F. De Lalla

Antibiotic Prophylaxis in Orthopedic Prosthetic Surgery

Abstract Staphylococci account for approximately 70% of postoperative infections in orthopedic prosthetic surgery, with the leading organism being Staphylococcus epidermidis. Therefore, the antibiotics most widely used for prophylaxis are cefazolin, cefamandole and cefuroxime, by virtue of their excellent activity against these pathogens. However, methicillin-resistant coagulase-positive and -negative staphylococci are increasingly being reported as the causative agents of postoperative infection in clean prosthetic surgery, therefore prompting the use of glycopeptide antibiotics (vancomycin and teicoplanin) in the prophylaxis for total joint replacement, particularly in hospitals in which there is high methicillin-resistance among these pathogens. Furthermore, in total primary knee replacement (TKR) performed with tourniquet application, regional prophylaxis with teicoplanin (i.e. the injection of teicoplanin into a foot vein of the leg to be operated on after occlusion of the systemic circulation by inflating the tourniquet) has been shown to be a safe and valuable prophylactic technique. Apart from providing teicoplanin concentrations in the operative field higher than those achievable by conventional systemic prophylaxis (i.e. by injecting the antibiotic into an arm vein before application of the tourniquet), regional prophylaxis was found in a prospective, controlled, open study on patients undergoing primary monolateral or bilateral TKR to result in a rate of postoperative infection similar to those achievable with conventional prophylactic regimens.

Postoperative Infections Following Total Knee Replacement: An Epidemiological Study

Abstract From January 1991 to June 1997 217 patients undergoing monolateral or bilateral total knee replacement (TKR) were consecutively enrolled in a prospective study on the incidence of postoperative infections and related risk factors. Regional antimicrobial prophylaxis (teicoplanin 400 mg) was used in 263 (95%) prostheses implanted; in the remaining 14 implants (5%) periopera-tive antibiotic prophylaxis (teicoplanin 800 mg) was administered as usual by systemic route. None of the patients experienced local or systemic adverse effects. Over the 2-year follow-up period, 8 (2.9%) primary site infectious complications were recorded, i.e. 4 superficial infections, which were cured without involvement of the prostheses, and 4 deep infections, which required prosthesis removal. Six infections occurred in patients who had undergone previous surgery of the same knee joint, and 2 in patients undergoing primary TKR (p=0.0005); diabetic patients had infections (13%) more frequently than non-diabetic patients (1.9%, p=0.01). Staphylococci were the leading organisms isolated from infections; however 3 strains of Escherichia coli were isolated from patients who had undergone a previous prosthesis implantation at the same knee joint. Regional administration of teicoplanin appears to be a safe and valuable prophylactic technique; however, in patients at risk of infection a prophylactic regimen which is also active against Gram-negative bacteria should probably be considered.

Outpatient parenteral antibiotic therapy in the elderly: an Italian observational multicenter study

Abstract Bacterial infections are the most frequent cause of hospitalization in elderly patients. In the early eighties, the advantages of Outpatient parenteral Antibiotic therapy (OPAT) were identified in the United States, and suitable therapeutic programs were established. In order to understand the different ways of managing OPAT, a National OPAT Registry was set up in 2003 in Italy. This study analyzes data concerning bacterial infections in 176 elderly patients including demographics, therapeutic management, clinical response, and side-effects. Bone and joint infections (48.9%) and skin and soft tissue infections (27.8%) were the most common infections treated with OPAT. Teicoplanin (28.9%) and ceftriaxone (22.1%) were the top two antibiotics chosen. OPAT was mainly performed at a hospital infusion center (52.8%). The clinical success rate was high and side-effects were low (12.6% of cases). Management of bacterial infections in the elderly with an outpatient program is effective and safe.

Three-Times Weekly Teicoplanin in the Outpatient Treatment of Acute Methicillin-Resistant Staphylococcal Osteomyelitis: A Pilot Study

Abstract Treatment of osteomyelitis requires prolonged hospital stay, lengthy antibiotic therapy and adequate surgical debridement. Outpatient parenteral antibiotic therapy (OPAT) is a new approach to reduce patient discomfort and hospital costs. Teicoplanin, a glycopeptide antibiotic with a long half-life (72 hours), is one of the most useful drugs for OPAT. We performed a pilot study to assess the safety and efficacy of three-times weekly teicoplanin in the treatment of methicillin-resistant (MR) acute staphylococcal osteomyelitis. Ten patients with acute post-traumatic osteomyelitis were enrolled. Pathogens were MR Staphylococcus aureus (5 patients) and MR coagulase-negative staphylococci (5 patients). After a loading dose of 400 mg b.i.d. for 3 days, patients were treated with an intravenous dose of 1000 mg on Mondays and Wednesdays and with a 1200 mg dose on Fridays. Teicoplanin trough levels were maintained within a 10 to 20 mg/L range. If hardware removal had been possible at enrollment, treatment was carried out for at least 4 weeks. If, on the contrary, hardware removal had not been possible, teicoplanin was administered as sup-pressive therapy until hardware removal. Treatment was successfully performed in 9 out of 10 patients, whereas in one patient only improvement was achieved. Side effects were not recorded. Three times weekly teicoplanin seems to be a valuable option in the treatment of acute MR staphylococcal osteomyelitis. Further studies are warranted in order to better define the role of this new administration schedule in this field.

Clostridial Orthopedic Infections: Case Reports and Review of the Literature

Abstract Clostridia are anaerobic Gram-positive bacilli that can be isolated from the soil and the intestinal tract of humans. These microorganisms are recognized as the cause of devastating soft tissue infections, such as cellulitis, myositis, and gas gangrene. However, such bacteria may also be involved in various postoperative orthopedic infections, including prosthetic joint infection. We present three clinical cases of clostridial orthopedic infection and review the related medical literature.

Clinical Features of Bacterial Meningitis in Italy: a Multicenter Prospective Observational Study

Abstract We carried out a prospective observational study on clinical features of bacterial meningitis. Between October 2002 and June 2005, 322 adult bacterial meningitis cases in 49 infectious disease wards in Italy (MENTORE study group) were enrolled in the study. 133 cases were due to Streptococcus pneumoniae, 44 to Neisseria meningitides and 145 to other microorganisms. A high SAPS score and coma on admission, as well as need for mechanical ventilation, were more frequent in the pneumococcal meningitis group. Neurological impairment was present in 151 out of 311 patients, and was more frequent in pneumococcal meningitis. A single antibiotic was employed in only 90 of 315 cases; a combination of ceftriaxone and ampicillin was the most frequently administered treatment. Ceftriaxone was also the single most used drug. Adjunctive treatment with steroids was administered in 210 out of 303 patients for a median duration of 7 days. Median duration of fever was 4 days, and median hospital stay was 16 days; hospitalization was significantly longer in the pneumococcal meningitis group. At discharge, neurological impairment was still present in 59 (21%) of 277 patients. Twenty (6.9%) out of 289 patients died during hospitalization. Distribution of adverse outcome (death and neurological impairment) in patients treated with or without steroids and within different time zones between onset of symptoms and commencement of antibiotics was studied; a trend toward a worse prognosis was seen in patients treated more than 24 hours after onset of the disease. In our study, infectious disease clinicians made extensive use of steroids as adjuvant therapy for bacterial meningitis, even in absence of detailed national and local guidelines. Mortality seemed to be lower in comparison with the literature.

Chemioprofilassi Antibiotica in Chirurgia Protesica Ortopedica.

SummaryIn elective orthopedic surgery, as well as in any type of clean operations, it is now advised to administer antibiotic prophylaxis only when extraneous material is implanted (prostheses). Given the most frequent appearance of staphylococcal postoperative infections, in orthopedic surgery the antibiotic used for prophylaxis should be particularly active against these microorganisms. Therefore, the first- (cefazolin) and second-generation (cefuroxime or cefamandole) cephalosporins are usually recommended. Because prosthetic infections are more and more frequently caused by methicillin-resistant staphylococci, the glycopeptides (vancomycin and teicoplanin) are often recommended for prophylaxis and more frequently used in routine practice, at least in hospital environments in which these microorganisms often appear. Indeed, various investigations have demonstrated that a single dose of teicoplanin is equally protective as multiple doses of other antibiotics usually used. Regardless of the type of surge...

PIPERACILLIN VERSUS CEFOTETAN AS SINGLE-DOSE PROPHYLAXIS IN ABDOMINAL HYSTERECTOMY: A PROSPECTIVE, RANDOMIZED, MULTICENTER STUDY

Five hundred and sixty-six women, consecutively admitted to nine different hospitals for elective abdominal hysterectomy, were randomized to receive a single 2 g i.v. dose of either cefotetan or piperacillin at induction of anesthesia. Five patients were excluded and 561 (287 given cefotetan and 274 given piperacillin) could be evaluated. In 10 patients (5 for each drug) the concentrations of either cefotetan or piperacillin in serum and subcutaneous tissue at the beginning and at the end of surgery and in uterus, salpinx and ovary samples, were microbiologically assessed. No significant differences could be found between cefotetan and piperacillin groups for any of the considered infectious complications (bacteremia, wound or vaginal cuff infection, pelvic cellulitis and febrile morbidity) nor for the pooled data (cefotetan group: 4.9%, piperacillin group: 5.8%, p:NS). As for the concentrations of prophylactic drugs, serum levels throughout surgery were found to be adequate.

Failure of Intravenous Linezolid to Treat Clostridium difficile Associated Diarrhea

Linezolid, a new oxazolidinone drug, is currently used in the treatment of Gram-positive infections, including infections due to methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis, and penicillin-resistant Streptococcus pneumoniae 1. Furthermore, this drug possesses in vitro inhibitory activity against a broad range of Gram-positive bacteria, including anaerobic cocci 2. A bactericidal effect of linezolid against Clostridium perfringens and Clostridium difficile has been documented 3. The latter microorganism is the major cause of nosocomial diarrhea and antimicrobial associated colitis. Since few antimicrobials are effective in the treatment of these infections, there is a great deal of interest on the possible clinical use of new antibiotics. We describe the first case of failure of a linezolid treatment to cure a C. difficile related diarrhea. A 57-year-old female patient was admitted to our department complaining of fever, abdominal pain, and diarrhea. She had been treated with chemotherapy for a myeloblastic acute leukemia until 10 days before admission. A week before admission, the patient was also treated with oral ciprofloxacin for 3 days because of a transient episode of fever. In the hematology outpatient service, a stool culture for evidence of vancomycin-resistant Enterococcus faecium was obtained 3 days before admission, according to a local protocol of epidemiological surveillance, and was positive. The clinical examination showed a painful and tender abdomen and mild signs of dehydration. The patient’s white blood cell count was 23,000/mm3, erythrocyte sedimentation rate was 82, and C-reactive protein was 11.2 U\L. Journal of Chemotherapy Vol. 15 n. 3 (299-300) 2003

The application of cost effectiveness analysis to derive a formulary for urinary tract infections.

Abstract According to economic principles an inappropriate prescription is the choice of an antimicrobial with higher/equivalent cost and lower effectiveness (or higher cost and equivalent/lower efficacy) than an alternative (in this case, the former is specified as a “dominated” drug). To identify cost-effective antibiotics we applied the principles of incremental cost-effectiveness analysis (ICEA) to microbiological data of San Bortolo Hospital. Its 27 wards were grouped in 9 functional areas. The resistance patterns of 8 urinary pathogens in the 1997 microbiology data base were assessed. The measure of antibiotic effectiveness was expressed as the percentage of isolates susceptible to each antibiotic tested. The difference in cost (i.e. the incremental change) between each antibiotic and the next more expensive alternative was calculated, and compared with the incremental change in effectiveness. Calculations were made for each pathogen. The antibiotics remaining after exclusion of all “dominated” antibiotics were pooled on a list defined as “Specific Area Formulary”. The implications of the use of economic principles within a general antimicrobial policy are discussed.