Am J Med, 1991 Dec 30, 91(6A), 76S - 80S Effect of temafloxacin on the pharmacokinetics of theophylline; Ruff F et al.; A number of fluoroquinolones have been shown to interact adversely with theophylline . We studied the influence of coadministration of temafloxacin, a new fluoroquinolone antimicrobial agent, on steady-state theophylline pharmacokinetics . Twelve healthy subjects (8 males, 4 females; average age and weight 34 years and 62 kg, respectively) were given oral controlled-release theophylline in an individualized dosage to achieve a target plasma level of 10 mg/L . Once steady state was achieved, temafloxacin 600 mg given orally twice daily was concomitantly administered for 4-5 days . Serial blood samples were collected before and during simultaneous temafloxacin administration and plasma assayed for theophylline using a high-performance liquid chromatography technique . Theophylline pharmacokinetic parameters were determined noncompartmentally, and results of single and combined administration were compared . Theophylline plasma concentrations did not differ significantly with temafloxacin coadministration, and similar area-under-the-curve (AUC) values were observed . Theophylline oral clearance increased from 2.67 +/- 1.01 L/hour to 2.69 +/- 0.93 L/hour, when given alone and with temafloxacin, respectively (p = 0.92) . Only 2 of 12 subjects showed an appreciable decrease in clearance when theophylline and temafloxacin were administered together, while 2 subjects demonstrated increases greater than 15% and 8 showed no change . We conclude that temafloxacin does not interact significantly with theophylline and that these agents can be safely administered together. Am J Med, 1991 Dec 30, 91(6A), 150S - 152S Fluoroquinolones for the treatment of nongonococcal urethritis/cervicitis; Segreti J; Approximately 50% of cases of nongonococcal urethritis reported among men are caused by Chlamydia trachomatis . Other pathogens implicated in the bacterial etiology of nongonococcal urethritis that occur independently or concurrently with gonorrhea include Ureaplasma urealyticum and species of Mycoplasma, including Mycoplasma hominis . The etiology of up to half of the cases, however, remains uncertain . Historically, C . trachomatis genital infections have been difficult to diagnose because of the need for expensive cell-culture methods that are technically difficult and produce delayed results . In addition, women with nongonococcal cervicitis/mucopurulent cervicitis are frequently asymptomatic except for vaginal discharge . Nongonococcal urethritis may also be asymptomatic in men . Increased morbidity is associated with unidentified and untreated C . trachomatis infections, especially in women and children . Currently, the Centers for Disease Control recommends that all patients diagnosed with nongonococcal urethritis, nongonococcal cervicitis, or gonorrhea--along with their sexual partners--receive adequate antimicrobial therapy that includes antimicrobial activity against chlamydiae . A tetracycline antibiotic is most commonly recommended . However, tetracyclines have variable in vitro activity against U . urealyticum and Mycoplasma species . New antibiotic therapy options with broader antimicrobial coverage are needed for the management of nongonococcal urethritis and cervicitis. Science, 1991 Dec 20, 254(5039), 1773 - 6 A fungal gene for antibiotic resistance on a dispensable ("B") chromosome; Miao VP et al.; A family of cytochrome P-450 (Pda) genes in the pathogenic fungus Nectria haematococca is responsible for the detoxification of the phytoalexin pisatin, an antimicrobial compound produced by garden pea (Pisum sativum L.) . The Pda6 gene was mapped by electrophoretic karyotype analysis to a small meiotically unstable chromosome that is dispensable for normal growth . Such traits are typical of B chromosomes . The strains of Nectria studied here have no sequences that are homologous to the Pda family other than Pda6 and therefore demonstrate that unique, functional genes can be found on B chromosomes . Unstable B chromosomes may be one mechanism for generating pathogenic variation in fungi. JAMA, 1991 Dec 18, 266(23), 3309 - 17 Antimicrobial therapy for otitis media with effusion ('secretory' otitis media); Cantekin EI et al.; OBJECTIVE--To determine the effectiveness of antimicrobial treatment for otitis media with effusion ("secretory" otitis media) in children . DATA SOURCE--We report the reexamination of a previously published study by Mandel et al that evaluated the efficacy of a 2-week course of antimicrobials (amoxicillin trihydrate) with and without a 4-week course of an oral decongestant-antihistamine combination in a double-blind, placebo-controlled, randomized trial involving 518 infants and children with otitis media with effusion . DATA SYNTHESIS--At 4 weeks, amoxicillin efficacy as determined by a tympanometric criterion (P = .121) or by a measure of improvement in hearing (P = .311) was insignificant . Only by otoscopic judgment, which is shown to contain a systematic bias as used in this clinical trial, could an argument be made for a marginal efficacy of amoxicillin at the 4-week end point . Logistic regression analyses of the combined effects of treatment and prognostic factors showed no significant differences between placebo- and antibiotic-treated groups for unilateral effusions and for bilateral effusions . When subjects with unilateral and bilateral effusions were combined, the estimated efficacy of antibiotic treatment was 12.3% by otoscopy (P = .014) and 4.8% by tympanometry (P = .171) . We also demonstrate the sensitivity of outcome to diagnostic measures used and provide statistical evidence questioning the validity of otoscopic observations in this study . Six weeks after the termination of amoxicillin therapy, the recurrence of effusion was two to six times higher in the amoxicillin-treated children than in those treated with placebo (P = .001), and resolution of effusion was not significantly different among antibiotic and placebo groups (13.6% and 11.3%, respectively; P = .477) . CONCLUSIONS--Amoxicillin with and without decongestant-antihistamine combination is not effective for the treatment of persistent asymptomatic middle-ear effusions in infants and children. J Immunol, 1991 Dec 15, 147(12), 4313 - 21 Characterization of host cell-derived membrane proteins of the vacuole surrounding different intracellular forms of Trypanosoma cruzi in J774 cells . Evidence for phagocyte receptor sorting during the early stages of parasite entry; Hall BF et al.; Trypanosoma cruzi, an obligate intracellular protozoan parasite, exhibits developmental regulation of virulence . Although both noninfective epimastigote and infective trypomastigote stages of T . cruzi enter phagocytic cells via the formation of a parasitophorous vacuole (PV), only the latter developmental stages survive ingestion and perpetuate the infection . To determine whether the membrane composition of PV surrounding these different stages might contribute to differences in the outcome of infection, we identified selected membrane constituents by immunofluorescence and intracellular radioiodination, and studied their incorporation into PV . Complement receptors (CR3) are incorporated preferentially into the PV membrane surrounding serum-opsonized epimastigotes but not culture-derived metacyclic trypomastigotes . FcR are not preferentially incorporated into PV membranes unless epimastigotes or culture-derived metacyclic trypomastigotes are opsonized with anti-T . cruzi antibody . PV surrounding either parasite stage contain beta 1 integrins and lysosomal membrane glycoproteins (lgp) . These results indicate that the plasma membrane glycoproteins incorporated into the surrounding PV membrane differ depending upon the stage of parasite being internalized, and that these differences reflect, at least in part, selective ligation of cell surface receptors mediating uptake . Furthermore, they imply that although virulent trypomastigote stages may avoid host cell uptake by conventional phagocytic receptors, i.e., CR3 or FcR, they do not escape fusion with an lgp-containing vacuole where they could still be exposed to lysosomal antimicrobial mechanisms. J Immunol, 1991 Dec 15, 147(12), 4211 - 7 Differential effects of neutrophil-activating peptide 1/IL-8 and its homologues on leukocyte adhesion and phagocytosis; Detmers PA et al.; Several structural homologues of the chemotactic peptide neutrophil-activating peptide 1/IL-8 (NAP-1/IL-8) were tested for their ability to influence the expression and function of adhesion-promoting receptors on human polymorphonuclear leukocytes (PMN) . NAP-2, melanoma growth stimulatory activity, and two forms of NAP-1/IL-8 (ser-NAP-1/IL-8 and ala-NAP-1/IL-8, consisting of 72 and 77 amino acids, respectively), each caused an increase in the expression of CD11b/CD18 (CR3) and CR1, which was accompanied by a decrease in the expression of leukocyte adhesion molecule-1 (LAM-1, LECAM-1) . The binding activity of CD11b/CD18 was also enhanced 3- to 10-fold by these peptides, but enhanced function was transient: binding of erythrocytes coated with C3bi reached a maximum by 30 min and declined thereafter . Ser-NAP-1/IL-8, ala-NAP-1/IL-8, NAP-2, and melanoma growth stimulatory activity also caused a two- to threefold enhancement of the phagocytosis of IgG-coated erythrocytes (EIgG) by PMN without causing a large increase in the expression of Fc gamma receptors . Enhanced phagocytosis of EIgG appeared to be mediated through CD11b/CD18, because F(ab')2 fragments of an antibody directed against CD18 inhibited NAP-1/IL-8-stimulated ingestion of EIgG . The four active peptides caused a rapid, transient increase in the amount of F-actin within PMN, indicating that they are capable of influencing the structure of the microfilamentous cytoskeleton, which participates in phagocytosis . Two other NAP-1/IL-8-related peptides, platelet factor 4 and connective tissue-activating peptide III, were without effect on expression of CD11b/CD18, CR1, and LAM-1, binding activity of CD11b/CD18, or Fc-mediated phagocytosis, and increased actin polymerization only slightly . Our observations indicate that several members of the NAP-1/IL-8 family of peptides were capable of promoting integrin-mediated adhesion and Fc-mediated phagocytosis, processes important in the recruitment of PMN to sites of inflammation and antimicrobial responses of PMN. Pharm Weekbl Sci, 1991 Dec 13, 13(6), 248 - 53 Cost of hospital antimicrobial chemotherapy . A method for global cost calculation; Gyssens IC et al.; We will describe the method of cost-identification analysis, which was performed in a Dutch hospital during a review of antimicrobial drugs usage . In the present Dutch hospital budget system, in-patients' drug costs generate no revenues . Efforts to diminish drug costs result in financial benefit for the institution . To maximize cost containment, efforts are to be directed to all cost components . We chose wholesale purchase prices of antimicrobial drugs and national prices for salaries and hospital costs . Global cost comparison shows the most cost effective system of intravenous administration . Push injection is the most economic way to administer intravenous drugs which do not require dilution or prolonged infusion time . For stable solutions, such as metronidazole, ready-to-infuse bags are the most economic system . A global cost calculation is listed for commonly used antimicrobial drugs for in-patients . A cost comparison is given for vancomycin CP and teicoplanin, two antistaphyloccocal drugs, which are probably equieffective . The result of global cost comparison contributes to the decision to include new drugs into the hospital formulary or to replace older ones. Surg Clin North Am, 1991 Dec, 71(6), 1231 - 46 Venous access . Preoperative, operative, and postoperative dilemmas; Lowell JA et al.; The past two decades have seen a tremendous increase in the use of central venous catheters and its associated complications . The increased sophistication that physicians now have with regard to nutritional and metabolic needs has escalated the use of central venous catheters . As the acquired immunodeficiency syndrome epidemic grows, so too will the number of patients with infections and metabolic complications, many of whom will have conditions severe enough to benefit from the use of central venous catheters to deliver antimicrobial drugs and other supportive intravenous therapy . Our ability to sustain patients with short-bowel syndrome also relies critically on central venous access . Likewise, treatment of patients with leukemias and certain solid tumors frequently requires placement of these catheters . Central venous catheters are essential for bone marrow transplantation . Efforts to minimize the risks associated with placement of a central venous catheter by more frequent use of catheter exchange rather than another venipuncture should be encouraged when possible . Techniques to prevent arrhythmia during overinsertion of guide wires are also important . Vigilant searches for, and prompt treatment of, catheter-related sepsis and central vein thrombosis are critical . Better prophylaxis against the development of catheter-related sepsis and catheter-related thrombosis is also needed . Further prospective investigations should be performed, however, to define precisely cost-effective methods of detection and duration of therapy for patients with both catheter-related sepsis and catheter-related thrombosis . Further advances in the technology and management of catheters need to continue to meet these ongoing challenges. J Bone Joint Surg Am, 1991 Dec, 73(10), 1469 - 74 Metachronous infections in patients who have had more than one total joint arthroplasty; Murray RP et al.; Sixty-eight patients who had had 159 replacement arthroplasties of more than one major joint between 1975 and 1984 and who had had an infection after at least one of these procedures were identified in a retrospective review . Subsequent infection in another total joint replacement was documented in ten of these patients . The risk of development of an infection about another total joint replacement after an infection had occurred about one total joint replacement in a patient who had had more than one arthroplasty was 18 per cent, according to the survivorship-analysis method of Kaplan and Meier . Many variables that were previously thought to increase the risk of infection, such as rheumatoid arthritis, older age of the patient, previous operations, and the use of corticosteroids or immunosuppressive agents, or both, were not found to increase the risk of a subsequent infection in patients who had had more than one arthroplasty with infection of one of the arthroplasties . The recent occurrence of a major systemic infection did increase the risk of infection about the other total joint replacements . Eight of the ten subsequent joint infections were due to the same causative organism as the index infection about a total joint replacement and occurred within the first year after the index infection . The initial treatment of the index infection included specific parenteral antimicrobial therapy combined with debridement and excisional arthroplasty in forty patients, removal of the components and arthrodesis in three patients, and debridement with retention of the prosthesis in twenty-five patients.(ABSTRACT TRUNCATED AT 250 WORDS) J Intensive Care Med, 1992 Jan-Feb, 7(1), 36 - 47 Rapid and definitive diagnosis of infectious diseases using peripheral blood smears; Lehmann LS et al.; A timely diagnosis is essential in the management of septicemia and septic shock . Three patients are described, all of whom presented with fever and one of whom was hypotensive at the time of admission . In each patient, rapid diagnosis of the cause of fever was possible because microorganisms were identified on a peripheral blood smear obtained at the time of admission . This identification permitted prompt initiation of appropriate antimicrobial therapy . In addition, a literature review of use of peripheral blood smears in the diagnosis of bacterial, fungal, and parasitic infections is provided. Crit Care Med, 1991 Dec, 19(12), 1486 - 90 Selective decontamination of the digestive tract in cardiac surgical patients; Fox MA et al.; OBJECTIVE: To test the hypothesis that selective decontamination of the digestive tract improves outcome in cardiac surgical patients . DESIGN: Prospective, consecutive, controlled trial over two 4-month periods . SETTING: Eight-bed, open-plan postcardiac surgery ICU . PATIENTS: All patients undergoing cardiac bypass surgery were eligible . Patients requiring endotracheal intubation for greater than 4 days were included in the analysis . In the initial 4 months, 12 (8.5%) of 141 patients required greater than 4 days of intubation . These 12 patients were not treated with selective decontamination of the digestive tract . We therefore used these patients as the control group . In the second 4-month period, 12 (6.6%) of 180 patients were treated with selective decontamination of the digestive tract and formed the study group . MAIN OUTCOME MEASURES: The primary measure was mortality . Secondary measures included oropharyngeal decontamination and the presence of lower airway infection . INTERVENTIONS: Cephradine prophylaxis . The study group received every 6 hrs 4 mL orally and 20 mL intragastrically a suspension of antimicrobial agents (tobramycin 80 mg, polymyxin E 100 mg, amphotericin B 500 mg), starting on postoperative day 1 . The control group did not receive any oral antimicrobial agents . RESULTS: Mortality rate was significantly (p less than .05) reduced from eight (66%) of 12 patients in the control group to two (16.7%) of 12 patients in the selective decontamination of the digestive tract group . No differences in oropharyngeal decontamination or lower airway infection rates between the two groups were found . CONCLUSIONS: There is a reduced mortality rate in patients receiving selective decontamination of the digestive tract . However, the reader should recognize the small sample size studied . A simple suspension of the antimicrobial agents failed to rid the oropharynx of bacteria. Am J Respir Cell Mol Biol, 1991 Dec, 5(6), 579 - 85 Interleukin-8 gene expression from human alveolar macrophages: the role of adherence; Standiford TJ et al.; The human alveolar macrophage (AM) is an important immune effector cell of the lung, as this cell possesses potent antimicrobial activities and has the ability to present antigen . In addition, the Am can secrete a number of regulatory and chemotactic cytokines in response to both endogenous and exogenous stimuli . In this study, we demonstrate that the adherence of AM to plastic or cellular substrates is an important activation event leading to the gene expression of novel chemotactic cytokine interleukin (IL)-8 . The culturing of AM on plastic induced the time-dependent accumulation of IL-8 mRNA . In addition, adherence of these cells induced the gene expression of the proinflammatory cytokines tumor necrosis factor-alpha and IL-1 beta . This adherence phenomenon was not specific to plastic, as AM cultured on collagen- or fibronectin-coated plates also expressed IL-8 mRNA upon adherence . The adherence of Am resulted in the induction of de novo IL-8 mRNA synthesis, as this mRNA accumulation was completely abrogated by actinomycin D . Adherence-induced IL-8 mRNA expression was not altered by cycloheximide, suggesting that de novo or ongoing protein synthesis was not required for induction of IL-8 message . Adherence of AM to plastic not only upregulated IL-8 mRNA levels but also induced the production of extracellular IL-8 immunoreactive protein . Both adherent and nonadherent AM treated with lipopolysaccharide generated substantial amounts of IL-8 mRNA . Adherence and lipopolysaccharide, however, acted in a synergistic fashion to dramatically augment the production of extracellular IL-8 from these cells . Our findings would suggest that AM adherence is an important macrophage-activating event that may play a critical role in the modulation of lung inflammatory responses. Infect Immun, 1991 Dec, 59(12), 4684 - 6 Gamma interferon-activated human macrophages and Toxoplasma gondii, Chlamydia psittaci, and Leishmania donovani: antimicrobial role of limiting intracellular iron; Murray HW et al.; Iron-saturated transferrin did not reverse the intracellular killing or inhibition of Toxoplasma gondii, Chlamydia psittaci, or Leishmania donovani by gamma interferon-activated human macrophages . Deferoxamine, an iron chelator, also did not impair replication within unstimulated macrophages . Limiting the availability of intracellular iron is an unlikely mechanism in human macrophage activity against these three diverse pathogens. J Chemother, 1991 Dec, 3(6), 357 - 62 In vitro activity of clarithromycin alone or in combination with other antimicrobial agents against Mycobacterium avium-intracellulare . Complex strains isolated from AIDS patients; Mascellino MT et al.; The activity of clarithromycin and five other antimicrobial agents, namely amikacin, rifampicin, rifabutin, clofazimine and ciprofloxacin, was assessed both by an agar dilution and a radiometric method in broth on 11 Mycobacterium avium-intracellulare complex (MAC) strains, recently isolated from AIDS patients . Minimum inhibitory concentrations (MICs) radiometrically determined were, in general, several times lower than MICs assessed in agar, probably because of a partial degradation of antimicrobials during the long incubation period needed for tests in solid medium . When tested in broth, rifabutin and clofazimine showed very low MICs 90 (0.24 and 0.78 microgram/ml, respectively) . Ciprofloxacin and clarithromycin also had MICs90 in the range of peak serum levels (1.93 and 3.76 micrograms/ml, respectively) . Moreover, all these antimicrobials are known to concentrate several times in macrophages . MICs90 were higher for amikacin (11 micrograms/ml) and for rifampicin (8 micrograms/ml) . When clarithromycin was tested against three MAC strains in combination with another drug, it showed a synergistic effect only when combined with rifampicin . Some synergistic effect was observed also when combining clarithromycin with rifampicin and amikacin, whereas in combination with rifabutin and clofazimine there was only an additive effect. Vet Clin North Am Equine Pract, 1991 Dec, 7(3), 627 - 39 Standing abdominal surgery; Ross MW; Safe, effective surgery can be performed in the standing, conscious horse using a combination of mechanical and chemical restraint . Clear indications for performing standing abdominal surgery exist, but many procedures are best performed under general anesthesia . The preferred approach involves a modified grid incision of the left paralumbar fossa . Flank celiotomy allows the surgeon to thoroughly explore the abdominal cavity, but few structures can be exteriorized, and visibility of abdominal contents is poor . Indications for standing abdominal surgery include diagnosis of abdominal masses, drainage and biopsy techniques, correction of left dorsal displacement of the large colon, and evaluation of rectal injuries, and performing loop colostomy techniques, laparoscopy, removal of retained testicles, correction of uterine torsions, surgical embryo transfer, ovariectomy in normal mares, and some experimental procedures . Standing surgical techniques are most useful and appropriate for surgical exploration, to correct uterine torsions, and to perform loop colostomy and surgical embryo transfer techniques . Perioperative antimicrobial and antiinflammatory therapy is recommended . Mild discomfort and ventral incisional swelling after surgery are expected. Oralprophylaxe, 1991 Dec, 13(4), 133 - 41 {Effects of dequalinium chloride and sanguinarine on the ultrastructure of early supragingival plaque}; Rau I et al.; The influence of antimicrobial mouthrinses containing dequalinium chloride or sanguinarine on early plaque formation was assessed in vivo in a clinical-experimental study . Rinses with water served as controls . After 24 and 72 hours, plastic films, which were applied to the buccal surfaces of six upper front teeth at the start of experiment, were removed and processed for transmission electron microscopic study . Dequalinium chloride or sanguinarine applied on plaque resulted in an increased and higher structured surface coating . Degenerated microorganisms were observed and the variety of bacteria seemed to be reduced . Both mouthrinses effected the early supragingival plaque formation . The effect of sanguinarine was more intensive than that of dequalinium chloride. Pharmazie, 1991 Dec, 46(12), 878 - 81 {Rough sets theory in structure-activity relationship analysis of quaternary pyridinium compounds}; Krysinski J; Relationship between chemical structure and antimicrobial activity of 53 quaternary pyridinium compounds is analysed using the theory of rough sets . The compounds are described by 8 attributes concerning structure and are divided into 5 classes of activity . The description builds up an information system . Using the rough sets approach a smallest set of attributes significant for a high quality of classification has been found . A decision algorithm has been derived from the information system showing important relations between structure and activity . It may be helpful in supporting decisions concerning synthesis of new antimicrobial compounds. J Ethnopharmacol, 1991 Dec, 35(2), 155 - 7 Antimicrobial activity of the essential oil of young pine shoots (Picea abies L.); Kartnig T et al.; The antimicrobial activity of the essential oil of young pine shoots was investigated and compared with that of a commercial pine needle oil and chloramphenicol . The correlation between the antimicrobial activity of the essential oils and their compositions, analysed by gas chromatography, is discussed. Curr Opin Dent, 1991 Dec, 1(6), 734 - 6 Cleanliness, disinfection, and sterilization of the root canal; Martin H; Disinfection is a key aspect in the preparation of root canals prior to obturation . Irrigation and intracanal medicaments are the chemical means of debridement . The bacterial role is significant, and intracanal medicaments must be cidal in their effect on bacteria and the dentinal tubules . Topical application of medicaments seem to be as effective or more effective than antibiotic applications . Glutaraldehyde and calcium hydroxide are two of the more recently studied medicaments . Calcium hydroxide shows promise as an effective microbicide . The importance of removal of bacteria and necrotic debris from the canal by chemomechanical means--mechanical preparation, cidal irrigation, antimicrobial medicaments--will enhance the successful outcome of endodontic therapy. Bratisl Lek Listy, 1991 Dec, 92(12), 589 - 93 Effects of antibiotics on the developing immune system; Dostal M et al.; A combination of penicillin and cloxacillin (Ampiclox, Beecham Research Laboratories) is indicated for prophylaxis and treatment of bacterial infections in premature babies or neonates . We studied the functional development of the immune system in the offspring of female ICR mice administered Ampiclox on days 13-16 of pregnancy in clinically relevant doses . Immune functions were assayed after immunization with sheep red blood cells in the 5th and 10th postnatal week . Changes of hemagglutinin antibodies, delayed-type hypersensitivity and proliferative responses of spleen lymphocytes and thymocytes were observed . Ampiclox influenced humoral immunity also when administered directly to rat young on postnatal days 9-11 or 14-16 . Although the clinical relevance of our experimental data remains to be established an increased sensitivity of the developing immune system to immunomodulatory effects should be considered also in the context of antimicrobial therapy . (Fig . 6, Ref . 27.) Bratisl Lek Listy, 1991 Dec, 92(12), 582 - 5 Use of drugs during pregnancy in Japanese women; Yoshioka H et al.; The use of drugs during pregnancy was studied in 890 women, who were delivered of their babies in 11 obstetric departments of general hospitals in Japan, during the one month period of November 1989 . Of these women, 889 (99.9%) took one or more drugs during the whole period of pregnancy and the number of drugs taken averaged 9.6 . During pregnancy 172 women (19.3%) did not take drugs, and the remaining 718 (80.7%) took a total of 1766 medications . The most commonly used drugs were anti-anemic, anti-abortion medications, digestives, and antimicrobials . Bronchodilators, psychotropic agents, anticonvulsants, and steroids were each prescribed during pregnancy for about 1% of the women . Malformations were found at birth in 12 infants (1.3%) . No significant relations were found between these anomalies and ingestion of particular drugs . During pregnancy, 9.3% of the women continued to smoke, and 1.9% continued to consume moderate amounts or more of alcohol . (Tab . 8, Ref . 7.) FEMS Microbiol Lett, 1991 Dec 1, 68(3), 301 - 5 Antibiotic production by the marine photosynthetic bacterium Chromatium purpuratum NKPB 031704: localization of activity to the chromatophores; Grant Burgess J et al.; Over 200 strains of marine purple photosynthetic bacteria were isolated . Two strains showed antibiotic activity towards Saccharomyces cerevisiae and were tentatively identified as Chromatium purpuratum . Crude antibiotic, prepared by solvent extraction, showed a broad antimicrobial spectrum . The highest activity was found in the chromatophore fraction . Chromatographic separation of purified light harvesting complex from one strain, NKPB 031704, showed the presence of two separate pigmented compounds which were responsible for antimicrobial activity . Our findings reveal the unexpected ability of photosynthetic bacteria to produce broad spectrum antibiotics . In addition, this is the first example of intracellular localization of antibiotic activity in a marine bacterium. Ann Plast Surg, 1991 Dec, 27(6), 559 - 61 Penetration of antibiotics through omiderm in vitro and on split-thickness skin grafts in burn patients; Russavage JM et al.; Penetration of antibiotic preparations (gentamicin, neomycin, silver sulfadiazine, mupirocin) through Omiderm, a synthetic wound covering, was tested in vitro and in 5 patients with full-thickness burns who had undergone tangential excision and split-thickness skin grafting . All antibiotic preparations tested penetrated both meshed and unmeshed Omiderm . Omiderm did not affect the zones of inhibition of antimicrobial activity as compared with controls. J Biol Buccale, 1991 Dec, 19(4), 343 - 8 Chlorhexidine and thymol release from a varnish system; Huizinga ED et al.; The release of chlorhexidine and/or thymol from an antimicrobial containing varnish in an in vitro model was investigated . Four varnishes with the same polymer base were studied; one with chlorhexidine only, one with thymol only, one with both agents and a placebo varnish without the active agents . Microscope glass slides were covered with the varnishes and stored in water . During the following three months liquid samples were regularly withdrawn and analysed for chlorhexidine and thymol content . The released amounts of chlorhexidine and/or thymol were determined by means of U.V . spectrophotometry . The results showed that chlorhexidine was released slowly from the chlorhexidine-only varnish compared with the thymol release from the thymol-only varnish . In the case of the clinically tested varnish (containing both active ingredients chlorhexidine and thymol) the amounts of thymol and chlorhexidine released were comparable . Most important, however, was the observation that in the last mentioned case both agents continued to be released after 3 months. J Biol Buccale, 1991 Dec, 19(4), 267 - 70 Concentration of antimicrobial proteins in human saliva . The effect of six months use of an antiplaque dentifrice on levels of antimicrobial proteins in unstimulated saliva from 102 adults; Turner GA et al.; Student nurses (aged 20-26 years) were assigned to two groups that were matched for plaque levels and gingival health . For six months, one group used a standard fluoride dentifrice while the other used an identical dentifrice to which zinc citrate (1%, w/w) and Triclosan (0.2%, w/w) had been added . Levels of natural antimicrobial proteins (lysozyme, lactoferrin, salivary peroxidase and Immunoglobulin A) in whole, unstimulated saliva taken from the students at the start and on completion of the six months were measured . No statistically significant differences were found in the levels of antimicrobial proteins in saliva between the test and placebo groups. J Antimicrob Chemother, 1991 Dec, 28 Suppl C, 1 - 8 Impact of chemical structure on quinolone potency, spectrum and side effects; Percival A; Following the discovery of nalidixic acid in 1962, numerous structural modifications have been made to the quinolone nucleus to increase antimicrobial activity and improve pharmacokinetic performance . A major advance occurred during the 1980s with the discovery that a fluorine at position 6 conferred broad and potent antimicrobial activity, (e.g . norfloxacin) but still with relatively less activity for Gram-positive and anaerobic organisms than Gram-negative bacteria . Subsequent developments produced quinolones with further improvements, predominantly in either solubility (e.g . ofloxacin), antimicrobial activity (e.g . ciprofloxacin) or prolonged serum half-life (e.g . pefloxacin) . Recent modifications have attempted to achieve an optimal blend of favourable properties together with minimal potential for undesirable side-effects . An example is temafloxacin with comparatively enhanced activity against Gram-positive pathogens, a balanced pharmacokinetic profile, minimal CNS penetration, and without interaction with theophylline elimination . Improvements in antimicrobial activity combined with adequate blood and tissue concentrations do offer expectancy of enhanced therapeutic efficacy for new derivatives in those infections by organisms which are 'marginally' sensitive to currently used quinolones . The possibility of resistance emerging in these organisms during treatment, should also be reduced. J Antibiot (Tokyo), 1991 Dec, 44(12), 1312 - 7 Dunaimycins, a new complex of spiroketal 24-membered macrolides with immunosuppressive activity . I . Taxonomy of the producing organisms, fermentation and antimicrobial activity; Karwowski JP et al.; The dunaimycins are a new complex of spiroketal 24-membered macrolides discovered in the fermentation broth of two actinomycetes . Based on taxonomic studies these two cultures, which were isolated from soil, were identified as Streptomyces diastatochromogenes strains AB 1691Q-321 and AB 1711J-452 . The dunaimycins possess both immunosuppressive and antimicrobial activity. J Am Vet Med Assoc, 1991 Dec 1, 199(11), 1616 - 22 Septic tenosynovitis in horses: 25 cases (1983-1989); Honnas CM et al.; The medical records of 25 horses with septic tenosynovitis treated over 7 years (1983 to 1989) were reviewed to determine clinical features of the disease and response to treatment . The median age of horses with septic tenosynovitis was 5 years (range, 1 month to 21 years) . Fourteen fore limbs and 11 hind limbs were affected . Sepsis was located in the sheath of the digital flexor tendons of 22 horses . Sepsis was located in the sheath of the extensor carpi radialis tendon (1 horse), sheath of the long digital extensor tendon (1 horse), or sheath of the common digital extensor tendon (1 horse) in the remaining horses . Nine horses received only medical treatment, using a combination of broad-spectrum parenterally administered antimicrobial drugs (8 of 9 horses), nonsteroidal anti-inflammatory drugs (8 of 9 horses), or irrigation of the wound (4 of 9 horses) . Fourteen horses were treated surgically with either transection of the palmar/plantar annular ligament of the metacarpo/metatarsophalangeal joint (5 of 14 horses), lavage of the sheath after insertion of drains into the sheath (7 of 14 horses), or both (2 of 14 horses) . All horses treated surgically were concurrently treated parenterally with broad-spectrum antimicrobial drugs and nonsteroidal anti-inflammatory drugs . Two horses with septic tenosynovitis were not treated and were euthanatized at the owners' request . Five horses were euthanatized before discharge from the hospital . Two horses (both treated medically) were lost to follow-up . Follow-up information was obtained for 18 horses, 6 to 55 months after discharge from the hospital.(ABSTRACT TRUNCATED AT 250 WORDS) Clin Obstet Gynecol, 1991 Dec, 34(4), 702 - 14 Mechanical factors in the etiology of premature rupture of the membranes; Polzin WJ et al.; The physiologic cascade that results in PROM is cyclic and probably can be entered at many points--through the production of collagenases, peroxidases, phospholipases, or prostaglandins . It can be initiated or exacerbated by bacteria . In addition, PROM is the result of direct bacterial insults or host-mediated autodestruction in response to bacterial presence or challenge . It may be affected by physical properties and stresses that are mechanical . This review of the mechanical factors that support normal chorioamnion membranes may provide an understanding of where the support can be eroded, thus leading to PROM . With this basic overview of the pathophysiology contributing to PROM, the clinician can justify clinical decisions better, depending on the patient's presentation and gestational age . The judicious use of various tocolytic agents, antimicrobial agents, and/or corticosteroids singly or in combination is predicated on the effect each of these iatrogenically administered agents will have on the mother and fetus . As more investigations are done, we will gain greater insight into the mechanical factors involved in causing PROM. Arch Pathol Lab Med, 1991 Dec, 115(12), 1235 - 40 Antimicrobial testing using oxygen consumption as the indicator of susceptibility; Murray M et al.; In the presence of inhibitory concentrations of antibiotics, a decrease in oxygen consumption precedes and predicts changes in growth rates, bacterial stasis, or death of bacteria . The susceptibility of bacteria to various antibiotics was determined by growing the microorganisms in liquid media in the presence of varying concentrations of antibiotics . The oxygen consumption was then measured with an electrode at a specified time at each concentration of the antibiotic plus a positive and negative control . The decrease in oxygen consumption by the bacteria inhibited by the antibiotic precedes changes in numbers of bacteria and is predictive of the outcome of the standard minimum inhibitory concentration . This method determines antibiotic susceptibilities in approximately 3 hours and the minimum inhibitory concentration obtained corresponds with literature values and current minimum inhibitory concentration techniques. Pediatr Infect Dis J, 1991 Dec, 10(12), 918 - 23 Imipenem compared with ceftazidime plus vancomycin as initial therapy for fever in neutropenic children with cancer; Riikonen P; Two antibiotic regimens were assessed, imipenem as monotherapy and ceftazidime plus vancomycin as combination therapy, for initial empiric therapy in febrile neutropenic children with cancer . In a prospective randomized trial of 89 evaluable consecutive episodes, 45 were treated with imipenem and 44 with ceftazidime-vancomycin . In 87% of the episodes the neutropenia was severe . Of the 89 episodes 20% were bacteremias, 10% were clinically defined focal infections and 70% were considered fevers of unknown origin . The initial treatment was successful in 82% of the imipenem group and 59% of the ceftazidime plus vancomycin group . Both regimens were well-tolerated . There was no mortality, probably owing to the prompt admission and institution of antimicrobial therapy . All of the patients were treated until neutrophil recovery; no recurrent infections were seen . In conclusion imipenem monotherapy was well-tolerated and effective as initial therapy for fever in neutropenia in children. Pediatr Infect Dis J, 1991 Dec, 10(12), 899 - 906 Comparative efficacy of erythromycin-sulfisoxazole, cefaclor, amoxicillin or placebo for otitis media with effusion in children; Mandel EM et al.; We randomly assigned children with otitis media with effusion to receive either erythromycin-sulfisoxazole, cefaclor, amoxicillin or placebo for a 2-week period, primarily to determine whether either erythromycin-sulfisoxazole or cefaclor would have greater short term efficacy than that found previously for amoxicillin, and secondarily to supplement earlier data on outcomes in placebo-treated subjects . Interim analyses showed no statistically significant (P less than 0.05) differences between the three antimicrobial treatment groups in the primary outcome measures, i.e . the prevalence of middle-ear effusion 2 and 4 weeks after entry, and indicated that postulated differences favoring the erythromycin-sulfisoxazole and cefaclor groups over the amoxicillin group were unlikely to be found even if the originally calculated sample size were attained . Subject accrual was therefore terminated . Final analysis showed no significant between-group differences in other outcome measures as well . In antimicrobial vs . placebo comparisons neither erythromycin-sulfisoxazole nor cefaclor gave more favorable outcomes than placebo, whereas more children were effusion-free in the amoxicillin group than in the placebo group at 2 weeks (31.6% vs . 14.1%, P = 0.007), but not at 4 weeks . We conclude that when antimicrobial treatment for otitis media with effusion is deemed advisable, neither erythromycin-sulfisoxazole nor cefaclor should replace amoxicillin as first line treatment. J Periodontol, 1991 Dec, 62(12), 761 - 74 The neutrophil: mechanisms of controlling periodontal bacteria; Miyasaki KT; The control of potentially periodontopathic microorganisms by host neutrophils is crucial to periodontal health . Neutrophils may use oxidative or nonoxidative mechanisms and either kill bacteria, influence bacterial growth, or modify bacterial colonization in the periodontium . Delivery of antimicrobial substances by neutrophils involves respiratory burst activity, phagocytosis, secretion, or cytolysis/apoptosis . Neutrophils contain a number of antimicrobial components including calprotectin complex, lysozyme, defensins, cofactor-binding proteins, neutral serine proteases, bactericidal/permeability increasing protein, myeloperoxidase, and a NADPH oxidase system . Many of these components are multifunctional and exhibit several mechanisms of antimicrobial activity . When comparisons are made among periodontal bacteria, differences in sensitivity to different components are observed . A hypothesis of specific defense is presented: That specific periodontal diseases can result from the failure of specific aspects of the host immune system (the neutrophil, in particular) in its interaction with specific periodontal pathogens . Failure may be due to phenotypic variation (pleomorphism) within the host or bacterial evasive strategies. Experientia, 1991 Dec 1, 47(11-12), 1228 - 9 Antimicrobial and antiviral activity of xylosyl-methylthio-adenosine, a naturally occurring analogue of methylthio-adenosine from Doris verrucosa; Pani A et al.; Xylosyl-methylthio-adenosine, a naturally occurring analogue of 5'-deoxy-5'-methylthio-adenosine, has been postulated to play a protective role during egg development in the mollusc Doris verrucosa . However, in vitro tests showed that this analogue is devoid of activity against fungi, bacteria and viruses. Can J Surg, 1991 Dec, 34(6), 548 - 50 Antimicrobial prophylaxis in general surgery; Bohnen JM; When used appropriately, antimicrobial prophylaxis is highly beneficial and cost effective . Antibiotics are not indicated for "clean procedures" such as hernia and breast surgery . A single preoperative dose will suffice, followed by an intraoperative dose if the operation takes more than 3 hours . For vascular (prosthesis or groin wound), head and neck (pharynx entered), thoracic (gastrointestinal or respiratory entrance) and high-risk gastroduodenal and biliary procedures, cefazolin, 1 g intravenously, is indicated . For procedures involving small intestine, appendix or penetrating abdominal trauma, cefoxitin or cefotetan, 2 g intravenously, is indicated . For colorectal procedures, either oral neomycin plus erythromycin or intravenous aminoglycoside plus clindamycin (or metronidazole) are effective . If valvular heart disease is present, endocarditis prophylaxis should be administered. J Fam Pract, 1991 Dec, 33(6), 579 - 84 Complications in a series of 1224 vasectomies; Alderman PM; BACKGROUND . The assessment of a vasectomy technique should be based on the incidence of complications resulting from the procedure . Differing diagnostic criteria for defining complications and the belated occurrence of some adverse events, however, have made such appraisals difficult . The purpose of this paper is to suggest criteria for defining vasectomy-related problems and to present the results of a long-term study of 1224 vasectomies . METHODS . The records of 1224 men who had a vasectomy performed by the same technique during a 4-year period were reviewed, and documented complications were tabulated and evaluated . Patients were referred residents of the lower mainland of British Columbia, and the majority were married . The group included a wide spectrum of ages, races, and occupations . Twelve categories of potential complications were defined, of which 10 were actually encountered in the study group . Infection was defined as having had antimicrobial drugs prescribed, and regret as having returned to discuss a reversal; all other complications were diagnosed based on a documented clinical diagnosis . RESULTS . Complications had been documented in 124 cases (10.6%) and included 46 minor infections (3.8%), 2 serious infections (0.16%), 23 instances of epididymitis (1.9%), 16 cases of sperm granuloma (1.3%), and 4 minor hemorrhages (0.33%) . Of 3 failures, only one (0.08%) was due to recanalization . No serious hemorrhages or late failures were seen . CONCLUSIONS . Satisfactory results were believed to be related to surgical technique and the liberal use of antimicrobial drugs . The low recanalization rate was attributed to the treatment of the ends of the vas with multiple loops of polyglycolic acid ligaturePIP: The assessment of a vasectomy technique should be based on the incidence of complications resulting from the procedure . Differing diagnostic criteria for defining complications and the belated occurrence of some adverse events, however, have made such appraisals difficult . This paper offers criteria for defining vasectomy-related problems and presents the results of a longterm study of 1224 vasectomies . The records of 1224 men who had undergone vasectomies by the same technique over a 4-year period were reviewed, and documented complications were tabulated and evaluated . Patients were referred residents of the lower mainland of British Columbia, and the majority were married . The group spanned many ages, races, and occupations . 12 Categories of potential complications were defined, of which 10 were actually encountered in the study group . Infection was defined as having had antimicrobial drugs prescribed, and regret was defined as having returned to discuss a reversal; all other complications were diagnosed based on a documented clinical diagnosis . Complications were documented in 124 cases (10.6%) an included 46 minor infections (3.8%), 2 serious infections (0.16%), 23 instances of epididymitis (1.9%), 16 cases of sperm granulomas (1.3%), and 4 minor hemorrhages (0.33%) . Of 3 failures, only 1 (0.08%) was the result of recanalization . No serious hemorrhages or late failures were seen . Satisfactory results were believed to be related to surgical technique and the liberal use of antimicrobial drugs . The low recanalization rate was the result of treatment of the ends of the vas with multiple loops of polyglycolic acid ligature . author's modified J Exp Med, 1991 Dec 1, 174(6), 1549 - 55 Macrophage deactivation by interleukin 10; Bogdan C et al.; Recombinant mouse interleukin 10 (IL-10) was exceedingly potent at suppressing the ability of mouse peritoneal macrophages (m phi) to release tumor necrosis factor alpha (TNF-alpha) . The IC50 of IL-10 for the suppression of TNF-alpha release induced by 0.5 microgram/ml lipopolysaccharide was 0.04 +/- 0.03 U/ml, with as little as 1 U/ml suppressing TNF-alpha production by a factor of 21.4 +/- 2.5 . At 10 U/ml, IL-10 markedly suppressed m phi release of reactive oxygen intermediates (ROI) (IC50 3.7 +/- 1.8 U/ml), but only weakly inhibited m phi release of reactive nitrogen intermediates (RNI) . Since TNF-alpha is a T cell growth and differentiation factor, whereas ROI and RNI are known to inhibit lymphocyte function, it is possible that m phi exposed to low concentrations of IL-10 suppress lymphocytes . m phi deactivated by higher concentrations of IL-10 might be permissive for the growth of microbial pathogens and tumor cells, as TNF-alpha, ROI, and RNI are major antimicrobial and tumoricidal products of m phi . IL-10's effects on m phi overlap with but are distinct from the effects of the two previously described cytokines that suppress the function of mouse m phi, transforming growth factor beta and macrophage deactivation factor . Based on results with neutralizing antibodies, all three m phi suppressor factors appear to act independently. Geriatrics, 1991 Dec, 46(12), 26 - 32 Pneumonia in the elderly: empiric antimicrobial therapy; Norman DC; Pneumonia, the leading cause of death due to infectious disease in the elderly, can be difficult to diagnose in this age group because clinical signs and symptoms are often muted . Without a definitive isolate, the physician must institute empiric therapy with broad-spectrum antibiotics according to the patient's condition and the setting in which the pneumonia developed . The cephalosporins, because of their safety profiles, are often used alone or in combination with other drugs to achieve broad antimicrobial coverage in elderly patients with pneumonia . In general, elderly patients with pneumonia should be hospitalized, although nursing home residents may be managed in the nursing home if adequate staff and resources are available. Antimicrob Agents Chemother, 1991 Dec, 35(12), 2625 - 9 Stimulation with cytokines enhances penetration of azithromycin into human macrophages; Bermudez LE et al.; An effective intracellular concentration of an antimicrobial agent is essential for therapy of infections caused by organisms of the Mycobacterium avium complex . We previously reported on the effect of the combination of azithromycin and tumor necrosis factor (TNF) against M . avium infection in macrophages . We now report that stimulation of macrophages either with recombinant human gamma interferon (IFN-gamma, 10(2) U/ml) or with recombinant human TNF-alpha (10(2) U/ml) resulted in an increase in the intracellular concentration of azithromycin by approximately 200% within 3 h, compared with the concentration in unstimulated macrophages . Infection of macrophages with M . avium complex led to a decrease in the uptake of {14C}azithromycin by infected cells, compared with that by uninfected controls . Stimulation of infected macrophages with recombinant IFN-gamma or TNF-alpha overcame the inhibitory effect associated with infection . These results suggest that the increased bactericidal activity of the TNF-alpha-azithromycin or IFN-gamma-azithromycin combination against M . avium is related to enhanced uptake of the antibiotic by the stimulated phagocyte. Poult Sci, 1991 Dec, 70(12), 2450 - 9 Action spectrum of antiviral factor from chicken sera; Whitfill C et al.; Rous sarcoma virus infections of regressor line chickens stimulate the transient production of antiviral factors in the serum . Earlier the present authors reported that a viral neutralization factor (VNF) inactivated Rous sarcoma virus during a 3-h incubation . The VNF is likely to have a broad antiviral and antimicrobial spectrum because it is active against several unrelated pathogenic poultry viruses . The present study measured the activity of VNF against Newcastle disease virus, infectious bursal disease virus, and infectious bronchitis virus . The VNF is active in immunologically incompetent systems and must be preincubated with the virus in order to inhibit it . Based upon the current experiments, it is proposed that VNF is not an immunomodulator but directly inactivates the virus . The VNF agent appears to be one of a newly identified class of nonspecific antiviral agents produced in vivo in chickens in response to a viral infection. J Vet Pharmacol Ther, 1991 Dec, 14(4), 359 - 66 Intramuscular and oral disposition of enrofloxacin in African grey parrots following single and multiple doses; Flammer K et al.; The intramuscular (IM) and oral (PO) disposition of enrofloxacin, a new fluoroquinolone antimicrobial drug, were evaluated in African grey parrots . Peak enrofloxacin concentration, mean (+/- SEM), at 1 h following a 15-mg/kg IM dose was 3.87 (+/- 0.27) micrograms/ml and declined with a mean residence time of 3.05 h . Peak enrofloxacin plasma concentrations at 2 to 4 h following oral doses of 3, 15, and 30 mg/kg were 0.31 (+/- 0.11), 1.12 (+/- 0.11), and 1.69 (+/- 0.23) micrograms/ml, respectively, and declined with a mean residence time of 3.44-5.28 h . The relative bioavailability of the 15-mg/kg oral dose was 48% . An equipotent metabolite, ciprofloxacin, was detected in plasma at concentrations ranging from 3 to 78% of those of enrofloxacin . Enrofloxacin concentrations and area under the curve were significantly lower, the mean residence time significantly shorter and the ciprofloxacin/enrofloxacin ratios higher, following 10 days of oral treatment at 30 mg/kg every 12 h . Following 10 days of treatment, no significant biochemical changes were noted; however, polydipsia and polyuria occurred in treated birds, but resolved quickly upon discontinuation of enrofloxacin administration . These studies indicate that a rational starting dose for enrofloxacin in psittacines (7.5-30 mg/kg BID) should be higher than those in other domestic animals. Am J Gastroenterol, 1991 Dec, 86(12), 1761 - 4 Helicobacter pylori-associated gastritis is rare in AIDS: antibiotic effect or a consequence of immunodeficiency? Edwards PD, Carrick J, Turner J, Lee A, Mitchell H, Cooper DA. Helicobacter pylori is the principal cause of type B histologic gastritis . AIDS is associated with increased susceptibility to Gram-negative enteric infections . Using a retrospective study design, we have determined the prevalence of H . pylori-associated histologic gastritis (based on gastric histopathology) in 201 patients with AIDS . These data were compared with H . pylori prevalence rates (based on serology) from healthy HIV-negative, age-matched Australian controls (n = 785) and a cohort (n = 137) of HIV-negative, dyspeptic patients undergoing panendoscopy and antral biopsy, at a community endoscopy center . Twenty-five of 201 (12.5%) patients with AIDS had histologic gastritis and, of these, six (25%) had H . pylori . The 3% (six of 201) H . pylori prevalence rate in the AIDS patients was significantly less than age-matched HIV-negative controls (22%) p = 0.001 and endoscopy center controls (59%) p = 0.009 . The explanation for this unexpectedly low prevalence of H . pylori is not possible from these data . It may be a consequence of antimicrobial therapy . Other potential explanations may include specific HIV-related host factors, including hypochlorhydria or an inadequate mucosal inflammatory response, which may impair successful colonization of H . pylori. Biochim Biophys Acta, 1991 Nov 18, 1070(1), 259 - 64 Interactions of an antimicrobial peptide, tachyplesin I, with lipid membranes; Matsuzaki K et al.; Tachyplesin I, isolated from the acid extracts of hemocytes of Tachypleus tridentatus, is a cyclic broad-spectrum antimicrobial peptide forming a rigid, antiparallel beta-sheet because of two intramolecular S-S linkages . The strong binding of the peptide to lipopolysaccharides cannot explain the susceptibilities of gram positive bacteria and fungi to the peptide . We found that tachyplesin I caused a rapid K+ efflux from Escherichia coli cells, concomitant with a reduced cell viability . This result suggests that the peptide-induced permeability enhancement of the bacterial membranes may be a plausible action mechanism . Thus, we studied the interactions of tachyplesin I with various large unilamellar vesicles (LUVs) to reveal the molecular machinery of the antimicrobial activity . Tachyplesin I induced the leakage of calcein, a trapped fluorescent marker, from LUVs of acidic phospholipids, especially phosphatidylglycerol (PG), but not from phosphatidylcholine LUVs . A detailed analysis found that the affinity of the peptide to the PG membranes is very strong and that the binding of one peptide molecule to approx . 200 lipid molecules leads to a significant leakage . The location of tachyplesin I in membranes was estimated by use of the Trp-2 fluorescence of the peptide . The presence of PG LUVs caused a blue shift of the maximum wavelength, an increase in the quantum yield, and a complete protection from fluorescence quenching by an aqueous quencher, acrylamide . Moreover, the degree of fluorescence quenching of the Trp residue by n-doxylstearates was in the order n = 5 greater than 7 greater than 12 approximately equal to 16 . These results show that the Trp residue of tachyplesin I seems to locate in a hydrophobic environment near the surface of the PG bilayers. Cell, 1991 Nov 15, 67(4), 651 - 9 Molecular cross talk between epithelial cells and pathogenic microorganisms; Wick MJ et al.; The conference brought together epithelial cell biologists and molecular microbiologists and emphasized that these seemingly diverse disciplines are intricately intertwined . The model systems discussed throughout the meeting emphasized the novel approaches available to address key issues and begin to understand the molecular details of responses triggered at the microbial-epithelial interface . For example, co-crystallization of native ligand-receptor complexes as well as biologically or chemically altered forms of these complexes will allow fine details of receptor-ligand interactions to be determined . This approach is critical in development of new generation antimicrobial agents . Furthermore, transfection techniques that allow receptor expression in model epithelia, development of representative animal model systems, and development of transgenic mouse strains will aid in dissecting microbial-epithelial interactions and will provide further advances in studies on pathogenesis and tissue and host tropism . We are only beginning to uncover the nature of the bidirectional regulatory signals that occur between microbes and hosts . We know little about how these signals relate to the disease state, to microbial virulence, or to immune function . Clearly the cross talk between cell biologists and microbiologists is an important step in unraveling the events occurring between microbes and eukaryotic cells. JAMA, 1991 Nov 13, 266(18), 2605 - 11 Pelvic inflammatory disease . Key treatment issues and options; Peterson HB et al.; OBJECTIVE.--To examine available data regarding optimal antimicrobial therapy for pelvic inflammatory disease (PID) and to address selected treatment issues confronting clinicians caring for women with PID . DATA SOURCES.--Studies evaluated to help establish the Centers for Disease Control's 1989 Sexually Transmitted Diseases Treatment Guidelines and other reports published since 1985 . A MEDLINE search of English-language literature was conducted using the indexing terms "pelvic inflammatory disease" or "pelvic infections" or "salpingitis" and "treatment" . In addition, abstracts and bibliographies of articles and books were reviewed . STUDY SELECTION.--Studies were selected for detailed review if they evaluated the effectiveness of an antimicrobial regimen for treatment of PID . DATA EXTRACTION.--All studies were evaluated to determine the numbers of women treated and the percentage with clinical or microbiologic evidence of cure . DATA SYNTHESIS.--A variety of combination antimicrobial regimens are highly effective in providing clinical and microbiologic evidence of cure; few data are available to assess optimal therapy for prevention of late sequelae . Because PID is polymicrobial in cause, recommended antimicrobial regimens are broad-spectrum in coverage . CONCLUSIONS.--No single agent that provides sufficient coverage is currently available . Several combination regimens appear highly effective clinically even among women with tubo-ovarian abscess formation . Uncertainties regarding the effectiveness of antimicrobial therapy for prevention of late sequelae complicate decisions regarding the choice among regimens and the appropriateness of ambulatory treatment of women with PID . Pending better data, hospitalization should be strongly considered, where feasible, particularly for those women with PID desiring further childbearing . Sex partners of all women with PID should be treated. Am Fam Physician, 1991 Nov, 44(5 Suppl), 73S - 77S, 80S Ambulatory management of lower respiratory tract infections; Tan JS et al.; Clinical manifestations and radiographic findings are unreliable guides to the selection of antimicrobial therapy for lower respiratory infections . Laboratory evaluation is necessary to identify the etiologic agent . Multiple oral antibiotics are available for outpatient treatment of bronchitis or pneumonia suspected to be of bacterial origin. J Clin Microbiol, 1991 Nov, 29(11), 2407 - 11 Clinical and laboratory features of Nocardia nova; Wallace RJ Jr et al.; Recent studies have shown that Nocardia asteroides isolates have five major antibiotic resistance patterns; one of these patterns identifies isolates of Nocardia farcinica . In the current study, we investigated a second pattern characterized by susceptibility to ampicillin and erythromycin . This pattern was seen in 17% of 223 clinical isolates identified by standard techniques as N . asteroides and associated with diseases typical for nocardiae . Biochemically, isolates with this drug pattern were relatively homogeneous and identical to the type strain and previous descriptions of Nocardia nova . The strains studied were unique among nocardiae in having both alpha- and beta-esterase activity (85 and 95%, respectively) . However, the arylsulfatase activity at 14 days (75%) and antimicrobial susceptibility patterns, including susceptibility to erythromycin (100%), were the only routinely available methods that would separate N . nova strains from other members of N . asteroides . N . asteroides should be considered a complex because current clinical identification schemes include isolates of N . farcinica and N . nova and may well include additional species . This is the first detailed description of N . nova as a pathogen in humans. Nature, 1991 Nov 7, 354(6348), 84 - 6 Generation and use of synthetic peptide combinatorial libraries for basic research and drug discovery; Houghten RA et al.; Existing methods for the synthesis and screening of large numbers of peptides are limited by their inability to generate and screen the requisite number (millions) of individual peptides and/or their inability to generate unmodified free peptides in quantities able to interact in solution . We have circumvented these limitations by developing synthetic peptide combinatorial libraries composed of mixtures of free peptides in quantities which can be used directly in virtually all existing assay systems . The screening of these heterogeneous libraries, along with an iterative selection and synthesis process, permits the systematic identification of optimal peptide ligands . Starting with a library composed of more than 34 million hexa-peptides, we present here the precise identification of an antigenic determinant recognized by a monoclonal antibody as well as the straightforward development of new potent antimicrobial peptides. Pediatr Ann, 1991 Nov, 20(11), 622 - 6 The diagnosis and management of mastoiditis in children; Myer CM 3rd; Even though mastoiditis as a complication of AOM is uncommon, its recognition is imperative to institute timely therapy . Acute coalescent mastoiditis generally follows a severe bout of AOM . Intravenous antimicrobial therapy and myringotomy drainage are usually satisfactory measures . However, refractory cases may require a simple mastoidectomy . Chronic mastoiditis in children is treated initially with intravenous antimicrobial therapy and vigorous aural toilet, which is successful in most patients . Mastoidectomy may be required in selected patients . The clinician must be aware of the differential diagnosis of chronic otorrhea so that biopsies can be obtained whenever a neoplasm is suspected. Pediatr Ann, 1991 Nov, 20(11), 609 - 10, 612-4, 616 Strategies to control recurrent acute otitis media in infants and children; Teele DW; Recurrent AOM is a plague in many societies . The considerable attendant morbidity is best reduced through extended periods of antimicrobial prophylaxis . Children who are not helped by this intervention and who are experiencing sufficiently severe disease become candidates for surgical management with tympanostomy tubes . Should both strategies fail, then an adenoidectomy should be considered . In every case, the practitioner must weigh the severity of the recurrent illness against the real costs and risks of surgery. Pediatr Ann, 1991 Nov, 20(11), 600 - 1, 603-8 Antibiotic treatment failures in acute otitis media; Harrison CJ et al.; When the clinician is presented with apparent treatment failure, noncompliance must be considered first . If this is the problem, the medication should be reinstituted after the parents are counseled . Next, the possibility of a superimposed viral illness also must be considered . When satisfied that these are not the problems, the clinician must consider whether the MEE has created so much positive pressure that antimicrobials cannot completely penetrate the middle ear space . If positive pressure is considered the problem, the same or another antimicrobial should be continued for a second 10-day course, allowing the pressure to decrease with time permitting more complete antibiotic penetration into the MEE . Alternately, clinicians with appropriate training may elect to relieve the pressure by tympanocentesis or myringotomy . If the clinician decides that it is more likely that the patient has a pathogen resistant to the initial choice of an antimicrobial agent, a second course of a more potent second-line antimicrobial is appropriate . Patients who fail a second course of antimicrobials should receive an alternate second-line antimicrobial or undergo drainage of the middle ear abscess . Those who fail a third course of antimicrobials should be referred to an otolaryngologist for evaluation or surgical intervention . Antimicrobials should be continued until the consultation occurs . This article has outlined potential clinical presentations for treatment failures as well as choices for second-line antibiotics . The relation of anatomic, environmental, microbial, and antimicrobial factors in persistent AOM must be considered in order to determine if the clinician should do more than merely prescribe second-line antibiotics.(ABSTRACT TRUNCATED AT 250 WORDS) Postgrad Med, 1991 Nov 1, 90(6), 115 - 8, 121-2 Appropriate use of antimicrobial agents . Nine principles; Sawyer MD et al.; After determining that a patient with an infection would benefit from an antimicrobial agent, several factors must be weighed to arrive at an appropriate choice: seriousness of the infection, the patient's drug allergies, and drug efficacy, toxicity, and cost . Rapid stains, cultures, and sensitivity studies are often helpful in guiding therapy and are critical to appropriate treatment of serious infections . Consideration should also be given to other forms of management, such as control of the source of infection, prophylaxis, and physiologic management. J Urol, 1991 Nov, 146(5), 1413 - 7 Antimicrobial tissue penetration in a rat model of E . coli epididymitis; Tartaglione TA et al.; Following induction of unilateral epididymitis by intratesticular injection of E . coli, a single intraperitoneal dose of amdinocillin, ampicillin, doxycycline, tobramycin, or trimethoprim/sulfamethoxazole was administered to five groups of rats . The animal was sacrificed serially and concentrations of antibiotic in serum, infected epididymides, and non-infected epididymides were determined by high performance liquid chromatography . The ratio of infected to non-infected tissue area under the curve values was 1.05 for trimethoprim, 1.58 for sulfamethoxazole, 1.67 for amdinocillin, 2.01 for tobramycin, 2.25 for doxycycline, and 2.58 for ampicillin . Except for trimethoprim, infected tissue concentrations were significantly greater than compared to uninfected epididymal levels (p less than 0.05) . Antibiotic concentrations in infected epididymides compared to serum revealed overall penetration of 34% for amdinocillin, 66% for sulfamethoxazole, 70% for ampicillin, 76% for tobramycin, 256% for trimethoprim, and 257% for doxycycline . In a rat model of epididymitis, trimethoprim and doxycycline demonstrated the greatest degree of epididymal penetration compared to serum . All antibiotics except trimethoprim had significantly greater penetration into infected tissue when compared to non-infected epididymal tissue. Am J Emerg Med, 1991 Nov, 9(6), 551 - 2 Ciprofloxacin interaction with sodium warfarin: a potentially dangerous side effect; Renzi R et al.; Ciprofloxacin, a quinolone antibiotic which exhibits minimal side effects and has broad antimicrobial spectrum, is being used frequently to treat various infections . A patient is reported who had previously maintained a stable prothrombin time on Coumadin for 5 years, and who exhibited a marked prolongation of prothrombin time when placed on ciprofloxacin for gastroenteritis. J Immunol, 1991 Nov 1, 147(9), 3210 - 4 Cloning of the cDNA for the serine protease homolog CAP37/azurocidin, a microbicidal and chemotactic protein from human granulocytes; Morgan JG et al.; Human cationic antimicrobial protein (CAP37) is a neutrophil granule protein with monocyte chemotactic and antibacterial activity . A CAP37 cDNA clone of 899 bp was isolated from an HL-60 cDNA library using degenerate oligonucleotide probes based on partial N-terminal sequence of the CAP37 protein . The cDNA sequence predicts an open reading frame of 753 bp encoding a protein of 251 amino acids . A 26-residue eukaryotic signal peptide and a potential 7 amino acid pro-peptide are present at the N-terminus of the protein . The cDNA sequence also predicts three N-linked glycosylation attachment sites and eight intramolecular cysteines . The deduced amino acid sequence of CAP37 shows 44, 42, and 32% homology at the amino acid level to neutrophil elastase, myeloblastin, and cathepsin G, respectively, suggesting that CAP37 is a member of the serine protease gene family . CAP37 does not possess serine protease activity probably due to mutations in two of three residues in the catalytic triad of the "charge relay system." Whereas CAP37 is expressed in undifferentiated HL-60 cells no message is detected in mature neutrophils. Vet Med (Praha), 1991 Nov, 36(11), 657 - 63 {Use of the anticoccidial agent, tortrazuril (Baycox, Bayer) in coccidiosis in suckling pigs}; Koudela B et al.; At present neonatal coccidiosis caused by Isospora suis is known to be an important disease in piglets . The coccidium I . suis was diagnosed as the causative agent of diarrhoeic disease in piglets on a large pig farm with continuous farrowing operation . The diagnosis of coccidiosis was based on clinical history, gross lesions, histopathology, stained impression smears and aided by detection of oocysts in the faeces . Coccidiosis was associated with diarrhoea in piglets at the age of five to fourteen days . The disease was characterized by variable morbidity and only a portion of the litters was usually affected at one time . The piglets appeared listless, and suffered from yellow watery scours progressing to yellow pasty scours over a three- to five-day period . The lack of response to common antimicrobial therapy, and/or vaccination of sows for E . coli was observed . The prophylactic and therapeutic efficacy of tortrazuril (Baycox, Bayer) against coccidiosis was evaluated in naturally infected piglets . Tortrazuril at a dose of 20 mg/kg, given perorally to each piglet on days 6 and 8 of age, proved to be efficacious in preventing clinical coccidiosis in piglets . Tortrazuril fully controlled the oocyst output, prevented the development of diarrhoea but not improved the weight gains in three-week-old piglets if compared to the untreated controls . The prophylactic and therapeutic efficacy of tortrazuril was compared with another drug--amprolium (Amprovin, MSD) . Amprolium at a dose of 100 mg/kg, given perorally to piglets from day 6 to 8 of age, was not efficacious in preventing clinical porcine neonatal coccidiosis . Amprolium reduced the oocyst output, but not prevented the development of diarrhoea . Tortrazuril (Baycox, Bayer) is clearly effective against porcine neonatal coccidiosis caused by I . suis. Antimicrob Agents Chemother, 1991 Nov, 35(11), 2246 - 52 Double-blind comparison of teicoplanin versus vancomycin in febrile neutropenic patients receiving concomitant tobramycin and piperacillin: effect on cyclosporin A-associated nephrotoxicity; Kureishi A et al.; A prospective, randomized, and double-blind study comparing teicoplanin with vancomycin in the initial management of febrile neutropenic patients was conducted . Teicoplanin was administered at 6 mg per kg of body weight every 24 h (q24h) intravenously (i.v.) after initial loading at 6 mg/kg q12h for three doses . Vancomycin was administered at 15 mg/kg q12h i.v . Patients also received piperacillin (3 g q4h i.v.) and tobramycin (1.5 to 2.0 mg/kg q8h i.v.) . Of 53 patients enrolled, 50 were judged to be evaluable . Among these, 25 received teicoplanin and 25 received vancomycin . At enrollment, both groups were comparable in age, sex, renal function, underlying hematologic condition, and concurrent therapy . Both groups had similar sites of infection and microbial pathogens . Empirical antimicrobial therapy resulted in the cure of or improvement in 23 (92%) teicoplanin patients and 21 (84%) vancomycin patients (P = 0.67) . Failures occurred with two vancomycin patients but no teicoplanin patients . Clinical response was indeterminate for two patients in each group . Adverse reactions occurred significantly more often in the vancomycin group than in the teicoplanin group (P = 0.01), and these reactions required the termination of the study regimens of 6 vancomycin versus 0 teicoplanin patients (P = 0.02) . Nephrotoxicity was observed more frequently in the vancomycin group (10 versus 2 patients; P = 0.02) . Subgroup analysis revealed a significant deterioration of renal function when vancomycin and cyclosporin A, but not teicoplanin and cyclosporin A, were used concurrently (P = 0.02) . Among patients who received vancomycin and amphotericin B or teicoplanin and amphotericin B concurrently, deterioration in renal function was equivalent in both groups . Teicoplanin in the dosage employed was tolerated better than vancomycin in the empirical treatment of fever and neutropenia in our patient population. Indian J Pediatr, 1991 Nov-Dec, 58(6), 783 - 7 Cost effective strategy for promotion of appropriate case management of diarrheal diseases--establishment of DTUs; Patwari AK; Oral rehydration therapy (ORT) is one of the essential components of child survival technologies which are currently being utilised to reduce morbidity and mortality on account of common illnesses . ORT has made it possible to undertake a global effort to reduce deaths from dehydration and diarrhea associated malnutrition . Appropriate case management can also combat deaths from dysentery and persistent diarrhea . During the last decade considerable success has been achieved by incorporating this simple, effective and economic therapeutic intervention in the primary health care package . However, the ultimate objective of improved case management of diarrhea including the use of ORT at all levels of health care system is yet to be achieved . Patients with dysentery need antimicrobial therapy apart from ORT . Clinical experience has shown that with ORT and appropriate dietary therapy, most patients with persistent diarrhea can be managed effectively . Unfortunately, injudicious use of intravenous fluids and irrational prescription of antibiotics and anti-diarrheal agents is quite common even in the hands of pediatricians . The training of mothers visiting health facilities is poor for ORT and feeding . Establishment of diarrhea training and treatment units (DTUs) is aimed to improve current practices in the teaching hospitals and to promote appropriate case management of diarrhea by all health personnel. J Protozool, 1991 Nov-Dec, 38(6), 161S - 163S Hemolytic properties of lytic peptides active against the sporozoites of Cryptosporidium parvum; Arrowood MJ et al.; Cryptosporidium parvum is a protozoan parasite that causes mildto-severe diarrheal disease in animals and humans . There are currently no effective chemotherapeutic agents available for the treatment of cryptosporidiosis . Recently, small, naturally occurring antimicrobial lytic peptides with anti-protozoal activities have been described . In the present study, we compare the in vitro anti-cryptosporidial activities of synthetic lytic peptides and their corresponding hemolytic activities after a 30 min incubation at 37 degrees C . Sporozoite viability was assessed microscopically by the uptake of the vital dyes fluorescein diacetate (FDA) and propidium iodide (PI) . Hemolysis was assessed spectrophotometrically by the release of soluble hemoglobulin . The most active peptide, Hecate-1, reduced sporozoite viability by 85.5% with a corresponding hemolytic activity of 21.5% at a concentration of 10 microM. J Nat Prod, 1991 Nov-Dec, 54(6), 1625 - 33 Antimicrobial diterpenes of Croton sonderianus, 1 . Hardwickic and 3,4-secotrachylobanoic acids; McChesney JD et al.; The hexane-extracted resin of the roots of Croton sonderianus showed antimicrobial activity in standardized bioassays . Fractionation of the resin yielded two acid diterpenes, (-)-hardwickic acid {2} and the new 3,4-secotrachylobanoic acid {5} as major bioactive materials. Arch Pharm (Weinheim), 1991 Nov, 324(11), 847 - 51 Synthesis and antimicrobial evaluation of some cephem derivatives; Kalcheva V et al.; Two novel cephem derivative series were synthesized: 7-(D-alpha-aminophenyl-acetamido-)-3-methyl-3-cephem-4-carboxylic acid monohydrate (Cephalexin) derivatives and those of 7-amino-3-(1-methyl-1H-tetrazol-5-yl)-thio methyl-3-cephem-4-carboxylic acid (7-AMTCA) . The antimicrobial activity of the prepared compounds was studied and compared to that of known cephalosporin antibiotics of the first generation against 12 standard strains and 189 clinical isolates of Gram-positive and Gram-negative microorganisms . The Cephalexin derivatives 4a-f show a narrow activity spectrum and are inactive while 5c and 5d are more active than the Cephalexin and Cephazolin antibiotics against clinically isolated S . aureus and S . epidermidis strains. Arch Pharm (Weinheim), 1991 Nov, 324(11), 827 - 32 {Rough sets theory in the analysis of structure-activity relationships of quaternary quinolinium- and isoquinolinium compounds}; Krysinski J; Relationship between chemical structure and antimicrobial activity of 72 quaternary quinolinium and isoquinolinium compounds is analyzed using the theory of rough sets . The compounds are described by 11 attributes concerning structure and are divided into 3 classes of activity . The description builds up on information system . Using the rough sets approach a smallest set of attributes significant for a high quality of classification has been found . A decision algorithm has been driven from the information system showing up important relations between structure and activity . This may be helpful in supporting decisions concerning synthesis of new antimicrobial compounds. Antimicrob Agents Chemother, 1991 Nov, 35(11), 2395 - 400 Influence of the unbound concentration of cefonicid on its renal elimination in isolated perfused rat kidneys; Rodriguez CA et al.; The effect of variations in plasma protein binding on the renal excretion of cefonicid was assessed by using isolated perfused rat kidneys . Cefonicid exhibits preferential binding ex vivo to human serum albumin (HSA), as opposed to bovine serum albumin (BSA), and is eliminated mainly by tubular secretion, a process that was reported to be dependent on the total drug concentration . This contradicts previous studies with antimicrobial compounds and other drugs of low renal extraction in which the unbound drug concentration was shown to be the driving force for carrier-mediated tubular transport . To clarify this discrepancy, we performed perfusion studies by using 6% BSA at initial concentrations of 200 micrograms/ml (n = 6) and 20 micrograms/ml (n = 9) and in a combination of 4% BSA plus 2% HSA at initial concentrations of 200 micrograms/ml (n = 4) . The excretion ratio {ER = CLR/(fu x GFR)} of cefonicid decreased with increasing unbound concentrations, whereas no apparent relationship with the total concentration was evident . At similar total concentrations of cefonicid, the renal clearance remained unchanged; the secretion clearance increased significantly in the 4% BSA-2% HSA experiments, reflecting the reduced unbound fraction and unbound drug concentration of cefonicid . The excretion ratio data were compatible with a model in which Michaelis-Menten kinetics were required to describe active transport and secretion was dependent on the unbound cefonicid concentration . As a result, changes in plasma protein binding as a result of drug interactions or disease states could significantly influence the tubular transport capability of compounds with low renal extraction. Diagn Microbiol Infect Dis, 1991 Nov-Dec, 14(6), 519 - 21 Antimicrobial activity of three investigational oral cephalosporins (BK-218, cefdinir, and RU29246) against Legionella; Jones RN et al.; Three new, orally administered cephalosporins (BK-218, cefdinir, RU29246) were tested against 13 representative strains of Legionella . Cefdinir was most active {50% minimum inhibitory concentration (MIC50), 1 micrograms/ml}, a potency comparable to the reference drug cefixime and eightfold less active than erythromycin . BK-218 was the least active cephalosporin (MIC50, 8 micrograms/ml) or 100-fold less potent than rifampin . These investigational cephems appear poorly suited by activity assays for Legionellosis therapy. Diagn Microbiol Infect Dis, 1991 Nov-Dec, 14(6), 465 - 71 Oxazolidinones, a new class of synthetic antituberculosis agent . In vitro and in vivo activities of DuP-721 against Mycobacterium tuberculosis; Ashtekar DR et al.; DL-S-n-(3-(4-acetyl)-2-oxo-5-oxazolidynyl methyl) acetamide (DuP-721) is an orally active representative of the oxazolidinone series of antimicrobials . At concentrations ranging from 1.5 to 4 micrograms/ml, DuP-721 inhibited equally the strains of Mycobacterium tuberculosis susceptible and resistant to conventional antituberculosis drugs . DuP-721 inhibited M . gordonae and M . fortuitum at 3.9 micrograms/ml, M . kansasii at 1.95, and M . scrofulaceum at 15.6 micrograms/ml . It was not active against M . avium and M . intracellulare at concentrations of 250 micrograms/ml . The inhibition of the metabolism of M . tuberculosis as indicated by the liquid scintillation radiometric method was 56% at fourfold the minimum inhibitory concentration (MIC) of DuP-721 that compared well to that of the fourfold MIC concentrations of rifampicin and isoniazid . The in vitro activity of DuP-721 was not affected by reducing the pH from 6.8 to 5.5 . In mice infected with M . tuberculosis, the 50% effective dose (ED50) for DuP-721 was 13.2 mg/kg when administered daily beginning 4 hr postinfection for 17 days . The ED50 was 71.8 mg/kg when DuP-721 was administered only on days 11 and 12 postinfection . A 100% survival rate was obtained at 50 and 160 mg/kg when DuP-721 was administered daily for 17 days, and only on days 11 and 12 after the infection, respectively . The increase in the survival time by DuP-721 at 100 mg/kg (eightfold the ED50 dose) when administered daily for 17 days beginning 4 hr after infection was inferior to that by eightfold the ED50 dose of rifampicin and isoniazid administered on days 11 and 12 postinfection.(ABSTRACT TRUNCATED AT 250 WORDS) Int J Clin Pharmacol Ther Toxicol, 1991 Nov, 29(11), 451 - 3 New bioavailability parameters to compare the efficacy of antimicrobial drugs in dosage forms; Koeleman HA et al.; Pharmacokinetic parameters such as AUC, Cmax and tmax have been used to represent the rate and extent of absorption of drugs from dosage forms in comparative bioequivalence testing . None of these parameters gives a direct indication of how long the drug concentration is maintained above an acceptable level e.g . minimum inhibitory concentration (MIC) or the minimum effective concentration (MEC) . This is clinically important in evaluating the onset and duration of a therapeutic effect obtained from a test dosage form in comparison to the reference dosage form . The purpose of this study is to investigate the possibility of a bioavailability parameter which relates the time that the drug concentration in the systemic circulation is maintained above a certain level (te) and the first time that the blood concentration exceeds this level (to) . Two methods were used to calculate the time that drug levels are maintained above a certain minimum level . The proposed parameters proved to be valuable when the efficacy of erythromycin was used as an example . Although some problems, such as undefined MIC/MEC may arise, te and to can be used along with the conventional bioequivalence parameters to obtain a better indication of the clinical efficacy. Biol Mass Spectrom, 1991 Nov, 20(11), 669 - 76 Silicon membrane interface for the direct analysis of Kathon CG in aqueous solutions and cosmetic emulsions; Favretto D et al.; An easy determination of Kathon CG, an antimicrobial agent widely used in cosmetic and toiletry products, has been achieved by means of silicone membrane interfaced mass spectrometry . Low levels of the above preservative (up to p.p.b.) could be easily detected in both aqueous solutions and cosmetic emulsions . Valuable information has been obtained on the stabilization and decomposition processes to which the organic components of Kathon CG are subject . The role of magnesium ions, which are present as a stabilizing agent in Kathon CG formulation, in these processes has been investigated, leading to the identification of some degradation products. Allergy Proc, 1991 Nov-Dec, 12(6), 361 - 4 Management of patients allergic to antimicrobial drugs; Sullivan TJ; Allergic reactions to antimicrobial drugs cause significant morbidity in approximately 1% of treated patients . Those who express allergic reactions to antimicrobial drugs or who are at increased risk of reacting also can present difficult diagnostic and management problems . Recent studies suggest that patients who have expressed allergic reactions to antimicrobial drugs in the past or who are the offspring of antimicrobial drug-allergic parents are at increased risk of antimicrobial drug allergy . This propensity to antimicrobial drug allergy is not restricted to specific classes of drug or to specific patterns of allergic reactions . The concept that antimicrobial drug allergy often is a recurrent disease rather than an isolated event has generated new approaches to the comprehensive management of high-risk patients . This concept also has suggested new areas for investigation that may provide fundamental new insights into why some persons express immune responses to haptens and others do not. Acta Pharm Hung, 1991 Nov, 61(6), 317 - 23 Constituents and biological activity of Bidens pilosa L . grown in Egypt; Sarg TM et al.; Column chromotography and preparative TLC of the light petroleum-diethyl ether extract from Bidens pilosa L . afforded tridecapentyn-1-ene, trideca-2,12-diene-4,6,8,10-tetrayne-1-ol, trideca-3,11-diene-5,7,9-triyne-1,2-diol and trideca-5-ene-7,9,11-triyne-3-ol . The compounds were identified on the bases of UV, 1H-NMR spectra and comparison with reported data . The chloroform extract was chromatographed to yield B-amyrin, phytosterin-B, esculetin and B-sitosterol glucoside . The petroleum ether extract afforded long chain ester, saturated hydrocarbon, long chain alcohol, B-amyrin, phytosterin-B, lupeol and lupeol acetate . GLC analysis of the fatty acids indicated the presence of 5 acids . The antimicrobial test was carried out to indicate an evident activity . The antidiabetic activity showed non significant decrease of blood glucose. Eur J Epidemiol, 1991 Nov, 7(6), 677 - 81 Mycobacterium xenopi isolation from clinical specimens in the Florence area: review of 46 cases; Tortoli E et al.; The occurrence of Mycobacterium xenopi (MX) isolates is not homogeneous in various geographic zones . In the Florence area, between 1975-1989, strains of MX from 64 different patients have been isolated . The review of bacteriological and clinical data of 46 of them, from whose sputum MX had been grown, allowed to diagnose for 26% the commensal nature of this finding, for 41% the concomitance with a tubercular infection and for the remaining 33% the pathogenicity of this microorganism . The increased occurrence of MX isolates, their high rate of pathogenicity and the remarkable homogeneity of their biochemical, cultural and antimicrobial sensitivity patterns seem to suggest the hypothesis of an endemic focus of this species in the Florence area. Rev Infect Dis, 1991 Nov-Dec, 13(6), 1151 - 62 Hemolysis and infection: categories and mechanisms of their interrelationship; Berkowitz FE; Different cause-and-effect relationships between hemolytic and infectious processes are categorized in a clinically useful manner as follows: infections causing hemolysis by invasion of red blood cells (RBCs), by hemolysins, or by immune mechanisms; oxidative damage to RBCs during infections; hemolysis secondary to infection-induced pathologic processes; hemolytic effects of antimicrobial therapy; and predisposition of an individual to infection caused by an underlying hemolytic disorder or therapy for that disorder . The mechanisms of these interrelationships are discussed in detail. Nihon Kyobu Shikkan Gakkai Zasshi, 1991 Nov, 29(11), 1420 - 4 {Clinical study of respiratory infections complicating bronchial asthma}; Konishi M et al.; We conducted a clinical study on respiratory infections complicating bronchial asthma . Transtracheal aspiration (TTA) was performed 37 times in 22 patients . The most frequently isolated organism was H . influenzae . The patients in whom organisms were isolated on TTA had a high incidence of fever and evidence of inflammation . Antimicrobial therapy caused a decrease in indices of inflammation (white blood cell count and ESR), but was less effective against the asthmatic symptoms . Respiratory infection may play a complex role in the clinical picture of bronchial asthma. HNO, 1991 Nov, 39(11), 419 - 23 {Current antibiotic treatment of ENT infections in the child}; Luckhaupt H; Most acute infections of the upper respiratory tract are primary viral infections . Bacterial infections and superinfections in the head and neck in children require appropriate antibiotic therapy to prevent complications . No essential change of the bacterial spectrum of ENT infections of children has been seen in recent years . Penicillins and macrolides are important antimicrobial agents in current therapy . Beta-lactams are an important therapeutic advance. Bone Marrow Transplant, 1991 Nov, 8(5), 363 - 7 An assessment of the efficacy of antimicrobial prophylaxis in bone marrow autografts; Wimperis JZ et al.; Fifty-three patients undergoing autologous bone marrow transplantation received antimicrobial prophylaxis with ciprofloxacin with or without erythromycin and low dose intravenous amphotericin B . Eight patients remained afebrile throughout the neutropenic period . All other patients had one or more febrile episodes . The median time to fever after the onset of neutropenia was 7 days . There were no gram-negative organisms isolated from blood cultures during any of these episodes whereas gram-positive organisms were isolated in 28 . There was one death in this series associated with sepsis . The use of low-dose prophylactic parenteral amphotericin did not prevent the subsequent successful use of full dose amphotericin for antibiotic-resistant fever . Ciprofloxacin effectively prevents gram-negative sepsis . The addition of erythromycin does little to prevent gram-positive sepsis . The use of regimens with agents with activity against gram-positive organisms is appropriate initial treatment of all febrile neutropenic episodes. J Clin Immunol, 1991 Nov, 11(6), 357 - 62 Indomethacin-sensitive monocyte killing defect in a child with disseminated atypical mycobacterial disease; Ridgway D et al.; A child with disseminated disease due to Mycobacterium avium had progressive disease in spite of 4.5 years of therapy with multiple antimicrobial agents selected on the basis of in vitro sensitivity testing of her organism . A defect in monocyte bactericidal activity was detected which was corrected in vitro by exposure of the patient's monocytes to indomethacin and normal serum . Indomethacin therapy resulted in normalization of monocyte bactericidal activity and striking, albeit temporary, clinical improvement. Vet Clin North Am Food Anim Pract, 1991 Nov, 7(3), 793 - 804 Treatment of Mycobacterium paratuberculosis infection in ruminants; St-Jean G et al.; Paratuberculosis is a chronic, debilitating, fatal condition that usually is clinically undetectable until the onset of copious diarrhea . Paratuberculosis is caused by an acid-fast organism, M . paratuberculosis . Successful eradication of paratuberculosis depends on the early detection of infected animals, thereby allowing removal of carrier animals from the herd . Treatment for paratuberculosis is therefore rarely indicated or undertaken; however, treatment may be considered for animals of exceptional genetic value or companion animals . Antimicrobials reviewed in this article for the treatment of paratuberculosis include isoniazid, rifampin, streptomycin, amikacin, clofazimine, and dapsone . Treatment of paratuberculosis requires daily medication for extended periods and results in palliation of the disease rather than a definitive cure . The treatment for paratuberculosis recommended by the authors is isoniazid at 20 mg/kg administered orally every 24 hours for the rest of the animal's life . When the animal has acute onset of diarrhea, rifampin at 20 mg/kg every 24 hours is also administered orally . In severe, imminently life-threatening cases, an aminoglycoside should be administered concurrently for 3 to 8 weeks . This protocol (isoniazid, rifampin, and an aminoglycoside) will help ensure that Mycobacteria organisms are sensitive to at least two of the antibiotics . Rifampin treatment can be discontinued if clinical signs of paratuberculosis disappear and the cost of therapy is judged excessive . The combined therapeutic approach has been used in three animals, and the results are presented in this article . Because isoniazid, rifampin, and some aminoglycosides are not approved for use in food animals in the United States of America, the meat or milk from treated animals should not be used for human consumption. Vet Clin North Am Food Anim Pract, 1991 Nov, 7(3), 729 - 46 Treatment of cardiovascular disease in cattle; McGuirk SM; Cardiac diseases of cattle may involve valvular structures, myocardium, pericardium, or blood vessels and are manifested by the clinical signs of cardiac dysrhythmias, cardiac murmurs, generalized edema, muffled heart sounds, jugular venous distention, jugular venous pulsations, pulmonary edema, pleural effusion, or ascites . Digoxin, quinidine, and furosemide can be used effectively to control signs of CHF and cardiac arrhythmias . Combination antimicrobial therapy can be successful for cows with infective endocarditis and thrombophlebitis . Pericardial fluid drainage may temporarily improve cattle with traumatic pericarditis or lymphosarcoma so that short-term goals may be reached. Vet Clin North Am Food Anim Pract, 1991 Nov, 7(3), 695 - 711 Clinical pharmacology of antimicrobial drugs for the treatment of septic neonatal calves; Wilcke JR; For a given infection, each antibiotic will have a probability of producing a beneficial outcome . Decisions that increase the antibacterial activity of the therapeutic regimen against the bacterial infection will increase the probability of a beneficial outcome . Unfortunately, such decisions may increase the cost of therapy or the risks of toxicity . Finally, neonatal calves presented for therapy are not of uniform value . It is logical to employ different antimicrobial drugs and ancillary therapies when the value of the individual calf is considered . A constructive balance between efficacy, cost, and toxicity establishes the value of a therapeutic approach for the client. Vet Clin North Am Food Anim Pract, 1991 Nov, 7(3), 659 - 68 Problems and practice in mass medication of beef cattle; Pollreisz JH et al.; Mass medication is a health management tool that, when used appropriately, results in cost savings and sound economic return to the food animal producer . Careful planning and consideration should precede the implementation of a mass treatment program, clearly defining the goal to be achieved and a detailed plan of execution . For economic as well as professional reasons, indiscriminate administration of antimicrobials to large groups of food animals should be avoided. J Periodontol, 1991 Nov, 62(11), 649 - 51 Reduction of salivary bacteria by pre-procedural rinses with chlorhexidine 0.12%; Veksler AE et al.; The purpose of this study was to assess the effect of pre-procedural rinsing (2 consecutive rinses) with 0.12% chlorhexidine gluconate (CHX) on salivary bacteria during scaling and root planing procedures (S&RP) . Because blood and debris arising from S&RP could inactivate CHX and decrease its antimicrobial effect, patients were evaluated throughout their appointment . Forty subjects rinsed with either 15 ml of CHX rinse or control (sterile water) for 30 seconds, expectorated and immediately rinsed again for 30 seconds . Unstimulated saliva samples were obtained at baseline (immediately before rinsing), and at 1 minute, 30 minutes, and 60 minutes after baseline . All 30 and 60 minute samples contained visible blood and debris . Samples were immediately diluted in transport fluid containing a CHX-neutralizer and then plated on trypticase soy agar for enumeration of the total aerobic and facultative bacterial load . The dual rinses with 0.12% CHX immediately reduced the salivary bacterial load 97% and this reduction persisted for 60 minutes during S&RP . At 30 minutes and at 60 minutes aerobic bacteria were reduced 77% compared to control, and 96% compared to baseline . CHX was not inactivated by the high organic load (blood and debris) present during the procedure . Pre-procedural rinsing with CHX has a profound and sustained effect on the aerobic and facultative flora of the oral cavity, which may contribute to a variety of clinical benefits . Pre-procedural rinsing may also be of value in protecting patients and dental professionals during dental manipulations. J Infect, 1991 Nov, 23(3), 297 - 302 Two cases of Nocardia asteroides sternotomy infection treated with ofloxacin and a review of other active antimicrobial agents; Yew WW et al.; Two patients who developed post-operative sternotomy infections due to Nocardia asteroides were treated successfully with ofloxacin, in vitro susceptibility of the organisms being used as a guide to dosage . The place of this drug in the treatment of infection due to Nocardia asteroides merits further investigation. J Infect, 1991 Nov, 23(3), 271 - 8 Comparison of clinical and environmental strains of Escherichia coli isolated in Spain; Pont D et al.; Susceptibilities to antimicrobial agents, bacteriophage lysis patterns and enzymatic polymorphism analysis were used to study genetic variability in Escherichia coli in order to study the relationship between clinical and environmental isolates of the species . Enzymatic polymorphism analysis proved the most useful . The findings were complemented by numerical analysis of phage typing and antimicrobial susceptibilities. Am J Hosp Pharm, 1991 Nov, 48(11), 2414 - 8 Sterility testing of antimicrobial-containing injectable solutions prepared in the pharmacy; Akers MJ et al.; The need for sterility testing of antimicrobial-containing injectable solutions is discussed and specific testing methods are described . Despite their antimicrobial activity, antimicrobial-containing injectable drug products are not necessarily self-sterilizing and can become contaminated . In addition to practicing aseptic technique, pharmacists must perform end-product sterility testing on intravenous solutions to ensure their sterility . The United States Pharmacopeia provides guidelines for the performance and validation of two sterility test methods: membrane filtration and direct transfer to culture media . Membrane filtration is the method of choice for sterility testing of many antimicrobial-containing injectable solutions . After the test article is filtered, the membrane is rinsed with sterile fluid to remove residual antimicrobial agent, cut into two portions, and immersed in two types of culture medium . Visible turbidity of a sample within the appropriate incubation period indicates the presence of a contaminating microorganism . Closed filtration systems minimize false-positive results . In the direct transfer method, samples of the test article are directly inoculated into vessels of culture media, and antimicrobial activity is eliminated by dilution or by deactivation with chemical or enzymatic agents . Sterility testing as well as aseptic technique is needed to ensure the sterility of antimicrobial-containing injectable solutions. Zhonghua Yi Xue Za Zhi, 1991 Nov, 71(11), 616 - 9, 42 {Purification and antimicrobial activity of human neutrophil defensins}; Qu X et al.; Neutrophils are one of the weapons of host defenses against microbial infection . Their ability to kill the invading microorganisms depends on two principle mechanisms . One depends on production of reactive oxygen intermediates (ROI) by stimulated neutrophils, and the other depends on the delivery of antimicrobial contents of the neutrophils' cytoplasmic granules, oxygen-independent . The defensins have the highest concentration in the neutrophils, and the broadest antimicrobial spectrum, being capable of killing gram-positive and gram-negative bacteria, fungi and some envelope viruses . We purified human defensins from the neutrophils' granules by gel permeation chromatography and SDS-preparative acrylamide gel electrophoresis . The molecular weight of human defensins is between 3,000-4,000 daltons . After testing, C . neoformans was susceptible to these defensins . Under condition of 37 degrees C, pH 7.4 and low ionic strength, antifungal activity by human defensins was related to its concentration and incubating time . All of these illustrate that nonoxidative killing mechanism of neutrophils, especially the function of defensins is very important in host defenses. Am J Vet Res, 1991 Nov, 52(11), 1835 - 41 Pharmacokinetic properties of enrofloxacin in rabbits; Broome RL et al.; The pharmacokinetic properties of the fluoroquinolone antimicrobial enrofloxacin were studied in New Zealand White rabbits . Four rabbits were each given enrofloxacin as a single 5 mg/kg of body weight dosage by IV, SC, and oral routes over 4 weeks . Serum antimicrobial concentrations were determined for 24 hours after dosing . Compartmental modeling of the IV administration indicated that a 2-compartment open model best described the disposition of enrofloxacin in rabbits . Serum enrofloxacin concentrations after SC and oral dosing were best described by a 1- and 2-compartment model, respectively . Overall elimination half-lives for IV, SC, and oral routes of administration were 2.5, 1.71, and 2.41 hours, respectively . The half-life of absorption for oral dosing was 26 times the half-life of absorption after SC dosing (7.73 hours vs 0.3 hour) . The observed time to maximal serum concentration was 0.9 hour after SC dosing and 2.3 hours after oral administration . The observed serum concentrations at these times were 2.07 and 0.452 micrograms/ml, respectively . Mean residence times were 1.55 hours for IV injections, 1.46 hours for SC dosing, and 8.46 hours for oral administration . Enrofloxacin was widely distributed in the rabbit as suggested by the volume of distribution value of 2.12 L/kg calculated from the IV study . The volume of distribution at steady-state was estimated at 0.93 L/kg . Compared with IV administration, bioavailability was 77% after SC dosing and 61% for gastrointestinal absorption . Estimates of predicted average steady-state serum concentrations were 0.359, 0.254, and 0.226 micrograms/ml for IV, SC, and oral administration, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) Brain Res, 1991 Oct 25, 562(2), 344 - 6 Quinolones do not interact with NMDA receptor in dissociated rat hippocampal neurons; Shirasaki T et al.; Interaction of quinolone antimicrobials and fenbufen, anti-inflammatory agents, with the N-methyl-D-aspartate (NMDA) receptor was investigated in rat hippocampal neurons with the conventional patch-clamp technique . Simultaneous applications of quinolones and a metabolite of fenbufen had no effects on the glutamate- and NMDA-induced currents . The blocking effects of Mg2+ and MK-801 on NMDA responses were also unaffected . Therefore, the convulsive action induced by quinolones and fenbufen does not seem to involve the function change of NMDA receptor. J Biol Chem, 1991 Oct 25, 266(30), 20218 - 22 Interaction with phospholipid bilayers, ion channel formation, and antimicrobial activity of basic amphipathic alpha-helical model peptides of various chain lengths; Agawa Y et al.; Basic amphipathic alpha-helical peptides Ac-(Leu-Ala-Arg-Leu)3 or 4-NHCH3 (4(3) or 4(4)) and H-(Leu-Ala-Arg-Leu)3-(Leu-Arg-Ala-Leu)2 or 3-OH (4(5) or 4(6)) were synthesized and studied in terms of their interactions with phospholipid membranes, biological activity, and ion channel-forming ability . CD study of the peptides showed that they form alpha-helical structures in the presence of phospholipid liposomes and thus they have amphipathic distribution of the side chains along the axis of the helix . A leakage study of carboxyfluorescein encapsulated in phospholipid vesicles indicated that the peptides possess a highly potent ability to perturb the membrane structure . Membrane current measurements using the planar lipid bilayer technique revealed that the peptide 4(6), which was long enough to span the lipid bilayer in the alpha-helical structure, formed cation-selective ion channels at a concentration of 0.5 microM in a planar diphytanoylphosphatidylcholine bilayer . In contrast, other shorter peptides failed to form discrete and stable channels though they occasionally induced an increase in the membrane current with erratic conductance levels . The probability of detecting a conductance increase was in the order of 4(6) greater than 4(5) greater than 4(4) greater than 4(3), which corresponds to the order of the peptide chain lengths . Furthermore, 4(6) but not 4(5) showed an antimicrobial activity against both Gram-positive and -negative bacteria . The structure of ion channels formed by 4(6) and the relationship between the peptide chain length and biological activity of the synthetic peptides are discussed. Brain Res, 1991 Oct 25, 562(2), 329 - 31 Interaction of various non-steroidal anti-inflammatories and quinolone antimicrobials on GABA response in rat dissociated hippocampal pyramidal neurons; Shirasaki T et al.; Interaction of various non-steroidal anti-inflammatory drugs (NSAIDs) and quinolone antimicrobials with gamma-aminobutyric acid (GABA)A receptor-Cl- channel complex was investigated in rat dissociated hippocampal CA1 neurons by using whole-cell mode patch-clamp technique . Neither NSAIDs nor quinolones alone affected the GABA-induced chloride current (ICl) . In the presence of norfloxacin (NFLX), one of quinolones, some NSAIDs suppressed the GABA response in a concentration-dependent manner . The inhibitory potency of NSAIDs was 4-biphenylacetic acid (BPA), a metabolite of fenbufen much greater than indomethacin = naproxen greater than mefenamic acid greater than diclofenac greater than piroxicam . The results suggest that fenbufen, indomethacin and naproxen in the presence of quinolones may induce the epileptogenic neurotoxicities via pharmacological interaction with GABAA receptor. Lancet, 1991 Oct 19, 338(8773), 993 - 7 Reduction in total under-five mortality in western Nepal through community-based antimicrobial treatment of pneumonia; Pandey MR et al.; Pneumonia is a leading cause of death among children world wide but those at highest risk in developing countries have limited access to clinical services; effective and low-cos