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Background: A frequent cause of conjunctivitis is an acute bacterial infection, presenting with mucopurulent discharge and conjunctival hyperemia. The authors compared the clinical and microbiologic efficacy, safety and acceptability of 1% fusidic acid viscous drops (Fucithalmic) with 0.3% tobramycin ophthalmic solution (Tobrex) in the treatment of suspected bacterial conjunctivitis., Methods: Patients were recruited at 20 sites in Ontario, Saskatchewan and Alberta from October 1995 to December 1998. Patients who presented to their primary care physician with suspected bacterial conjunctivitis, as identified by conjunctival hyperemia and purulent or mucopurulent discharge, were eligible for the study. Patients were randomly assigned to receive 7 days of treatment with either 1% fusidic acid (one drop applied twice daily) or 0.3% tobramycin (one to two drops applied four to six times daily). The investigators were blinded as to treatment status. Bacteriologic samples were taken from the inferior conjunctival cul-de-sac on day 0 and at the end of treatment. Signs and symptoms of conjunctivitis were assessed at baseline and after 3 and 7 days of treatment. The acceptability of treatment was assessed by having the patient or the parent or guardian complete a questionnaire on degree of compliance and ease of use after 3 and 7 days of treatment., Results: Conjunctival swabs were obtained from 484 patients (410 over 9 years of age and 74 aged 2 to 9 years) to determine baseline bacteriology. Of the 484, 319 (65.9%) (63% of the older patients and 80% of those aged 2 to 9 years) had positive results of culture for bacteria. Ninety-four patients (19%) (63 [15%] of the older patients and 31 [42%] of those aged 2 to 9 years) had per-protocol pathogens as defined by quantitative bacteriology criteria. There was a direct correlation between the presence of mucopurulent discharge and the presence of per-protocol pathogens. There were no significant differences in clinical or bacteriologic efficacy between the treatment groups. Treatment compliance was similar between the treatment groups for the older patients; however, for those aged 2 to 9 years, compliance was significantly better in the fusidic acid group than in the tobramycin group (85% vs. 47%) (p < 0.001). Significantly more patients in the fusidic acid group than in the tobramycin group rated treatment as convenient or very convenient, particularly among younger patients (97% vs. 54%) (p < 0.001)., Interpretation: The clinical and bacteriologic efficacy of fusidic acid viscous drops combined with the convenience of a twice-daily dosage regimen establishes this antibiotic as first-line treatment for suspected acute bacterial conjunctivitis and a favourable alternative to other broad-spectrum antibiotics.

Purpose: To compare the clinical and bacteriological effects of fucidic acid (Fucithalmic: 1.0%) and chloramphenicol (Minims(R): 0.5%) eye drops in neonates with a clinical diagnosis of acute conjunctivitis of suspected bacterial origin., Methods: A TOTAL OF 456 N: ewborns with gestational age > 32 weeks with acute conjunctivitis of suspected bacterial origin acquired within the first 28 days of life were included in the study. They were randomly assigned to a 7-day treatment with eye drops using either fucidic acid (1.0%) (Fucithalmic) applied twice per day, or chloramphenicol (0.5%) (Minims Chloramphenicol) applied six times per day. The subjects were followed up with two visits (on days 1 and 8) and by telephone 2 weeks after the end of treatment., Results: Eighty-nine per cent of the neonates treated with Fucithalmic were cured, compared to 87.9% of those treated with Minims Chloramphenicol (n.s). The drug was used as instructed in 90.7% of patients treated with Fucithalmic and in 78.0% of those treated with Minims Chloramphenicol (P < 0.001)., Conclusion: Treating neonatal conjunctivitis with fucidic acid is easier than with chloramphenicol and is equally effective.

Objective: To test the hypothesis that fusidic acid would not increase the treatment effect of disinfecting with povidone-iodine alone in children with impetigo., Design: Randomised placebo controlled trial., Setting: General practices in Greater Rotterdam., Participants: 184 children aged 0-12 years with impetigo., Main Outcome Measures: Clinical cure and bacterial cure after one week., Results: After one week of treatment 55% of the patients in the fusidic acid group were clinically cured compared with 13% in the placebo group (odds ratio 12.6, 95% confidence interval 5.0 to 31.5, number needed to treat 2.3). After two weeks and four weeks the differences in cure rates between the two groups had become smaller. More children in the placebo group were non-compliant (12 v 5) and received extra antibiotic treatment (11 v 3), and more children in the placebo group reported adverse effects (19 v 7). Staphylococcus aureus was found in 96% of the positive cultures; no strains were resistant to fusidic acid., Conclusions: Fusidic acid is much more effective than placebo (when both are given in combination with povidone-iodine shampoo) in the treatment of impetigo. Because of the low rate of cure and high rate of adverse events in the placebo group, the value of povidone-iodine in impetigo can be questioned.

We describe a 55-year-old man who developed spinal osteomyelitis and diskitis 14 months after orthotopic heart transplantation. The infective organism was Staphylococcus aureus and the patient was successfully treated with flucloxacillin and fusidic acid.

We studied the effects of the immunosuppressant sodium fusidate (fusidin) on murine immunoinflammatory diabetes mellitus (DM) induced by multiple low doses of streptozotocin (SZ). Fusidin was given by gavage to three strains of mice (C57KsJ, C57BL/6, CD1) at doses 10 or 100 mg/kg body weight every other day. The drug was administered as an early or late prophylactic regime starting either 1 day prior to the first or after the fifth and last injection of SZ. In both situations the largest dose of fusidin successfully reduced the clinical, chemical and histological signs of DM, the treated mice having significantly lower glycaemic values and milder (often absent) insulitis compared with sham-treated animals or controls given SZ alone. The antidiabetogenic effect was long-lasting as it was maintained up to 1 month after cessation of therapy. In contrast, fusidin prophylaxis failed to prevent development of hyperglycaemia acutely induced by one single and high (160 mg/kg) dose of SZ, which is a model of DM primarily due to the toxic action of SZ on the beta cells and does not involve immunopathogenetic mechanisms. On day 14 after SZ, fusidin markedly altered the circulating cytokine profile induced in vivo by ConA, reducing the levels of IFN-gamma, IL-2 and TNF-alpha and augmenting the level of IL-6. However, only the inhibitory effect of the drug on the synthesis/release of IFN-gamma seemed to be causally related to its capacity to counteract the SZ-induced DM. In fact, the disease was prevented by a neutralizing monoclonal antibody (mAb) against IFN-gamma, but not by anti-IL-2 receptor mAb, a soluble form of TNF-receptor type 1 or recombinant human IL-6. The prevention of disease by fusidin was also partly reversed by exogenously administered recombinant mouse IFN-gamma. The data provide further in-vivo evidence for the anti-diabetogenic and immunomodulatory properties of fusidin and indicate that this drug could have a role in prevention and treatment of human type 1 DM., (Copyright 2000 Academic Press.)

Eighty-nine cats and 38 dogs naturally infested with the ear mite Otodectes cynotis were randomly allocated into two treatment groups. One group was treated with a product containing miconazole nitrate, polymyxin B sulphate and prednisolone acetate, the other with a combination of diethanolamine fusidate, framycetin sulphate, nystatin and prednisolone. The treatment (five drops in each ear) was applied twice daily for 14 days, and its efficacy was evaluated on days 7, 14 and 21 on the basis of an otoscopic examination of the external ear canal, a microscopical examination of scrapings for the presence of ear mites and clinical signs of pruritus, pain, erythema and/or exudate. Both treatments were highly effective, and there were no significant differences between the two products, either in efficacy or in the clinical improvements observed. Apart from an allergic reaction in one cat treated with the second product, no adverse effects were observed.

The effect of local treatment of nostrils with fusidic acid cream was investigated in 30 previously untreated lepromatous leprosy patients. The cream was applied in the nostrils after flushing the nostrils with normal saline, twice a day for a period of four weeks. It was found that 20 mg/gm of sodium fusidate was effective in reducing the morphological index of the nose-blow smear to zero in two weeks in majority of the patients. No untoward side effect was seen in any of the patients. Such nasal treatment along with multidrug therapy may help in reducing the patient's level of infectiousness to their contacts, since the nose is recognized to be an important portal of exit of M. leprae.

A retrospective study was carried out to investigate possible reasons for a marked increase in fusidic acid-resistant Staphylococcus aureus (FusR S. aureus) identified by our routine hospital microbiology service. Information was obtained on a sample of 64 consecutive patients from whom resistant S. aureus had been cultured. The source of isolates was found to be diffuse within the hospital and community. The site of sample was most frequently chronic cutaneous infections (68%). All the S. aureus isolates were resistant to both fusidic acid and penicillin and many were resistant to multiple antibiotics. Topical fusidic acid had been used by 40% of patients in the preceding 6 months and none had received oral fusidic acid (sodium fusidate). Most (80%) had received an oral antibiotic in the preceding 2 years. Information from the Prescriptions Pricing Authority revealed that the total number of prescriptions for fusidic acid-containing preparations for the period September 1997 to August 1998 was markedly higher in Harrogate than in five other local areas where increases in (FusR) S. aureus have not been observed.

A new cream formulation of mupirocin developed to improve patient compliance was compared with systemic and topical antibiotics commonly used to treat primary and secondary skin infections. A mouse surgical wound model infected with Staphylococcus aureus or Streptococcus pyogenes was used. Topical treatment was applied at 4 and 10 h postinfection or oral treatment at a clinically relevant dose was administered 4, 8, and 12 h postinfection; treatments were continued three times daily for a further 3 days. Mupirocin cream was significantly more effective than (P < 0.01; two of eight studies) or not significantly different from (six of eight studies) mupirocin ointment in reducing bacterial numbers. Mupirocin cream was similar in efficacy to oral flucloxacillin but significantly more effective (P < 0.001) than oral erythromycin. It was also similar in efficacy to cephalexin against S. pyogenes but superior against S. aureus (P < 0.01). Mupirocin cream had a similar efficacy to fusidic acid cream against S. aureus but was significantly superior against S. pyogenes (P < 0.01). A hamster impetigo model infected with S. aureus was also used. Topical or oral treatment was administered at 24 and 30 h postinfection (also 36 h postinfection for oral therapy) and then three times daily for a further 2 days. On day 5, mupirocin cream was significantly more effective than mupirocin ointment in one study (P < 0.01) and of similar efficacy in the other two studies. Mupirocin cream was not significantly different from fusidic acid cream or neomycin-bacitracin cream, but it was significantly superior (P < 0.01) to oral erythromycin and cephalexin. Mupirocin cream was as effective as, or superior to, oral and other topical agents commonly used for skin infections.

Carriers of methicillin-resistant Staphylococcus aureus (MRSA) in hospital constitute a reservoir of infections and increase the risk of bacteremia and wound infection. In this prospective randomized trial, we tested the effectiveness of oral fusidic acid for eradication of MRSA colonization. From March 1997 through February 1998, patients with MRSA colonization in medical intensive care units in a large urban teaching hospital were randomly assigned to receive fusidic acid 500 mg q8h orally for 7 days or no anti-staphylococcal treatment. Twenty-three MRSA carriers were found during the study period and 16 were eligible for evaluation; six of them received fusidic acid. MRSA colonization was cleared in only two of the six patients with fusidic acid treatment, and later recurred in one of them. MRSA disappeared for 1, 2, 7, 7, and 8 weeks, respectively, in five of the 10 patients without treatment. MRSA persisted in the other five cases. Although all MRSA isolates found in the initial surveillance culture were susceptible to fusidic acid (MIC /= 256 microg/mL). Pulsed-field gel electrophoresis pattern analysis showed that the resistant strains were genetically identical to the susceptible strains isolated from the same patient before fusidic acid treatment, in both cases. However, genetically distinct strains colonized in the same individual during follow-up were found in four out of 16 cases. We conclude that oral fusidic acid alone is not suitable for eradication of MRSA colonization, and may lead to the emergence of resistant strains.

Background: A study was designed to assess a computer-based program for continuous registration of antibiotic resistance, statistics concerning severity of illness, and consumption of antibacterial drugs., Methods: The frequency of antibiotic resistance among bacteria in eight ICUs in southeastern Sweden was investigated yearly from 1995 through 1997. The antibiotic consumption in the ICUs was registered as defined daily doses (DDD) and compared to severity of illness (APACHE-II scores)., Results: There was a statistically significant increase in ampicillin resistance among Enterococcus spp. between 1996 and 1997, which was due to a shift from Enterococcus faecalis to Enterococcus faecium. A high prevalence of resistance among coagulase-negative staphylococci to oxacillin (approximately 70%), ciprofloxacin (approximately 50%), fucidic acid (approximately 50%) and netilmicin (approximately 30%) was seen in all ICUs during the whole study period. There was a statistically significant increase in ciprofloxacin resistance among Escherichia coli and Enterococcus spp. The resistance among Enterobacter spp. to cefotaxime decreased but this change was not statistically significant. Efforts were made to avoid betalactam antibiotics, except carbapenems, for treatment of infections caused by Enterobacter spp. and the consumption of cephalosporins decreased whereas the consumption of carbapenems increased. The total antibiotic consumption decreased by 2.5% during the study period. There was no correlation between APACHE II scores and antibiotic consumption., Conclusions: Each ICU within a hospital ought to have a program for "on-line" antibiotic resistance surveillance of drugs used in that unit so that changes in empirical treatment can be made when there is an increase in antibiotic-resistant isolates within that unit.

The immunomodulating antibiotic drug fusidic acid and its sodium salt sodium fusidate (fusidin) ameliorate several organ-specific immunoinflammatory diseases. Because preliminary observations suggest that fusidin may also exert a beneficial effect in Guillain-Barré syndrome (GBS), here we have studied the effects of fusidin on actively induced experimental autoimmune neuritis (EAN) in rats, a known animal model for GBS. Both prophylactic and therapeutic treatment with fusidin (4 mg/rat day ip) markedly ameliorated the clinical course of the disease compared to vehicle-treated animals. The beneficial effects were associated with profound modifications of the capacity of these rats to produce and release pro- and anti-inflammatory cytokines such as IFN-gamma, TNF-alpha and IL-10, which are important in regulating the development of EAN., (Copyright 1999 Academic Press.)

Sore, cracked nipples are commonly experienced by breastfeeding mothers. We have previously reported a strong correlation between sore, cracked nipples and S. aureus colonization. A prospective, randomized clinical trial was performed to compare four treatment regimes for S. aureus infected sore nipples. Eighty-four breastfeeding mothers were enrolled in the study. After 5 days to 7 days of treatment, only 8% of mothers showed improvement in the "optimal breastfeeding technique alone" group, 16% improved with topical mupiricin, 29% improved with topical fusidic acid, yet 79% improved with oral antibiotics (p < .0001). Optimal breastfeeding techniques and topical antibiotics ointment failed to heal most infected, sore, cracked nipples. Mastitis developed in 12% to 35% of mothers not treated with systemic antibiotics compared to 5% of mothers treated with systemic antibiotics (p < .005). In conclusion, S. aureus infected sore, cracked nipples should be diagnosed as a potentially widespread impetigo vulgaris and treated aggressively with systemic antibiotics in order to improve healing and decrease the risk of developing mastitis due to an ascending lactiferous duct bacterial infection.

The in vitro activity of fusidic acid against Staphylococcus aureus is confirmed in clinical studies which demonstrate that this antibiotic in combination with other agents, particularly beta-lactams, is efficacious in non-MRSA septicaemia. Some reports suggest that fusidic acid when used in combination, may significantly diminish the risk of relapse after cessation of therapy. However, in spite of over 30 years of use and its recommendation in a number of guidelines, published evidence is insufficient to allow reliable comment on the efficacy of the antibiotic in the treatment of endocarditis.

The prominence of staphylococci as the causative agent in bone and joint infections suggests that fusidic acid (FA) has a potentially important role in their treatment. FA has been studied in a broad range of orthopaedic infections, mostly in combination with other antimicrobials. For susceptible organisms, particularly Staphylococcus aureus, it has demonstrable efficacy in acute osteomyelitis, chronic osteomyelitis, specialised forms of osteomyelitis such as calcaneal and vertebral infection, septic arthritis, prosthetic and other device-related infections. A small number of studies have also examined the use of FA alone for the treatment of bone infections, with evidence of good efficacy, as well as the local application of FA in plaster-of-Paris (POP) beads, or incorporated into bone cement, again with promising results. Further studies are required to confirm the efficacy of FA in the treatment of orthopaedic infections caused by methicillin-resistant strains of S. aureus.

Skin and soft skin tissue infections are usually caused by Staphylococcus aureus and Streptococcus pyogenes. In vitro data show good activity of fusidic acid against staphylococci but the minimal inhibitory concentrations for streptococci are relatively high indicating marginal activity. A limited number of clinical trials have been performed using oral fusidic acid and although all have methodological problems the difference in susceptibility of these two organisms is apparent. The end of study cure rates for these studies were 91-99% for S. aureus and 75-85% for S. pyogenes. Topical therapy has been used in a number of forms and for different skin infections. Comparative studies have been conducted with mupirocin, trimethoprim/polymixin cream, hydrogen peroxide and combination steroid preparations. For most of these studies fusidic acid was equivalent to the comparator agent except where there was a proven S. pyogenes infection. Studies with topical fusidic acid have also been reported in specific disease states such as acne, erythrasma, and abscesses with good results.

The emergence of MRSA in the 1960s coincided with the introduction of fusidic acid. Since that time, the antibiotic has been widely used against this organism, both in the 1960s and 1970s and against the more modern multi-resistant version of the 1980s and 1990s. Although showing potent in vitro activity, experimental in vivo and in vitro investigations have demonstrated disappointing results. Clinical efficacy has been demonstrated in a series of small studies and case reports, particularly when fusidic acid is used in combination for the treatment of MRSA carriage. Given the widespread use of fusidic acid against MRSA, published evidence supporting its efficacy is limited and does not support the use of the agent as monotherapy.

Fusidic acid, both systemic and topical, has been used for a wide variety of less common infections. Efficacy for oral fusidic acid has been demonstrated in the treatment of Clostridium difficile colitis and in staphylococcal infections in patients with cystic fibrosis. Topical fusidic acid gel is also effective in bacterial conjunctivitis and other minor external eye infections, and may be effective in reducing bacterial flora in the conjunctival sac prior to eye surgery. Studies suggest a potential role for fusidic acid in neurosurgical prophylaxis, as adjunctive therapy in bacterial endophthalmitis and Legionella pneumonia, and in leprosy. Topical fusidic acid has no effect in the treatment of chlamydial conjunctivitis or the prevention of staphylococcal infections in patients on continuous ambulatory peritoneal dialysis.

Bacteremia may occur after disruption of the oral mucous membrane, particularly after dental treatment. 18 mentally handicapped patients who underwent dental treatment with general anesthesia were included in our study. None of the patients had general illnesses or received antibiotic protection. From each patient several blood samples were drawn aseptically during dental treatment and cultured. The majority of aerobic bacteria recovered belonged to Streptococcus sp and Gemella sp., anaerobic bacteria mainly belonged to Porphyromonas gingivalis and Peptostreptococcus sp. Resistance of the isolated bacteria to penicillin as well as to oxacillin, erythromycin and Co-trimoxazole was substantial. The highest resistance rate could be shown against fucidic acid.

The pharmacokinetics of fusidic acid (FA) were studied in 10 infected severe burns patients (35 +/- 5 yrs, 81 +/- 17 kg) i.e. 43 +/- 10% in 3rd degree. Treatment was given at the dose of 500 mg/8 hours (2-hour infusion). The kinetics of FA were evaluated on D1 (1st infusion) and at steady state on D4 (10th infusion), each sequence involving 9 whole blood samples. Samples were assayed by high-performance liquid chromatography. Data were analysed by a non-compartmental method. Mean duration of treatment, considered effective in all cases, was 5.9 +/- 2.1 days. The systemic safety of FA was felt to be good. Kinetic analysis revealed the existence of significant differences between D1 and D4 concerning the parameters Cmax, Cmin, AUC, Cl and Vss. These events are attributable to the non-linear nature of the human kinetics of FA. Accumulation ratios R1 and R2 did not differ i.e. 1.51 +/- 0.25 and R2 = 2.44 +/- 0.68. Kinetic modelling based upon the experimental tracing obtained on D1 revealed good coincidence of the predictive tracing in relation to data determined on D4. The dosage algorithm of 500 mg/8 hours was microbiologically satisfactory with Cmin measured on D1 and at steady state constantly greater than the MIC of the main organisms concerned (< to 2 micrograms/ml). Reduction in the parameters Cmax and AUC in comparison with a group of healthy subjects ultimately led to shortening of the mean T1/2 of FA. In the absence of impaired liver function, this is attributable to the known increase in hepatic clearances in burns patients and, to a certain extent, to the existence of translesional extra-hepatic clearance, which could contribute to the success of treatment.

Twenty-four specific-pathogen-free-derived cats aged four to 11 months were challenged by ocular application of a field isolate of Chlamydia psittaci to evaluate the effect of topical and systemic therapy on the course of disease. The cats were monitored for 35 days post-challenge, with severity of clinical signs being measured using a scoring system, and ocular shedding of the organism monitored by culture of conjunctival swabs. All cats developed active C psittaci infection, and after 7 days the cats were randomly assigned to one of four treatment groups: Group P (placebo) was given twice-daily ophthalmic tear-replacement ointment; group F was given twice-daily topical 1% fusidic acid ophthalmic viscous drops; group C was given twice-daily topical 1% chlortetracycline ophthalmic ointment; and group D was given doxycycline at 10 mg/kg daily per os in addition to twice-daily topical 1% fusidic acid ophthalmic ointment. Within 24 h of commencement of therapy, group D had significantly lower median clinical scores than group P, and with the exception of day 16, this trend was maintained throughout the observation period. Median clinical scores of cats in group F were not appreciably different to those in group P, whereas the median scores of cats in group C generally fell between those of groups P and D. The median duration of C psittaci shedding was 10 and 15 days for groups D and C respectively, but four of the six cats in groups F and P were still shedding organisms at the end of the study (day 35). In this study, systemic therapy with doxycycline proved superior to topical therapy in the treatment of feline chlamydiosis., (Copyright 1999 European Society of Feline Medicine.)

We describe 2 cases of methicillin-resistant Staphylococcus aureus neck infections resulting in a deep neck abscess in one and formation of a tracheo-oesophageal fistula in the other. Predisposing factors, preventive measures and the principles of management are discussed. The role of carrier detection and rational use of antibiotics are highlighted.

Fusidic acid is an antibiotic that belongs to a group of its own, the fusidanes. The molecule has a steroid-like structure but does not possess any steroid activity. The structure is thought to be responsible for the steroid-like high penetration, and for the fact that no cross-resistance or cross-allergy has been seen with other antibiotics in routine clinical use. The anti-microbial activity of fusidic acid is specifically aimed at the most common skin pathogens, including Staphylococcus aureus, towards which it is one of the most potent antibiotics. The place of fusidic acid in dermatology is in the treatment of mild to moderately severe skin and soft-tissue infections, e.g. impetigo, folicullitis, erythrasma, furunculosis, abscesses and infected traumatic wounds, whereas it is of less use in conditions such as hidradenitis suppurativa, chronic leg ulcers, burns and pressure sores. The topical combinations of fusidic acid with either betamethasone or hydrocortisone are extremely useful in the treatment of atopic dermatitis/eczema whenever staphylococcal/secondary infection is suspected, and in more persistent cases of eczema where staphylococcal superantigen may be playing an important exacerbating role.

Background: New therapies designed to downregulate the aberrant immune response associated with severe acute necrotizing pancreatitis (ANP) are being increasingly investigated in different experimental models of ANP. The aim of this study was to test the potential effects of sodium fusidate on the course of severe ANP in rabbits., Methods: ANP was induced in 20 rabbits by retrograde injection of 5 per cent chenodeoxycholic acid into the pancreatic duct followed by duct ligation. The rabbits were allocated to pretreatment with intravenous physiological saline or sodium fusidate 80 mg/kg 30 min before the induction of ANP. Levels of serum amylase, lipase, tumour necrosis factor (TNF) alpha, interleukin (IL) 8, glucose and calcium, and leucocyte count were measured every 3 h for a total of 12 h. At the end of the experiment, ascitic fluid was collected and the pancreatic, lung and kidney tissues were obtained for histological examination., Results: Pretreatment with sodium fusidate reduced the mortality rate from six of ten to three of ten (P < 005) and reduced the output of ascitic fluid from 5 2 to 2.0 ml/h (P < 0001). Serum levels of TNF-alpha and IL-8 were reduced significantly in the treated group from 5 min up to 9 h after induction of ANP. The leucopenia observed after 3 h in the untreated group was not significantly improved in the group treated with sodium fusidate (P = 0.055). By contrast, both treated and untreated rabbits had similar biochemical changes including levels of amylase, lipase, glucose and calcium as well as similar histological changes in the pancreas and lungs., Conclusion: Pretreatment with sodium fusidate resulted in a considerable reduction in mortality rate and ascitic fluid output in rabbits with bile-induced ANP, probably by lowering the TNF-alpha and IL-8 blood levels. However, pretreatment with sodium fusidate did not alter the local or systemic manifestations of ANP. Thus, cytokines other than TNF-alpha and IL-8 are likely to mediate the local and systemic symptoms of ANP.

Objective: We evaluated pertinent features of impetigo in French Guyana due to the increasing number of therapeutic failures with macrolides and fusidic acid., Patients and Methods: A prospective study study was conducted over a 14-month period in the dermatology unit of the Cayenne hospital. Two groups of patients were identified: group 1 included patients with impetigo and group 2 patients with infected skin reactions. Epidemiological, bacteriological, toxinological (exofoliatines, leukocidine) and antibiotic data were recorded., Results: Forty-one patients with impetigo and 31 patients with infected skin reactions were included. Staphylococcus infection alone was identified in most patients (68 p. 100) in the impetigo group. Exfoliatine-producing strains were strongly associated with Staphylococcus-induced bullous and non-bullous impetigo (93 p. 100) compared with other origins (impetigo with streptococcal infection or infected skin reactions). Resistance to macrolides was high (erythromycin 41 p. 100, fusidic acid 42 p. 100) for all isolated strains of Staphylococcus aureus., Conclusion: A sub-group of patients with impetigo was identified. These patients had pure staphylococcal infections characterized by strong association with exfoliatine production. The rate of resistance to macrolides was particularly high in this sub-group. Resistance to fusidic acid was high for all Staphylococcus strains isolated.

A patient with Guillain-Barré syndrome is reported on who responded favourably to a short course treatment with the novel immunosuppressant sodium fusidate (Fucidin), given at a daily dose of 1.5 g for one week. Along with prompt and clear cut clinical improvement, treatment with Fucidin was associated with a rapid decline in the blood concentrations of inflammatory cytokines presumably implicated in the pathogenesis of Guillain-Barré syndrome such as interleukin-2, interferon-gamma, and tumor necrosis factor-alpha. The ex vivo production of these cytokines was also markedly diminished compared with pretreatment values. Fucidin was well tolerated and no clinical or biochemical side effects were seen.

Cutaneous and mucosal carriage of Staphylococcus intermedius was investigated in six healthy beagles before and after application of fusidic acid to mucosal surfaces as 1 per cent viscous eye drops twice daily for seven days. Bacterial populations were determined repeatedly over four weeks using quantitative techniques. The overall cutaneous populations of S intermedius reduced significantly (P < 0.001) two days after treatment but returned to pretreatment levels after a further week. The mucosal frequency of S intermedius reduced significantly (P < 0.01) two days after treatment and remained reduced (P < 0.01) at the end of the study. The mucosal populations were also reduced (P < 0.01) two days after treatment and remained lower (P < 0.05) after a further week. No such changes occurred in the control group of six beagles. The study indicates the importance of mucosae as carriage sites for S intermedius in dogs. This form of therapy may be useful as an additional tool against canine recurrent pyoderma.

An outbreak of nosocomial diarrhea that occurred in a pediatric orthopedic service between 1 December 1993 and 15 April 1994 is reported. A total of 37 patients (mean age, 9.6 years; range, 2 months-19.3 years) were involved in the outbreak, including six patients with bacteriologically documented Clostridium difficile infection. A multivariate analysis identified lincomycin treatment for at least three days as the only significant risk factor. Stool samples from four asymptomatic patients were also positive for Clostridium difficile and its cytotoxins. Isolates from all patients belonged to serogroup C, were highly resistant to lincomycin, and exhibited the same restriction pattern by pulsed-field gel electrophoresis. The outbreak ended after treatment with lincomycin was discontinued and hygiene control measures were implemented.

Background: Vancomycin is the drug of choice for methicillin-resistant Staphylococcus. Antibiotherapy failure is rarely clinically related to Staphylococcus with vancomycin low susceptibility., Case Report: A surgical cure of an aortic stenosis in a neonate was complicated by a Staphylococcus mediastinitis. After initiation of antibiotherapy with vancomycin and rifampin and surgical debridement, there was a rapid improvement. Few days later, failure of therapy was obvious. Despite continuous infusion of vancomycin, with a serum level of 29 mg/L, blood cultures were positive again to Staphylococcus. There was no endocarditis or inadequate surgical drainage. Susceptibility of the Staphylococcus was tested, looking for a tolerant strain. The vancomycin minimum bactericidal concentration was 30 mg/L (above usual value 2 to 8 mg/L), while the minimum inhibitory concentration was 3.75 mg/L. A higher dosage of vancomycin associated with fusidic acid was rapidly efficient, and total recovery was achieved., Conclusion: In case of failure of vancomycin therapy, despite correct serum levels, the susceptibility of the Staphylococcus strain has to be determined. A low susceptibility strain prescribes more prolonged combination of two antibiotics.

Infection of an implantable cardioverter defibrillator developed 2 weeks after implantation, presenting with fever, swelling, redness, and tenderness of the skin above the generator site. A cloxacillin resistant coagulase-negative staphylococcus was repeatedly cultured from the abdominal wall pocket fluid. The infection was successfully treated with a combination of two antibiotics, fusidic acid and rifampin, given orally for 3 months. Although the device was not removed, infection did not recur during a 24-month follow-up.

We describe the results of a single-centre, double-blind, vehicle-controlled, parallel group study on the quantitative effects of 2% fusidic acid lotion (Fucidin lotion) in facial acne vulgaris. The trial was completed by 52 patients aged 15-25 years with mild to moderate acne who had been randomized to either Fucidin Lotion (n = 25) or its base (n = 27). Primary outcome measures included colony counts of Propionibacterium acnes and micrococcaceae and measurements of skin surface lipid free fatty acids and sebum excretion rate. Clinical assessment was based on the acne grade, count of inflamed and non-inflamed lesions and evidence of a primary irritant dermatitis. There was a variable but gradual reduction in lesion counts with the maximum improvement at 12 weeks for inflamed lesions, where the reduction was 19.9% for fusidic acid and 24.7% for the placebo. The non-inflamed lesions decreased by 10.8% in the fusidic acid group and increased by 15.9% in the placebo group; this difference was not statistically significant. Although the fusidic acid reduced the micrococcaceae count by 1 log cycle, inferring adequate compliance, there was no reduction in the counts of P. acnes, surface free fatty acids or sebum excretion rate. This study has failed to explain the mechanism of action of topical fusidic acid.

We measured the sensitivity to antibacterials of Staphylococcus aureus isolated from impetigo lesions during one year (from July 1994 to July 1995). The largest number of strains was resistant to gentamicin, followed by erythromycin. Few methicillin-resistant S. aureus strains were isolated and few strains were resistant to more than one drug. We conclude that nadifloxacin and tosufloxacin are likely to be most effective against S. aureus, but fusidic acid is more suitable for the treatment of children.

Objectives: To evaluate the development of resistance to fosfomycin or fucidic acid in severe infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and to assess the relationship with serum levels of vancomycin, Methods: A retrospective study was performed in patients hospitalized in our intensive care unit during a 3-year period (1993-1995) who were treated for severe MRSA infection with continuous infusion vacomycin and fosfomycin or fucidic acid. We analyzed the development of resistance and serum levels of vancomycin., Results: During this period, only 20 patients received continuous infusion vancomycin plus fucidic acid or fosfomycin. MSRA resistant to fucidic or fosfomycin developed in 9. Vancomycin serum levels were significantly lower in patients who developed resistance to focidic acid or fosfomycin, both during the first 5 days of treatment (16.68 +/- 1.07 micrograms/ml vs. 22.64 +/- 1.05 mg/ml, p < 0.01) and throughout treatment duration (17.29 +/- 1.07 micrograms/ml vs. 21.85 +/- 0.78 microgram/ml, p < 0.01)., Conclusions: Our findings confirm that in spite of continuous vancomycin infusion at an initial rate of 2 g/24 h, Staphylococcus aureus resistance to fosfomycin or fucidic acid an develop during ongoing treatment. Vancomycin levels of at least 20 micrograms/ml should be obtained as rapidly as possible.

The efficacy and safety of ciprofloxacin ophthalmic solution (0.3%) and fusidic acid gel (1%) were compared in the treatment of bacterial conjunctivitis and blepharitis in a randomized, open, parallel group study. Thirty-nine patients, 21 treated with ciprofloxacin solution and 18 treated with fusidic acid gel, were culture-positive on admission and were evaluable for efficacy. At the end of a 7-day treatment, the infecting organism was eradicated in 81% of those treated with ciprofloxacin and 72% of those treated with fusidic acid gel. There was clinical cure or improvement in 95% and 89% respectively. The clinical cure rate appeared to be higher with ciprofloxacin than fusidic acid (62% compared with 28%) but this was related to the higher proportion of patients with acute conjunctivitis in the ciprofloxacin group. Two patients using ciprofloxacin had mild discomfort and stinging on instillation and one given fusidic acid had moderate edema and discomfort; the latter patient stopped treatment. Topical ciprofloxacin is effective and well tolerated and is a useful treatment of bacterial conjunctivitis and blepharitis.

Infective endocarditis is an uncommon disease but retains a high mortality. Glycopeptides are used for patients with resistant pathogens, those allergic to penicillins or for those outside the hospital. The once daily administration of teicoplanin and its low toxicity suggest that it would be suitable for use in the long courses required for endocarditis. However, the dosage and combinations to be used require further study. A retrospective review has been made of 104 episodes of endocarditis treated with teicoplanin in 101 patients seen over 7 years. Most patients had been referred to major London hospitals following failure of medical treatment. After three loading doses of 400 mg, teicoplanin was given at a dose of 400 mg/day in combination with other antibiotics such as gentamicin. Follow up was for one year. The most common pathogens were Streptococcus sanguis (15 cases), Staphylococcus aureus (13 cases) and Staphylococcus epidermidis (10 cases). Of 80 patients febrile at the start of treatment with teicoplanin, 63 (79%) lost their fever within a median of 2 days (1-35 days). Cure without surgery was effected in 50 (48%) and 75% of patients survived. Other antibiotics, usually gentamicin or rifampicin, were used in 92 (90%) of patients. Two strains of Streptococcus spp. were said to be resistant but there was no relationship between MIC of teicoplanin and outcome. Pathogens with a high MBC tended to be more likely to resist treatment. Adverse effects resulted in the withdrawal of teicoplanin in 20 cases (19%) but most events were mild and renal deterioration occurred in only five patients. Teicoplanin was effective in the treatment of endocarditis and appeared to be safe given the severity of disease in the patients treated.

Forty-five patients with presumed acute bacterial conjunctivitis were treated in an investigator-masked randomized multicenter study with either lomefloxacin 0.3% or fucidic acid 1% eye drops twice daily. Clinical signs and symptoms were rated by slit-lamp examination and conjunctival swab cultures were performed to evaluate clinical and microbiological efficacy. A total of 57 ocular isolates were tested for susceptibility to nine antibiotics. A significant decrease in clinical symptomatology was achieved by both treatments with a gradual improvement over the treatment period of 7-9 days. Bacteriological recovery was frequently achieved already at the first control visit (day 3-5), but the recovery rate was statistically significant (p = 0.014) only in the lomefloxacin group. The relatively high in vitro resistance rate (46%) to fucidic acid was not reflected by lower clinical efficacy. Two unrelated adverse events (one in each treatment group) and minimal local intolerance problems were observed in both treatment groups. A significantly higher incidence of burning sensation was observed with fucidic acid than with lomefloxacin (p < 0.01). All four treatment failures in the study occurred in the fucidic acid group. Lomefloxacin 0.3% ophthalmic solution demonstrated a high efficacy and good tolerance in the management of acute bacterial conjunctivitis.

Insulin-dependent diabetes mellitus (IDDM) is a major cause of morbidity and mortality from long-standing complications. The autoimmune nature of IDDM has encouraged use of immunosuppressive and antiinflammatory strategies to better preserve residual pancreatic beta-cell function at the time of diagnosis. Fusidic acid and its sodium salt, fusidin, is a relatively atoxic antibiotic used mainly in the treatment of staphylococcal infections. Recently, fusidin has been demonstrated to possess immunosuppressive functions in vitro and in vivo, and the drug has shown promise in preventing the disease in animal models of IDDM and in a preliminary trial in IDDM patients.