[THE ROLE OF ANTISEPTICS AND STRATEGY OF BIOFILM REMOVAL IN CHRONIC WOUND]. / ULOGA ANTISEPTIKA I STRATEGIJA UKLANJANJA BIOFILMA KRONICNE RANE.

Chronic wound does not heal within the expected time frame because it remains in the inflammation phase of healing. The reason for this is the presence of necrotic tissue and a large number of microorganisms, primarily bacteria that secrete the biofilm, along with ischemia, hypoxia and edema. Biofilm is present in 90% of chronic wounds and 6% of the acute ones. Biofilm is a corporative association of microbes which adhere to the surface of the wound, guided by quorum sensing molecules. The association is surrounded by a moisturizing matrix of extracellular polymeric substances (slime) which protect the microbes from the impact of antibiotics, antiseptics, macro-organism defense and stress. Biofilm is the primary cause of the wound chronicity because it causes permanent inflammation, delayed granulation tissue formation and migration of epithelium cells, thus providing a reservoir of microbes that lead to infection of the chronic wound. The aim of good clinical practice is to enable healing of a chronic wound within the expected time frame. In order to achieve this aim, it is necessary to reduce and thoroughly remove the biofilm from the wound and prevent its reappearance. This is achieved by the application of active anti-biofilm compounds and procedures that disintegrate the quorum sensing molecules, degrade the extracellular polymeric substances and block adherence to the surfaces. Recent researches have shown that the application of antiseptics is effective in the prevention of infection and is a support to targeted treatment. However, the fact is that only some antiseptics are applicable to chronic wounds and can have an impact on biofilms of the primary infective agents such as Staphylococcus spp., Streptococcus spp., and Pseudomonas aeruginosa. Effective antiseptics are octenidine dihydrochloride, polyhexanides, povidone and cadexomer iodine, nanocrystal silver and Manuka-type honey. Immobile biofilm is a persistent problem of chronic and chronic infected wounds. In fact, there is no isolated therapeutic procedure or an individual antiseptic that can fully destroy the biofilm. For this reason, modern strategy in the management of chronic wound applies a multimodal approach which combines mechanical-chemical procedures such as debridement, antiseptics, and antimicrobial supportive compresses. Debridement creates a therapeutic 'window' for the action of antiseptics and antibiotics in a 72-hour period, which enables removal of the biofilm and active destruction of the sessile and planktonic bacteria. This approach also prevents de novo formation of the biofilm. The above procedures must be intensively repeated, and antiseptics and supportive compresses changed, depending on the phase of the wound bed and comorbidity factors in the patient. The results of clinical studies show that only such a proactive approach to chronic wound enables achievement of healing within the expected period of time.

[Recognition and treatment of chronic wound infection]. / Prepoznavanje i lijecenje infekcije kronicne rane.

Recognition and treatment of a chronic wound infection is an extraordinarily complex task that requires team work and purposeful and graduate resolving of the problem. Chronic wound infection is the most risky complication because it may have fatal outcome for the patient. The principles of best clinical practice include thorough examination of the patient with respect to endogenous diseases and risk factors, defining the locality of infection and wound characteristics, along with clinical symptoms of infection. Based on the wound status, diagnostic procedures are initiated and the causative agent and its sensitivity to antibiotics determined. With respect to the seriousness of the clinical picture, a plan of surgical interventions is developed. The main procedure is debridement, followed by supportive treatment methods, the choice depending on the indications and contraindications. The targeted method of treatment is systemic administration of antibiotics along with debridement. It is important to know that on approaching a chronic infected wound, the principles of sepsis and antisepsis should be observed. In clinical practice, there is a discrepancy between the adopted criteria for efficient treatment based on the evidence-based practice and objective and subjective problems that obstruct it. Thus, according to statistical data, 50% of antibiotics are prescribed wrongly or are rendered inefficient for some reason. Only half of the patients are treated correctly. It is high time to reach consensus on this issue and accept the facts relevant for the treatment of chronic infected wound, i.e. evidence-based medicine.

[Prevention of chronic wound infection]. / Prevencija infekcije kronicne rane.

An integral follow-up of the patient starting with medical history, present status and the wound itself will lead us to decide which plan of prevention, care and treatment will be efficient. The interaction of host immune abnormalities and growth of the microbial population invading the wound have a significant impact on the clinical presentation and direction of the development of the wound. Infection of a chronic wound is a consequence of a large number and composition of microbe populations in the tissue, along with the presence of virulence factors depending on the type and representation in the biofilm as a factor of greatest importance, the synergy of various microbial communities of aerobes-anaerobes in various combinations, and the host immune response. The basic procedures in preventing the development of infection from the colonization status are reduction of the total mass of microbes along with necrotic tissue, removal or destruction of virulent factors such as the biofilm, destruction of the synergy of various microbial communities, and increasing the level and quality of the host immune response. Prevention of the chronic wound infection demands numerous strategies or procedures, which should be applied simultaneously, but must rapidly and frequently follow each other in succession. Therefore, various methods are being applied depending on the indications, such as mechanical washing and cleaning, application of antiseptics, debridement, vacuum-assisted closing of the wound, oxygenation, moist wound healing - active and passive compresses, methods of removal or destruction of the biofilm, application of specific cells, i.e. factors of growth, and removal of mechanical stress. Antibiotics are not used in the prevention of chronic wound infection. They are used only in a targeted fashion when infection has been proven and the agent identified, as well as its sensitivity to antibiotics obtained from target samples. An ideal prevention would be a method that would prevent the development of the wound and be applied while the skin is still intact. Irrespective of all knowledge accumulated so far, the good clinical practice has not yet fully defined preventive measures for the care and prevention of chronic wound infection, and, likewise, these measures are not universally accepted. The aim of preventive procedures is at the same time the battle against microbes and the underlying disease that caused the development of chronic wound, with the aim of preventing the development of infection.

[Atypical agents of wound infection and targeted samples]. / Atipicni uzrocnici infekcije rane i ciljani uzorci.

All open wounds are primarily contaminated and subsequently colonized by microorganisms, predominantly bacteria. Only about 30% of chronic wounds are also infected. Factors which favor the development of infection are the following: large quantity of bacteria, presence of virulence factors, their quantity and number, predominantly the synergy of aerobic and anaerobic bacteria, and formation of biofilm. Common agents of infection of acute and chronic wounds are Staphylococcus aureus, MRSA, Streptococcus beta-haemolyticus, Pseudomonas aeruginosa, Bacteroides spp., and Candida albicans. Difference between acute and chronic wound is in the predominance of individual agents, with an observation that Staphylococcus aureus is predominant in both cases. Atypical agents of chronic wound infection are rare, unusual, not found in the area in which we live, not proven by standard microbiological methods, but molecular methods are needed instead. They are predominantly opportunists, varying in the expression of virulence factors, or they have changed their phenotype characteristics and are not the agents of primary wound infections. They are the agents of secondary infections. Atypical agents of the chronic wound infection are diverse, from the anaerobe group, Peptoniphilus spp., Anaerococcus spp., Bacteroides ureolyticus, Finegoldia magma, the group of gram positive rods of the Corynebacterium genus, the group of bacteria from aquatic environment Mycobacterium fortuitum complex, and Vibrio alginolyticus. The targeted samples are biopsy sample as the "gold standard" and/or aspirate, when a significant quantity of exudate is present. Targeted samples are obligatory when there is a progression and decomposition of the base of the wound, increase in the size or depth of the wound, isolation of multiresistant microbes, or absence of clinical response to empirical antimicrobial therapy. In the diagnosis of opportunistic pathogens or atypical agents of chronic wound infection, it is necessary to be thorough, meticulous, and conduct revision of the patient, diagnosis, treatment and samples. Crucial for the detection of the agents atypical wound infection is discussion and agreement with clinical microbiologist. Essential for the quality diagnosis is decontamination of the wound before taking targeted samples. The targeted sample is biopsy specimen as the "gold standard", less frequently aspirate, depending on the quantity and content of the wound. Swab as a sample is not recommended. If there is no other choice, only exceptionally surface swabs may be taken, but only under the following conditions: decontamination of the wound with the application of Levine's or Z-technique of taking of swabs.

An intrauterine device as a possible cause of change in the microbial flora of the female genital system.

AIM: An intrauterine device (IUD), used by millions of women worldwide, is one of the most efficient methods of contraception. The goal of our study was to compare a group of women using the IUD to a control group. MATERIAL & METHODS: The survey included 236 women of fertile age from gynaecological practices in the area of Split and Dalmatia County, Croatia. The subjects were divided into two groups: IUD users and a control group (women not using any contraception methods). Sampling, transportation, sample processing in the laboratory and interpretation of results were conducted using standard microbiological procedures and methods. RESULTS: Opportunistic bacteria were statistically more frequently isolated among IUD users (P < 0.001). The most frequently isolated bacteria in both groups were Escherichia coli and Ureaplasma urealyticum with significantly higher rates in IUD users (P < 0.001). Both colonization and infection had higher rates in IUD users (P < 0.001). There were no significant differences either in the frequency of bacteria isolation regarding different IUD types (P = 0.93), or in relation to duration of IUD use (P = 0.67). CONCLUSIONS: Based on the data in our study IUD users have an increased chance of developing a cervical infection caused by the bacteria Escherichia coli and Ureaplasma urealyticum. Therefore, before IUD insertion women should be screened and treated for asymptomatic vaginal or cervical infections to prevent possible serious IUD-associated infections.

[Can introduction of guidelines for use of an intrauterine device reduce changes in microbial flora of female genital system in IUD-users?]. / Moze li uvodenje postupnika za postavljanje intrauterinoga uloska smanjiti promjenu mikrobioloske flore spolnoga sustava u zena koje ga rabe?

The intrauterine device (IUD), one of the most effective and most common methods of reversible contraception, is used by millions of women worldwide. Although various studies indicate the benefits of its use as a contraceptive method, the greatest concern regarding IUDs is the potential risk for infection. The presence of the IUD gives a solid surface for bacterial attachment and biofilm formation. Infections due to biofilm formation are chronic and difficult to resolve. However, women should be screened and treated for asymptomatic vaginal or cervical infections before IUD insertion. Based on the data in the literature and the data in study conducted in Croatia, it can be concluded that IUD users are at increased risk for development of infection. Treatment strategies in Croatia should take into consideration that Escherichia coli and Ureaplasma urealyticum are dominant causative agents. We conclude that guidelines for the use of IUD in Croatia are a necessity.

The importance of P-glycoprotein multidrug transporter activity measurement in patients with Helicobacter pylori infection.

P-glycoprotein is important in local antibiotic resistance. Aim was to evaluate the role of P-glycoprotein in local antibiotic resistance in patients with antral gastritis during antibiotic therapy to Helicobacter pylori infection. In the group of 53 patients with pathohistologically verified gastritis and microbiologically confirmed H. pylori infection (no signs of antimicrobial resistance) we have determined P-glycoprotein activity in gastric mucosa biopsy specimens, and compared them with the P-glycoprotein activity in 12 control subjects with normal endoscopic findings. The H. pylori positive patients were treated according to Maastricht protocol with short-term 7-day therapy consisting of two antibiotics (amoxicillin and azithromycin/metronidazole and clarithromycin) and a proton pump inhibitor P-glycoprotein activity was determined in rhodamine dye efflux test and quantified by ratio of the mean fluorescence (RMF) in flow cytometry analysis. H. pylori was successfully eradicated in the first cycle in 20 patients, whereas therapy was continued in 33 patients. The mean pre-treatment RMF values were higher in patients with H. pylori infection then in control subjects (p < 0.0046). RMF was also higher in patients with multiple therapeutic failure than in those with successful H. pylori eradication (p < 0.0001). RMF increased significantly during the antibiotic therapy (p < 0.05). P-glycoprotein might be one of the causes of therapy failure in patients with H. pylori. Our study confirms the importance of quantitative evaluation of P-glycoprotein expression during antibiotic treatment response.

[Necrotizing soft tissue infection of upper extremity complicated with toxic shock syndrome--clinical presentation and treatment options]. / Nekrotizirajuca infekcija mekih cesti ruke uz razvoj sindroma toksicnog soka--klinicki tijek i lijecenje.

Necrotizing soft tissue infections (NSTI) are uncommon infections associated with considerable morbidity and mortality (20%-40%). They are characterized by rapidly progressive necrosis of soft tissue that primarily involves subcutaneous fat and fascia with variable involvement of the overlying skin and muscle. Extensive soft tissue necrosis is often accompanied by systemic toxicity. Establishing the diagnosis in the early stage of the infection can be difficult, which leads to a delay in surgical treatment and a poor outcome. The principles of treatment are early and aggressive surgical debridement, broad spectrum antimicrobial therapy administered empirically and reassessed pending culture and sensitivity results, and intensive care management. We report a case of NSTI of the arm in a 64-year-old female patient caused by group A Streptococcus and Staphylococcus aureus complicated with toxic shock-like syndrome with emphasis on the pathophysiology of toxic shock-like syndrome and treatment modalities. NSTI developed 10 days after a knife cut wound of the thumb. The patient had no significant comorbidity. Treatment included aggressive surgical debridement with removal of necrotic tissue and extensive fasciotomies 24 h of admission, cardiovascular stabilization and monitoring at intensive care unit, and repeat surgical debridement at 72 h of admission. Early triple drug antimicrobial therapy included high-dose clindamycin, which inhibits protein synthesis and bacterial exotoxin production that is responsible for inflammatory response and toxic shock-like syndrome. In addition, the patient received hyperbaric oxygen therapy (8 treatments in total). The above management led to control of the infective process. Prolonged surgical wound care followed by thin split-skin grafting and placement of secondary sutures on day 36 of admission preserved the extremity with good functional and cosmetic result.

[Characteristics of war wound infection]. / Osobitosti infekcije ratne ozljede.

War wounds are the most complex type of non-targeted injuries due to uncontrolled tissue damage of varied and multifold localizations, exposing sterile body areas to contamination with a huge amount of bacteria. Wound contamination is caused by both the host microflora and exogenous agents from the environment (bullets, cloth fragments, dust, dirt, water) due to destruction of the host protective barriers. War wounds are the consequence of destructive effects of various types of projectiles, which result in massive tissue devitalization, hematomas, and compromised circulation with tissue ischemia or anoxia. This environment is highly favorable for proliferation of bacteria and their invasion in the surrounding tissue over a relatively short period of time. War wounds are associated with a high risk of local and systemic infection. The infection will develop unless a timely combined treatment is undertaken, including surgical intervention within 6 hours of wounding and antibiotic therapy administered immediately or at latest in 3 hours of wound infliction. Time is a crucial factor in this type of targeted combined treatment consisting of surgical debridement, appropriate empirical antimicrobial therapy, and specific antitetanic prophylaxis. Apart from exposure factors, there are a number of predisposing factors that favor the development of polymicrobial aerobic-anaerobic infection. These are shock, pain, blood loss, hypoxia, hematomas, type and amount of traumatized tissue, age, and comorbidity factors in the wounded. The determinants that define the spectrum of etiologic agents in contaminated war wounds are: wound type, body region involved, time interval between wounding and primary surgical treatment, climate factors, season, geographical area, hygienic conditions, and patient habits. The etiologic agents of infection include gram-positive aerobic cocci, i. e. Staphylococcus spp, Streptococcus spp and Enterococcus spp, which belong to the physiological flora of the human skin and mucosa; gram-negative facultative aerobic rods; members of the family Enterobacteriacea (Escherichia coil, Proteus mirabilis, Klebsiella pneumoniae, Enterobacter cloacae), which predominate in the physiological flora of the intestines, transitory flora of the skin and environment; gram-negative bacteria, i. e. Pseudomonas aeruginosa, Serratia marcescens, Acinetobacter calcoaceticus - A. baumanii complex; environmental bacteria associated with humid environment and dust; anaerobic gram-positive sporogeneous rods Clostridium spp, gram-negative asporogeneous rods Bacteroides spp and gram-positive anaerobic cocci; Peptostreptococcus spp and Peptococcus spp. The latter usually colonize the intestine, primarily the colon, and the skin, while clostridium spores are also found in the environment. Early empirical antibiotic therapy is used instead of standard antibiotic prophylaxis. Empirical antimicrobial therapy is administered to prevent the development of systemic infection, gas gangrene, necrotizing infection of soft tissue, intoxication and death. The choice of antibiotics is determined by the presumed infective agents and localization of the wound. It is used in all types of war wounds over 5-7-10 days. The characteristics of antibiotics used in war wounds are the following: broad spectrum of activity, ability to penetrate deep into the tissue, low toxicity, long half-life, easy storage and application, and cost effectiveness. The use of antibiotics is not a substitution for surgical treatment. The expected incidence of infection, according to literature data, is 35%-40%. If the time elapsed until surgical debridement exceeds 12 hours, or the administration of antibiotics exceeds 6 hours of wound infliction, primary infection of the war wound occurs (early infection) in more than 50% of cases. The keys for the prevention of infection are prompt and thorough surgical exploration of the wound, administration of antibiotics and antitetanic prophylaxis, awareness of the probable pathogens with respect to localization of the wound, and optimal choice of antibiotics and length of their administration.

Increased activity of Pgp multidrug transporter in patients with Helicobacter pylori infection.

AIM: To determine whether local antibiotic resistance involves P-glycoprotein (Pgp)-mediated active drug out-pumping during Helicobacter pylori (H pylori) infection treatment with classic antibiotic therapy. METHODS: Pgp activity was determined in gastric mucosa biopsy specimens obtained from 53 patients with pathohistologically verified gastritis and microbiologically confirmed H pylori infection, and compared with the Pgp activity in 12 control subjects with normal endoscopic findings. The H pylori positive patients were treated with short-term 7-d therapy consisting of two antibiotics (amoxicillin and azithromycin/metronidazole and clarithromycin) and a proton pump inhibitor. Pgp activity was determined by flow cytometry in the test of rhodamine dye efflux and quantified as mean fluorescence ratio (RMF). RESULTS: Upon the first cycle, H pylori was successfully eradicated in 20 patients, whereas therapy was continued in 33 patients. In the course of antibiotic therapy, RMF increased (P<0.05) and gastric cells showed higher rhodamine dye efflux. The mean pre-treatment RMF values were also higher (P<0.0001) in patients with multiple therapeutic failure than in those with successful H pylori eradication and control subjects. CONCLUSION: Pgp might be one of the causes of therapy failure in patients with H pylori and antibiotic therapy could be chosen and followed up on the basis of the Pgp transporter local activity.

[Is the methicillin-resistant Staphylococcus aureus heteroresistant to vancomycin in Croatia?]. / Ima li u Hrvatskoj sojeva Staphylococcus aureus heterorezistentnih na vankomicin?

INTRODUCTION: Staphylococcus (S.) aureus with reduced susceptibility to vancomycin has attracted much attention all over the world since the first report of Staphylococcus aureus isolate intermediarily resistant to vancomycin (VISA) in Japan 1997. Other authors from different parts of the world have also described VISA isolates in patients with treatment failures after prolonged vancomycin therapy. Most of the isolates were heterogeneously resistant (hVISA), i. e. only a part of the population showed resistance and the rest showed susceptibility to vancomycin. AIM: Aim of the study was to determine the existence of methicillin-resistant S. aureus (MRSA) strains with reduced susceptibility to vancomycin in Croatia. METHODS: Abbreviated population analysis was used for detection of strains with reduced susceptibility to vancomycin. Forty-eight MRSA strains from three different hospitals in Croatia were tested on brain-heart infusion agar (BHIA) screen plate containing 4 mg/L vancomycin. Thirty-three (68.7%) strains that showed growth on a screen plate were inoculated on BHIA plates with rising vancomycin concentrations (1-20 mg/L). After subcultivation and growth on a vancomycin-free BHIA plate, minimal inhibitory concentrations (MICs) were determined for all strains. RESULTS: Fourteen of 48 (29.1%) strains had vancomycin 8 mg/L and 1/48 (2.0%) strain had vancomycin 16 mg/L. In 3/48 (6.2%) MIC were stable after storage in liquid nitrogen for six months. Vancomycin MIC50 and MIC90 of all 33 strains grown on screen plate were 1 and 2 gm/L, respectively, when tested on Mueller-Hinton agar (MHA) before inoculation on BHIA with growing concentrations of vancomycin. Immediately thereafter, MIC were 4 and 8 mg/L, and after six months of storage, they were 4 and 4 mg/L, respectively. CONCLUSION: The prevalence of hVISA in Croatia is low, but there are some strains with reduced susceptibility to vancomycin. Unfortunately, because of lack of clinical data neither clinical correlation with laboratory findings nor therapeutic failures can be discussed.

[Pseudomonas aeruginosa--a significant hospital pathogen and resistance to carbapenem]. / Pseudomonas aeruginosa--znacajan bolnicki patogen i rezistencija na karbapeneme.

Pseudomonas aeruginosa (P. aeruginosa) is an etiologic agent of nosocomial infections of various localizations. The frequency of infections is a consequence of an increased number of immunocompromised patients, large surgical interventions, long-term hospital care and virulence factors of the bacterium. The use of carbapenems in the treatment of infections caused by P. aeruginosa and other gram-negative bacteria entail an unfortunate consequence of creating resistance to carbapenems. P. aeruginosa exhibits numerous mechanisms of resistance and is singularly problematic for combining intrinsic resistance and acquired resistance due to multiple mutations. It is also a carrier of the multiple-resistance plasmide. Carbapenems are a class of beta-lactam antibiotics with broad-spectrum activity to gram-positive, gram-negative and strictly anaerobic bacteria. The resistance of P. aeruginosa to carbapenems is complex and heterogeneous. It is determined by weakening the penetration through the outer membrane due to the loss of porin D2, decrease in the accumulation of antibiotic in the cell consequentially to active efflux due to hyperproduction of proteins, hydrolysis of carbapenem by specific metallo-beta-carbapenemases, and alteration in the target area of antibiotic activity on the bacterial cell. The loss of porin D2 results in resistance to imipenem with MIC values of 8.0-32.0 microg/mL. Selective low-level resistance to meropenem in the hyperproduction of the efflux system results in MIC values of 2.0-4.0 microg/mL. A high-level resistance to carbapenems with MIC values above 128 microg/mL for imipenem and meropenem is a consequence of the secretion of IMP and VIM series beta-carbapenemases. The frequency of resistance to P. aeruginosa to carbapenems varies worldwide from 15% to > or = 35%. In Croatia, resistance to carbapenems in the year 2003 was estimated to 12%. The problems in clinical practice are the increased resistance of P. aeruginosa to carbapenems, the presence of beta-carbapenemases and acquisition of these enzymes in certain types of Enterobacteriacea. The problems in laboratory practice are those of precise determination of the level and phenotype resistance of P. aeruginosa to carbapenems.

[Coagulation tests in septic surgical patients]. / Koagulacijski testovi u sepsi kirurskih bolesnika: kohortna studija.

AIM: To determine whether sequential change in coagulation parameters such as activated partial thromboplastin time (aPTT), prothrombin time (PT), platelets count and fibrinogen level may predict the outcome of patients in sepsis. STUDY DESIGN: Cohort longitudinal study. PATIENTS AND METHODS: Patients with positive two or more clinical criteria for sepsis were eligible for the study. Thirty patients were included, 24 male and 6 female. Eight patients survived, while 22 deceased. Median age of survivors was 66 years (range 23-77), and in non-survivors it was 69 years (range 48-79), p=0.37. In 9 patients malignancy was an underlying disease. APACHE II score was calculated at admittance, median value for survivors was 10 (range 7-15) and for non-survivors it was 26 (range 6-35), p=0.001. Calculated MODS score at the time blood cultures was 2 (range 0-9) for survivor and 6.5 (range 2-13) for non-survivors, p=0.007. Blood cultures were taken at the onset of sepsis, and in 29 patients they were positive. Coagulation parameters were measured at admittance, at the onset of sepsis and 48 hours after the introduction of the specific antimicrobial therapy. RESULTS: Analysis of variance for repeated measurements between survivors and non-survivors has shown that there were no differences in values of coagulation parameters. The only significant difference between these groups of patients was APACHE II and MODS score. In 7 patients with severe thrombocytopenia (<33,000 x 10(9)/L) as a result of irreversible septic shock a clinically visible bleeding was present in only one patient. DISCUSSION: Disseminated intravascular coagulation (DIC) is a clinical-pathological syndrome in which wide-spread intravascular coagulation is induced by procoagulants that are introduced or produced in the blood circulation and overcome the natural anticoagulant mechanisms. DIC causes tissue ischemia from occlusive microthrombi as well as bleeding from both the consumption of platelets and coagulation factors and the anticoagulant effect of products of secondary fibrinolysis. In sepsis, tissue factor which is the most common trigger of DIC can be generated and expressed on membranes of monocytes and endothelial cells during the systemic inflammatory response syndrome (SIRS). The wide-spread generation of thrombi in sepsis induces deposition of fibrin which leads to vessels obstruction and consumption of substantial amounts of haemostatic factors i.e. platelets, fibrinogen, factors V, VIII and others, protein C and antithrombin III (AT III). Intravascular thrombi trigger secretion of tissue plasmin activator (tPA) from endothelial cells which sets of compensatory thrombolysis which may reopen the occluded blood vessels. But byproducts of thrombolysis such as fibrin/fibrinogen degradation products may enhance bleeding by interfering with platelet aggregation, fibrin polymerization and thrombin activity. The typical feature of sepsis is depression of three powerful anticoagulant systems: protein C pathway, AT III pathway and tissue pathway factor inhibitor (TPFI). This sequence of events led us to hypothesize that alterations in coagulation parameters such as PT, aPTT, fibrinogen, platelets count may predict the outcome of disease, as it is well documented that the development of DIC confers prognosis of sepsis. The failure to distinguish survivors from non-survivors by the alteration in the coagulation parameters in this study may be due to a relatively low sample size or to the clinical necessity of an attending physician to substitute the deficient blood or coagulation product. CONCLUSION: The coagulation parameters PT, aPTT, platelet count and fibrinogen level can not serve as predictors of outcome in patients with sepsis. Further studies including more discerning coagulation parameters: AT III, D-dimer, soluble fibrin monomer, thrombin/antithrombin complex, plasmin/antiplasmin complex, fibrinopeptid A, fibrinopeptid B are necessary to evaluate whether these procoagulant and anticoagulant factors may help in predicting outcome and severity of sepsis.

Ilizarov technique in the treatment of chronic osteomyelitis caused by Vibrio alginolyticus.

We present a case of 26-year-old woman with posttraumatic chronic osteomyelitis caused by Vibrio alginolyticus, contracted after contamination of a tibial fracture with seawater. The patient underwent bone resection and bifocal osteosynthesis according to Ilizarov and was treated with a combination of ciprofloxacin and tetracycline. The patient responded in the same way to distraction osteogenesis as any other patient with chronic osteomyelitis with large defects.