Antibiotics And Pregnancy

Like anybody else, pregnant women are susceptible to infections. The correct treatment of these women, however, must consider along with pathogens, the infection site and antibiotic pharmacokinetics, the fetus and possible side effects to the child. When prescribing over this special condition, the physician must remember that the prescription will affect two organism and the drug must treat the mother without affecting the fetus. Beta-lactams having a long history of use without significant deleterious effects on the fetuses still are the safest choice during pregnancy. However, considering the constant increase of multi-resistant microorganisms, the physician has been forced to use different antimicrobial agents. Usually, data regarding safety during pregnancy are very limited, which causes serious doubts during prescription. In addition, many studies regarding the safe use of antibiotics during pregnancy are inconclusive or demand more evidence. The present study is a wide revision regarding the use of antibiotics during pregnancy, considering their pharmacokinetics and the clinical experience in recent years. It also intends to assist the physician during prescription and to give information to the pharma-cists to help pregnant women.607483493Ahlfors, C.E., Unbound bilirubin associated with kernicterus: A historical approach (2000) J Pediatr, 137, pp. 540-544Andrade, S.E., Gurwitz, J.H., Davis, R.L., Chan, K.A., Finkelstein, J.A., Fortman, K., McPhillips, H., Platt, R., Prescription drug use in pregnancy (2004) Am J Obstet Gynecol, 191, pp. 398-407Aselton, P., Jick, H., Milunsky, A., Hunter, J.R., Stergachis, A., First-trimester drug use and congenital disorders (1985) Obstet Gynecol, 65, pp. 451-455(2004) Ketek - Telithromycin, , http://www.fda.gov/cder/foi/label/2004/21144_ketek_lbl.pdf, searched May, 2004(2004) Rulide - Approved Product Information 2000, , http://www.pharma.aventis.com.au/corporate/products/pi/ Rulide%20and%20Rulide%20D.pdf, searched DecemberBeard, C.M., Noller, K.L., O'Fallon, W.M., Kurland, L.T., Dahlin, D.C., Cancer after exposure to metronidazole (1988) Mayo Clin Proc, 63, pp. 147-153Berkovitch, M., Pastuszak, A., Gazarian, M., Lewis, M., Koren, G., Safety of the new quinolones in pregnancy (1994) Obstet Gynecol, 84, pp. 535-538Bibler, M.R., Frame, P.T., Hagler, D.N., Bode, R.B., Staneck, J.L., Clinical evaluation of efficacy, pharmacokinetics, and safety of teicoplanin for serious gram-positive infections (1987) Antimicrob Agents Chemother, 31, pp. 207-212Birkenfeld, A., Anteby, S.O., The effect of ampicillin and colistin on post-Caesarean section endometritis with identification of possible risk factors (1983) Aust N Z J Obstet Gynaecol, 23, pp. 204-207Blanchard, M., Oppliger, R., Bucher, U., Positive direct Coombs' test in acute leukemias and other hemoblastoses: Relation to clavulanic acid-containing antibiotics? (1989) Schweiz Med Wschr, 14-119, pp. 39-45Boobis, A.R., Lewis, P., Drugs in pregnancy. Altered pharmacokinetics (1982) Br J Hosp Med, 28, pp. 566-573Briggs, G.G., Freeman, R.K., Yaffe, S.J., (2002) Drugs in Pregnancy and Lactation. 6th Ed., pp. 284-312. , Baltimore: Williams & Wilkins(2004) Bristol-Myers Squibb Company: AzactamR, , http://www.fda.gov/cder/foi/label/2002/50580slr033lbl.pdf, searched May 2004Bryskier, A., Ketolides-telithromycin, an example of a new class of antibacterial agents (2000) Clin Microbiol Infect, 6, pp. 661-669Bush, M.R., Rosa, C., Azithromycin and erythromycin in the treatment of cervical chlamydial infection during pregnancy (1994) Obstet Gynecol, 84, pp. 61-63Campoli-Richards, D.M., Brogden, R.N., Faulds, D., Teicoplanin - A review of its antibacterial activity, pharmacokinetic properties and therapeutic potential (1990) Drugs, 40, pp. 449-486Chambers, H.S., Antimicrobial agents: Protein synthesis inhibitors and miscellaneous antibacterial agents (1996) Goodman &ampGilman's the Pharmacological Basis of Therapeutics, 9 th Ed., pp. 1239-1272. , Hardman JG, Gilman AG, Limbird LE (ed.) , McGraw-HillChan, K.W., Ng, W.L., Gentamicin nephropathy in a neonate (1985) Pathology, 17, pp. 514-515Chastre, J., Brun, P., Fourtillan, J.B., Soler, P., Basset, G., Manuel, C., Trouillet, J.L., Gibert, C., Pulmonary disposition of roxithromycin (RU 28965), a new macrolide antibiotic (1987) Antimicrob Agents Chemother, 31, pp. 1312-1315Chimura, T., Morisaki, N., Funayama, T., Matsuo, M., Clinical studies on aztreonam in perinatal use (1990) Jpn J Antibiot, 43, pp. 696-699Christensen, B., Which antibiotics are appropriate for treating bacteriuria in pregnancy? (2000) J Antimicrob Chemother, 46 (SUPPL. 1), pp. 29-34Clark, P., Aztreonam (1992) Obstet Gynecol Clin North Am, 19, pp. 519-528Clemett, D., Markham, A., Linezolid (2000) Drugs, 59, pp. 815-827Conway, N., Birt, B.D., Streptomycin in pregnancy: Effect on the foetal ear (1965) Br Med J, 31, pp. 260-263Czeizel, A.E., Rockenbauer, M., A population-based case-control teratologic study of oral oxytetracycline treatment during pregnancy (2000) Eur J Obstet Gynecol Reprod Biol, 88, pp. 27-33Czeizel, A.E., Rockenbauer, M., Olsen, J., Use of antibiotics during pregnancy (1998) Eur J Obstet Gynecol Reprod Biol, 81, pp. 1-8Czeizel, A.E., Rockenbauer, M., Sorensen, H.T., Olsen, J., Teratogenic evaluation of oxacillin (1999) Scand J Infect Dis, 31, pp. 311-312Czeizel, A.E., Rockenbauer, M., Sorensen, H.T., Olsen, J., A population-based case-control teratologic study of oral erythromycin treatment during pregnancy (1999) Reprod Toxicol, 13, pp. 531-536Czeizel, A.E., Rockenbauer, M., Olsen, J., Sorensen, H.T., A teratological study of aminoglycoside antibiotic treatment during pregnancy (2000) Scand J Infect Dis, 32, pp. 309-313Czeizel, A.E., Rockenbauer, M., Olsen, J., Sorensen, H.T., Oral phenoxymethylpenicillin treatment during pregnancy. Results of a population-based Hungarian case-control study (2000) Arch Gynecol Obstet, 263, pp. 178-181Czeizel, A.E., Rockenbauer, M., Sorensen, H.T., Olsen, J., A population-based case-control teratologic study of oral chloramphenicol treatment during pregnancy (2000) Eur J Epidemiol, 16, pp. 323-327Czeizel, A.E., Rockenbauer, M., Sorensen, H.T., Olsen, J., The teratogenic risk of trimethoprim-sulfonamides: A population based case-control study (2001) Reprod Toxicol, 15, pp. 637-646Czeizel, A.E., Rockenbauer, M., Sorensen, H.T., Olsen, J., Use of cephalosporins during pregnancy and in the presence of congenital abnormalities: A population-based, case-control study (2001) Am J Obstet Gynecol, 184, pp. 1289-1296Czeizel, A.E., Rockenbauer, M., Sorensen, H.T., Olsen, J., A population-based case-control teratologic study of ampicillin treatment during pregnancy (2001) Am J Obstet Gynecol, 185, pp. 140-147Czeizel, A.E., Rockenbauer, M., Sorensen, H.T., Olsen, J., Augmentin treatment during pregnancy and the prevalence of congenital abnormalities: A population-based case-control teratologic study (2001) Eur J Obstet Gynecol Reprod Biol, 97, pp. 188-192Danisovicova, A., Brezina, M., Belan, S., Kayserova, H., Kaiserova, E., Hruskovic, I., Orosova, K., Matheova, E., Magnetic resonance imaging in children receiving quinolones: No evidence of quinolone-induced arthropathy. A multicenter survey (1994) Chemotherapy, 40, pp. 209-214Dashe, J.S., Gilstrap III, L.C., Antibiotic use in pregnancy (1997) Obstet Gynecol Clin North Am, 24, pp. 617-629Davey, P.G., Williams, A.H., A review of the safety profile of teicoplanin (1991) Antimicrob Chemother, 27 (SUPPL. B), pp. 69-73Dencker, B.B., Larsen, H., Jensen, E.S., Schonheyder, H.C., Nielsen, G.L., Sorensen, H.T., Birth outcome of 1886 pregnancies after exposure to phenoxymethylpenicillin in utero (2002) Clin Microbiol Infect, 8, pp. 196-201Dinsmoor, M.J., Gibbs, R.S., The role of the newer antimicrobial agents in obstetrics and gynecology (1988) Clin Obstet Gynecol, 31, pp. 423-434Donald, P.R., Sellars, S.L., Streptomycin ototoxicity in the unborn child (1981) S Afr Med J, 22, pp. 316-318Douthwaite, S., Hansen, L.H., Mauvais, P., Macrolide-ketolide inhibition of MLS-resistant ribosomes is improved by alternative drug interaction with domain II of 23S rRNA (2000) Mol Microbiol, 36, pp. 183-193Egen-Lappe, V., Hasford, J., Drug prescription in pregnancy: Analysis of a large statutory sickness fund population (2004) Eur J Clin Pharmacol, 60, pp. 659-666Einarson, A., Phillips, E., Mawji, F., D'Alimonte, D., Schick, B., Addis, A., Mastroiacova, P., Koren, G., A prospective controlled multicentre study of clarithromycin in pregnancy (1998) Am J Perinatol, 15, pp. 523-525Einarson, A., Shuhaiber, S., Koren, G., Effects of antibacterials on the unborn child: What is known and how should this influence prescribing (2001) Paediatr Drugs, 3, pp. 803-816Fonseca, M.R.C.C., Fonseca, E., Bergsten-Mendes, G., Prevalence of drug use during pregnancy: A pharmacopepidemiological approach (2002) Rev Saude Publica, 36, pp. 205-212(2000) Food and Drug Administration Revision BiaxinR Abbott Laboratories, , http://www.fda.gov/cder/foi/label/2000/50662S29lbl.pdf, searched May 2004(2002) Forrest Pharmaceuticals MonurolR FDA Label Information, , http://www.fda.gov/cder/foi/label/2002/50717SLR004_Monurol_lbl.pdf, searched December 2004Garland, S.M., O'Reilly, M.A., The risks and benefitis of antimicrobial therapy in pregnancy (1995) Drug Saf, 13, pp. 188-205Gomes, K.R., Moron, A.F., Silva, R., Siqueira, A.A., Prevalence of use of medicines during pregnancy and its relationship to maternal factors (1999) Rev Saude Publica, 33, pp. 246-254Grady, R., Safety profile of quinolone antibiotics in the pediatric population (2003) Pediatr Infect Dis J, 22, pp. 1128-1132Greenwood, D., Inhibitors of bacterial protein synthesis (1997) Antimicrobial Chemotherapy, 3rd Ed., 9, pp. 32-48. , Greenwood D (ed.) , Oxford University PressHautekeete, M.L., Hepatotoxicity of antibiotics (1995) Acta Gastroenterol Belg, 58, pp. 290-296Hedstrom, S., Martens, M.G., Antibiotics in pregnancy (1993) Clin Obstet Gynecol, 36, pp. 886-892Heikkila, A., Erkkola, R., Review of beta-lactam antibiotics in pregnancy. The need for adjustment of dosage schedules (1994) Clin Pharmacokinet, 27, pp. 49-62Heikkila, A., Renkonen, O.V., Erkkola, R., Pharmacokinetics and transplacental passage of imipenem during pregnancy (1992) Antimicrob Agents Chemother, 36, pp. 2652-2655Hernandez-Diaz, S., Werler, M.M., Walker, A.M., Mitchell, A.A., Folic acid antagonists during pregnancy and the risk of birth defects (2000) N Engl J Med, 30, pp. 1608-1614Honein, M.A., Paulozzi, L.J., Himelright, I.M., Lee, B., Cragan, J.D., Patterson, L., Correa, A., Erickson, J.D., Infantile hypertrophic pyloric stenosis after pertussis prophylaxis with erythromcyin: A case review and cohort study (1999) Lancet, 354, pp. 2101-2105Hooton, T.M., Stamm, W.E., Diagnosis and treatment of uncomplicated urinary tract infection (1997) Infect Dis Clin North Am, 11, pp. 551-581Jacobson, G.F., Autry, A.M., Kirby, R.S., Liverman, E.M., Motley, R.U., A randomized controlled trial comparing amoxicillin and azithromycin for the treatment of Chlamydia trachomatis in pregnancy (2001) Am J Obstet Gynecol, 184, pp. 1352-1354Jamjian, C., Biedenbach, D.J., Jones, R.N., In vitro evaluation of a novel ketolide antimicrobial agent, RU-64004 (1997) Antimicrob Agents Chemother, 41, pp. 454-459Jepsen, P., Skriver, M.V., Floyd, A., Lipworth, L., Schonheyder, H.C., Sorensen, H.T., A population-based study of maternal use of amoxicillin and pregnancy outcome in Denmark (2003) Br J Clin Pharmacol, 55, pp. 216-221Johnson, T.N., The development of drug metabolising enzymes and their influence on the susceptibility to adverse drug reactions in children (2003) Toxicology, 192, pp. 37-48Knight, M., Adverse drug reactions in neonates (1994) J Clin Pharmacol, 34, pp. 128-135Knothe, H., Dette, G.A., Antibiotics in pregnancy: Toxicity and teratogenicity (1985) Infection, 13, pp. 49-51Larsen, B., Glover, D.D., Serum erythromycin levels in pregnancy (1998) Clin Ther, 20, pp. 971-977Larsen, H., Nielsen, G.L., Sorensen, H.T., Moller, M., Olsen, J., Schonheyder, H.C., A follow-up study of birth outcome in users of pivampicillin during pregnancy (2000) Acta Obstet Gynecol Scand, 79, pp. 379-383Lewis, J.H., Drug-induced liver disease (2000) Med Clin North Am, 84, pp. 1275-1311Loebstein, R., Addis, A., Ho, E., Andreou, R., Sage, S., Donnenfeld, A.E., Schick, B., Koren, G., Pregnancy outcome following gestational exposure to fluoroquinolones: A multicenter prospective controlled study (1998) Antimicrob Agents Chemother, 42, pp. 1336-1339Loebstein, R., Koren, G., Clinical relevance of therapeutic drug monitoring during pregnancy (2002) Ther Drug Monit, 24, pp. 15-22Loebstein, R., Lalkin, A., Koren, G., Pharmacokinetic changes during pregnancy and their clinical relevance (1997) Clin Pharmacokinet, 33, pp. 328-343Louik, C., Werler, M.M., Mitchell, A.A., Erythromycin use during pregnancy in relation to pyloric stenosis (2002) Am J Obstet Gynecol, 186, pp. 288-290Mantovani, A., Calamandrei, G., Delayed developmental effects following prenatal exposure to drugs (2001) Curr Pharm des, 7, pp. 859-880Marynowski, A., Sianozecka, E., Comparison of the incidence of congenital malformations in neonates from healthy mothers and from patients treated because of tuberculosis (1972) Ginekol Pol, 43, pp. 713-715Matsuda, S., Suzuki, M., Oh, K., Ishikawa, M., Soma, A., Takada, H., Shimizu, T., Chimura, T., Pharmacokinetic and clinical studies on imipenem/cilastatin sodium in the perinatal period. A study of imipenem/cilastatin sodium in the perinatal co-research group (1988) Jpn J Antibiot, 41, pp. 1731-1741Mengue, S.S., Schenkel, E.P., Duncan, B.B., Schmidt, M.I., Drug use by pregnant women in six Brazilian cities (2001) Rev Saude Publica, 35, pp. 415-420Mensa, J., García-Vázquez, E., Vila, J., Macrólidos, cetólidos y estreptograminas (2003) Enferm Infecc Microbiolo Cin, 21, pp. 200-208(2004) Invanz - Food and Drug Administration, , www.fda.gov/medwatch/SAFETY/2004/apr_PI/Invanz_PI.pdf, searched December, 2004Murphy, J.F., Drugs and pregnancy (1984) Ir Med J, 77, pp. 52-56Nagai, A., Miyazaki, M., Morita, T., Furubo, S., Kizawa, K., Fukumoto, H., Sanzen, T., Kawamura, Y., Comparative articular toxicity of garenoxacin, a novel quinolone antimicrobial agent, in juvenile beagle dogs (2002) J Toxicol Sci, 27, pp. 219-228Niebyl, J.R., Antibiotics and other anti-infective agents in pregnancy and lactation (2003) Am J Perinatol, 20, pp. 405-414Ortiz-Ruiz, G., Vetter, N., Isaacs, R., Carides, A., Woods, G.L., Ertapenem versus ceftriaxone for the treatment of community-acquired pneumonia in adults: Combined analysis of two multicentre randomized, double-bind studies (2004) J Antimicrob Chemother, 53, pp. 59-66(1997) Parke-Davis: Coly-MycinR M Parenteral, , http://www.fda.gov/cder/ogd/rld/50108s21.pdf, searched December, 2004Patel, S.S., Balfour, J.A., Bryson, H.M., Fosfomycin tromethamine. A review of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy as a single-dose oral treatment for acute uncomplicated lower urinary tract infections (1997) Drugs, 53, pp. 637-656Perkins, R.P., Hydrops fetalis and stillbirth in a male glucose-6-phosphate dehydrogenase-deficient fetus possibly due to maternal ingestion of sulfisoxazolea case report (1971) Am J Obstet Gynecol, 111, pp. 379-381(2003) Pfizer Laboratories: ZithromaxR, , http://www.fda.gov/cder/foi/label/2004/50670slr021,50693slr008, 50730slr011_zithromax_lbl.pdf, searched May, 2004(2004) Pharmacia &ampUpjohn Company - ZyvoxR Label Information, , http://www.fda.gov/cder/foi/label/2004/21130se5-006,21131se5-007, 21132se5-006_zyvox_lbl.pdf, searched December, 2004Philipson, A., Sabath, L.D., Charles, D., Transplacental passage of erythromycin and clindamycin (1973) N Engl J Med, 288, pp. 1219-1221Philipson, A., Stiernstedt, G., Ehrnebo, M., Comparison of the pharmacokinetics of cephradine and cefazolin in pregnant and non-pregnant women (1987) Clin Pharmacokinet, 12, pp. 136-144Piper, J.M., Mitchel, E.F., Ray, W.A., Prenatal use of metronidazole and birth defects: No association (1993) Obstet Gynecol, 82, pp. 348-352Preston, S.L., The importance of appropriate antimicrobial dosing: Pharmacokinetic and pharmacodynamic considerations (2004) Ann Pharmacother, 38, pp. S14-S18Rastogi, N., Goh, K.S., Ruiz, P., Casal, M., In vitro activity of roxithromycin against the Mycobacterium tuberculosis complex (1995) Antimicrob Agents Chemother, 39, pp. 1162-1165Reid, D.W., Caille, G., Kaufmann, N.R., Maternal and transplacental kinetics of trimethoprim and sulfamethoxazole, separately and in combination (1975) Can Med Assoc J, 112, pp. 67-72Rodin, P., Hass, G., Metronidazole and pregnancy (1966) Br J Vener Dis, 42, pp. 210-212Sá Del Fiol, F., Rocha De Mattos Filho, T., Groppo, F.C., Evaluation in an animal model and in vitro of the combination clavulanic acid and cephalosporins against beta-lactamase producing and nonproducing Staphylococcus aureus strains (2000) Braz J Infect Dis, 4, pp. 36-42Saravanos, K., Duff, P., The quinolone antibiotics (1992) Obstet Gynecol Clin North Am, 19, pp. 529-537Schonwald, S., Kuzman, I., Oreskovic, K., Burek, V., Skerk, V., Car, V., Bozinovic, D., Radosevic, S., Azithromycin: Single 1.5 g dose in the treatment of patients with atypical pneumonia syndrome - A randomized study (1999) Infection, 27, pp. 198-202Shepherd, G.M., Hypersensitivity reactions to drugs: Evaluation and management (2003) Mt Sinai J Med, 70, pp. 113-125Sorensen, H.T., Larsen, H., Jensen, E.S., Thulstrup, A.M., Schonheyder, H.C., Nielsen, G.L., Czeizel, A., Safety of metronidazole during pregnancy: A cohort study of risk of congenital abnormalities, preterm delivery and low birth weight in 124 women (1999) J Antimicrob Chemother, 44, pp. 854-856Sorensen, H.T., Skriver, M.V., Pedersen, L., Larsen, H., Ebbesen, F., Schonheyder, H.C., Risk of infantile hypertrophic pyloric stenosis after maternal postnatal use of macrolides (2003) Scand J Infect Dis, 35, pp. 104-106Stein, G.E., Single-dose treatment of acute cystitis with fosfomycin tromethamine (1998) Ann Pharmacother, 32, pp. 215-219Swaney, S.M., Aoki, H., Ganoza, M.C., Shinabarger, D.L., The oxazolidinone linezolid inhibits initiation of protein synthesis in bacteria (1998) Antimicrob Agents Chemother, 42, pp. 3251-3255Teppler, H., Gesser, R.M., Friedland, I.R., Woods, G.L., Meibohm, A., Safety and tolerability of ertapenem (2004) J Antimicrob Chemother, 53, pp. 75-81Safety of antimicrobial drugs in pregnancy (1987) Med Let Drugs Ther, 29, pp. 61-63Weinstein, A.J., Gibbs, R.S., Gallagher, M., Placental transfer of clindamycin and gentamicin in term pregnancy (1976) Am J Obstet Gynecol, 124, pp. 688-691Weller, T.M.A., Rees, E.N., Antibacterial use in pregnancy (2000) Drug Saf, 22, pp. 335-338Williams, M.E., Thomas, D., Harman, C.P., Mintz, P.D., Donowitz, G.R., Positive direct antiglobulin tests due to clavulanic acid (1985) Antimicrob Agents Chemother, 27, pp. 125-127Yabe, K., Yoshida, K., Yamamoto, N., Nishida, S., Ohshima, C., Sekiguchi, M., Yamada, K., Furuhama, K., Diagnosis of quinolone-induced arthropathy in juvenile dogs by use of magnetic resonance (MR) imaging (1997) J Vet Med Sci, 59, pp. 597-59

Evaluation In An Animal Model And In Vitro Of The Combination Clavulanic Acid And Cephalosporins Against Beta-lactamase Producing And Nonproducing Staphylococcus Aureus Strains.

Beta-lactamase enzymes are the most common cause of bacterial resistance to Beta-lactam antibiotics. They hydrolyze the amide bound in the Beta-lactam ring and produce acidic derivatives that have no antibacterial properties. The aim of this study was to evaluate a combination of clavulanic acid with cephalosporins against Beta-lactamase-producing and nonproducing strains of Staphylococcus aureus using in vitro tests and a rat animal model. In vitro tests (MIC) of the drug combination were done using standard methods. In an animal model, rats were submitted to surgical implantation of polyurethane sponges in their backs to induce granulomatous tissue. After seven days, the animals received cephalexin, cephalexin with clavulanic acid, ceftriaxone, ceftriaxone with clavulanic acid or clavulanic acid alone. One hour after the drug administration, granulomatous tissue was removed and placed in Petri dishes previously inoculated with 10(8) cfu of producing or non-producing Beta-lactamase Staphylococcus aureus. After 24h at 37 degrees C, the inhibition zones formed by granulomatous tissue was measured and scored for statistical analysis. Both tests (ex vivo ¿animal model¿ and in vitro) showed that the cephalexin was more active than ceftriaxone against non-producing Beta-lactamase S.aureus (p<0.01). Against Beta-lactamase producing S.aureus, ceftriaxone was more active than cephalexin, which was inactive. Combinations of clavulanic acid with cephalexin or ceftriaxone had similar antimicrobial activity against non-producing Beta-lactamase S.aureus compared to the cephalosporins used alone. When tested using Beta-lactamase producing strains, the combination of clavulanic acid with cephalosporins showed synergism. We conclude that the combination of cephalosporins with clavulanic acid could be useful in staphylococcal infections caused by Beta-lactamase producing strains.41364

PARACOCCIDIOIDOMYCOSIS TREATMENT

SUMMARYConsidered to be an emerging endemic mycosis in Latin America, paracoccidioidomycosis is characterized by a chronic course and involvement of multiple organs in immunocompromised hosts. Infection sequelae are mainly related to pulmonary and adrenal insufficiency. The host-parasite interaction results in different expressions of the immune response depending on parasite pathogenicity, fungal load and genetic characteristics of the host. A few controlled and case series reports have shown that azoles and fast-acting sulfa derivatives are useful treatment alternatives in milder forms of the disease. For moderate/severe cases, more prolonged treatments or even parenteral routes are required especially when there is involvement of the digestive tract mucosa, resulting in poor drug absorption. Although comparative studies have reported that shorter treatment regimens with itraconazole are able to induce cure in chronically-infected patients, there are still treatment challenges such as the need for more controlled studies involving acute cases, the search for new drugs and combinations, and the search for compounds capable of modulating the immune response in severe cases as well as the paradoxical reactions

Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: The ASSENT-3 randomised trial in acute myocardial infarction

Background: Current fibrinolytic therapies fail to achieve optimum reperfusion in many patients. Low-molecular-weight heparins and platelet glycoprotein IIb/IIIa inhibitors have shown the potential to improve pharmacological reperfusion therapy. We did a randomised, open-label trial to compare the efficacy and safety of tenecteplase plus enoxaparin or abciximab, with that of tenecteplase plus weight-adjusted unfractionated heparin in patients with acute myocardial infarction. Methods: 6095 patients with acute myocardial infarction of less than 6 h were randomly assigned one of three regimens: full-dose tenecteplase and enoxaparin for a maximum of 7 days (enoxaparin group; n=2040), half-dose tenecteplase with weight-adjusted low-dose unfractionated heparin and a 12-h infusion of abciximab (abciximab group; n=2017), or full-dose tenecteplase with weight-adjusted unfractionated heparin for 48 h (unfractionated heparin group; n=2038). The primary endpoints were the composites of 30-day mortality, in-hospital reinfarction, or in-hospital refractory ischaemia (efficacy endpoint), and the above endpoint plus in-hospital intracranial haemorrhage or in-hospital major bleeding complications (efficacy plus safety endpoint). Analysis was by intention to treat. Findings: There were significantly fewer efficacy endpoints in the enoxaparin and abciximab groups than in the unfractionated heparin group: 233/2037 (11.4%) versus 315/2038 (15.4%; relative risk 0.74 [95% CI 0.63-0.87], p=0.0002) for enoxaparin, and 223/2017 (11.1%) versus 315/2038 (15.4%; 0.72 [0.61-0.84], p&lt;0.0001) for abciximab. The same was true for the efficacy plus safety endpoint: 280/2037 (13.7%) versus 347/2036 (17.0%; 0.81 [0.70-0.93], p=0.0037) for enoxaparin, and 287/2016 (14.2%) versus 347/2036 (17.0%; 0.84 [0.72-0.96], p=0.01416) for abciximab. Interpretation: The tenecteplase plus enoxaparin or abciximab regimens studied here reduce the frequency of ischaemic complications of an acute myocardial infarction. In light of its ease of administration, tenecteplase plus enoxaparin seems to be an attractive alternative reperfusion regimen that warrants further study

Update on tick-borne rickettsioses around the world: A geographic approach

Tick-borne rickettsioses are caused by obligate intracellular bacteria belonging to the spotted fever group of the genus Rickettsia. These zoonoses are among the oldest known vector-borne diseases. However, in the past 25 years, the scope and importance of the recognized tick-associated rickettsial pathogens have increased dramatically, making this complex of diseases an ideal paradigm for the understanding of emerging and reemerging infections. Several species of tick-borne rickettsiae that were considered nonpathogenic for decades are now associated with human infections, and novel Rickettsia species of undetermined pathogenicity continue to be detected in or isolated from ticks around the world. This remarkable expansion of information has been driven largely by the use of molecular techniques that have facilitated the identification of novel and previously recognized rickettsiae in ticks. New approaches, such as swabbing of eschars to obtain material to be tested by PCR, have emerged in recent years and have played a role in describing emerging tick-borne rickettsioses. Here, we present the current knowledge on tick-borne rickettsiae and rickettsioses using a geographic approach toward the epidemiology of these diseases