Unusual manifestations of brucellosis: a retrospective case series in a tertiary care Greek university hospital.

Brucellosis remains a diagnostic puzzle. We retrospectively studied the case notes of 105 patients with brucellosis who were admitted in the Department of Internal Medicine of the University of Patras Hospital, a tertiary care institution serving an extended rural area in western Greece, from 2003 to 2006. Five unusual causes of brucellosis were identified: hepatic, epidural and thyroid abscesses, intrahepatic cholestatic liver disease and pancytopenia. Virtually every human organ and system can be involved in brucellosis, which highlights the need to include brucellosis in the differential diagnosis, especially in endemic areas.

Bacteremic pneumonia due to gram-negative bacilli.

Bacteremic pneumonia due to aerobic gram-negative bacilli was diagnosed in 27 patients during a 20-month period. The mortality was high (81.5%) among these elderly patients (mean age, 61.2 years) with serious underlying disease, in spite of amikacin sulfate therapy that was appropriate as determined by susceptibility testing. Bacteremic pneumonia accounted for 14.1% of patients with gram-negative bacteremia but was responsible for 39.4% of the deaths in the total group of 191 patients. The worsened prognosis of patients with pneumonia was unrelated to the species of infecting organisms or the underlying conditions or disease.

Aqueous humor penetration of ciprofloxacin in the human eye.

Two doses of ciprofloxacin were administered intravenously, 200 mg every 12 hours, to 25 patients undergoing cataract surgery. Plasma and aqueous humor were obtained at 1, 3, 5, 7, and 9 hours after the administration of the second dose of the drug. Peak intraocular concentrations (mean +/- SD), 0.21 +/- 0.1 mg/L, were detected at one hour following ciprofloxacin administration. A time-dependent decrease of the penetration was observed, and by nine hours after the administration, ciprofloxacin levels were 0.05 mg/L. These results illustrate that ciprofloxacin may be an effective antimicrobial agent for prophylactic use in ophthalmologic surgery and also for the treatment of intraocular infections due to susceptible organisms.

Remote abscess formation during interferon-alpha therapy for viral hepatitis.

Abscess formation at the injection site is an unusual infectious complication of interferon-alpha (IFN-alpha) treatment of chronic hepatitis C virus (HCV) infection, but remote abscess formation during IFN-alpha therapy is very rare. In the present communication, we report three cases of remote abscess formation detected among 68 patients with chronic viral hepatitis treated with IFN-alpha, and review the pertinent English literature. We believe that, as fever and constitutional symptoms are common side effects of IFN-alpha treatment, a high index of suspicion is indicated to exclude abscess formation in cases of unexplained fever during IFN-alpha therapy.

Five-day moxifloxacin therapy compared with 7-day co-amoxiclav therapy for the treatment of acute exacerbation of chronic bronchitis.

In this randomized, non-blinded study, the efficacy and safety of a 5-day course of moxifloxacin (one 400 mg tablet daily) was compared with that of co-amoxiclav (one 625 mg tablet every 8h) for 7 days, for the treatment of acute exacerbations of chronic bronchitis (AECB). A total of 162 patients with clear signs of an acute exacerbation of chronic bronchitis were enrolled. Of these, 153 could be studied. Seventy-nine patients were randomized in the moxifloxacin arm and 74 in the co-amoxiclav arm of the study. The primary efficacy parameter was clinical response at 14 days in the evaluable population. A clinical success was classified as resolution or improvement of symptoms. Variables used to assess clinical response included wheeze, cough, dyspnoea, sputum volume, rales and ronchi. The success rate in the moxifloxacin group was 88.6% (70 of 79) and that for co-amoxiclav group was 89.2% (66 of 74). At follow-up (28-35 days post-treatment), the continued clinical cure rates were 90.0% (63 of 70) for moxifloxacin and 89.4% (59 of 66) for co-amoxiclav. No significant differences were detected between the two groups. A total of 78 pathogenic bacteria were isolated from the sputum samples of the patients, with Moraxella catarrhalis, Haemophilus influenzae and Streptococcus pneumoniae being the most frequently isolated pathogens. The eradication rate at 14 days in the valid patients was similar for both groups, 90.9% (20 of 22) for the moxifloxacin group and 90.0% (18 of 20) for the co-amoxiclav group. Both drugs were well tolerated with no differences in the drug-related adverse effects or the patients withdrawing because of an adverse event. These results and the good spectrum of antibacterial activity make moxifloxacin a promising and also safe alternative for the empirical treatment of AECB.

Results of a prospective, randomized, double blind comparison of the efficacy and the safety of sequential ciprofloxacin (intravenous/oral)+metronidazole (intravenous/oral) with ceftriaxone (intravenous)+metronidazole (intravenous/oral) for the treatment of intra-abdominal infections.

The efficacy and the safety of sequential intravenous/oral (i.v./p.o.) ciprofloxacin (CIPX) plus i.v./p.o. metronidazole (MTR) was compared with i.v. ceftriaxone (CTRX) plus i.v./p.o. MTR in the treatment of complicated intra-abdominal infections. One hundred and forty two patients received study medications. Of these, 135 could be studied. Sixty-nine patients were randomized in the CIPX arm of the study and 66 in the CTRX arm. In the CIPX group 58 patients were switched to oral treatment and 11 patients remained in the intravenous arm. In the CTRX group 57 patients switched to oral MTR continuing i.v. CTRX and 9 patients remained in the i.v. branch. Success rates at the end of treatment in patients who switched to oral were 100% in both the CIPX group and the CTRX group. For validated patients continuing on oral, the success rates at the end of treatment were 63.6 and 33.3% in the CIPX and CTRX groups respectively. Overall success rates at the end of treatment and follow-up in all patients were 94.2% in the CIPX group and 89.4% in the CTRX group. Overall success rates at the end of treatment in patients with proven bacterial infection were 92.9% in the CIPX group and 88.3% in the CTRX group. Duration of hospitalization (days) for studied patients was 22.7+/-8.2 in the CIPX and 19.6+/-14.5 in the CTRX group. There was no statistical difference between the CIPX and CTRX groups in both the intent to treat and in the modified intent to treat populations. Conversion to oral therapy with CIPX/MTR was as effective as continued intravenous therapy with CTRX and oral MTR in those patients able to tolerate oral feeding.

Cost-minimisation analysis of sequential treatment with ofloxacin or ciprofloxacin in hospitalised patients.

This study evaluated the cost of sequential treatment with once-daily ofloxacin or twice-daily ciprofloxacin in 474 hospitalised patients in different countries. The patients were treated intravenously for at least 3 days, then orally for 7 to 10 days or for 3 days beyond the disappearance of infection-related symptoms. The overall clinical cure rate (86.8% with ofloxacin and 89.6% with ciprofloxacin) and the overall bacteriological response rate (89.9 and 89.0%, respectively) were similar, and a cost-minimisation analysis was conducted. The acquisition costs for ofloxacin and ciprofloxacin in Greece, Israel, Slovenia and Turkey were used and converted to Deutschmarks (DM), and the costs of administration were analysed for each hospital. The different cost categories for oral and intravenous (IV) treatment (e.g. antimicrobial acquisition, drug monitoring, drug delivery costs) were used to identify any differences. The total costs per patient varied between the countries involved, but were higher for ciprofloxacin (ofloxacin: DM239 to DM724; ciprofloxacin: DM540 to DM976). In a sensitivity analysis using identical daily acquisition costs for the 2 fluoroquinolones, the total cost of treatment was higher for ciprofloxacin, as a result of the lower cost of administration of ofloxacin in the once-daily regimen. Continuing IV therapy would be approximately 50% more expensive than switching to oral administration; however, whenever possible, both drugs can be switched from IV to oral treatment.

Differences in adherence to buccal epithelial cells, in phagocytosis and in killing by neutrophils between human and non-human strains of Candida albicans.

The adherence of strains of Candida albicans to buccal epithelial cells as well as the phagocytosis of these organisms by human polymorphonuclear leucocytes (PMNL) was studied. The strains of C. albicans were obtained from patients' urine. from bird faeces and from soil. The strains of C. albicans obtained from patients and the environment displayed greater adhering ability (23.8 +/- 6.4 and 27.5 +/- 5.2 respectively) than the avian strains (14.4 +/- 2.2) (P < 0.01). Strains obtained from the environment were resistant to phagocytosis (81.6 +/- 0.2 organisms ingested per 200 PMNL) and killing (8.4 +/- 2.6%) by PMNL as compared to human and avian strains (P < 0.01). These observations indicate that environmental strains of C. albicans may be more virulent for human beings.

Defective phagocytic and bactericidal function of polymorphonuclear leucocytes in patients with beta-thalassaemia major.

The phagocytic and bactericidal activity of polymorphonuclear leucocytes (PMNL) obtained from 50 non-splenectomised patients with homozygous beta-thalassaemia was studied. Polymorphonuclear leucocytes suspended in the serum of patients from whom they were derived ingested fewer Escherichia coli, 72.2 +/- 21.8 (mean +/- s.d.) per 50 PMNLs compared with 144.5 +/- 36.8 bacteria phagocytosed by PMNLs from healthy volunteers and suspended in normal serum (P less than 0.01). Killing of ingested bacteria by the PMNLs from patients was also significantly reduced. These abnormalities are in part serum-associated and are due to the presence of heat-labile inhibitor(s) in the patients' serum. When PMNLs from patients were suspended in patients' heat-inactivated serum, phagocytosis increased to 99.2 +/- 29.2 (P less than 0.01). Similar improvement was noted in PMNL bactericidal activity. These abnormalities provide additional information that helps to explain the increased susceptibility to bacterial infections of patients with homozygous beta-thalassaemia.

Phagocytosis and antimicrobicidal activity of polymorphonuclear leucocytes against gentamicin-sensitive and resistant strains of Pseudomonas aeruginosa.

The ability of human polymorphonuclear leucocytes (PMNs) to ingest and kill gentamicin-sensitive and resistant Pseudomonas aeruginosa strains was studied. Strains becoming resistant to gentamicin either by laboratory training or through an R-factor were more susceptible to the phagocytic and bactericidal function of the PMNs. These results may explain previous clinical and laboratory observations indicating that gentamicin-resistant strains are less virulent.

Primary sternal osteomyelitis.

Primary sternal osteomyelitis is a rare condition. Only few cases have been reported in the English literature. We describe the case of a young woman presenting with persistent fever and chest pain. Radionuclide bone scan and computed tomography of the chest were consistent with metastatic neoplasm. Surgical intervention, however, revealed primary staphylococcal osteomyelitis and the patient was successfully treated with combined extensive surgical debridement and intravenous antibiotics.

Use of oral ciprofloxacin in community-acquired pneumonia.

Twenty-five acutely ill patients, 21 men and 4 women aged 20-90 years (mean, 54 years) with acute community-acquired bacterial pneumonia, were treated with ciprofloxacin orally. The diagnosis of pneumonia was based on clinical and roentgenographic evidence of pulmonary infiltrate and a Gram stain of sputum demonstrating neutrophils and bacteria. Initially, 12 patients received 750 mg of ciprofloxacin orally every 12 hours for 3-6 days (mean, 3.8 days) followed by 500 mg of oral medication twice daily for 4-7 days (mean, 4.8 days). The remaining 13 patients received 500 mg of ciprofloxacin orally for 8-15 days (mean, 8.5 days). Treatment was successful in all patients (100%). No superinfections occurred, and there was no development of resistance. The drug was well tolerated and only moderate transient elevation of transaminase levels (serum glutamic-oxaloacetic transaminase and serum glutamine pyruvic transaminase) was noted in one patient.

A comparative study on aztreonam, ceftazidime and amikacin in the treatment of complicated urinary tract infections.

In a prospective, randomized trial, aztreonam (1 g intravenously or intramuscularly, twice daily) was compared with ceftazidime (1 g intravenously or intramuscularly, twice daily) and amikacin (500 mg intravenously or intramuscularly, twice daily) in 76 patients aged 24 to 84 years (mean, 59.7 years) with complicated urinary tract infections. Initial pathogens included Escherichia coli (47.5%), Pseudomonas aeruginosa (22.5%), Klebsiella spp. (9%), Proteus spp. (7.5%) and Enterobacter spp (6%). In four patients initial urine cultures yielded more than one organism. All pathogens were sensitive to the three study drugs. Including performance of 4- to 6-week follow-up cultures, eradication of the pathogens occurred in 72% of patients treated with aztreonam, in 74% of those treated with ceftazidime and in 71% treated with amikacin (p greater than 0.05). Clinical success was observed in 84% of patients treated with aztreonam, in 82% of those treated with ceftazidime and in 85% treated with amikacin (p greater than 0.05). All drugs were well tolerated. It is concluded that aztreonam, ceftazidime and amikacin are equally effective and safe for the treatment of complicated urinary tract infections due to susceptible organisms.

Repeated point prevalence survey of nosocomial infections in a Greek university hospital.

Two point prevalence surveys of nosocomial infections (NIs) were carried out in a Greek University hospital on an annual basis in 1998 and 1999. The overall prevalence of NIs was 9.5% and 9.1% in the first and second study, respectively. The average length of stay of patients in the hospital (ALOS) was 7.7 and 9.6 days in these two studies, respectively. Of the 97 NIs detected, the most frequent were lower respiratory tract infections (36%). Urinary tract infections, bloodstream infections, surgical site infections, and gastrointestinal infections were found in 25.8%, 19.6%, 7.2% and 4.1% of patients, respectively. The prevalence of antibiotic usage was 55.6% in 1998 and 54.1% in 1999. Empiric antibiotic therapy prevailed over prophylactic and rational therapies. These percentages are higher than those reported from other countries, emphasizing the need for rational antibiotic usage to decrease pharmacy expenses and discourage the development of resistant microorganisms. A nationwide network of surveillance of NIs in Greece is now being developed using these experiences.

In vivo potentiation of polymorphonuclear leukocyte function by ciprofloxacin.

Ciprofloxacin was administered to 10 healthy volunteers at a dose of 250 mg orally. Serum and polymorphonuclear leukocytes (PMNLs) were obtained from all subjects before the administration of the drug and 12 hours after the administration. In addition serum was obtained from all subjects at 24 and 48 hours after ciprofloxacin administration. All sera and PMNLs were used for the chemotactic, phagocytic and killing determinations of the PMNLs. The results demonstrated that serum obtained 12 hours after the administration of ciprofloxacin potentiates PMNL chemotactic activity (chemotactic index (CI) = 33.0 +/- 4.2 microns (means +/- S.D.)) as compared to the chemotactic activity generated by serum obtained prior to administration of the drug, CI = 20.4 +/- 4.4 microns (p < 0.01). Serum obtained 24 and 48 hours after ciprofloxacin administration did not stimulate PMNL function. The administration of ciprofloxacin did not have any direct influence on the PMNLs in terms of their chemotactic response. Furthermore, serum obtained after the administration of ciprofloxacin markedly enhanced PMNL phagocytosis and killing of all organisms tested. Ciprofloxacin also acted directly on the PMNLs and increased their bactericidal activity. These results demonstrate that ciprofloxacin potentiates PMNL function in vivo which may be of potential clinical benefit.

Effects of methylprednisolone and dexamethasone on polymorphonuclear leukocyte adherence in vivo.

It has been proposed that corticosteroids may be effective in the treatment of shock and the adult respiratory distress syndrome (ARDS) by inhibiting complement-induced granulocyte aggregation and by disaggregating granulocyte aggregates in vitro. In the present investigation we have examined the effects of sera from patients who had received comparable doses of methylprednisolone (MP) and dexamethasone (DEX) on the adherence of polymorphonuclear leukocytes (PMNs). Sera obtained from patients that had received MP markedly reduced PMN adherence with maximum effect noted by 8 h. In contrast, sera from patients receiving DEX had no effect on PMN adherence. The results of this study indicate that MP may be more effective in the treatment of septic shock and other conditions associated with microvascular leukostasis.

A multinational, multicentre, non-blinded, randomized study of moxifloxacin oral tablets compared with co-amoxiclav oral tablets in the treatment of acute exacerbation of chronic bronchitis.

The aim of this study was to compare the efficacy and safety of once daily dosing with moxifloxacin (BAY 12-8039) with that of coamoxiclav given three times daily for the treatment of acute exacerbation of chronic bronchitis (AECB). Moxifloxacin (one 400 mg tablet daily) was administered orally for 5 days and co-amoxiclav (three 625 mg tablets daily) was given orally for 7 days. The study was randomized, non-blinded, multinational (12 countries) and multicentre (68 centres). A total of 575 patients, all with clear signs of AECB, were treated, 292 with moxifloxacin and 283 with co-amoxiclav. Of these, 512 patients were evaluable for efficacy (261 in the moxifloxacin group and 251 in the co-amoxiclav group). The primary efficacy parameter was clinical response at 14 days in the evaluable population. A clinical success was classified as resolution or improvement of symptoms. Variables used to assess clinical response included wheeze, cough, dyspnoea, sputum volume, rales and rhonchi. The success rate for moxifloxacin in the evaluable patients was 96.2% and that for co-amoxiclav was 91.6%. The 95% confidence intervals for this difference (0.4%; 8.7%) indicate equivalence in the treatments. Sputum samples were taken from patients and 140 of these contained a pathogen, Haemophilus influenzae being the most frequently isolated. Moraxella catarrhalis and Streptococcus pneumoniae were also commonly isolated pathogens. The eradication rate at 14 days in the evaluable patients was 87.7% in the moxifloxacin group and 89.6% in the coamoxiclav group. Both drugs were well tolerated with no significant differences in the numbers of drug-related adverse events or the numbers of patients withdrawing because of an adverse event. These results and the broad spectrum of antibacterial activity make moxifloxacin a promising and safe alternative to conventional therapy for the empirical treatment of AECB.

Adherence of Candida albicans to epithelial cells from normal and cancerous urinary bladders.

Patients with malignancies are at high risk to develop infections by Candida albicans. We have compared the adherence of C. albicans isolated from urine cultures to bladder epithelial cells obtained from healthy volunteers and patients with cancer of the bladder. The mean number of C. albicans adhering per epithelial cell from areas infiltrated from cancer was significantly higher as compared to cells obtained from intact areas of cancerous bladders and from normal bladders. The increased adherence of C. albicans to cancerous epithelial cells suggests that malignancies are associated with alterations of the epithelial cell surface which render the cells more susceptible to colonization by C. albicans. The increased colonization may predispose these patients to C. albicans infections.