A century of the synthesis of dapsone: its anti-infective capacity now and then.

BACKGROUND: Although dapsone was first synthesized in 1908, a quarter of a century was to pass before it was used in the treatment of bacterial infections. Dapsone was, however, too toxic for humans (because of the excess dosage which was administered at that time) and was thus considered to be of no value in the treatment of common bacterial infections. Since the early 1950s, dapsone has been recognized as being uniquely effective against a number of noninfectious, inflammatory diseases and, today, this is its main indication. Thus, the reason why dapsone was first introduced into medicine, namely the treatment of bacterial infections, has been set aside and its main current applications are the treatment of noninfectious, inflammatory, autoimmune, and bullous diseases. OBJECTIVE: To study the anti-infective capacity of dapsone against common bacterial infections. As many patients who receive dapsone for the treatment of noninfectious, inflammatory diseases have a concomitant bacterial infection or a superinfection of their skin disease, we thought that, if dapsone proved to be effective against common bacterial infections, it may obviate the need for an additional antimicrobial drug in these patients. METHODS: Three bacterial ATCC> strains (Streptococcus pyogenes, Staphylococcus aureus, and Escherichia coli) were tested by a macrodilution minimal inhibitory concentration (MIC) test for dapsone. Dapsone concentrations were between 0.06 and 1125 microg/mL. RESULTS: Even the highest concentration of dapsone of 1125 microg/mL did not inhibit bacterial growth. CONCLUSIONS: Our results indicate that dapsone has no antibacterial effects whatsoever. Even at very high concentrations, it does not suppress the growth of most susceptible strains of bacteria. The story of dapsone (i.e. the long time that elapsed between its synthesis to its use for the chemotherapy of infectious diseases) will not repeat itself this time.

Epidemiology of vascular catheter-related bloodstream infections in a large university hospital in Israel.

Intravascular catheter-related infection and associated bacteraemia constitute a serious and increasing problem among nosocomial infections. As a part of an ongoing survey of positive blood cultures, all catheter-related bloodstream infections (CR-BSI) were reviewed in the authors' Medical Center in 1996, in order to evaluate the magnitude and seriousness of this problem. The largest group (28%) of hospital-acquired bacteraemia by 1 source of infection during 1996 was CR-BSI, identified in 110 patients with 126 episodes. The vascular line was central in 83 (66%), peripheral in 24 (19%), tunnelled in 18 (14%) and arterial in 1 (1%). Among the 83 central CR-BSI no sign of local inflammation was detected in 65%. Gram-positive and gram-negative bacteria shared equal parts among the 145 blood isolates; Staphylococcus aureus was the most common species (43/145, 30%) followed by Klebsiella pneumoniae (15/145, 10%); 11 (8%) isolates were Candida species. Fungal isolates were more common among tunnelled catheter infections than among others (6/18, 33% vs. 5/108, 5%, p < 0.001). Crude mortality was 35% (38/110), while attributable mortality was 14% (15/110), mostly associated with central line infection. Catheter-associated bacteraemias cause significant morbidity and mortality, and have become the most common source of hospital-acquired bacteraemia. There is a need to implement more effective infection-control measures and more advanced technologies in an effort to reduce this unacceptably high incidence.

Epidemiology of ceftazidime-resistant Klebsiella pneumoniae in a large university hospital in Tel Aviv.

BACKGROUND: An increase in multiple drug-resistant Klebsiella pneumoniae due to extended spectrum beta-lactamase production has recently been reported from many centers around the world. There is no information in the literature regarding this problem in Israel. A high prevalence of ceftazidime-resistant K. pneumoniae was noted in our Intensive Care Unit in the first few months of 1995. OBJECTIVE: To describe the epidemiology of ceftazidime-resistant K. pneumoniae in our medical center, as representing the situation in tertiary care hospitals in Israel. METHODS: We vigorously restricted the use of ceftazidime in the ICU and enforced barrier precautions. The susceptibility rate of K. pneumoniae was surveyed in the ICU and throughout the hospital before and after the intervention in the ICU. RESULTS: Following the intervention, the susceptibility rate of K. pneumoniae increased from 11% (3/28) to 47% (14/30) (P < 0.01) among ICU isolates, from 55% (154/280) to 62% (175/281) (P = 0.08) among total hospital isolates, and from 61% (50/82) to 74% (84/113) (P < 0.05) among total hospital blood isolates, although no additional control measures were employed outside the ICU. CONCLUSIONS: The epidemiology of ceftazidime-resistant K. pneumoniae in our medical center is similar to that reported from other centers around the world. Early awareness to the emergence of this resistance, identification of the source of the epidemic, and prompt action at the putative source site may reduce the rate of acquisition and spread of such resistance inside and outside of the source unit.

Detection of enterotoxigenic Escherichia coli in stool specimens by polymerase chain reaction.

A polymerase chain reaction (PCR) protocol for rapid (7 h) detection of enterotoxigenic Escherichia coli (ETEC) is described. This protocol has been validated on 57 stool samples from young children by comparing it with the colony hybridization technique. A good agreement was found between the two methods with Cohen's kappa statistics of 0.87 and 0.79 for the detection of the heat-stable toxin (ST) and heat-labile toxin (LT), respectively. Of 26 samples positive for LT and 15 samples positive for ST by colony hybridization, 21 (81%) and 15 (100%) were also found to be positive for LT and ST by PCR, respectively. Only one sample identified as LT-negative by colony hybridization was found to be positive by PCR. However, 3 of 42 samples of ST-negative by colony hybridization were detected as positive by PCR. A reconstruction experiment revealed that PCR could detect LT-producing and ST-producing ETEC at minimal concentrations of 2.5 x 10(3) cfu and 2.5 x 10(2) cfu per gram of feces, respectively. These data indicate the possible use of this method for rapid identification of ETEC-associated diarrhea in clinical and epidemiological settings.

Assessment of immunological mechanism in infertility of the rat after experimental testicular torsion.

A necrotic torted testis left in the scrotum affects the contralateral testis, resulting in depressed fertility. It was suggested that testicular torsion provoked a systemic response of an immunologic nature. In order to prove this theory, 56 rats were operated. Ten had a sham operation, in 17 a testis was torted and excised after 24 h, and in 29 a testis was torted and excised after 24 h, and in 29 a testis was torted but left in situ till the sacrifice. Antisperm-antibodies were not found in any phase of the experiment in the sham group. Using indirect immunofluorescence, antisperm-antibodies were found in the sera of 8/17 rats of the orchiectomy group and in 24/29 of the detorted group. In the direct immunofluorescence study, all the antibodies were localized in the tail of the spermatozoid. The antisperm-antibodies disappeared after 3 to 6 months.