Antifungal properties of selective serotonin reuptake inhibitors against Aspergillus species in vitro.

This study investigated the fungicidal activity of selective serotonin reuptake inhibitors (SSRIs) against clinical isolates of Aspergillus fumigatus (n = 11), Aspergillus flavus (n = 9), Aspergillus terreus (n = 10) and Candida parapsilosis (ATCC 22019). The common drugs fluoxetine, seroxate, sertraline, paroxetine and reboxetine were applied in a broth microdilution test. In addition, we examined whether a post-antibiotic effect occurs following short exposure to the drugs. The various SSRIs showed time- and dose-dependent effects and were fungicidal towards the organisms tested. Sertraline and fluoxetine were the most active drugs, yet there were differences in the susceptibility of the various isolates tested. A lag of regrowth was dependent on the various SSRIs tested and their concentration. Treatment for 4 h at concentrations of sertraline below and equipotent to the minimal fungicidal concentration resulted in a lag of regrowth of 8-24 h for isolates of A. fumigatus and A. flavus. In conclusion, our in vitro studies clearly demonstrate antifungal effects of SSRIs. Animal studies are needed to evaluate the potential role of these psychotropic drugs in the management of fungal infections.

Antifungal activity against Candida species of the selective serotonin-reuptake inhibitor, sertraline.

Three patients with premenstrual dysphoric disorder (PMDD) and recurrent vulvovaginal candidiasis (VVC) underwent sertraline therapy (Tresleen, a selective serotonin-reuptake inhibitor; Pfizer) for PMDD. During sertraline intervention, patients had no recurrent episodes of acute VVC. Antifungal activity was observed for sertraline against various isolates of Candida species.

The postantibiotic effect of N-chlorotaurine on Staphylococcus aureus. Application in the mouse peritonitis model.

This study was designed to investigate the delay of regrowth (postantibiotic effect) in the presence of N-chlorotaurine (NCT), an endogenous active N-chlorine compound, of Staphylococcus aureus, strain Smith diffuse. The low reactivity of NCT enabled clear temporal separation of the postantibiotic and killing effect to be defined. Delay of regrowth proved to be dependent both on concentration of NCT, and incubation time. The maximum delay was 3 h. Using the model of lethal staphylococcal peritonitis in mice, in-vivo delay of regrowth of bacteria pretreated with N-chlorotaurine could be demonstrated to correlate with survival. It is concluded that the postantibiotic effect of N-chlorotaurine could be an important factor on decreasing virulence of bacteria. This effect was observed after relatively short incubation times.

Local application of antimycotics in mucormycosis cerebri: a case report.

A 65 year old man was found to have mucormycosis cerebri during immunosuppression after treatment of hairy cell leukaemia with 2-chlorodeoxyadenosine. Although mucormycosis cerebri has a poor prognosis, the patient survived after systemic administration of high dose amphotericin B, extensive excision of the abscess, and additional local application of amphotericin B with the help of an absorbable gelatin sponge.

[Gas gangrene as a manifestation of endogenous Clostridium septicum infection]. / Gasbrand als Manifestation einer endogenen Clostridium-septicum-Infektion.

Endogenous, nontraumatic clostridial myonecrosis has a frequent association with colon carcinoma, leukemia, diabetes mellitus, and drug-induced immunosuppression. We present two cases of Clostridium septicum myonecrosis. An 18-year-old girl developed severe abdominal pain on day 7 after hospitalization for cytostatic treatment of acute lymphoblastic leukemia. Blood cultures yielded Clostridium septicum and histopathological exam of muscle tissue showed extended myonecrosis. Eventually the patient recovered with antibiotics and surgical therapy. A 72-year-old diabetic woman was treated as an outpatient with an intramuscular injection of steroidal antiphlogistics for "acute lumbar disc disease". The next morning persistence of hip pain and discoloration of the right thigh caused hospitalization under the suspected diagnosis "fracture of the neck of the femur". Clostridium septicum was cultured from intraoperatively taken swabs. At autopsy, in addition to the gangrene, there was an adenocarcinoma of the cecum, which had not been diagnosed during life.

Toxic shock syndrome in transsphenoidal neurosurgery.

An overlooked toxic shock syndrome (TSS) may lead to a fatal outcome. In neurosurgery a transsphenoidal approach with post-operative nasal tamponade may promote toxic shock syndrome without signs of local wound infection. By discussing the case history of a patient after hypophysectomy by the transsphenoidal route, we propose that after the appearance of the first signs of toxic shock syndrome, quick removal of the nasal tamponade is a life saving procedure.

Neopterin modulates toxicity mediated by reactive oxygen and chloride species.

Neopterin, a pyrazino-pyrimidine derivative, is synthesized in excess by human monocytes/macrophages upon stimulation with interferon-gamma, a cytokine derived from activated I cells. Neopterin is furthermore produced constitutively. A relatively constant ratio between neopterin and its reduced form. 7,8-dihydroneopterin, has been described in human serum. In the study presented here we tested the ability of neopterin and its reduced form to modulate the effects of cytotoxic substances like hydrogen peroxide or hypochlorous acid and N-chloramine derivatives. We show that 7,8-dihydroneopterin potently reduces biological and chemical effects of these substances independently from the pH value. In contrast, at slightly alkaline pH (pH 7.5) neopterin enhances hydrogen peroxide and chloramine-T activity. This is demonstrated by increase of signal intensity in a luminol assay and also by enhancement of toxicity towards bacteria. Thus, the macrophage derived substance neopterin is able both to enhance and to reduce cytotoxicity in dependence of pH value and its oxidation state, and it may have a pivotal role in modulation of macrophage mediated effector mechanism.

[Antibacterial chemotherapy of "septic kidney"]. / Antibakterielle Chemotherapie der "Septischen Niere".

In the present retrospective study we report on antibacterial chemotherapy in patients suffering from a septic kidney. The results were documented in a course table, in which the septic parameters were divided into scores from 0 to 4 allowing to follow each patient's course with respect to the indicated scores. Two antibacterial substances were applied as short infusions with intervals of 4-6 hours between the administration of the different substances (Innsbruck scheme of chemotherapy). In all cases within 6 days from the onset of this therapy the septic parameters turned to normal values. None of the 24 patients suffering from a severe course of urosepsis, all treated at the University Hospital of Urology in Innsbruck between 1980 and 1990, died.

[The treatment of septicemia in childhood using time-spaced administration of antibiotic combinations]. / Behandlung von Sepsiserkrankungen im Kindesalter mit zeitlich versetzter Gabe von Antibiotika-kombinationen.

Theoretical consideration, empirical findings since 1972 and in vitro results had suggested that a combination of antibiotics for treatment of sepsis is more effective if the 2 or 3 antibiotics are not applied simultaneously but individually and sequentially at short intervals of 4 hours. Between January 1986 and March 1990 100 children were treated with spaced administration of antibiotic combinations at the University Hospital Innsbruck (Department of Paediatric). Causative agents isolated compared well to data published for other institutions; staphylococci were the dominating species. Anaerobic bacteria and fungi accounted for only 1% each, 60% of the cases were nosocomial infections. Overall, the fatality was 4%, a result significantly below the values reported in the literature for conventional therapeutic regimens.

[Percutaneous drainage of complicated infections of the upper urinary tract]. / Perkutane Drainage bei komplizierten Infektionen des oberen Harntraktes.

Acute pyelonephritis associated with obstruction may result in urosepsis and septic shock. Besides the administration of antimicrobial agents, quick removal of the obstruction is the essential part of the therapeutic regimen. In 43 patients with urosepsis the obstruction which was mainly due to urinary calculi was removed by percutaneous nephrostomy. Nephrostomy drainage was the only therapeutic measure required in all but 3 patients in whom nephrectomy had to be performed. 1 patient died after nephrectomy; no death occurred after percutaneous nephrostomy. Once diuresis has started after drainage, the patient will improve. If the kidney does not produce urine immediately after drainage the decision has to be made as soon as possible whether nephrectomy has to be performed for survival or whether it is justified to wait. Perfusion studies with radioisotopes have proven to be very helpful in such decisions. If there is no perfusion, immediate nephrectomy is mandatory; however, if perfusion can be demonstrated, recovery of the kidney can be expected. 21 patients with pyonephrosis were drained percutaneously. In 2 patients the infection could be controlled by nephrectomy only. The rate of secondary nephrectomy because of a non-functioning kidney was 50%. Percutaneous drainage has proven to be very effective in 6 patients with infected renal cysts, 7 patients with intrarenal abscesses and 4 patients with perinephric abscesses. There was only 1 patient presenting with intrarenal abscess in whom percutaneous drainage was insufficient and surgical intervention became necessary.

[Lyophilized cartilage--an antibiotic carrier]. / Lyophilisierter Knorpel--ein Antibiotikaträger.

Human lyophilized bruised costal cartilage was tested in vitro for its ability to act as a carrier medium for antibiotics. A remarkable capacity of accumulating streptomycin, gentamicin, tobramycin, vancomycin and ciprofloxacin was observed; whereas beta-lactum antibiotics and fosfomycin were released at a high rate. This release pattern was not influenced by the sterilization procedure, but rather by the size of the cartilage granula. Lyophilized cartilage--rehydrated in antibiotic-solutions--be helpful adjunct in the surgical management of osseous infections.

[High-dose short-term antibiotic therapy in bacteremia and infection in severely burned patients]. / Hochdosierte antibiotische Kurzzeittherapie der Bakteriämie und Sepsis bei Schwerbrandverletzten.

60 to 70% of all late deaths in patients with severe burns are due to sepsis. Thus, treatment with antibiotics is essential in the overall management of such patients, which in our hospital is carried out according to the following principles: 1. No prophylactic antibiotic treatment. 2. Careful evaluation of the bacterial spectrum of the burns, nasopharyngeal area, anal region, sputum and blood cultures. 3. In case of bacteriaemia we start high-dose combination therapy with two different, specific chemotherapeutic agents, given alternately every 4 to 6 hours. 4. In concordance with the clinical picture antibiotic therapy is discontinued as soon as three subsequent blood cultures remain sterile. Since 1980, 58 patients with severe burns (extent: 20 to 90% of body surface) have been treated according to these principles. Mortality due to sepsis was low, namely 9.5% (2 out of 21 patients presenting with bacteriaemia), so that our method of treatment has proven to be effective.

[Principles of the Innsbruck chemotherapy schedule in bacterial infections]. / Grundzüge des Innsbrucker Chemotherapieschemas bakterieller Infektionen.

Presented here are the ideas and the experimental results which led us to this scheme for the chemotherapy of severe bacterial infections. The approach is twofold, administering mainly two chemotherapeutics not concomitantly but alternating every four hours by means of a short-time i.v. infusion. Furthermore, immediately after admittance and even before the outbreak of an infection the patients' bacterial spectrum of wounds, the pharynx or the urine is monitored by carrying out bacteriological tests. These prophylactic diagnostics allow the identification of a dangerous proliferation of germs even before the outbreak of a florid infection. Therefore, an early chemotherapy can be put into practice considering the available evaluations of resistance studies.

[The kinetics of bacterial killing by fluctuating concentrations of antibiotics]. / Absterbekinetik von Keimen unter fluktuierenden Konzentrationen von Antibiotika.

Differences in kill kinetics and the regrowth pattern of bacteria under the influence of various antibiotics are frequently not represented by their MIC values. The area under the concentration curve represents antimicrobial activity more accurately than the peak concentration. Readministration of antibiotics should occur prior to bacterial regrowth for optimal efficacy. When administering combinations of antibiotics non-simultaneous dosing is superior to simultaneous administration.

[Infectious complications in the early phase following kidney transplantation]. / Infektiöse Komplikationen in der Frühphase nach Nierentransplantation.

A retrospective analysis of 533 patients receiving kidney transplantation was performed to study the incidence of infection in the early postoperative period. Mostly localized in the lungs and renal system, bacterial complications arose in 133 patients. As compared with the unproblematic management of the urinary tract infections, 45 pulmonary infections were characterized by difficulties in diagnosis and treatment. Poor graft function was closely related to pulmonary infections: mean creatinine was 2.4 mg% (in patients without pneumonia - 1.5 mg%). Out of 45 patients with pneumonia, the graft failed in 16 patients. 6 patients died as a result of pneumonia. Rapid detection of the pathogenic organism is required, if necessary by invasive diagnosis. The administration of erythromycin before identification of the responsible pathogen may be indicated, in view of the fatal outcome in several patients subsequently diagnosed as having Legionella infection.

[Septic disease pictures in Salmonella infections]. / Septische Krankheitsbilder bei Salmonella-Infektionen.

3715 strains of salmonella have been isolated from various sources from 1976 to 1985. 26 of these isolates have been S. typhi and paratyphi B, 3689 isolates were nontyphoid strains. 7 isolates of S. typhi and S. paratyphi have been isolated from blood cultures. All persons infected with these strains have acquired these organisms in tropical and subtropical areas. In contrast, salmonella gastroenteritis is mainly confined to the intestinal tract. 21 isolates of nontyphoid salmonellae, however, have been isolated from blood cultures. The vast majority of these patients showed compromised host defense mechanisms. Newborn infants up to 3 months are considered particularly vulnerable for bloodstream invasion with nontyphoid salmonellae. Patients with chronic consuming disorders, solid tumors and haematologic malignancies, and the treatment of these ailments with immunosuppressive drugs and corticosteroids predisposes patients for extraintestinal spread of an enteric salmonella infection. Corticosteroid therapy seems to be particularly responsible for a fulminant course of the disease and poor outcome of the infection.

Kill kinetics of bacteria under fluctuating concentrations of various antibiotics. II. Description of experiments.

Differences in kill kinetics and regrowth patterns of bacteria under the influence of various antibiotics are frequently not represented by their MIC values. The area under the concentration curve represents antimicrobial activity more accurately than the peak concentration. Readministration of antibiotics should occur prior to bacterial regrowth for optimal efficacy. When administering antibiotics in combinations nonsimultaneous dosing is superior to simultaneous administration.

Kill kinetics of bacteria under fluctuating concentrations of various antibiotics. I. Description of the model.

Traditional antimicrobial susceptibility testing uses fixed concentrations of an antibiotic over 24 hours. In order to imitate conditions closer to the actual in vivo situation we developed a model which allows us to simulate serum and tissue concentrations observed under clinical conditions in vitro. Kill kinetics and regrowth pattern of various bacteria have been investigated under the influence of different antibiotics in this kinetic model.