Efficacy and safety of tigecycline compared with vancomycin or linezolid for treatment of serious infections with methicillin-resistant Staphylococcus aureus or vancomycin-resistant enterococci: a Phase 3, multicentre, double-blind, randomized study.

INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) are causing serious nosocomial infections. Tigecycline was evaluated in hospitalized patients with MRSA or VRE infection. PATIENTS AND METHODS: A randomized (3:1), double-blind, multicentre, Phase 3 study compared the safety and efficacy of tigecycline with vancomycin or linezolid in hospitalized patients with MRSA or VRE infection, respectively. Patients were treated for 7-28 days and the test-of-cure (TOC) assessment was made 12-37 days after the last dose. The primary efficacy endpoint was the clinical response (cure, failure and indeterminate) in the co-primary, microbiologically evaluable (ME) and microbiologically modified intent-to-treat (m-mITT) populations at the TOC assessment. RESULTS: For MRSA infection, clinical cure rates in the ME population (n = 117) were 81.4% (70 of 86 patients) with tigecycline and 83.9% (26 of 31 patients) with vancomycin. In the m-mITT population (n = 133), clinical cure occurred in 75 of 100 tigecycline-treated patients (75.0%) and in 27 of 33 vancomycin-treated patients (81.8%). In patients with complicated skin and skin structure infections caused by MRSA, cure rates were similar with tigecycline or vancomycin (86.4% versus 86.9% in ME population; and 78.6% versus 87.0% in m-mITT population). In patients with MRSA infection, nausea or vomiting occurred more frequently with tigecycline than with vancomycin (41.0% versus 17.9%); most cases were mild, with only three patients discontinuing treatment. In patients with VRE (total enrollment, 15), 3 of 3 and 3 of 8 patients in the ME and m-mITT populations, respectively, were cured by tigecycline, compared with 2 of 3 patients in the ME and m-mITT populations treated with linezolid. CONCLUSIONS: Tigecycline is safe and effective in hospitalized patients with serious infection caused by MRSA. There were too few cases of VRE to draw any conclusions.

[Retroperitoneal postoperative necrotizing fasciitis]. / Retroperitonealen sledoperativen nekrotichen fastsiit.

This is a report on clinical experience had with 17 patients presenting necrotizing fasciitis--a complication ever more frequently encountered. The case material is distributed in two group differing by origin and clinical course of the complication. In group one (n = 11) it is a matter of postoperative development of postoperative complication, consistent with the classical "per continuitatem" and "per contiguitatem" mechanisms, while in group two (n = 6) the process originates, evolves and speads within the retroperitoneal space proper. Comprehensive microbiological examinations performed in 13 cases show that in either group different microorganisms are identified. In group one aerobic-anaerobic mixed infection is documented in all patients, with predominance of Enterobacteroidaceae among aerobic ones. In group two, anaerobic bacterial species, mainly Clostridium sp, prevail in all the isolates. The clinical study points to a substantial difference in the time of septic complication occurrence, as well as between the clinical picture of the two species. Accordingly, the final results are radically different--in group one survivorship amounts to 62.6%, whereas in group two--to 16.6% only.

Bilophila wadsworthiain brain abscess: case report.

A case of a patient with a 20-year history of chronic otitis media complicated by cholesteatoma and brain abscess is described. A CT scan with contrast material showed three abscess cavities in the right cerebellar hemisphere. A culture from a specimen of the cholesteatoma yielded a significant amount of growth of Bilophila wadsworthia, Bacteroides fragilis and Prevotella oris and a moderate growth of alpha-streptococci and Staphylococcus simulans. From the pus of the brain abscess we also isolated numerous Bilophila wadsworthia, Bacteroides fragilis and Prevotella oris and some Prevotella buccae and Peptostreptococcus anaerobius. No aerobes were present. The patient underwent a craniotomy and the biggest abscess was removed together with the capsule. The antimicrobial therapy included penicillin plus metronidazole and later augmentin. The result of the treatment was a complete cure and total recovery of the patient. This is the first documentation of isolation of B. wadsworthia in chronic otitis media and in brain abscess.

Fournier's Gangrene: a clinical and bacteriological study.

Bacteriological studies were conducted in patients presenting with Fournier's Gangrene (FG) in our Department during a period of 11 years. These studies showed high numbers of anaerobes (96%) and the ratio of aerobes to anaerobes was reported to be 1.4: 3.2. Among the anaerobes,Peptostreptococci, Bacteroides and Prevotella were more frequently isolated. The predominant facultative aerobic microorganisms were Streptococci and Escherichia coli. Clinical investigation showed necrotic cellulitis and fasciitis of the scrotum due to mixed aerobic-anaerobic infection. Patients with complicated paraproctitis and periurethral abscesses and urinary phlegmones who also presented with symptoms of FG were treated during this same period. Microbiological studies gave similar results and clinical studies showed that the process had spread to the scrotum. The question was then raised whether FG should be diagnosed as an independent nosological entity in cases where the underlying cause of the disease was obscure or if FG should be the result of different pathological processes which occurred within the scrotal surfaces. In other cases, FG is secondary and occurred after reaching the scrotum per continuitatem.

[Postoperative anaerobic sepsis]. / Sledoperativen anaeroben sepsis.

As shown by clinical practice, postoperative anaerobic sepsis is a complication more common than usually thought of or microbiologically verified. The exceptionally difficult microbiological verification, regardless of the fact that original registered transport media are employed, is the underlying cause of obligate non-spore forming microorganisms from hemoculture being demonstrated in four patients only. In all of them Bacteroides fragilis is isolated and identified. Also, in all patients a fully developed clinical picture of sepsis is present along with the characteristic laboratory septic syndrome constellation as well. After pointing out the difficulties in diagnosing "post-operative anaerobic sepsis", and more particularly its verification, emphasis is laid on the clinical and laboratory symptoms presented by the patients, and on the important role played by the SIRS system, contributing greatly to an adequately oriented clinical thinking.

[Problems in the surgical treatment of diabetic gangrene]. / Problemi v khirurgichnoto lechenie na diabetnata gangrena.

Parallel to life expectancy prolongation and constantly improving life style of diabetic patients in this country, observed during the last decade, the problems relating to complications in diabetes become of primary importance. From 60 to 70 per cent of the diabetics with foot ulcerations have neuropathy. The serious forms of nerve involvement appear to be a major cause of lower extremity amputation. Analysis of the clinical case material, covering 382 patients with diagnosis diabetic gangrene, is done with the purpose to reduce the percentage of disabling high-level amputations, and determine with precision the scope of operative activity, indications for operative intervention and type of surgical procedure in diabetic patients. A total of 58 major amputations are performed, with their overall rate amounting to 13.6 per cent. The main trends of the therapeutic approach to diabetic foot are aimed at performing sparing, economically more beneficial operations, not leading to invalidization.

[Postoperative necrotizing fasciitis of the anterior abdominal wall]. / Sledoperativen nekrotichen fastsiit na prednata koremna stena.

Postoperative necrotizing fasciitis of the anterior abdominal wall is a serious and life-endangering complication of an acute progressive synergistic infective process. There is an absolute increase in its incidence rate attributable to a number of situations in modern life. Morphological and clinical studies are carried out on personal case material of 28 patients, followed up over a 3-year period. The presence of aerobic-anaerobic mixed polyinfection, consisting of average 3.75 bacterial species of which 1.43 aerobes and 2.32 anaerobes, is demonstrated microbiologically. Of the latter non-spore-bearing obligate anaerobes predominate among which B fragillis is the most common. As shown by the study, the process is characterized by slow initial course with ensuring rapid spreading by neighbourhood. The process reveals all signs of a mixed aerobic-anaerobic polyinfection, thereby necessitating subordination of both antibiotic therapy and surgical tactics to the latter.

[Clostridial surgical infection]. / Klostridilna khirurgichna infektsiia.

An ever increasing attention of clinicists is being focused on nontraumatic clostridal surgical infections. Personal clinical case material consisting of 390 patients with microbiologically proved clostridial infection are subjected to clinical and microbiological investigations aimed at establishing the nature of the infective process. In 377 patients (group one) signs of mixed aerobic-anaerobic polyinfection are clinically documented, fully confirmed by the comprehensive microbiological examinations performed. In 120 patients of this group 162 Clostridida species are isolated, but none of them, including the severest cases, are suspected for gas gangrene presence. In 13 patients of group two presenting clinical picture of a typical gas gangrene, the latter is both demonstrative and impressive. Here the microbiological examinations are absolutely analogical to those in group one which warrants the assumption of the endogenous character of the infective process, leading in turn to inferenceshaving important practical implications and recommendation to modify the antiepidemiological measures with a special reference to the endogenous character of the infective process.