Vladimir Cordeiro de Carvalho

Periprosthetic Joint Infections

Implantation of joint prostheses is becoming increasingly common, especially for the hip and knee. Infection is considered to be the most devastating of prosthesis-related complications, leading to prolonged hospitalization, repeated surgical intervention, and even definitive loss of the implant. The main risk factors to periprosthetic joint infections (PJIs) are advanced age, malnutrition, obesity, diabetes mellitus, HIV infection at an advanced stage, presence of distant infectious foci, and antecedents of arthroscopy or infection in previous arthroplasty. Joint prostheses can become infected through three different routes: direct implantation, hematogenic infection, and reactivation of latent infection. Gram-positive bacteria predominate in cases of PJI, mainly Staphylococcus aureus and Staphylococcus epidermidis. PJIs present characteristic signs that can be divided into acute and chronic manifestations. The main imaging method used in diagnosing joint prosthesis infections is X-ray. Computed tomography (CT) scan may assist in distinguishing between septic and aseptic loosening. Three-phase bone scintigraphy using technetium has high sensitivity, but low specificity. Positron emission tomography using fluorodeoxyglucose (FDG-PET) presents very divergent results in the literature. Definitive diagnosis of infection should be made by isolating the microorganism through cultures on material obtained from joint fluid puncturing, surgical wound secretions, surgical debridement procedures, or sonication fluid. Success in treating PJI depends on extensive surgical debridement and adequate and effective antibiotic therapy. Treatment in two stages using a spacer is recommended for most chronic infections in arthroplasty cases. Treatment in a single procedure is appropriate in carefully selected cases.

Recommendations for the treatment of osteomyelitis

With the advances in surgical treatment, antibiotic therapy and the current resources for accurate diagnosis and differentiated approaches to each type of osteomyelitis, better results are being obtained in the treatment of this disease. After a careful literature review carried out by a multiprofessional team, some conclusions were made in order to guide medical approach to different types of osteomyelitis, aiming to obtain better clinical outcomes and reducing the social costs of this disease. Acute and chronic osteomyelitis are discussed, with presentation of the general epidemiological concepts and the commonly used classification systems. The main guidelines for the clinical, laboratory and imaging diagnosis of infections are discussed, as well as the guidelines for surgical and antimicrobial treatments, and the role of hyperbaric oxygen as adjuvant therapy.

The incidence and microbiological profile of surgical site infections following internal fixation of closed and open fractures

Objective To evaluate the incidence and microbiological profile of surgical site infections (SSIs) associated with internal fixation of fractures and to compare differences in the SSIs observed among patients with closed and open fractures. Methods Retrospective study. Analyzed data included information from all patients who underwent surgery for fixation of closed or open fractures from January 2005 to December 2012 and remained outpatients for at least one year following surgery. Incidence of surgical site infection (SSI) was compared between patients with closed and open infection, as well as polymicrobial infection and infection related to Gram-negative bacilli (GNB). Cumulative antibiograms were performed to describe microbiological profiles. Results Overall incidence of SSI was 6%. This incidence was significantly higher among patients with open fractures (14.7%) than among patients with closed fractures (4.2%). The proportions of patients with polymicrobial infections and infections due to GNB were also significantly higher among patients with open fractures. Staphylococcus aureus and coagulase-negative Staphylococcus (CoNS) species were the primary infectious agents isolated from both groups. The overall incidence of MRSA (methicillin-resistant S. aureus) was 72%. A. baumannii was the predominant GNB isolate recovered from patients with open fractures and P. aeruginosa was the most frequent isolate recovered from patients with closed fractures, both exhibited low rates of susceptibility to carbapenems. Conclusions Incidence of SSIs related to the internal fixation of fractures was significantly higher among patients with open fractures, indicating that an open fracture can be a risk factor for infection. Among the bacterial isolates, S. aureus (with a high prevalence of MRSA) and CoNS species were most prevalent. A. baumannii and P. aeruginosa isolates underscored the low rate of susceptibility to carbapenems that was observed in the present study.

Septic arthritis of the knee: clinical and laboratory comparison of groups with different etiologies

OBJECTIVES: To clinically and epidemiologically characterize a population diagnosed with and treated for septic arthritis of the knee, to evaluate the treatment results and to analyze the differences between patients with positive and negative culture results, patients with Gram-positive and Gram-negative bacterial isolates and patients with S. aureus- and non-S. aureus-related infections. METHODS: One hundred and five patients with septic knee arthritis were included in this study. The clinical and epidemiological data were evaluated. Statistical analysis was performed to compare patients with and without an isolated causative agent, patients with Gram-positive and Gram-negative pathogens and patients with S. aureus-related and non S. aureus-related infections. RESULTS: Causative agents were isolated in 81 patients. Gram-positive bacteria were isolated in 65 patients and Gram-negative bacteria were isolated in 16 patients. The most commonly isolated bacterium was S. aureus. Comparing cases with an isolated pathogen to cases without an isolated pathogen, no differences between the studied variables were found except for the longer hospital stays of patients in whom an etiological agent was identified. When comparing Gram-positive bacteria with Gram-negative bacteria, patients with Gram-positive-related infections exhibited higher leukocyte counts. Patients with S. aureus-related infections were more frequently associated with healthcare-related environmental encounters. CONCLUSION: S. aureus is the most common pathogen of septic knee arthritis. Major differences were not observed between infections with isolated and non-isolated pathogens and between infections with Gram-positive and Gram-negative bacteria. S. aureus infections were more likely to be associated with a prior healthcare environment exposure.

Hepatite grave e icterícia durante a evolução de infecção pelo vírus da dengue: relato de caso

We describe the case of a female patient who presented a condition of dengue hemorrhagic fever that evolved with jaundice and significant coagulation abnormalities. Dengue was diagnosed through the presence of anti-dengue IgM antibodies (MAC-ELISA). This disease needs to be taken into consideration in the differential diagnosis for acute febrile jaundice.

Outpatient parenteral antimicrobial therapy for orthopedic infections - a successful public healthcare experience in Brazil.

Treatment of orthopedic infections usually requires prolonged antimicrobial therapy, ranging from 14 days up to 6 months. Nowadays, rising levels of antimicrobial resistance demands parenteral therapy for many patients. Outpatient parenteral antimicrobial therapy (OPAT) is a modality that allows treatment out of hospital in these situations. In Brazil, where a public universal healthcare system allows full coverage for all citizens, implantation and dissemination of OPAT programs would be beneficial for patients and for the system, because it would allow a better allocation of health resources. The Instituto de Ortopedia e Traumatologia do Hospital das Clínicas da Faculdade de Medicina da USP (IOT) started, in July 2013, a partnership with municipal health authorities in Sao Paulo, Brazil, in order to initiate an OPAT program in which patients discharged from that hospital would be able to continue antimicrobial therapy at primary care facilities. When necessary, patients could also receive their therapy at the day-hospital located at IOT. Primary care nursing and physician staff were trained about antimicrobial infusion and peripherally inserted central catheter manipulation. An OPAT specific antimicrobial protocol was designed and a special reference and counter-reference organized. As a result, 450 primary healthcare professionals were trained. In the first year of this program, 116 patients were discharged for OPAT. Chronic and acute osteomyelitis were most frequent diagnosis. Teicoplanin, ertapenem and tigecycline were the most used drugs. Duration of treatment varied from 10 to 180 days (average 101, median 42). Total sum of days in OPAT regimen was 11,698. Only 3 patients presented adverse effects. Partnership between services of different levels of complexity allowed implantation of a safe and effective public healthcare OPAT program for treatment of orthopedic infections. This program can serve as a model for developing similar strategies in other regions of Brazil and Latin America.

Incidence and risk factors associated with infection after intramedullary nailing of femoral and tibial diaphyseal fractures: Prospective study

BACKGROUND Diaphyseal fractures of femur and tibia are prominent due to its high incidence and high economic and social impact. Intramedullary nailing (IN) is the surgical procedure of choice. Surgical site infection (SSI) related to this procedure is considered a difficult to treat complication. AIMS Determine the incidence of SSI after IN of femoral and tibial diaphyseal fractures and evaluate possible risk factors. METHODS Prospective observational cohort study. SSI was defined according to CDC-NHSN criteria and surveillance period for the occurrence of infection was 12 months. Incidence of SSI was calculated as the ratio between the number of patients with SSI and total number of patients. Analysis of potential risk factors included patients-related factors (age, gender, body mass index, active foci of infection, immunosuppressive conditions, ASA score, alcohol or illicit drug abuse, smoking, polytrauma, etiology of fracture, type of fracture if closed or open, classification of fracture according to Müller AO, Tcherne classification for closed fractures, Gustilo-Anderson classification for open fractures, previous surgical manipulation, use of blood products); environmental and surgical-related factors (surgical wound classification, duration of surgery, hair removal, intraoperative contamination, antimicrobial use, presence of drains, hypothermia or hypoxia in the perioperative period, type of IN used, reaming, need for soft tissue reconstruction, use of negative pressure therapy) and microbiota-related factors (cultures of nasopharyngeal swabs forStaphylococcus aureus and axillary/inguinal/perineal swab for Acinetobacter baumannii). RESULTS 221 patients were included and completed the 12-month follow-up period. Incidence of SSI was 11.8%. In the initial analysis by unadjusted logistic regression, following factors were associated SSI: Müller AO classification of the fracture morphology groups 2 or 3, previous use of external fixator, presence of drains, use of negative pressure therapy and need for muscle or skin flap repair. In the multiple logistic regression-adjusted analysis, previous use of external fixator and need for muscle or skin flap repair remained associated with SSI. CONCLUSIONS Incidence of SSI associated with IN for femoral and tibial diaphyseal fractures was 11.8%. Previous use of external fixators and need for muscle or skin flap repair were factors associated with occurrence of infection.

Osteonecrosis of the femoral head in people living with HIV: anatomopathological description and p24 antigen test

Objective To examine the presence of HIV in bone tissue of people living with HIV (PLWHIV) with osteonecrosis of femoral head and describe clinical and anatomopathological findings. Design This is a case series which included 44 PLWHIV with osteonecrosis of femoral head who underwent total hip arthroplasty. Methods Clinical data were obtained through analysis of the patients’ medical records. Bone tissue obtained during total hip arthroplasty was retrieved and sent for conventional and immunohistochemical analysis. Monoclonal antibodies were used to mark the p24 (HIV), CD31 (vascular endothelial cells), CD68 (macrophages), and D240 (cells of the lymphatic endothelium) antigens. Results Dyslipidemia was found in 48% of the patients and lipodystrophy in 31%. Histological analysis showed similar characteristics for the entire sample. Degeneration of joint cartilage was visualized with the presence of fissures and fibrillations, as well as subchondral sclerosis and necrosis of the subchondral cancellous bone tissue. Lymphoplasmocytic inflammatory reaction was observed, with the presence of macrophages containing a foamy, vacuolated cytoplasm, as well as the presence of ceroid pigment and occasional granulation tissue. The reaction with the monoclonal anti-p24 antibody was negative in the samples from all 44 PLWHIV undergoing hip arthroplasty. Reactions with the anti-CD31 and anti-D240 antibodies were negative. Staining with CD68 antibody confirmed that the cells visualized with foamy, vacuolated cytoplasm were macrophages. Conclusion p24 HIV antigen was not detected in the bone tissue of PLWHIV and osteonecrosis. The most frequent anatomopathological findings were extensive necrosis of bone tissue, large vacuoles filled with fat cells, inflammatory lymphoplasmocytic reaction with macrophages containing vacuolated cytoplasm, and the presence of ceroid pigment.

Optimizing the treatment of osteomyelitis with antimicrobial drugs: current concepts

The success of osteomyelitis treatment, particularly in cases related to implants, depends on extensive surgical debridement and adequate and effective antibiotic therapy. Direct administration of antimicrobial agents through their incorporation into orthopaedic cement is an important adjuvant therapy. The capacity for biofilm to form by causative agents of osteomyelitis is an obstacle to antimicrobial treatment of these infections. Bacteria present in biofilm usually has greater bacterial resistance and higher expression of virulence factors than sessile bacteria, as well as mechanisms to escape the host immune response. The ability of causative agents of infection, particularly Staphylococcus aureus, to form small colony variants (SCV), a phenotype capable of invading and infecting osteoblasts, is another important mechanism that contributes to exacerbation of osteomyelitis to a chronic state. To optimize the antimicrobial treatment of osteomyelitis and improve patients’ prognosis, it is fundamental to consider these complicating factors, as well as the antimicrobial susceptibility profile of the causative microorganisms. Rifampicin should always be considered as part of the therapeutic regimen because it presents good bone concentration and has proven capacity to act on strains present in biofilm and in SCV.

Recommendations for outpatient parenteral antimicrobial therapy in Brazil

A panel of national experts was convened by the Brazilian Infectious Diseases Society in order to determine the recommendations for outpatient parenteral antimicrobial therapy (OPAT) in Brazil. The following aspects are covered in the document: organization of OPAT programs; patient evaluation and eligibility criteria, including clinical and sociocultural factors; diagnosis of eligibility; venous access and antimicrobial infusion devices; protocols for antimicrobial use and monitoring and cost-effectiveness.