The clinical and pharmacoeconomic analysis of invasive aspergillosis in adult patients with haematological diseases.

Invasive pulmonary aspergillosis (IPA) poses major management problems for clinicians caring for patients with haematological diseases. The clinical courses of patients with IPA who had been hospitalised in Hematology Unit, Bone Marrow Transplantation Unit and Infectious Diseases and Clinical Microbiology Unit between 1998 and 2005, the efficacy and adverse effects and costs of antifungal drugs (conventional amphotericin B deoxycholate, liposomal amphotericin B, amphotericin B lipid complex and caspofungin) used in the therapy of these patients were analysed in this study. Ninety-three patients with IPA were reviewed retrospectively. Mean age of the patients was 40.4 +/- 15.1 years (range 14-70 years). Fifty-eight male patients and 35 female patients were included in the study. Manageable hypopotassemia, nausea/vomiting and headache were the most commonly observed side-effects during antifungal (AF) therapy. While it was not found to be statistically significant with regard to the mean time to resolution of fever (P = 0.8), it was found to be statistically significant with regard to radiological regression at 30th day, and mean duration of therapy between patients who were dead or alive (P < 0.05, P < 0.001). Total cost of AF therapy for 93 patients was found to be US$4 461 824 (minimum US$387-maximum US$279 023). Of this amount, US$4 272 845 represents the payment for AF drugs, US$188 979 the payment for other expenditures. Mean cost of therapy for a patient with IPA was found to be US$49 336. Although it seemed to be difficult, investigations should primarily focus on providing standardisation of parameters relating to the duration of AF therapy. Despite the less-than-optimal safety profile of CAB, it often remains to be the preferred first line option for the treatment of fungal infections because of its broad spectrum, activity and low acquisition cost.

The diagnosis of osteomyelitis of the foot in diabetes: microbiological examination vs. magnetic resonance imaging and labelled leucocyte scanning.

AIMS: Foot infections and their sequelae are among the most common and severe complications of diabetes mellitus. As diabetic patients with foot infections develop osteomyelitis and may progress to amputation, early diagnosis of osteomyelitis is critical. METHODS: We compared the diagnostic values of labelled leucocyte scanning with Tc(99)m, magnetic resonance imaging (MRI) and microbiological examination of bone tissue specimens with histopathology, the definitive diagnostic procedure. Thirty-one diabetic patients with foot lesions were enrolled in the study and histopathological examination was performed in all. Patients had clinically suspected foot lesions of > or = grade 3 according to the classification of Wagner. RESULTS: Bone specimens were obtained for histopathological examination. Microbiology had a sensitivity of 92% and specificity of 60%. Labelled leucocyte scanning had a sensitivity of 91%, specificity of 67%, and MRI a sensitivity of 78%, specificity of 60%. CONCLUSIONS: Microbiological examination may be as useful as and less costly than other diagnostic procedures and is the only method which can guide the choice of antibiotic therapy.

Tuberculous meningitis in adults--experience from Turkey.

BACKGROUND: The annual incidence of tuberculous meningitis (TM) is unknown. TM is a disease that still often results in residual sequelae, and has a mortality rate ranging between 15 and 51%. Experience of countries such as Turkey where drug-resistant tuberculosis and TM are prevalent is important. METHODS: Clinical and laboratory findings of 42 patients with TM, followed between 1991 and 2002, were evaluated retrospectively. RESULTS: Twenty-eight female and 14 male patients were included in this study. The mean age of the patients was 33.9 +/- 13.2 years (range, 16-60 years). Fourteen had a history of pulmonary tuberculosis; 12 reported close contact with a person with active pulmonary tuberculosis; three were diagnosed with active pulmonary tuberculosis; two, with HIV infection; two, with Pott's disease; and one, with systemic lupus erythematosus. On admission, 17 patients were diagnosed with stage I; 15, with stage II; and 10, with stage III disease. Hemiparesis (35.7%), cranial nerve palsy (30.9%), and altered consciousness (26.9%) were the most common neurological deficits. Prolonged duration of pre-existing symptoms and female gender were found as significant risk factors in those who develop neurological sequelae (p < 0.01 and p < 0.05, respectively). Cranial computerised tomography revealed various pathological findings in all but five patients. Sulcus effacement was the most common radiological finding. Enlargement of ventricles, focal cerebral oedema/shunt, calcification of meninges, tubercle, and infarction were other common abnormal radiological findings. CONCLUSIONS: Prolonged duration of pre-existing symptoms and female gender are predictors of neurological sequelae of TM. Early identification of such patients and prompt initiation of anti-tuberculosis therapy may improve their outcome.

A study of serological markers of hepatitis B and C viruses in Istanbul, Turkey.

OBJECTIVE: This study was undertaken to investigate the prevalence of HBsAg, anti-HBs and anti-HCV positivity in Istanbul, Turkey. SUBJECTS AND METHODS: The frequencies of HBsAg, anti-HBs and anti-HCV positivity were determined in 1,157 randomly selected patients attending the outpatient clinic of Istanbul University Hospital, Istanbul, Turkey, during the years 1998 and 2001. All patients underwent complete physical and various routine laboratory examinations. RESULTS: Of the 1,157 patients, the prevalence of HBsAg, anti-HBs and anti-HCV was 6.6, 28.1 and 2.4%, respectively. It appeared that having dental and surgical procedures formed the risk factors for HBV infection. HBsAg positivity in the health care workers was not different from that of the other professions, but anti-HBs was significantly higher in this group. CONCLUSIONS: Our findings indicate that HBV infection occurs more frequently than HCV in Istanbul, and this poses an important health problem in the community.

The characteristics of infections in crush syndrome.

OBJECTIVE: To analyze the results of clinical and bacteriological examinations of crush syndrome patients admitted to our institute after the Marmara earthquake. METHODS: Data were collected retrospectively from patients' files. Forty patients are included. Their mean age was 31.5 +/- 13.5 years and 18 were male. Their mean time under the rubble was 13.1 +/- 14.4 h. Fasciotomies were performed on 41 extremities of 30 patients. One hundred and twelve (mean 2.9 +/- 1.9 samples/patient) bacteriological samples were collected from wounds (51), blood (23), urine (25) and catheters (13). RESULTS: Microbial growth was detected in 67 samples from 38 (95%) patients. Non-fermenting Gram-negative bacilli, Gram-positive cocci, Enterobacteriaciace and yeast-like fungi were isolated in 67%, 17%, 12% and 4% of the samples, respectively. Acinetobacter (36%) and Pseudomonas aeruginosa (21%), the major bacterial isolates from wound infections, were resistant to carbapenems and sensitive to quinolones. As the hospitalization period increased, other infections supervened. Gram-positive cocci and non-fermenting Gram-negative bacilli were detected in six blood and seven catheter samples and methicillin-resistant Staphylococcus aureus was the major isolate. Nine (22%) of the patients died due to sepsis despite all supportive therapies. CONCLUSIONS: Infections are still major factors in crush syndrome-related deaths.

Rhinocerebral mucormycosis treated with 32 gram liposomal amphotericin B and incomplete surgery: a case report.

BACKGROUND: Mucormycosis (or zygomycosis) is the term for infection caused by fungi of the order Mucorales. Mucoraceae may produce severe disease in susceptible individuals, notably patients with diabetes and leukemia. Rhinocerebral mucormycosis most commonly manifests itself in the setting of poorly controlled diabetes, especially with ketoacidosis. CASE PRESENTATION: A 31-year-old diabetic man presented to the outpatient clinic with the following signs and symptoms: headache, periorbital pain, swelling and loss of vision in the right eye. On physical examination his right eye was red and swollen. There was periorbital cellulitis and the conjunctiva was edematous. KOH preparation of purulent discharge showed broad, ribbonlike, aseptate hyphae when examined under a fluorescence microscope. Cranial MRI showed involvement of the right orbit, thrombosis in cavernous sinus and infiltrates at ethmoid and maxillary sinuses. Mucormycosis was diagnosed based on these findings. Amphotericin B (AmBisome(R); 2 mg/kg.d) was initiated after the test doses. Right orbitectomy and right partial maxillectomy were performed; the lesions in ethmoid and maxillary sinuses were removed. The duration of the liposomal amphotericin B therapy was approximately 6 months and the total dose of liposomal amphotericin B used was 32 grams. Liposomal amphotericin B therapy was stopped six months later and oral fluconazole was started. CONCLUSIONS: Although a total surgical debridement of the lesions could not be performed, it is remarkable that regression of the disease could be achieved with medical therapy alone.

Risk factors for early-onset, ventilator-associated pneumonia in critical care patients: selected multiresistant versus nonresistant bacteria.

BACKGROUND: Ventilator-associated pneumonia is the leading nosocomial infection in critically ill patients. The frequency of ventilator-associated pneumonia caused by multidrug-resistant bacteria has increased in recent years, and these pathogens cause most of the deaths attributable to pneumonia. The authors, therefore, evaluated factors associated with selected multidrug-resistant ventilator-associated pneumonia in critical care patients. METHODS: The authors prospectively recorded potential risk factors at the time of intensive care unit admission. An endotracheal aspirate was obtained in all patients who met clinical criteria for pneumonia. Patients were considered to have ventilator-associated pneumonia only when they met the clinical criteria and aspirate culture was positive for bacteria 48 h or more after initiation of mechanical ventilation. Pediatric patients were excluded. Adult patients with ventilator-associated pneumonia were first grouped as "early-onset" (< 5 days) and "late-onset," determined by episodes of ventilator-associated pneumonia, and then, assigned to four groups based on the bacteria cultured from their tracheal aspirates: Pseudomonas aeruginosa, Acinetobacter baumanii, methicillin-resistant staphylococci, and all others. The first three bacteria were considered to be multidrug resistant, whereas the others were considered to be antibiotic susceptible. Potential risk factors were evaluated with use of univariate statistics and multivariate regression. RESULTS: Among 486 consecutive patients admitted during the study, 260 adults underwent mechanical ventilation for more than 48 h. Eighty-one patients (31%) experienced 99 episodes of ventilator-associated pneumonia, including Pseudomonas(33 episodes), methicillin-resistant staphylococci (17 episodes), Acinetobacter(9 episodes), and nonresistant bacteria (40 episodes). Sixty-six of these episodes were early onset and 33 episodes were late onset. Logistic regression analysis identified three factors significantly associated with early-onset ventilator-associated pneumonia caused by any one of the multidrug-resistant bacterial strains: emergency intubation (odds ratio, 6.4; 95% confidence interval, 2.0-20.2), aspiration (odds ratio, 12.7; 95% confidence interval, 2.4-64.6), and Glasgow coma score of 9 or less (odds ratio, 3.9; 95% confidence interval, 1.3-11.3). A. baumanii-related pneumonia cases were found to be significantly associated with two of these factors: aspiration (odds ratio, 14.2; 95% confidence interval, 1.5-133.8) and Glasgow coma score (odds ratio, 6.0; 95% confidence interval, 1.1-32.6). CONCLUSIONS: The authors recommend that patients undergoing emergency intubation or aspiration or who have a Glasgow coma score of 9 or less be monitored especially closely for early-onset multidrug-resistant pneumonia. The occurrence of aspiration and a Glasgow coma score of 9 or less are especially associated with pneumonia caused by A. baumanii.

Antimicrobial resistance of gram-negative isolates from intensive care units in Turkey: comparison to previous three years.

Resistance rates to selected antibiotics of gram-negative bacteria isolated from intensive care units (ICU) of 16 Turkish hospitals during 1998 were evaluated and compared to data from the previous 3 years. Antibiotic susceptibilities to imipenem, ceftazidime, ceftazidime-clavulanate, cefoperazone-sulbactam, ceftriaxone, cefepime, cefodizime, cefuroxime, piperacillin-tazobactam, ticarcillin-clavulanate, gentamicin, amikacin and ciprofloxacin were determined by Etest. A total of 1,404 isolates from 1,060 patients were collected, mainly from urinary and respiratory tracts. As in the previous 3 years, Pseudomonas spp. was the most frequently isolated gram-negative species (29.7%), followed by Escherichia coli, Acinetobacter and Klebsiella spp. Imipenem was the most active in vitro agent (73.4% susceptible), followed by ciprofloxacin (60.6%), cefoperazone-sulbactam (58.7%), cefepime (56.7%), piperacillin-tazobactam (55.0%) and amikacin (54.7%). In 1996, a decline in susceptibility rates of all antibiotics was evident. With the exception of imipenem, resistance to which remained stable, rates somewhat increased in 1997. In 1998, susceptibility to imipenem and cefepime remained stable, amikacin resistance tended to increase and susceptibility rates to other antibacterials showed a favorable increase. These results may in part be due to the implementation of a surveillance program and increased understanding of the magnitude of the resistance problem.

Surveillance of antimicrobial resistance among gram-negative isolates from intensive care units in eight hospitals in Turkey.

With the participation of eight major reference hospitals in Turkey, 749 aerobic Gram-negative isolates obtained from 473 intensive care patients in 1997 were tested for their susceptibility to 13 commonly employed antibacterial agents. The frequency with which species were isolated and resistance rates were compared with data from the previous 2 years. Imipenem was the most active agent against the majority of isolates (75%), followed by ciprofloxacin, cefepime and amikacin. The per cent susceptibility to all antibiotics declined from 1995 to 1996. With the exception of imipenem, for which there was no change in resistance, the per cent susceptibility somewhat increased in 1997. However, it was still lower than in 1995.

A surveillance study of antimicrobial resistance of gram-negative bacteria isolated from intensive care units in eight hospitals in Turkey.

This study was carried out with the participation of eight hospitals in Turkey to determine the frequency of gram-negative bacteria isolated in intensive care units (ICU) and to compare their resistance rates to selected antibiotics. Aerobic gram-negative bacteria isolated from ICUs during 1996 were studied. Antibiotic susceptibilities to imipenem, ceftazidime, ceftazidime-clavulanate, ceftriaxone, cefotaxime, cefepime, cefodizime, cefuroxime, piperacillin/tazobactam, amoxycillin-clavulanate, gentamicin, amikacin and ciprofloxacin were determined by Etest. A total of 748 isolates were obtained from 547 patients. The majority of organisms were isolated from the respiratory (38.8%) and urinary tracts (30.9%). Pseudomonas spp. were the most frequently isolated gram-negative species (26.8%), followed by Klebsiella spp. (26.2%). Escherichia coli, Acinetobacter spp. and Enterobacter spp. were the other commonly isolated organisms. High resistance rates were observed for all antibiotics studied. Imipenem appeared to be the most active agent against the majority of isolates. Although resistance rates exceeded 50%, ciprofloxacin, cefepime and amikacin were found to be relatively effective. Extended-spectrum beta-lactamase (ESBL) production appeared to be a major mechanism of resistance to beta-lactam antibiotics. In contrast to ceftazidime-clavulanate, piperacillin/tazobactam showed poor activity against organisms thought to produce ESBL, suggesting the presence of an enzyme resistant to tazobactam action. This study has yielded high rates of resistance in aerobic gram-negative isolates from ICUs in Turkey. High resistance rates to all the other antibacterials studied leave imipenem as the only reliable agent for the empirical treatment of ICU infections in Turkey.

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.

Spontaneous ascitic infection in different cirrhotic groups: prevalence, risk factors and the efficacy of cefotaxime therapy.

OBJECTIVE: To investigate the prevalence of spontaneous ascitic infection (SAI) in different cirrhotic groups, the risk factors for development of SAI, and the efficacy of cefotaxime therapy. DESIGN: A prospective study. SETTING: In-patient clinic of a university hospital. PATIENTS: Eighty cirrhotic patients with ascites were assigned to four groups: hepatitis B or D virus-related 34, alcoholic 18, hepatitis C virus-related 14, miscellaneous 14. INTERVENTIONS: Paracentesis was performed on 80 patients during 92 consecutive hospitalizations. Ascitic fluid was cultured by the method of bedside inoculation of blood culture bottles with ascites. The patients with SAI were treated with cefotaxime (2 g, three times daily, intravenously) for 5 days. MAIN OUTCOME MEASURES: Frequency of SAI in cirrhotic groups; clinical, bacteriological and biochemical findings of SAI; rate of recovery-from infection. RESULTS: Twenty SAI episodes (22%) were found in 16 patients; 8 episodes were spontaneous bacterial peritonitis, 2 bacterascites, and 10 culture-negative neutrocytic ascites. SAI occurred more frequently in patients with hepatitis B or D virus-related liver cirrhosis (32%) than in the alcoholic (6%, P < 0.05), hepatitis C virus-related (14%) or miscellaneous (14%) cirrhotic groups in multivariate analysis, independent predictive factors associated with the development of SAI are chronic hepatitis B virus infection, ascitic fluid total protein and serum bilirubin. Escherichia coli was obtained in 5 of 10 positive ascitic fluid cultures. Cure of the infection was achieved in 95% of episodes. Hospitalization mortality rate in infected patients was 20%. CONCLUSION: Spontaneous ascitic infection occurs in approximately 20% of cirrhotic patients hospitalized with ascites. The patients with low ascitic protein concentration, high serum bilirubin level or hepatitis B virus cirrhosis are more predisposed to SAI. Cefotaxime may be an effective first-choice antibiotic for ascitic fluid infection.

A randomised, multinational study with sequential therapy comparing ciprofloxacin twice daily and ofloxacin once daily.

In a multinational, open, randomised, controlled clinical study, 474 hospitalised patients with moderate or severe infections were treated with sequential regimens of ofloxacin or ciprofloxacin. Ofloxacin 400 mg once daily or ciprofloxacin 200 mg twice daily were given intravenously for at least 3 days followed by oral treatment with ofloxacin 400 mg once daily or ciprofloxacin 500 mg twice daily. Overall cure rates of 86.8% (85.7%) in the ofloxacin group and 89.6 (89.5%) in the ciprofloxacin group were achieved in the intention-to-treat analysis (per protocol analysis). The overall bacteriological response rate (ofloxacin 89.5%, ciprofloxacin 89.0%) was comparable to the clinical cure rate. Both drugs were well tolerated and adverse events were rarely observed. It is concluded that ofloxacin and ciprofloxacin can be used successfully in the treatment of hospitalised patients with aerobic gram-positive and gram-negative infections. Ofloxacin has the advantage of a once-daily regimen, compared to the twice-daily regimen with ciprofloxacin.

Treatment of tuberculous meningitis in Turkey.

A prospective study was performed on 72 cases of tuberculous meningitis studying various treatments. 37 patients were treated with a combination of isoniazid, rifampicin, pyrazinamide and streptomycin for 2 months, followed by a combination of isoniazid and rifampicin for 6 months. 35 patients were treated with various combinations of antituberculous drugs for 12-16 months. Disappearance of symptoms took (mean) 17 days. Mean duration of therapy for the hospitalized patients was 36 +/- 4 days. Seven (9.7%) patients died, 5 in the short-course therapy group and 2 in the long-course therapy group. Sequelae persisted in 18 (31%) cases, 8 of which cases were in the short-course therapy group and 10 in the long-course therapy group. No relapse was observed in either of the groups.

Living unrelated (paid) kidney transplantation in Third-World countries: high risk of complications besides the ethical problem.

Due to inadequate cadaveric and living related organ supply, many end-stage renal disease patients go to third-world countries for living unrelated (paid) kidney transplantation. Thirty-four patients who have had transplantations in two centres in India before coming to our centre for post-transplant care and follow-up are reported in this study. In the post-transplant phase at our centre, the mean follow-up period of the patients was 209.7 +/- 137.3 (range 6-450) days. Fourteen of them, having an uneventful course, were followed on an outpatient clinic basis. The rest of the patients were hospitalized because of the following surgical and/or medical complications, during admission: urinary fistula in two patients; lymphocele in three patients; urinary tract obstruction in two patients; decubitus ulcer in one patient; severe wound infection in one patient; subacute myocardial infarction in one patient; acute irreversible vascular rejection in two patients; urinary tract infection in two patients; pneumonia in two patients; congestive heart failure and severe electrolyte disturbance in two patients; post-transplant diabetes mellitus and ketoacidosis in one patient; cyclosporin nephrotoxicity in two patients; cyclosporin nephro-, hepato-, and neurotoxicity in one patient. Plasmodium falciparum malaria in three patients, generalized mucormycosis infection in one patient, and genitourinary aspergillosis in one patient were seen during the first month. Hepatitis B virus infection followed by chronic active hepatitis was diagnosed in two patients, 2 and 4 months after the operation; and Kaposi's sarcoma was noted in another two patients, 1 and 5 months after the operation.(ABSTRACT TRUNCATED AT 250 WORDS)