptibility data, especially the prevalence of methicillin-resistant S. aureus (MRSA) or other resistant organisms. Definitive therapy should be based on both the culture results and susceptibility data and the clinical response to the empirical regimen (C-III). 11. There is only limited evidence with which to make informed choices among the various topical, oral, and parenteral antibiotic agents. Virtually all severe and some moderate infections require parenteral therapy, at least initially (C-III). Highly bioavailable oral antibiotics can be used in most mild and in many moderate infections, including some cases of osteomyelitis (A-II). Topical therapy may be used for some mild superficial infections (B-I). 12. Continue antibiotic therapy until there is evidence that the infection has resolved but not necessarily until a wound has healed. Suggestions for the duration of antibiotic therapy are as follows: for mild infections, 12 weeks usually suffices, but some require an additional 12 weeks; for moderate and severe infections, usually 24 weeks is sufficient, depending on the structures involved, the adequacy of debridement, the type of soft-tissue wound cover, and wound vascularity (A-II); and for osteomyelitis, generally at least 46 weeks is required, but a shorter duration is sufficient if the entire infected bone is removed, and probably a longer duration is needed if infected bone remains (B-II). 13. If an infection in a clinically stable patient fails to respond to 1 antibiotic courses, consider discontinuing all antimicrobials and, after a few days, obtaining optimal culture specimens (C-III). 14. Seek surgical consultation and, when needed, intervention for infections accompanied by a deep abscess, extensive bone or joint involvement, crepitus, substantial necrosis or gangrene, or necrotizing fasciitis (A-II). Evaluating the limb's arterial supply and revascularizing when indicated are particularly important. Surgeons with experience and interest in the field should be recruited by the foot-care team, if possible. 15. Providing optimal wound care, in addition to appropriate antibiotic treatment of the infection, is crucial for healing (A-I). This includes proper wound cleansing, debridement of any callus and necrotic tissue, and, especially, off-loading of pressure. There is insufficient evidence to recommend use of a specific wound dressing or any type of wound healing agents or products for infected foot wounds. 16. Patients with infected wounds require early and careful follow-up observation to ensure that the selected medical and surgical treatment regimens have been appropriate and effective (B-III). 17. Studies have not adequately defined the role of most adjunctive therapies for diabetic foot infections, but systematic reviews suggest that granulocyte colony-stimulating factors and systemic hyperbaric oxygen therapy may help prevent amputations (B-I). These treatments may be useful for severe infections or for those that have not adequately responded to therapy, despite correcting for all amenable local and systemic adverse factors. 18. Spread of infection to bone (osteitis or osteomyelitis) may be difficult to distinguish from noninfectious osteoarthropathy. Clinical examination and imaging tests may suffice, but bone biopsy is valuable for establishing the diagnosis of osteomyelitis, for defining the pathogenic organism(s), and for determining the antibiotic susceptibilities of such organisms (B-II). 19. Although this field has matured, further research is much needed. The committee especially recommends that adequately powered prospective studies be undertaken to elucidate and validate systems for classifying infection, diagnosing osteomyelitis, defining optimal antibiotic regimens in various situations, and clarifying the role of surgery in treating osteomyelitis (A-III).
BACKGROUND: Diabetic foot ulcers cause major treatment morbidity and cost of care. This study evaluated quality of life in patients with unhealed and healed diabetic foot ulcers. METHODS: This was a cross-sectional study of adult diabetic patients (age 45 years or older) treated in a tertiary care foot clinic who had foot ulcers within the preceding 2 years. Patients with other diabetic complications or conditions that would potentially affect quality of life were excluded. Two patient groups of comparable age, gender distribution, and duration of diabetes were studied: 57 patients with unhealed ulcers (minimum duration, 6 months) and 47 patients with healed ulcers. Telephone interviews were done using the Short Form 12 (SF-12) (both groups) and a Cardiff Wound Impact Scale (CWIS) (unhealed ulcer group). RESULTS: The mean SF-12 Physical Component Summary score was significantly lower for the group with unhealed ulcers (unhealed, 35 +/- 8 points; healed, 39 +/- 10 points; p = 0.04); these scores for both groups were significantly lower than published Short Form 36 (SF-36) scores for general, diabetic, and hypertensive populations. The mean SF-12 Mental Component Summary scores of the groups did not differ significantly from each other or from published population scores. CWIS responses showed that patients with unhealed ulcers were frustrated with healing and had anxiety about the wounds, resulting in marked negative impact on the average Well-being Component Score (35 +/- 6 points). CONCLUSIONS: Individuals with diabetic foot ulcers experience profound compromise of physical quality of life, which is worse in those with unhealed ulcers.
BACKGROUND: Osteomyelitis in the foot of a diabetic individual is a common complication of peripheral neuropathy, peripheral vascular disease, and infection. Operative facilities and home intravenous antibiotic therapy programs may not be available in remote or rural communities. Limited data are available regarding the treatment results of oral antimicrobial therapy, with or without limited office debridement for diabetic foot osteomyelitis. METHODS: This retrospective medical record review of 325 consecutive diabetic patients who were evaluated at a multidisciplinary foot clinic identified 94 (29%) patients with 117 episodes of osteomyelitis. The most common group of organisms isolated were aerobic gram-positive cocci, and the single most frequent organism was Staphylococcus aureus. A mean of 1.6 +/- 0.8 (range 1 to 4) pathogens were recovered per episode of osteomyelitis. Therapy was guided by culture results. There were 93 episodes of osteomyelitis (79 patients) that were treated with a mean of 3 +/- 1 oral antimicrobial agents (with or without an initial short course of intravenous antimicrobial agents) and had adequate followup to evaluate outcome of treatment; office treatment included bone debridement in 26 (28%) and toe amputation in nine (10%) of the 93 episodes (79 patients). RESULTS: Of the 93 episodes treated with oral antimicrobial agents (with or without an initial short course of intravenous antimicrobial agents), 75 (80.5%) episodes were put into remission. Mean duration of oral antimicrobial therapy was 40 +/- 30 weeks. Mean relapse-free followup duration was 50 +/- 50 weeks. CONCLUSIONS: Diabetic foot osteomyelitis was effectively managed with oral antimicrobial therapy with or without limited office debridement in most patients. This regimen may be especially useful in communities where infectious disease specialists and operative resources are limited.
BACKGROUND: Limited access to basic foot care and protective footwear may contribute to diabetic foot complications. The purpose of this study was to determine the prevalence of foot complications, ongoing foot care, and footwear use in diabetic subjects in a remote northern Canadian Aboriginal community. METHODS: This was a cross-sectional cohort study of 169 diabetic people, including interview, physical examination, and retrospective chart review. RESULTS: The mean age of the 169 diabetic individuals in the study was 56 +/- 12 years and their duration of diabetes 10 +/- 7 years. There were 139 (82%) individuals who had 418 diabetic foot complications (average, 3.0 complications per subject with complications), including toenail pathology, foot and ankle deformities, calluses, impaired pulses, neuropathy, past or present ulcer, amputation, and Charcot arthropathy. Risk classification showed that 69 (41%) individuals were at risk for future ulceration. Fifty-five (33%) individuals had inadequate footwear for their foot risk category, and only 11 (17%) of 66 individuals in the higher risk categories (categories 2 and 3) had suitable footwear. In a 7-year period, only 0.7 screening foot examinations per diabetic subject per year were documented. However, during this period, foot problems accounted for 498 (18%) local emergency room visits, 359 (16%) hospitalization days, 109 (11%) nonemergency transfers, and 4 (6%) emergency transfers to a tertiary care hospital. CONCLUSIONS: Foot and ankle complications of diabetes in this remote Aboriginal community were common and associated with substantial morbidity. Preventive diabetic foot screening examinations and footwear were inadequate. The results suggest that programs for prevention and early detection of complications are needed, including foot screening, provision of appropriate footwear, and foot care.
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There has been a marked increase in the frequency with which breast prosthesis are being used, both for reconstructive and cosmetic purposes. Although breast implant-related infections are uncommon, they are typically caused by bacterial skin flora, specifically Staphylococcus aureus and the coagulase negative staphylococci. There have been infrequent reports of breast implant infection caused by the atypical mycobacteria. This report summarizes the case of a young female who underwent augmentation mammoplasty who presented shortly thereafter with clinical evidence of an infected breast prosthesis. Despite a protracted course of empiric antibiotic therapy and multiple surgical interventions, she failed to improve. Additional microbiologic investigations allowed for a diagnosis of Mycobacterium fortuitum group breast implant infection to be established. A prolonged course of anti-mycobacterial therapy, based upon susceptibility results, allowed for eradication of the infection and subsequent successful re-implantation of the prosthesis.
OBJECTIVE: To compare and contrast disability and quality of life (QOL) in Aboriginal and non-Aboriginal subjects with diabetes who had lower-extremity amputation (LEA) and were living in urban and rural communities in Canada. DESIGN: Descriptive study using an interviewer-administered questionnaire and hospital medical record review. SETTING: Tertiary care center. PARTICIPANTS: Forty-four diabetic subjects (minimum age, 18 y) not receiving dialysis, including 21 Aboriginal (8 urban, 13 rural) and 23 non-Aboriginal (16 urban, 7 rural) subjects. Subjects were living in their current residence and had undergone LEA above the level of the ankle 6 months or more before interview. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Qualitative and quantitative data about symptoms, impairment, and QOL. RESULTS: Aboriginal subjects were younger than non-Aboriginal subjects at the time of diabetes diagnosis (Aboriginal, 42+/-10 y; non-Aboriginal, 52+/-14 y; P<.005) and first major LEA (Aboriginal, 57+/-7 y; non-Aboriginal, 64+/-11 y; P<.015). All subjects received rehabilitation after amputation. More rural non-Aboriginal subjects (83%) used their prosthesis both in and outside the home for all movements than other subjects (P<.048). Rural non-Aboriginal subjects had the lowest and urban non-Aboriginal subjects had the highest frequency of walking-aid use outside the home. Assistance with personal care was required by a minority of subjects, but assistance with daily housework was required by the majority of subjects. Qualitative analysis revealed that participants were, in most cases, comfortable with their postamputation life. CONCLUSIONS: Although the majority of participants in this study generally felt satisfied with their current status, major functional changes were noted after LEA that had a large negative impact on QOL.
OBJECTIVES: To compare the effect of tigecycline monotherapy, a first-in-class, expanded broad spectrum glycylcycline, with the combination of vancomycin and aztreonam (V + A) in the treatment of complicated skin and skin structure infections (cSSSI). METHODS: A phase 3, double-blind study conducted in 8 countries enrolled adults with cSSSI who required intravenous (IV) antibiotic therapy for > or =5 days. Patients were randomly assigned (1:1) to receive either tigecycline or V + A for up to 14 days. Primary endpoint was the clinical cure rate at the test-of-cure visit. Secondary endpoints included microbiologic efficacy and in vitro susceptibility to tigecycline of bacteria that cause cSSSI. Safety was assessed by physical examination, laboratory analyses, and adverse event reporting. RESULTS: A total of 596 patients were screened for enrollment, 573 were analyzed for safety, 537 were included in the clinical modified intent-to-treat (c-mITT) population, 397 were clinically evaluable (CE), and 228 were microbiologically evaluable (ME). At test-of-cure, cure rates were similar between tigecycline and V + A groups in the CE population (82.9% versus 82.3%, respectively) and in the c-mITT population (75.5% versus 76.9%, respectively). Microbiologic eradication rates (subject level) at test-of-cure in the ME population were also similar between tigecycline and V + A. Frequency of adverse events was similar between groups, although patients receiving tigecycline had higher incidence of nausea, vomiting, dyspepsia, and anorexia, while increased ALT/SGPT, pruritus, and rash occurred significantly more often in V + A-treated patients. CONCLUSIONS: This study demonstrates that the efficacy of tigecycline monotherapy for the treatment of patients with cSSSI is statistically noninferior to the combination of V + A.
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Skin and soft tissue infections are among the most common reasons for people to seek medical advice. They also represent one of the most common indications for antimicrobial therapy and account for approximately 7-10% of hospitalisations in North America. Although non-limb and non-life threatening infections may be treated on an out-patient basis with oral antibiotics, patients with more serious acute skin and soft tissue infections may require admission to hospital for management; this decision is especially true if the infection is rapidly progressive. We provide a concise overview of the differential diagnosis and approach to management of community-acquired rapidly progressive skin and soft tissue infections.
BACKGROUND: Meropenem, a broad-spectrum carbapenem with potent in vitro activity, is postulated to be an effective monotherapy for the treatment of complicated skin and skin structure infections (cSSSI). METHODS: This multicenter, international, double-blind, randomized, prospective study of hospitalized patients with cSSSI evaluated the efficacy, safety, and tolerability of meropenem (500 mg IV q8h) versus imipenem-cilastatin (500 mg IV q8h). The primary efficacy endpoint was clinical outcome at follow-up in the clinically evaluable (CE) and modified intent-to-treat populations (MITT; patients who met eligibility criteria and received at least one dose of study drug). The study aimed to demonstrate non-inferiority (delta of 10%, 95% confidence intervals) in clinical response in the CE population. Clinical responses for all pathogens at follow-up were assessed in the fully evaluable population (CE population with baseline pathogen and follow-up cultures). RESULTS: In total, 1,076 patients were enrolled. Of these, 692 patients comprised the MITT population (334 and 358 patients randomized to meropenem and imipenem-cilastatin, respectively) and 548 the CE population (261 and 287 patients randomized to meropenem and imipenem-cilastatin, respectively). Cure rates were 86.2% (meropenem) and 82.9% (imipenemcilastatin; 95% CI, -2.8, 9.3) in the CE population and 73.1% (meropenem) and 74.9% (imipenem-cilastatin; 95% CI, -8.4, 4.7) in the MITT population. The frequencies of adverse events and drug-related adverse events were similar between treatment groups. CONCLUSION: In one of the largest studies conducted to date of hospitalized patients with cSSSI, meropenem, 500 mg IV q8h had comparable safety and efficacy to imipenem-cilastatin, 500 mg IV q8h.
The carbapenems are beta-lactam-type antibiotics with an exceptionally broad spectrum of activity. Ertapenem is a new carbapenem developed to address the pharmacokinetic shortcomings (short half-life) of imipenem and meropenem. Ertapenem shares similar structural features with meropenem, including its stability to dehydropeptidase-1, allowing it to be administered without a dehydropeptidase-1 inhibitor. Ertapenem, like imipenem and meropenem, demonstrates broad-spectrum antimicrobial activity against many Gram-positive and -negative aerobes and anaerobes and is resistant to nearly all beta-lactamases, including extended-spectrum beta-lactamases and AmpCs. However, it differs from both imipenem and meropenem in demonstrating limited activity against Enterococcusspp., Pseudomonasaeruginosa and other nonfermentative Gram-negative bacteria commonly associated with nosocomial infections. The extensive protein binding of ertapenem extends the half-life and allows for once-daily dosing. Prospective, multicenter, randomized, double-blind, comparative clinical studies demonstrate similar clinical efficacy of ertapenem compared with other agents. Clinical trials of complicated intra-abdominal infection, acute pelvic infection, complicated skin and soft-structure infection, community-acquired pneumonia and complicated urinary tract infections demonstrated that ertapenem has equivalent efficacy and safety compared with ceftriaxone and piperacillin/tazobactam. Ertapenem is a promising new carbapenem with excellent efficacy and safety for the treatment of a variety of community-acquired infections. It also appears to be of great value as an outpatient parenteral antimicrobial therapy.
The use of surgically implanted devices has increased as a result of their beneficial effect on quality of life, and in some circumstances, on patient survival rates. They can, however, be associated with a variety of complications, the most dreaded being infection. Device-related infections are important to understand because of the morbidity and mortality associated with them. Frequently, patients are managed with hospitalization, prolonged courses of antibiotics, and surgical interventions, all of which can negatively impact on patients' quality of life. Such care is also associated with increased costs to health care systems. Furthermore, these infections often represent a diagnostic challenge because of the lack of consensus definition of what constitutes an infection and its severity, as well as the paucity of well-designed, large studies addressing optimal methods of investigation and management. An implant-associated infection is defined as a host immune response to one or more microbial pathogens on an indwelling implant. An understanding of the pathogenesis of these infections provides a rationale for management. Development of device-related infections begins with colonization of the foreign material, followed by a complex metamorphosis by the microorganisms with resultant biofilm formation. In this surface-associated form, bacteria have altered phenotypic properties. This change, in conjunction with the physical protective layer provided by the biofilm, renders antimicrobial therapy ineffective when used alone. Because the microorganisms are able to reside on the hardware, they proliferate and cause local damage, such as loosening of implanted devices, wound dehiscence, or disruption of prosthetic valves, as well as systemic manifestations, such as fever or embolic phenomenon. The onset and clinical manifestations of device-related infections vary with the pathogen involved, as well as which component of the device is affected. The time period after device implantation that signs and symptoms develop can assist in the selection of empiric antimicrobial therapy. Optimal diagnostic microbiologic specimens are paramount in tailoring the antimicrobial therapy, which almost always has to be given for a prolonged period of time. Surgical removal of the device is usually necessary. Some studies of limited types of device-related infections, however, have defined indications for which salvage therapy may be warranted. In addition, some patients are not candidates for, or may not want, further surgical interventions, in which case indefinite suppressive antimicrobial therapy may be considered. This review provides an overview of infections related to various neurosurgical, cardiac, and orthopedic devices, as well as those related to cochlear, breast, and penile prostheses, with discussion of definitions of such infections, along with microbiology, pathogenesis, and management guidelines, including the limited indications for salvage techniques.