J Allergy Clin Immunol, 1990 Jul, 86(1), 10 - 8 Abnormal nasal glandular secretion in recurrent sinusitis; Jeney EV et al.; Recurrent sinusitis (RS) is a very common clinical problem for which no underlying cause can generally be ascertained . We examined nasal mucosal responses in 14 patients with RS to determine if a relative deficiency in secretion of glandular antimicrobial factors might play a role . Twenty-four subjects with no history of sinusitis were studied concurrently as normal control (NC) subjects . RS was defined by two or more episodes of acute sinusitis per year for 2 or more years . After provocation with 25 mg of methacholine or 1 mg of histamine, nasal washings were analyzed for total proteins: the plasma protein albumin, IgG, and nonsecretory IgA (nsIgA), and the glandular proteins secretory IgA (sIgA), lactoferrin (LFN), and lysozyme (LZM) . Although baseline secretions in patients with RS were relatively enriched with LFN and LZM as compared to that of secretions in NC subjects, patients with RS had a blunted cholinergic response with decreased secretion of albumin, IgG, nsIgA, sIgA, and LZM . Histamine responses were equivalent in both patients with RS and NC subjects . After 4 to 12 months of medical treatment, the abnormal cholinergic responses improved on repeat methacholine challenge in all eight subjects with RS rechallenged . Thus, patients with RS have a reversible reduction in nasal mucosal secretory responses to cholinergic stimulation . Since glandular secretions are rich in antimicrobial factors, such as LFN, LZM, and sIgA, it appears possible that the inability to secrete glandular proteins normally may predispose to recurrent infections. Crit Care Med, 1990 Jul, 18(7), 734 - 7 Audit of serum drug concentration analysis for patients in the surgical intensive care unit; Crisp CB et al.; Serum drug concentration measurements can help the practitioner attain maximal therapeutic efficacy and minimal undesirable effects of certain medications . It is necessary, however, to obtain serum samples appropriately to assure that the result will provide useful information . In preparation for expansion of clinical pharmacy services to the surgical ICU, a study was performed to a) identify the drugs for which serum samples were requested and b) assess whether the results of the serum samples were being used appropriately to adjust doses . Currently, the pharmacy pharmacokinetics service routinely analyzes serum concentrations for antimicrobial agents, theophylline, and other drugs as requested . By the end of this year, we expect further expansion to include phenytoin, pentobarbital, phenobarbital, procainamide/NAPA, lidocaine, and digoxin. Arch Otolaryngol Head Neck Surg, 1990 Jul, 116(7), 789 - 93 Management of animal and human bites in the head and neck; Stucker FJ et al.; Management of bites requires both local wound and systemic considerations . The authors will highlight their experience in 32 cases . Interestingly in this series, human bites were more common than animal bites . The bacteriology, antimicrobial therapy, and surgical treatment of human and animal bites will be reviewed . A management protocol that we use is based on whether the bite was inflicted by a human, dog, or other animal . The discussion will include cases demonstrating immediate and delayed reconstruction . Long-term follow-up was possible for a number of these patients. Farmaco, 1990 Jul, 45(7-8), 879 - 88 Synthesis and antimicrobial properties of substituted 3-aminoxypropionyl and 3-aminoxy-(E)-2-methoxyiminopropionyl monobactams; Balsamo A et al.; The substituted 3-aminoxyproprionyl (VII) and 3-aminoxy-(E)-2-methoxyiminopropionyl monobactams (VIII) which possess the monocyclic beta-lactam nucleus of aztreonam (IX) were synthesized by reaction of triethylammonium (3S, 4S)-3-amino-4-methyl-2-oxo-1-azetidinsulfonate with the aminoxy acids X and XI, respectively . Compounds VII and VIII were assayed in vitro for their antimicrobial properties against Gram-positive and Gram-negative bacteria, whether producers of beta-lactamases or otherwise . Both types of compounds (VII and VIII) exhibited a poor antibacterial activity towards Gram-positive bacteria, comparable to that of aztreonam . On the contrary VII and VIII proved to be practically inactive against Gram-negative microorganisms, towards which aztreonam exhibits a high degree of activity. Farmaco, 1990 Jul, 45(7-8), 867 - 77 Preparation and antimicrobial activity of 1-arylazo-3,4,6,7,8,9-hexahydroquinolizines; Sparatore A et al.; A set of 1-(R-arylazo)-3,4,6,7,8,9-hexahydroquinolizines, bearing different substituents on the benzene ring, were prepared and tested for antimicrobial activity . These compounds exhibit only a very weak activity against gram-positive and gram-negative bacteria, but are fairly active against several Candida species and other yeast-like fungi. Ann Oncol, 1990 Jul, 1(4), 255 - 61 Empiric treatment of infection during granulocytopenia; Klastersky J; Results from clinical trials conducted over the past 15 years suggest the following: a) Early empiric therapy with broad-spectrum antibiotics directed against Gram-negative bacillary bacteremia is necessary in febrile granulocytopenic cancer patients; b) The level and dynamics of the granulocyte count are extremely important in determining the outcome of bacteremia; c) Most empiric antimicrobial regimens will require therapeutic modifications; these alterations are necessary and contribute to a high overall success rate; d) Only microbiologically documented infections and especially bacteremias are useful for comparison of initial response to antimicrobial regimens; e) The response rate of Gram-negative bacillary bacteremia is clearly influenced by the susceptibility of the causative pathogen to the beta-lactam component of the empiric regimen; emergence of resistance to some beta-lactam antibiotics is quite common and necessitates successive modifications of empiric regimens with time; f) The combination of an anti-pseudomonal beta-lactam with an aminoglycoside is recommended as the standard for empiric therapy in febrile granulocytopenic cancer patients, especially in those with severe and persistent granulocytopenia who are suspected of having Gram-negative bacillary bacteremia; less neutropenic and/or asymptomatic patients may do well with monotherapy; g) Gram-positive pathogens have become a common cause of bacteremia in granulocytopenic cancer patients; the response rate to empiric regimens may be suboptimal but the associated mortality is low; h) Patients with severe granulocytopenia and protracted fever whose blood cultures remain negative are at high risk for contracting fungal infections; in these patients, empiric antifungal agents are probably indicated. Ukr Biokhim Zh, 1990 Jul-Aug, 62(4), 21 - 6 {Minor peptides of animal proteins as antibiotics and possible factors of nonspecific immunity}; Kharchenko EP et al.; Screening of more than twenty short synthetic peptides characteristic of different proteins has revealed antimicrobial activity of the KRFAE peptide--from human preproenkephalin A against gram-negative bacteria . Modification of the peptide structure by means of administration of d-amino acids has permitted obtaining dKRFdLE analogue with the expressed and stable antimicrobial activity in vitro when growing bacteria on the minimum glucose-mineral medium . Changes and rearrangements of aminoacids in the dKRFdLE peptide in the second, third and fourth positions sharply decreased anti-microbial activity . The weaker antimicrobial activity as compared with that in dKRFdLE was peculiar to peptides with the other primary structure . Possible participation of peptides as antibiotics in the mechanisms of nonspecific immunity as well as the methods of their rational search are discussed. J Gen Microbiol, 1990 Jul, 136 ( Pt 7), 1437 - 46 Lactoferrin and transferrin damage of the gram-negative outer membrane is modulated by Ca2+ and Mg2+; Ellison RT 3rd et al.; Lactoferrin and transferrin have antimicrobial activity against selected Gram-negative bacteria, but the mechanism of action has not been defined . We studied the ability of lactoferrin and transferrin to damage the Gram-negative outer membrane . Lipopolysaccharide release by the proteins could be blocked by concurrent addition of Ca2+ and Mg2+ . Addition of Ca2+ also blocked the ability of lactoferrin to increase the susceptibility of Escherichia coli to rifampicin . Transferrin, but not lactoferrin, increased susceptibility of Gram-negative bacteria to deoxycholate, with reversal of sensitivity occurring with exposure to Ca2+ or Mg2+ . In transmission electron microscopy studies polymyxin B caused finger-like membrane projections, but no morphological alterations were seen in cells exposed to EDTA, lactoferrin or transferrin . These data provide further evidence that lactoferrin and transferrin act as membrane-active agents with the effects modulated by Ca2+ and Mg2+. Eur J Clin Microbiol Infect Dis, 1990 Jul, 9(7), 548 - 51 Guidelines of the World Health Organization for clinical trials with antimicrobial agents; Lunde I; The WHO Consensus Documents Series on Clinical Investigation covers many different therapeutic drug groups including the antibacterial drugs . The documents have been produced by the WHO Regional Office for Europe in collaboration with a wide group of clinicians and other experts in order to define and promote agreement on current and emerging standards for the clinical investigation of drugs. Eur J Clin Microbiol Infect Dis, 1990 Jul, 9(7), 542 - 7 The clinical evaluation of antibacterial drugs: guidelines of the British Society for Antimicrobial Chemotherapy; Finch RG; Anti-infective agents differ in several respects from other classes of therapeutic drugs . They are aimed at the treatment or prevention of infection which can occur at several body sites and be caused by a wide range of microorganisms . The infectious process frequently modifies metabolic behaviour which in turn may affect the pharmacology of an agent . In addition, the issue of drug resistance raises concerns in individual patients, hospital units and the broader community . The difficulties in scientifically validating the clinical efficacy and safety of anti-infective drugs led to the Report on the Clinical Evaluation of Antibacterial Drugs of the British Society for Antimicrobial Chemotherapy . The report identifies general principles relevant to the study of these drugs in man and identifies the major microbiological and clinical considerations . Detailed comments on the conduct of pharmacokinetic studies and therapeutic trials are provided with particular emphasis on design, definitions, execution and analysis . Adverse event monitoring, assessment of severity and determination of causality are also reviewed . Pharmaco-economic considerations are identified as a significant issue for the future . The revision of the 1977 FDA guidelines on anti-infective drug development provides the opportunity to harmonise these issues, particularly within the major markets of North America, Europe and Japan. Eur J Clin Microbiol Infect Dis, 1990 Jul, 9(7), 537 - 41 Regulatory requirements for clinical evaluation of antimicrobial agents; Christ W; Evaluation of antimicrobial agents in governed mainly by interaction between the pharmaceutical industry and regulatory authorities . The 1977 FDA guidelines have been setting the standards for more than a decade now . Basic principles of the 1977 guidelines remain valid, however changes in the definition of end-points of response, as measured by both clinical and microbiological criteria, have occurred . The new (draft) FDA guidelines and the 1989 guidelines of the British Society of Antimicrobial Chemotherapy are more consistent with contemporary concepts of treatment . In general, the differences in the requirements are minimal with a few exceptions, namely the requirements concerning blinding and assessment of clinical efficacy by site of infection and by organism in the FDA guidelines. Eur J Clin Microbiol Infect Dis, 1990 Jul, 9(7), 530 - 3 Evaluation of safety and tolerance in clinical trials with antimicrobial agents; Lode H et al.; In this review the general and specific difficulties encountered in the evaluation of safety and tolerance of antimicrobial agents in clinical trials are discussed . In addition to the usual pharmacological and toxicological effects (adverse drug reactions) occurring in individual patients, microbiologically induced side-effects also have to be considered . The different methods for registration of side-effects and their limitations are discussed . A system is proposed for evaluation of the cause/effect relationships of adverse drug reactions . A system is also discussed for the evaluation of the severity of adverse drug reactions, and different classifications are presented. Eur J Clin Microbiol Infect Dis, 1990 Jul, 9(7), 506 - 9 Requirements for the documentation of pharmacokinetic properties of antimicrobial agents; Bergan T; Proper documentation of new antimicrobial drugs for governmental registration authorities includes extensive pharmacokinetic studies . Pharmacokinetics represents the bridge between the in vitro and in vivo phases of drug development . Both healthy human volunteers and patients must be studied, the former during the initial stages of the pharmacokinetic studies . The documentation should give information on the following: absorption from the gastrointestinal tract, bioavailability, pharmacokinetic model, impact of increasing doses (oral and intravenous), metabolism, routes and degree of elimination, interaction with food and other drugs, impact of the steady state, and serum protein binding . Basic pharmacokinetic parameters used are the serum half-life, clearance, distribution volume and dose dependence . The bioavailability of oral doses must be determined using the same dose sizes and subjects . Data on extravascular penetration should also be included in complete documentation . Key diseases in which the pharmacokinetics should be studied are reduced renal and liver function, heart failure, pregnancy, cystic fibrosis and intestinal diseases . The consequences of low age (e.g . newborns) and old age also require some attention. Eur J Clin Microbiol Infect Dis, 1990 Jul, 9(7), 492 - 5 European standards for antibiotic susceptibility testing: towards a theoretical consensus; Baquero F; Six different systems for antimicrobial susceptibility testing are used in Europe (BSAC, DIN, SFM, SIR, NCCLS and WRG) . Breakpoints defining susceptibility or resistance of bacteria to antimicrobial agents remain the subject of discussion . Nevertheless, it is possible to establish a theoretical consensus standard list of breakpoints such that more than 95% of the breakpoints proposed by the different systems differ from the consensus standard by no more than one dilution . In general, the BSAC and DIN systems recommend lower breakpoints, and the SFM and NCCLS systems higher breakpoints than the consensus standard . Two-thirds of the discrepancies are related to the breakpoints defining susceptibility . The breakpoint for susceptibility should reflect the intrinsic susceptibility of the isolate (absence of mechanisms of resistance), and the breakpoint for resistance the pharmacological potential of the drug . The scientific validation of breakpoints requires clinical verification. Eur J Clin Microbiol Infect Dis, 1990 Jul, 9(7), 488 - 91 Basic requirements for the toxicity testing of antimicrobial agents; Bass R et al.; The regulations in different countries on the toxicological testing of antimicrobial agents are similar and harmonized on an international basis . Existing requirements cover both the standard investigations performed with any other new class of therapeutic drug and investigations necessary due to the specific features of anti-infective agents . Such features are the therapeutic target (the microorganisms), the need to provide adequate treatment of patients even during clinical trials, and the potential of the drug to induce certain adverse reactions . The combination of toxicity tests used will be determined by the drug, its class and current knowledge. Eur J Clin Microbiol Infect Dis, 1990 Jul, 9(7), 462 - 5 Remarks on the screening of antibiotics for antibacterial activity; Zak O et al.; The general principles of screening antibiotics for antimicrobial activity are similar to those for screening for other pharmacological effects . The system should be adapted to the specific character of the test substance and the objectives of the program . In the screening of beta-lactams, standard tests, such as determination of the MICs, effects of inoculum size or activity against systemic infection in mice, should be supplemented by less conventional studies on for instance activity against dormant bacteria or, in the case of penems or carbapenems, stability in the presence of kidney and lung dehydropeptidases. Eur J Clin Microbiol Infect Dis, 1990 Jul, 9(7), 455 - 61 Screening of natural products for antimicrobial agents; Silver L et al.; Antimicrobial research is geared toward the discovery and development of novel chemical structures such as therapeutic antimicrobial agents . The continuing problem of development of resistance to existing antibacterial agents and the dearth of good antifungal agents motivates this effort toward innovation . Selection of possible new enzyme targets for antibiotic inhibition may be made on theoretical grounds, but it appears premature to select any single, previously unvalidated target for the intensive study required for rational drug design . Instead, a broad screen of chemical entities can be undertaken, dedicated to the discovery of novel antimicrobial inhibitors . A number of target areas are under investigation, including fungal mRNA splicing and bacterial DNA synthesis . A major part of the endeavor is in the historically productive area of natural product screening . To make the best use of natural product resources for the discovery of novel antibiotics, a balance is struct between screening for inhibitors of rationally chosen targets for which clinically useful inhibitors are not yet available, and screening more broadly to ensure that rare activities of unanticipated mode-of-action are not missed. Clin Ther, 1990 Jul-Aug, 12(4), 290 - 6; discussion 289 Dexamethasone and nonsteroidal anti-inflammatory agents in the treatment of bacterial meningitis; Roos KL; It has been shown in experimental models of bacterial meningitis that bacterial cell-wall components produce an inflammatory response in the subarachnoid space, probably by stimulating the release of inflammatory cytokines, such as tumor necrosis factor, interleukin-1, and prostaglandins . Interleukin-1 increases the concentration of prostaglandin E2 and leukotriene B4, metabolites of arachidonic acid, which are potent mediators of inflammation . Steroidal and nonsteroidal anti-inflammatory agents decrease formation of these metabolites and minimize the damage to the blood-brain barrier . There is also evidence that anti-inflammatory agents decrease cerebral edema in bacterial meningitis . The results of clinical trials in patients with bacterial meningitis demonstrate that dexamethasone can prevent sensorineural hearing loss and reduce mortality, without interfering with the antimicrobial action of antibiotics. Arzneimittelforschung, 1990 Jul, 40(7), 795 - 9 Rough sets approach to the analysis of the structure-activity relationship of quaternary imidazolium compounds; Krysinski J; The relationship between chemical structure and antimicrobial activity of 201 quaternary imidazolium 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 on information system . Using the rough sets approach, first a minimum set of 4 attributes significant for a high quality of classification has been found . The analysis of distribution of values of significant attributes in the best and worst class led to the definition of typical representatives of best and worst compounds in terms of significant attributes . Finally, a decision algorithm has been driven from information system, showing important relations between structure and activity . It may be helpful in supporting decisions concerning the synthesis of new antimicrobial compounds. Rev Infect Dis, 1990 Jul-Aug, 12 Suppl 6, S645 - 55 Treatment of Chlamydia trachomatis genital infection; Toomey KE et al.; Chlamydia trachomatis infections are the most frequent bacterial sexually transmitted diseases in the United States, with an estimated 4 million cases occurring annually . The mainstay of treatment for chlamydial infections has been the tetracyclines . Doxycycline, comparable in cost to tetracycline and with a less frequent dosage schedule, is the drug of first choice . Erythromycins are the drugs of choice for infections in pregnant women, nursing mothers, infants, children, and adults unable to tolerate tetracyclines . beta-Lactam antibiotics have had variable efficacy against C . trachomatis infections, although recent studies suggest that amoxicillin may be an effective alternative for C . trachomatis infection during pregnancy . Quinolones are currently being tested and may be used in alternative regimens in the future . The effectiveness of current antimicrobial regimens in preventing long-term complications of chlamydial infections should be determined in research studies. Vet Clin North Am Food Anim Pract, 1990 Jul, 6(2), 307 - 33 Perioperative antimicrobial considerations for gastrointestinal surgery of cattle; Brumbaugh GW; Perioperative use of antimicrobial drugs constitutes extra-label use of those drugs . Principles of therapeutic and prophylactic use of antimicrobial drugs can guide decisions about their perioperative use . Regimens currently suggested are based on those principles, theoretical information, pharmacokinetic and pharmacodynamic data, extrapolation from studies with other species, empirical data, personal bias, and experience . Controlled clinical investigations are necessary to provide objective data from which specific recommendations can be derived. Semin Hematol, 1990 Jul, 27(3 Suppl 3), 15 - 24 Effects of granulocyte-macrophage colony-stimulating factor in iatrogenic myelosuppression, bone marrow failure, and regulation of host defense; Gutterman J et al.; In early studies, recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) has been found to reduce the depth and duration of granulocytopenia in the settings of cancer chemotherapy and autologous bone marrow transplantation . In patients with myelodysplastic syndrome or aplastic anemia . GM-CSF has produced increased marrow cellularity and marked leukocyte responses, and multilineage effects have been observed in some patients . The available data suggest that the use of GM-CSF in these settings is associated with a decreased incidence of infection as compared with that in historical controls or pretreatment periods and that it may enhance the ability to deliver optimal doses of cancer chemotherapy . Other findings suggest that GM-CSF may be useful in regulating host response to infection when used in combination with antimicrobial therapy in neutropenic patients . However, a precise determination of the ability of this agent to significantly affect patient morbidity or mortality in these various contexts awaits the results of larger, longer-term, randomized, controlled trials. Clin Pharm, 1990 Jul, 9(7), 509 - 29 Clinical uses of intravenous immune globulin; Knapp MJ et al.; The preparation, pharmacokinetics, clinical uses, dosage and administration, and adverse effects of intravenous immune globulin (IVIG) are reviewed . IVIG, which consists primarily of immunoglobulin G (IgG), is initially prepared from pooled human plasma by using the Cohn-Oncley fractionation procedure . Secondary treatments render the preparation suitable for i.v . use . The specific antibody content of IVIG depends on the geographic location of the plasma donors, the product, and the product lot . The metabolism of IgG appears to follow a multicompartmental, first-order process . The half-life of IgG is dependent on the half-lives of the IgG subclasses; three of the four subclasses have half-lives in the range of 23-25 days . IVIG is indicated in the treatment of idiopathic thrombocytopenic purpura (ITP) and as replacement therapy in primary humoral immunodeficiencies (PHI) . IVIG has also been used for antimicrobial prophylaxis in bone marrow transplant and burn patients and in patients with malignancies . Patients with HIV infection, cystic fibrosis, neonatal sepsis, and respiratory syncytial virus infection may also benefit from prophylaxis or treatment with IVIG . The recommended dosage of IVIG in ITP is 400 mg/kg/day for two to five days . For the treatment of PHI, the usual dosage is 100-400 mg/kg every three or four weeks . Adverse reactions are often mild and are usually related to the infusion rate . Intravenous immune globulin is a valuable therapeutic tool in several immunodeficiency and autoimmune states, but IVIG products are expensive, and conclusive data on their efficacy in the treatment of many disorders remain to be obtained. Med Clin North Am, 1990 Jul, 74(4), 1059 - 76 Choice of antibiotics, pharmacokinetics, and dose adjustments in acute and chronic renal failure; Bernstein JM et al.; A multitude of antimicrobial agents have become available over the past two decades . Appropriate use of these drugs demands not only an understanding of the antimicrobial spectrum of the agent but of the necessary dose adjustments because of renal or hepatic impairment . The use of computer-assisted pharmacokinetic modeling for dosing potentially toxic drugs such as aminoglycosides and vancomycin should be utilized whenever possible. J Biol Regul Homeost Agents, 1990 Jul-Sep, 4(3), 93 - 7 Effects of alpha- and beta-interferon on oxidative burst responses of monocytes and monocyte-derived macrophages from patients with HIV infection; Muller F et al.; In the present paper, we have studied the effects of interferon (IFN) -alpha and IFN-beta on the oxidative burst (OB) responses in monocytes and monocyte-derived macrophages from patients with a relatively early phase of HIV infection . We found that in monocytes from patients with HIV infection, the defective OB response could be partially restored by pretreatment with IFN-beta when the cells were challenged with zymosan . No such stimulatory effect was seen in the control groups . In monocyte-derived macrophages, both IFN-alpha and IFN-beta stimulated the phorbol myristate acetate (PMA) induced OB response in the patient group as well as in the blood donor control group . Generation of an OB is an important part of the antimicrobial defence of mononuclear phagocytes . The positive effects of IFN on the OB responses of monocytes and macrophages from patients with HIV infection may be of importance when IFNs are considered in the treatment of HIV-related disease. Prakt Zubn Lek, 1990 Jul, 38(6), 161 - 4 {Antimicrobial action of a repin bandage in periodontology}; Slivka T et al.; The paper deals with the antimicrobial activity of repin bandages used commonly in periodontology . The main criterium for evaluation was the number of bacteria in the wound beneath the bandage, ass ossessed by cultivation . The authors compared three types of bandages (Repin with Traumacel, Repin with Framykoin and Repin alone) . Repin with Framykoin reduced most effectively the number of micro-organisms for the longest period of time . The results revealed that the amount of bacteriabacteria beneath the bandage is proportional to the period of time for which the bandage is left in the oral cavity . The optimal period is five days. Boll Chim Farm, 1990 Jul-Aug, 129(7-8), 248 - 50 Reactivity toward cysteine of antimicrobial carbamimidothioic acid phenylalkylesters salts; Tait A et al.; The rates of reaction toward cysteine of a series of carbamimidothioic acid phenylmethylesters halides were investigated in phosphate buffer pH 7.4 at 37 degrees C under pseudo-first-order conditions . The reaction involves nucleophilic attack of cysteine on the C-S bond of isothiouronium mojety and corresponding benzenemethanethiols were detected as product of the reaction . Apparent first-order rate constants were determined. J Nat Prod, 1990 Jul-Aug, 53(4), 771 - 92 Bioactive compounds from aquatic and terrestrial sources; Rinehart KL et al.; The world of nature provides a never-ending set of fascinating problems for the chemist . Many of the most intriguing problems, however, concern compounds available in only truly minute quantities . One solution is to focus on bioassay-guided separations . In so doing one can isolate compounds with novel structures or unsuspected activities from almost any phylum, including tunicates, sponges, insects, or even the much-studied terrestrial plants, as exemplified in several recent studies in our laboratory involving activities ranging from antiviral and antimicrobial activity to cytotoxicity and immunomodulation . Moreover, newer spectroscopic techniques, especially fast atom bombardment mass spectrometry and tandem mass spectrometry, enhance one's ability to study compounds present in minute quantities, including those of importance to the host organism, such as neuropeptides in insects or marine invertebrates. Dent Mater, 1990 Jul, 6(3), 201 - 3 In vitro and clinical examination of the effect of an antimicrobial impression material on the oral microflora; Brauner AW; The bacterial colonization of impression materials by the oral microflora is an indication that impressions need disinfection . Till now, particularly where alginate materials are concerned, the disinfection of impressions has had a negative influence on the working properties of the material . The addition of an antimicrobial substance to alginate Blueprint asept is meant to disinfect the impression after removal from the oral cavity . Using both test cultures as well as clinically examining 30 patients, I verified the claims of the manufacturer . Electromicroscopic examinations showed no reduction in accuracy of impressions taken with Blueprint asept as compared with current alginate materials. Diagn Microbiol Infect Dis, 1990 Jul-Aug, 13(4), 281 - 4 Positive Bactec resin cultures do not influence antimicrobial selection; Jessamine PG et al.; We performed a retrospective evaluation of Bactec resin blood cultures, submitted to the clinical laboratories of the University of Manitoba teaching hospitals, to determine the impact positive cultures might have on the selection of antimicrobial therapy . Of the 2919 resin cultures submitted in 1987, 151 were positive, with 161 separate isolates . Of these cultures, 13 were reported after the death of the patient and 8 could not be adequately assessed because of insufficient clinical information . Four positive cultures were obtained from patients not receiving antimicrobial therapy . Forty-four cultures (53 isolates) from 37 patients were judged to be contaminants . Each of the remaining 82 clinically significant positive cultures were monomicrobial . Isolates from 34 cultures were resistant to the antibiotics being administered and might have been expected to grow in nonresin blood cultures . Forty-eight isolates from 18 patients were susceptible to the antibiotic(s) being administered at the time the culture was drawn . In none of these patients did the positive result lead to a change in the choice of antimicrobial therapy . In only one case was there an increase in antibiotic dosage . It appears that positive Bactec resin blood cultures do not have a significant impact on antimicrobial selection, and routine use may not be justified. J Immunol, 1990 Jul 1, 145(1), 311 - 7 Nucleotide sequence and T cell epitopes of a membrane protein of Francisella tularensis; Sjostedt A et al.; A 17-kDa major membrane protein of the facultative intracellular bacterium Francisella tularensis is recognized by T cells from individuals previously undergoing tularemia or tularemia vaccination . Here the nucleotide sequence of the encoding gene is presented . The A + T rich sequence deduced a protein of 149 amino acids with a predicted m.w . of 15,772 . Evidence is presented suggesting that the 17-kDa protein is a lipoprotein . Also, homology was found to a peptidoglycan-associated lipoprotein of Escherichia coli . Thirteen overlapping synthetic peptides encompassing the entire deduced protein were tested on lymphocytes from F . tularensis-primed individuals . Three peptides induced a T cell response, as disclosed by lymphocyte proliferation and production of IL-2 and IFN-gamma . Out of five responding individuals, only one recognized more than one of the peptides . A murine mAb recognized an epitope separate from the T cell-reactive peptides . The identified T cell epitopes are presumably relevant to the host defense against F . tularensis, especially because IFN-gamma is known to enhance the antimicrobial activity of the host against intracellular bacteria. Am J Med, 1990 Jun 20, 88(6A), 34S - 37S Acute diarrhea associated with travel; Wolfe MS; Travelers' diarrhea, an acute illness that affects between 20 and 50 percent of travelers to high-risk areas, is usually acquired by eating contaminated food, drinking contaminated water, or coming in contact with the contaminated hands of an infected person . Travelers' diarrhea can be caused by bacterial, viral, and parasitic agents . The Travelers' Diarrhea Consensus Conference has recommended prophylactic measures, which include proper preparation of food and beverages, nonantimicrobial agents, and antimicrobial agents . The newer quinolone antibiotics and bismuth subsalicylate may also be useful prophylactically . Appropriate treatment methods include oral fluids and electrolyte replacement, nonspecific agents such as bismuth subsalicylate, antimotility agents such as loperamide hydrochloride and diphenoxylate hydrochloride, and antimicrobial and antiparasitic agents. J Biol Chem, 1990 Jun 15, 265(17), 9831 - 7 A novel mouse gene family coding for cationic, cysteine-rich peptides . Regulation in small intestine and cells of myeloid origin; Ouellette AJ et al.; Cryptdin is a Paneth cell corticostatin/defensin in the mouse small bowel . To help define the intestinal role of cryptdin, cryptdin-related sequence (CRS) mRNAs have been characterized with respect to developmental regulation, sequence homology, putative coding function, and occurrence in myeloid cells . Cryptdin, CRS1C, and CRS4C mRNAs are transcribed from separate genes, occur at equivalent abundance in small intestine, and appear in the small bowel in concert during the 2nd and 3rd weeks postpartum . Cryptdin and CRS1C mRNAs are not detectable in adult mouse bone marrow, but probes specific for the 5'- or the 3'-untranslated regions of CRS4C mRNA hybridize to a moderately abundant 1.05-kilobase bone marrow mRNA in contrast to a highly abundant 0.75-kilobase mRNA in small intestine . Nucleotide sequences corresponding to the deduced prepro-coding regions of cryptdin, CRS1C, and CRS4C mRNAs contain a highly conserved 200-base pair region of 92% sequence similarity (CSE.2), but the mRNAs are not homologous otherwise . The deduced CRS1C and CRS4C polypeptides are apparent precursors of secreted, cationic, proline- and cysteine-rich peptides that contain Cys-Pro-X repeats . Unlike cryptdin, however, the proposed CRS1C and CRS4C mature peptide regions lack the structural motif characteristic of defensins . Attempts to find homologies between the putative CRS peptides and existing protein sequences have been unsuccessful, leading us to speculate that CRS1C and CRS4C represent a new family of nondefensin antimicrobial peptides in the mouse small bowel. Pharmazie, 1990 Jun, 45(6), 422 - 3 {Antimicrobial activity of quaternary ammonium compounds}; Krysinski J; The antimicrobial properties of two new imidazolium and pyridinium chlorides in comparison with three currently in disinfection compounds applied are described . The following research was performed: resistance of organisms to disinfectants and disinfection of hands . The new 3-methyl-n-dodecylthiomethylpyridinium chlorid was the most active compound. Zentralbl Bakteriol, 1990 Jun, 273(2), 156 - 63 Resin versus standard blood culture media used with the new BACTEC automated infrared system: an evaluation in febrile granulocytopenic patients; Kern W et al.; Resin-containing aerobic and anaerobic blood culture media (NR 16A and NR 17A) for use with the new BACTEC infrared blood cultures system were compared with standard BACTEC media (NR 6A and NR 7A) in their efficacy to detect bacteremia in febrile granulocytopenic patients receiving antimicrobial treatment . A total of 1185 sets of blood cultures obtained from 341 patients during a 12-month period were evaluated . There were 109 positive cultures (9.2%) with 128 pathogenic organisms isolated from 52 patients (15.2%) . Statistically significant differences were found between aerobic media, but not between anaerobic media . Aerobic resin bottles (NR 16A) were more often positive (90 versus 78, p less than 0.05) than standard aerobic bottles (NR 6A) . They yielded a higher number of microorganismS (98 versus 80, p less than 0.05) per culture and per culture-positive patient (53 versus 42, p less than 0.01) . NR 16A cultures also were more often positive after 1-day incubation (44% versus 21%, p less than 0.01) than NR 6A cultures and allowed earlier subcultivation . The use of NR 16A medium instead of resin-free aerobic NR 6A medium may enhance the detection of bacteremia in selected groups of patients receiving antimicrobial treatment, and can shorten the time until detection of bacteremia. J S C Med Assoc, 1990 Jun, 86(6), 347 - 9 Improving survival in the burned patient; Yarbrough DR 3rd; Improving survival of burned patients has been reported by the majority of burn units over the past decade . Although many sophisticated studies have attempted to delineate the major factors responsible for this improvement, no single factor has emerged as being clearly dominant . On the MUSC burn service, increased survival has been particularly apparent in patients with burns involving 50-90% of the BSA . Little improvement in survival has yet been noted in patients with burns involving more than 90% of the BSA . We are convinced that general improvements in topical antimicrobials, antibiotics, techniques of critical care, improved wound care techniques and, very importantly, maintenance of the patient's nutritional status are all critical factors in improving survival in the burned patient . Attributing the increased survival of burned patients to any one of these factors alone currently does not seem to be clearly supported by data reported in the literature nor by our own experience . It is to be hoped that as the quality of skin substitutes and techniques of culturing skin improve, inroads into the extremely high mortality of burns involving more than 90% of the BSA can be made . The MUSC burn service is currently investigating the place of aggressive early burn wound excision and grafting with cultured epithelial autografts in achieving this goal. Antimicrob Agents Chemother, 1990 Jun, 34(6), 1189 - 93 Uptake of antibiotics by human polymorphonuclear leukocyte cytoplasts; Hand WL et al.; Enucleated human polymorphonuclear leukocytes (PMN cytoplasts), which have no nuclei and only a few granules, retain many of the functions of intact neutrophils . To better define the mechanisms and intracellular sites of antimicrobial agent accumulation in human neutrophils, we studied the antibiotic uptake process in PMN cytoplasts . Entry of eight radiolabeled antibiotics into PMN cytoplasts was determined by means of a velocity gradient centrifugation technique . Uptakes of these antibiotics by cytoplasts were compared with our findings in intact PMN . Penicillin entered both intact PMN and cytoplasts poorly . Metronidazole achieved a concentration in cytoplasts (and PMN) equal to or somewhat less than the extracellular concentration . Chloramphenicol, a lipid-soluble drug, and trimethoprim were concentrated three- to fourfold by cytoplasts . An unusual finding was that trimethroprim, unlike other tested antibiotics, was accumulated by cytoplasts more readily at 25 degrees C than at 37 degrees C . After an initial rapid association with cytoplasts, cell-associated imipenem declined progressively with time . Clindamycin and two macrolide antibiotics (roxithromycin, erythromycin) were concentrated 7- to 14-fold by cytoplasts . This indicates that cytoplasmic granules are not essential for accumulation of these drugs . Adenosine inhibited cytoplast uptake of clindamycin, which enters intact phagocytic cells by the membrane nucleoside transport system . Roxithromycin uptake by cytoplasts was inhibited by phagocytosis, which may reduce the number of cell membrane sites available for the transport of macrolides . These studies have added to our understanding of uptake mechanisms for antibiotics which are highly concentrated in phagocytes. Planta Med, 1990 Jun, 56(3), 274 - 6 Sarothralin G: a new antimicrobial compound from Hypericum japonicum; Ishiguro K et al.; A new antibiotic compound, sarothralin G from Hypericum japonicum Thunb . (Sarothra japonica) has been isolated and its structure was elucidated on the basis of spectroscopic data . The compound contains phloroglucinol and filicinic acid moieties. Eur J Clin Microbiol Infect Dis, 1990 Jun, 9(6), 381 - 9 Effects of a restrictive antibiotic policy on clinical efficacy of antibiotics and susceptibility patterns of organisms; Sturm AW; To assess the impact of a restrictive antimicrobial policy, the efficacy of therapeutic and prophylactic antibiotic regimens and the susceptibility patterns of infecting bacterial microorganisms were studied during a two-month period in 1986 in inpatients in a general hospital . Twenty-eight percent of patients received antimicrobial agents, 21% as treatment and 7% as prophylaxis . In the 359 evaluable episodes of infection cure was obtained in 88% of cases with the initial therapy and in 7% after a change of drugs, but treatment failed in 5% . Of the 18 cases of failure, improvement was seen in eight although the infection persisted . Ten patients died but in seven of them the infection only partially contributed to this outcome . Ten (8%) of 127 patients receiving antimicrobial prophylaxis developed an infection but in three there was no relation to the condition for which the prophylactic regimen was originally prescribed . No changes were found in the susceptibility patterns of microorganisms. J Dermatol, 1990 Jun, 17(6), 370 - 4 In vitro susceptibility of Mycobacterium marinum to dihydromycoplanecin A and ten other antimicrobial agents; Arai H et al.; The in vitro susceptibilities of 16 Mycobacterium marinum strains to 11 antimicrobial agents were determined by the Dubos Tween albumin liquid dilution technique . The results (MICs) were: 0.19-0.39 microgram/ml for dihydromycoplanecin A; 0.78-1.56 micrograms/ml for amikacin; 1.56-3.13 micrograms/ml for ofloxacin, norfloxacin and enoxacin; 1.56-6.25 micrograms/ml for minocycline; 1.56-25 micrograms/ml for sulfamethoxazole and sulfamethoxazole-trimethoprim; 3.13-12.5 micrograms/ml for oxytetracycline; 25-200 micrograms/ml for trimethoprim; and 50-200 micrograms/ml for pipemidic acid . The most active drugs were dihydromycoplanecine A and amikacin . Also active were minocycline, oxytetracycline, sulfamethoxazole and sulfamethoxazole-trimethoprim . Ofloxacin, norfloxacin and enoxacin demonstrated activity only at concentrations at or greater than those usually attained in serum . Pipemidic acid and trimethoprim were inactive. Burns, 1990 Jun, 16(3), 217 - 20 Patient tolerance study of topical chlorhexidine diphosphanilate: a new topical agent for burns; Miller LM et al.; Effective topical antimicrobial agents decrease infection and mortality in burn patients . Chlorhexidine phosphanilate (CHP), a new broad-spectrum antimicrobial agent, has been evaluated as a topical burn wound dressing in cream form, but preliminary clinical trials reported that it was painful upon application . This study compared various concentrations of CHP to determine if a tolerable concentration could be identified with retention of antimicrobial efficacy . Twenty-nine burn patients, each with two similar burns which could be separately treated, were given pairs of treatments at successive 12-h intervals over a 3-day period . One burn site was treated with each of four different CHP concentrations, from 0.25 per cent to 2 per cent, their vehicle, and 1 per cent silver sulphadiazine (AgSD) cream, an antimicrobial agent frequently used for topical treatment of burn wounds . The other site was always treated with AgSD cream . There was a direct relationship between CHP concentration and patients' ratings of pain on an analogue scale . The 0.25 per cent CHP cream was closest to AgSD in pain tolerance; however, none of the treatments differed statistically from AgSD or from each other . In addition, ease of application of CHP creams was less satisfactory than that of AgSD . It was concluded that formulations at or below 0.5 per cent CHP may prove acceptable for wound care, but the vehicle system needs pharmaceutical improvement to render it more tolerable and easier to use. Am J Hosp Pharm, 1990 Jun, 47(6), 1283 - 303 Hospital pharmacy services in the Great Lakes region; Raehl CL et al.; The results of a spring 1987 survey of hospital pharmacy services in seven states of the Great Lakes region are reported . The study group (n = 1087) comprised all hospitals in seven states that employed at least one full-time or part-time pharmacist and that had 50 or more licensed beds . The survey had a 63% response rate (681 usable responses) . Seventy percent of the hospitals were small (average daily census, less than 200), 20% were medium sized (200-399), and 11% were large (greater than or equal to 400) . Some 33% of the hospitals were affiliated with a college of pharmacy . Pharmacy directors who held an advanced degree (master of science or doctor of pharmacy) were more likely to work in larger hospitals and in those affiliated with educational institutions . The extent of unit dose services differed based on hospital teaching affiliation and pharmacy director's education . Provision of i.v . admixture services differed based on hospital teaching affiliation and pharmacy director's education but not hospital size . Pharmacy preparation of six specialty i.v . products differed according to pharmacy director's education and hospital teaching affiliation; however, pharmacy preparation of only three of the specialty products differed based on hospital size . Larger hospitals that were affiliated with an educational institution were more likely to employ a clinical coordinator, drug information specialist, or clinical pharmacist . Home health-care services involving pharmacists were provided by 26% of the hospitals; the most common programs were antimicrobial therapy and total parenteral nutrition therapy . Pharmacists provided services in ambulatory-care clinics in 24% of the hospitals, with the most common services being patient education, pharmacokinetics consultation, and dosage regimen adjustment . Provision of 10 of 12 inpatient clinical pharmacy services differed based on hospital size and teaching affiliation; 11 of the 12 services differed based on education of the pharmacy director . Workload and pharmacist staffing data for the inpatient clinical pharmacy services varied widely . Eleven of these services were expected to undergo a positive net growth, while one service, provision of admission medication histories, was expected to decline . An extensive survey of hospital pharmacy services in the Great Lakes region showed that the provision and scope of many services were related to hospital size, hospital teaching affiliation, and the education of the pharmacy director. Am J Infect Control, 1990 Jun, 18(3), 194 - 200 Intermittent use of an antimicrobial hand gel for reducing soap-induced irritation of health care personnel; Newman JL et al.; We evaluated the effects of an antimicrobial hand gel (containing 60% ethanol plus emollients) on skin condition when used as a supplement to handwashing . Volunteers washed their hands 10 times per day for 5 days with a bar soap . Between washings one hand was treated with 1.0 ml of the gel while the other hand was untreated . By the conclusion of the study the gel-treated hands exhibited significantly lower (p less than 0.05) photographic scores for cracking, scaling, and erythema (redness), the major symptoms of dry, irritated skin . The gel treatment also helped to maintain normal skin hydration levels as measured by transepidermal water loss and skin impedance . By reducing soap-induced irritation, an alcohol gel with the appropriate emollients can help eliminate a major deterrent to handwashing among health care personnel. Khirurgiia (Mosk), 1990 Jun, (6), 30 - 3 {Treatment of patients with thermal lesions with ointments on water-soluble base}; Sologub VK et al.; Treatment of patients with thermal burns by ointments prepared on a water-soluble base (Dioxidine and Dioxicol) makes it possible to reduce the bacterial dissemination within a short time and prepare the wound for autodermoplasty which, in turn, reduces the danger of the development of infectious complications . In addition to a marked antimicrobial effect, the ointment possess high hydrophobic and hydrophilic properties and do not induce allergic reactions and side effects. Antimicrob Agents Chemother, 1990 Jun, 34(6), 1048 - 52 Investigation of potential interaction of ciprofloxacin with cyclosporine in bone marrow transplant recipients; Kruger HU et al.; The effect of the 4-quinolone antimicrobial agent ciprofloxacin on the concentration in plasma and the pharmacokinetics of the immunosuppressive agent cyclosporine was studied in 10 bone marrow transplant recipients . There were no statistically or clinically significant changes in cyclosporine trough concentrations or areas under the concentration-time curve following oral doses of 500 mg of ciprofloxacin every 12 h for 4 days . The data suggest a lack of relevant pharmacokinetic interaction of ciprofloxacin with cyclosporine . There was no indication of an enhanced nephrotoxicity for this drug combination. J Chemother, 1990 Jun, 2(3), 156 - 8 Susceptibility of Eikenella corrodens to antimicrobial agents; Sofianou D et al.; Twelve Eikenella corrodens strains were isolated from dental infections and tested for their susceptibility to antimicrobial agents by an agar dilution method . All strains were susceptible to penicillin, ampicillin and tetracycline, and resistant to cephalexin and metronidazole and moderately resistant to erythromycin, gentamicin and cefaclor. Eur Respir J, 1990 Jun, 3(6), 715 - 22 Pharmacokinetics of antibiotics in the lungs; Valcke Y et al.; This paper reviews current knowledge on the relationship between local penetration or antibiotics and therapeutic efficacy in pulmonary and bronchial infections . The antimicrobial drug concentration at the site of infection is supposedly determinative for the efficacy of the antibiotic treatment but the number of studies in respiratory infections supporting this hypothesis is limited . The mechanisms responsible for the pulmonary deposition or orally or systemically administered antibiotics include passive diffusion, active transport, bulk flow and permeation . The penetration of antimicrobial drugs into the respiratory tract is influenced by both host-related factors, such as inflammation or mechanical injury, and drug-related factors, such as molecular weight . In addition, local bio-inactivation can occur . The final bioactive antibiotic concentration at the site of the respiratory infection is, therefore, the result or a very complex dynamic process . Different sampling and measuring methods have been used for the assessment of antibiotic concentrations at the site of respiratory infections . Concentrations in sputum, bronchial secretions and biopsy specimens have been correlated with serum concentrations and clinical outcome . Bronchoalveolar lavage could be a promising technique for evaluating antibiotic drug concentrations in alveolar lining fluid . For many antibiotics, data concerning penetration and pharmacokinetic behaviour in the respiratory tract are lacking. Tierarztl Prax, 1990 Jun, 18(3), 209 - 18 {Meaningful combinations of chemotherapeutic agents}; Lutz F et al.; It is frequently assumed that, in general, combinations of antibiotics and similar chemotherapeutic agents are more efficient than the single chemotherapeutic, and that they can be combined without disadvantages for the activity of the single component . However, the specific properties of the combined substances, such as their antimicrobial spectrum and resistance, their pharmacokinetics and side effects, as well as their physical properties and formulation, have an enormous impact on the activity of combined chemotherapeutics . They may lead to an advantageous, but also to an indifferent or diminished activity of the combination in patients . Some of the important requirements for an advantageous combination of antibiotics and similarly functioning compounds will be reviewed and ways of avoiding mistakes are described. Int J Lepr Other Mycobact Dis, 1990 Jun, 58(2), 281 - 95 Clinical trial of pefloxacin and ofloxacin in the treatment of lepromatous leprosy; Grosset JH et al.; Twenty-one previously untreated lepromatous patients were randomized into two groups and treated with either 800 mg pefloxacin (PEFLO) or 400 mg ofloxacin (OFLO) once daily . The trial consisted of two parts: monotherapy from day 0 to day 56; and combined with the World Health Organization multidrug therapy (WHO/MDT) regimen for multibacillary (MB) leprosy from day 57 to day 180 . Four patients were removed from the trial because the organisms recovered from their pretreatment biopsies failed to infect mice . Among the remaining 17 cases, four (23.5%) had primary resistance to dapsone but all of them were susceptible to rifampin . The initial (day 0) proportion of viable organisms, as measured by mouse foot pad inoculation, varied tremendously from patient to patient despite randomization during admission . Definite clinical improvement was noticed in virtually all patients after 22 doses of treatment with either PEFLO or OFLO . A significant fall in the morphological index (MI) occurred as early as after 8 doses of PEFLO or after 22 doses of OFLO; the bacterial load also showed a moderate degree of reduction during the period of monotherapy . Although single-dose PEFLO or OFLO displayed only a modest degree of bactericidal effect against Mycobacterium leprae, about 99.9%, or 4 logs, of organisms viable on day 0 were killed by 22 doses of either PEFLO or OFLO . No significant difference in the therapeutic effect was detected between the two regimens . During PEFLO or OFLO monotherapy, except in one patient (case no . 10), the side effects were few and mild . Case no . 10 developed a psychic disorder after 27 days of PEFLO monotherapy, presumably due to the treatment with PEFLO . All of the patients tolerated the period of combined therapy extremely well, although some asymptomatic and transient laboratory abnormalities were observed . Because both PEFLO and OFLO displayed rapid bactericidal activities in human leprosy and were well tolerated by the patients, further clinical trials and field trials in evaluating the therapeutic effects of combined regimens containing both rifampin and PEFLO or OFLO are being organized . Since this is the first clinical trial in leprosy employing nude mice, in combination with normal mice, for monitoring the therapeutic effects of antimicrobials, the advantages, limitations and appropriate timing in using nude mice are discussed. Prim Care, 1990 Jun, 17(2), 267 - 87 Otitis media; Kemp ED; Otitis media, one of the most common problems encountered in the care of children, remains fraught with controversy on the most appropriate methods of management . A proliferation of effective antimicrobial regimens has kept pace with emergence of resistant strains of pathogens, and sufficient information now exists to guide the clinician in making logical therapeutic decisions . Recommendations are given on appropriate use of terminology, diagnostic procedures, and therapeutic interventions for the various phases of otitis media. Crit Care Nurs Clin North Am, 1990 Jun, 2(2), 179 - 86 Antibiotic therapy in septic shock; Roach AC; Septic shock is a life-threatening illness characterized by hypotension, impaired organ function and/or failure, and metabolic abnormalities . Septic shock can develop in patients infected with a variety of gram-positive and gram-negative bacteria, viruses, fungi, rickettsiae, spirochetes, protozoa, and parasites . Immediate recognition, diagnosis, and treatment are key elements in reducing the morbidity and mortality associated with this condition . Rapid administration of appropriate antibiotics in correct doses plays a major role in patient survival . Infections with gram-negative bacteria appear to be associated with septic shock more than any other etiologic agent; therefore, antibiotic selection must include those drugs with superior gram-negative coverage . The selection of appropriate antibiotics should be based on sound clinical judgement plus knowledge of the antimicrobials used . The principles of rational therapy include the following: (1) know the type of microorganisms or suspected organism being treated; (2) be familiar with resistant organisms in both the community as well as the hospital; and (3) initiate combination therapy with a beta-lactam antibiotic plus an aminoglycoside or use monotherapy with either a carbapenem or selected third generation cephalosporin . After culture results are known, the antibiotic regimen should be narrowed to cover the specific infecting microorganism using the least expensive, least toxic antibiotic available . The beta-lactam antibiotics include all penicillins, cephalosporins, carbapenems, and monobactams . Penicillins with extensive gram-negative coverage include all the carboxy (carbenicillin, ticarcillin, and ticarcillin plus clavulanic acid) and ureido (piperacillin, mezlocillin, azlocillin) penicillins . The third generation cephalosporins (cefoperazone, cefotaxime, ceftazidime, ceftizoxime, ceftriaxone, and moxalactam) have the broadest gram-negative coverage within the cephalosporin family.(ABSTRACT TRUNCATED AT 250 WORDS) J Otolaryngol, 1990 Jun, 19(3), 175 - 8 The efficacy of pulse-dosed antibiotic therapy in the management of persistent otitis media with effusion; Donaldson JD et al.; Consensus has been achieved supporting the efficacy of antimicrobials in the management of acute otitis media with effusion (OME) . No such agreement has been reached into medical management of the patient in whom middle ear effusion (MEE) persists beyond the conventional 10- to 14-day treatment cycle . This study is designed to demonstrate the efficacy of antibiotics administered in a single daily dose in the management of persistent otitis media with effusion (POME) . Seventy-nine subjects who had MEE in 116 ears after conventional therapy were randomized into medication and placebo groups and followed by the authors on a blinded basis . The results demonstrate the efficacy of pulse-dosed antibiotics in the management of POME . Prevention of relapses during therapy was responsible for the superior outcome for children in the treatment group. J Otolaryngol, 1990 Jun, 19(3), 158 - 68 The basis of antibiotic resistance in bacteria; Shafran SD; The ability of bacteria to resist the inhibitory and lethal actions of antibiotics is a major clinical problem, and has been observed with every antimicrobial agent . In this article, the major mechanisms of antibiotic resistance are reviewed, and the clinical relevance of such resistance in selected bacteria is discussed. J Dent Res, 1990 Jun, 69(6), 1332 - 6 Plaque fluid as a bacterial milieu; Edgar WM et al.; Studies of the extracellular, free concentrations of substrates, growth factors, inhibitors, and end-products of metabolism to which the intact plaque microflora is exposed in situ can assist in the understanding of factors controlling plaque pathogenicity . Information is becoming increasingly available from analysis of fluid separated by centrifugation of plaques collected at various intervals after an intra-oral pulse of dietary or experimental substrate, or different procedures or treatments having cariostatic potential . Such analytical results give more information than those obtained by analysis of aqueous or other extracts, because they yield values of substrate concentration representing those occurring at the bacterial cell surface . The largest body of information concerns extracellular levels of acid end-products of sugar catabolism in relation to food quality or sequence, and of amino acids and other products of nitrogen metabolism, in relation to studies of the detailed metabolic events of the Stephan curve, and of the demineralizing effect of the plaque environment . Areas where little information is available and which merit further study include plaque clearance of salivary and other components with anti-caries activity (e.g., antibodies, enzymes, fluorides, cations, other antimicrobials, etc.), and substrate concentrations to determine gradients for diffusion into and out of plaque. Infect Immun, 1990 Jun, 58(6), 1807 - 11 Containment as a mechanism of nonspecific enhancement of defenses against bacterial infection; Polk HC Jr et al.; Observations made during the study of nonspecific enhancement of antimicrobial host defenses permitted some physiologic dissection of the anatomic basis for normal protective processes . Local growth of bacteria in the hind limb in muramyl dipeptide-treated mice was suppressed modestly, but lymphatic filtration was markedly improved, especially between the ipsilateral groin and iliac lymph nodes . Spontaneous containment, when it occurred in saline-treated controls, proceeded similarly . Certain regional lymph nodes acted to restrict the dissemination of bacteria from an anatomically isolated infection, reducing the degree of bacteremia and improving survival . Containment of local bacterial infection appears more important in a favorable host response than does dispersion and is accentuated by muramyl dipeptide. Farmaco, 1990 Jun, 45(6), 617 - 30 Carbamimidothioic acid phenylmethyl ester salts and their N,N'-tetramethyl derivatives as possible antimicrobial agents; Tait A et al.; A series of carbamimidothioic acid phenylmethyl ester salts and their N,N'-tetramethyl derivatives were synthesized, many of which exert an interesting inhibiting action on Gram-positive and Gram-negative bacteria and also on fungi . This activity is noteworthy in view of the large number of strains antagonized; the (3,4,5-trichlorophenyl) methyl ester chloride of carbamimidothioic acid appeared to be the best term of the series . The possible influence on this activity of decomposition kinetics to the corresponding mercapto-derivatives was investigated and compared with that of a series of N,N'-tetramethyl derivatives of previously studied carbamimidothioic acid phenyl ester salts. Antimicrob Agents Chemother, 1990 Jun, 34(6), 1035 - 40 Quantification of antibiotic drug potency by a two-compartment radioassay of bacterial growth; Boonkitticharoen V et al.; The two-compartment radioassay for microbial kinetics based on continuous measurement of the 14CO2 released by bacterial metabolism of 14C-labeled substrate offers a valuable approach to testing the potency of antimicrobial drugs . By using a previously validated radioassay with gram-positive and gram-negative bacteria, a group of protein synthesis inhibitors was evaluated for their effect on microbial growth kinetics . All tested drugs induced changes in both the slopes and intercepts of the growth curves . An exponential growth model was applied to quantify the drug effect on the processes of bacterial 14CO2 liberation and cell generation . The response was measured in terms of a generation rate constant . A linear dependence of the generation rate constant on the dose of spectinomycin was observed with Escherichia coli . Sigmoidal-shaped curves were found in the assays of chloramphenicol and tetracycline . The implications of dose-response curves are discussed on the basis of the receptor site concept for drug action . The assay sensitivities for chloramphenicol and tetracycline were similar to those obtained by the cell counting method, but the sensitivity of the radioassay was at least 10 times greater for spectinomycin. J Chemother, 1990 Jun, 2(3), 190 - 8 Pathogen-host interaction; Fraschini F et al.; Host defense, as it generally applies to humans, refers to the individual's ability to withstand infections . Human host defense mechanisms are numerous, diversified, complex, and often interdependent . The administration of drugs may influence some phases of immunocompetence mechanisms . The effect of several antimicrobial agents on organic defenses has been studied . The parameters considered were chemotaxis, phagocytosis, intracellular killing, superoxide-anion production, antibody production, lymphocyte subset behavior, and natural killer cell activity . Some antibacterial agents inhibit these parameters, whereas others can enhance some of these immune parameters to differing extents . Some antibacterial agents have a neutral effect on these parameters. Shigaku, 1990 Jun, 78(1), 21 - 47 {Studies on bone and suppurative lesion distribution of antimicrobial suppositories (Ampicillin and Ceftizoxime) to experimental infected rabbits}; Takamatsu K et al.; The investigation has been made regarding transfer of the antimicrobial agents into the osseous tissues in rabbit and into the mandibula in experimental infected rabbit model by making intrarectal administration of ampicillin (ABPC) and ceftizoxime (CZX) . The preparation of the infected model were made according to the procedure of Satoh and Heimdahl . Pharmacokinetic analysis was made by measuring concentration of these antimicrobial suppositories transferred according to the biological measuring method in serum, mandibula, maxilla, ilium, tibia, sternum, liver and pus . The results were as follows: 1) In the infected group given ABPC, the concentration of the drug in mandibula and maxilla were approx . 21.5-52.9% of those in serum . 2) In the normal healthy group given ABPC, their concentration in tissues were approx . 13.9-23.7% of those in serum . 3) In the infected group given CZX, their concentration in pus and osseous tissues were approx . 12.7-61.8% . 4) In the normal healthy group given CZX, their concentration in osseous tissues were approx . 12.4-22.9% of those in serum . 5) In a comparison made between the infected and normal healthy group, transfer of the drugs into the infected group were observed in higher rates in serum and all osseous tissues . 6) The serum concentration of the antimicrobial suppositories (ABPC and CZX) by intrarectal administration showed transfer in far higher rate than those by oral administration and exhibited transfer of concentration at its peak equal to that by intramuscular administration. Probl Vet Med, 1990 Jun, 2(2), 374 - 93 Antimicrobial therapy for gastrointestinal, pancreatic, and hepatic disorders; Davenport D; Antimicrobials are a common part of a symptomatic approach to the treatment of gastrointestinal disorders . Without an etiologic diagnosis, antimicrobial therapy is likely to be of little value and, in the worst case, may harm the patient either by altering normal gastrointestinal flora or by producing direct toxicity . This review is a systematic appraisal of antimicrobial therapy for gastrointestinal disease, beginning with the oral cavity, proceeding through the gastrointestinal tract and concluding with pancreatic and hepatic disorders . The intent is to highlight specific etiologies which form the basis for rational therapeutic choices . Controversies concerning the need for antimicrobial therapy or therapeutic alternatives are also explored . The review concludes with a discussion of adverse gastrointestinal effects of antimicrobial therapy. Probl Vet Med, 1990 Jun, 2(2), 362 - 73 Antimicrobial drugs for respiratory tract infections; Conlon PD; The respiratory tract of small animals is exposed to a large number of potential pathogens . If endogenous defense mechanisms are not able to remove the invading microorganism, infection may result . The veterinarian must then determine if antimicrobial therapy is appropriate and, if so, which drug to use, at which dose, and for how long . This article discusses the therapeutic problems that arise when deciding on antimicrobial therapy in small animal respiratory disease. Probl Vet Med, 1990 Jun, 2(2), 312 - 29 Tissue concentrations of antimicrobials . The site of action; Papich MG; The concentration of an antimicrobial drug at the site of infection is determined by its relative lipid solubility and the tissue in question . For drugs that are limited by their solubility to the extracellular fluid, the tissue concentrations in bone and soft tissue can be predicted from serum concentrations . Tissues with barriers to antimicrobial penetration include the prostate and central nervous system; there are special considerations when administering antimicrobials to treat infections in these areas or when intracellular drug concentrations are needed . Intermittent tissue concentrations of bactericidal antimicrobials that are 4-8 times the minimum inhibitory concentration (MIC) are usually sufficient for a clinical cure . However, there are situations when higher or more persistent drug concentrations are needed, such as when treating an immunosuppressed patient or when administering bacteriostatic drugs. Probl Vet Med, 1990 Jun, 2(2), 279 - 89 Therapeutic decisions . Choosing appropriate antimicrobial therapy; Wilcke JR; Certain principles and clinical techniques can be applied to antimicrobial therapy, whatever the specific circumstances . This review is intended to consider these general principles in the context of the decisions that must be made in order to apply antimicrobial therapy in veterinary patients . Attention is given to beneficial properties that contribute to action against bacterial infections, in both qualitative and quantitative terms . Selection of an antimicrobial is considered from the perspective of the laboratory test that can be used to support decisions . Finally, a structured and formal method for evaluating the overall decision making process is described. J Appl Bacteriol, 1990 Jun, 68(6), 587 - 91 Detection of antituberculous activity in plant extracts; Grange JM et al.; Ten of 408 ethanolic extracts of plants inhibited growth of Mycobacterium tuberculosis H37Rv at dilutions of 1 in 160 to 1280 and a high proportion of the other extracts inhibited growth at lower dilutions . Some of the plants, after purification, may be therapeutically useful . In view of the environmental threat to many plant species, screening of such plants for potential therapeutic properties, including antituberculous and other antimicrobial activities, are urgently required before they are lost forever. Semin Dermatol, 1990 Jun, 9(2), 102 - 4 The epidemiology of sexually transmitted diseases in Southeast Asia and the western Pacific; Thirumoorthy T; Sexually transmitted diseases (STDs) and their complications are common in Southeast Asia (SEA) and the Western Pacific region . Gonorrhea, chancroid, nongonococcal urethritis, and syphilis are still the major STDs . However, the clinical incidence of genital herpes and genital warts show a definite increase . The gonococcal infections in SEA show high levels of antimicrobial resistance . There is a high level of chromosomal-mediated and plasmid-mediated penicillinase resistance . The sex industry, strongly fueled by local consumption, travel, and tourism, continues to play an important focal role in maintaining the high level of transmission of STDs in SEA and the Western Pacific regionPIP: In incidence and epidemiology of sexually transmitted disease (STD)s in Southeast Asia and the Western Pacific, with gonorrhea, chancroid, nongonococcal urethritis, syphilis, genital herpes and genital warts at the forefront, are reviewed . The bacterial STDs gonorrhea, chancroid and syphilis are the major problems . Gonorrhea is the most prevalent STD in the region, with a high incidence of chromosomally-mediated resistant and penicillinase-producing strains comprising 35-53% of isolates . Clinical treatment failures due to spectinomycin-resistant gonococci are reported as increasing . Uncontrolled antibiotic sales are blamed for these resistant strains . Syphilis has declined in the 1950s, but has re-emerged . Chancroid is declining, while herpes is making up a greater share of ulcer disease . nongonococcal genital infection and chlamydia are thought to be the 2nd most common infection, however most centers do not have the facilities to isolate chlamydia . Genital warts are becoming a common cause for attendance at STD clinics and are a concern for cervical cancer . Prostitutes are most often cited as the source of male STD infection . The anonymity and large number of contacts of the sex industry, and high mobility of the indigenous population and of tourists are considered central in STD transmission . The high incidence of STDs in this area is a harbinger of future trends of HIV/AIDS in Asia . Otolaryngol Head Neck Surg, 1990 Jun, 102(6), 631 - 4 The effects of povidone-iodine preparation on the incidence of post-tympanostomy otorrhea; Baldwin RL et al.; Persistent otorrhea after tympanostomy tube placement in children is a common complication . Previous reports have suggested that bacteria present within the ear canal may be the cause of postoperative drainage . Preparation of the ear canal with povidone-iodine solutions has been recommended to decrease these infections . A prospective study evaluating the efficacy of povidone-iodine ear canal preparation before myringotomy and tube placement was performed in 111 children (220 ears) with documented chronic otitis media with effusion . One ear in each patient was prepared with povidone-iodine . The contralateral ear in each child was used as control . Postoperative otorrhea developed in seven (6.3%) of the treated ears within 14 days, compared to eleven (10%) of the ears in the control group . The difference was not statistically significant (p greater than 0.05) . Purulent or mucoid middle ear effusions and edematous or granular middle ear mucosa were associated with a significantly higher incidence of postoperative otorrhea (p less than 0.05) . This study suggests that postoperative otorrhea is generally a consequence of preoperative middle ear condition rather than contamination from the external canal . Antimicrobial therapy should be considered when purulent effusion or granulation tissue is seen. Zhonghua Ya Yi Xue Hui Za Zhi, 1990 Jun, 9(2), 75 - 82 {Effects of subgingival antimicrobial irrigation in chronic periodontitis--clinical observation}; Lin JM et al.; One week prior to the establishment of baseline records, 144 sites with a probing pocket depth of 5-7 mm in 13 periodontitis patients were treated with plaque control and root planning . Sites with periodontitis involvement in each patient were divided, by split mouth design, into 4 quadrants . Each quadrant was irrigated subgingivally with either 0.05% metronidazole or 0.05% ornidazole, or 0.2% chorhexidine, or 0.9% normal saline (control) once every 2-3 days for 4 weeks . The plaque index, sulcus bleeding index, probable pocket depth and gingival index were assessed at the baseline and at 4 weeks, 8 weeks and 12 weeks following initial preparation . All 4 clinical parameters in the ornidazole treated group showed significant improvement as compared with baseline values, but the improvements were not maintained to the end of the study . Except for improvement in the sulcus bleeding index and the gingival index in the ornidazole group, which was superior to that of the metronidazole group at the 4th week, there were no significant differences in other parameters between the ornidazole, metronidazole and chlorhexidine groups at the irrigation sites . From these data we can tentatively conclude that subgingival irrigation with ornidazole in deep pockets is more effective than metronidazole or chlorhexidine in nonsurgical periodontal therapy. Zhonghua Ya Yi Xue Hui Za Zhi, 1990 Jun, 9(2), 61 - 6 {An in vitro study of the antimicrobial effectiveness of ultrasonic instrumentation}; Chan C et al.; Successful endodontic therapy is based upon the classic triad of diagnosis, adequate canal preparation, and obturation . Preparation for a root canal has two major components--debridement and shaping . Debridement, or cleaning, consists of removal of necrotic intracanal dentin and organic debris, and reduction of the bacteria inside the root canal . According to the research, the endontic ultrasonic system plays a valuable and significant and synergistic role in aiding the bacteriocidal mechanisms based on the cavitation and acoustic streaming effect . The purpose of this study was to compare the antimicrobial effectiveness of two newly developed endodontic ultrasonic devices and the conventional hand-filing techniques . Eighty single root canal teeth with deep caries or apical lesions were selected and evenly divided into 4 groups . The root canals were prepared using conventional hand filing or one of two newly developed ultrasonic filing systems, ENAC and CAVI-ENDO . The contents of the root canals before and after debridement were cultured in a thioglycolate culture tube . The results showed that in the ultrasonically prepared specimens irrigated with a normal saline solution, the microbial culture numbers were significantly reduced and obviously different from those prepared by the hand instrumentation technique . The above mentioned differences were statistically significant at the level of p less than 0.05 by the McNemar test and Chi-square test. J Formos Med Assoc, 1990 Jun, 89(6), 491 - 7 {A evaluation of chlorhexidine as an endosonic irrigan}; Lee LW et al.; Chlorhexidine has been utilized as a root canal irrigant since 1971 . It is a broad-spectrum antimicrobial agent with minimal toxicity and residual long-term antibacterial capability . Although a sodium hypochlorite solution has been shown to have a better antimicrobial effect than chlorhexidine, its corrosive effect has prevented its further use especially since the in vitro antimicrobial effect of chlorhexidine has been shown to not be much less . However, the efficacy of chlorhexidine as an endodontic irrigant and intracanal medicament, requires further research in vivo . Therefore, in this study, the clinical effects of chlorhexidine were evaluated by comparing its antimicrobial properties with other endodontic irrigants . One hundred and fifty teeth were selected and evenly divided into 6 groups according to their pathological status . The root cancals were prepared with conventional hand filing or ultrasonic filing, respectively, and were rinsed singly with either chlorhexidine, EDTA or distilled water . The contents of each root canal before or after debridement were cultured in an incubator . The results showed that chlorhexidine with hand filing in one week and with endosonics in 48 hours had a better antimicrobial effect than did EDTA . As compared with the control group (distilled water), chlorhexidine showed marked antimicrobial effect in both hand and endosonic filing . It is concluded that chlorhexidine has an antibacterial effect as an endodontic irrigant in clinical applications. J Antibiot (Tokyo), 1990 Jun, 43(6), 623 - 33 A80915, a new antibiotic complex produced by Streptomyces aculeolatus . Discovery, taxonomy, fermentation, isolation, characterization, and antibacterial evaluation; Fukuda DS et al.; New semi-naphthaquinone antibiotics A80915A, B, C, and D were isolated from the fermented broth of Streptomyces aculeolatus A80915 (NRRL 18422) . Factors A and C, present in both the broth filtrate and mycelial methanol extract, and factors B and D, found predominantly in the broth filtrate, were recovered by extraction with ethyl acetate . Purification of the individual factors was accomplished by preparative reverse phase high performance liquid chromatograph on C18 bonded silica supports . Factors A through D show antimicrobial activity against Gram-positive aerobic and anaerobic organisms in vitro . Mechanism of action studies demonstrated nearly complete inhibition of macromolecular biosynthesis (protein, RNA, DNA, and cell wall) by A80915 factors A through D . A less highly cyclized semi-naphthaquinone, A80915 factor G, was isolated from the broth of the strain fermented in an alternate medium. Br Dent J, 1990 May 19, 168(10), 409 - 10 Current prophylaxis for prevention of infective endocarditis; Gould IM; A nationwide postal survey of dental and medical practitioners was undertaken to ascertain the degree of acceptance of the British Society for Antimicrobial Chemotherapy guidelines on prophylaxis for infective endocarditis . Questionnaires were circulated to 21,050 individuals . The overall response rate was 17% . Prophylaxis for infective endocarditis is widely practiced (99% of respondents) and the recommendations are generally accepted but there is still room for improvement in practice, particularly in drug dosing, timing and duration of prophylaxis . There is a disappointing lack of use of local policies, topical antibiotics and cardiac alert cards. Schweiz Med Wochenschr, 1990 May 19, 120(20), 745 - 9 {DF-2, a "new" gram-negative bacterium}; Malinverni R; Dysgonic fermenter 2 (DF-2) is a long, fastidious gram negative rod that leads to life-threatening infections in immunocompromised and especially splenectomized patients . It can also severely affect the healthy individual . It is mainly acquired through contact with dogs and after dog bites . The infection has rarely been described, due to difficulties in isolating DF-2, its relatively low virulence, its susceptibility to antimicrobial agents and the frequent administration of antibiotics after animal bites . A systematic approach to the practical management of dog bite wounds is proposed. J Am Vet Med Assoc, 1990 May 15, 196(10), 1628 - 30 Ulcerative duodenitis with luminal constriction in two horses; Ettlinger JJ et al.; Proximal enteritis was diagnosed on the basis of clinical signs of disease in 2 Standard-bred yearlings from the same farm . Large volumes of fluid were repeatedly obtained during gastric decompression . The horses did not respond to treatment with IV administered fluids, antimicrobial agents, cimetidine, and metoclopramide . Postmortem findings confirmed severe focal chronic active duodenitis with stricture formation . An etiologic agent was not identified. Am J Med, 1990 May 14, 88(5A), 46S - 50S Antibiotic susceptibilities and drug resistance in Moraxella (Branhamella) catarrhalis; Wallace RJ Jr et al.; PURPOSE: To summarize current knowledge of drug susceptibility and mechanisms of drug resistance in Moraxella (Branhamella) catarrhalis . MATERIALS AND METHODS: The current medical literature was reviewed, with careful attention to recent studies of the BRO beta-lactamases . RESULTS: Although intrinsically resistant to a small group of drugs that included vancomycin and trimethoprim, acquired drug resistance in Branhamella catarrhalis was unknown in the early years of antimicrobial therapy . During 1976 to 1977, however, two previously unrecognized beta-lactamases appeared in this species almost simultaneously around the world . At the same time these enzymes, now known as BRO-1 and BRO-2, also appeared in two closely related commensal species of Moraxella . Within four years the BRO enzymes were found in up to 75 percent of B . catarrhalis in the United States where they provide low-level resistance to penicillin and ampicillin but not to most cephalosporins . The BRO genes appear to be chromosomal but are readily transferred by conjugation within the Moraxella genus . Resistance to aminoglycosides and trimethoprim-sulfamethoxazole has been reported from Spain, and resistance to both erythromycin and tetracycline has recently been described among United States isolates of B . catarrhalis . CONCLUSION: Despite this drug resistance, numerous oral and parenteral agents are available and appear useful for treatment of clinical disease, including amoxicillin/clavulanic acid, erythromycin, the tetracyclines, ciprofloxacin, and trimethoprim/sulfamethoxazole . Recent changes in drug resistance in this species suggest that continued monitoring of drug resistance in B . catarrhalis is needed. Biochemistry, 1990 May 8, 29(18), 4490 - 6 Raman spectroscopy of synthetic antimicrobial frog peptides magainin 2a and PGLa; Williams RW et al.; Magainin and PGLa are 23- and 21-residue peptides isolated from the skin of the African clawed frog Xenopus laevis . They protect the frog from infection and exhibit a broad-spectrum antimicrobial activity in vitro . The mechanism of this activity involves the interaction of magainin with microbial membranes . We have measured the secondary structure and membrane-perturbing ability of these peptides to obtain information about this mechanism . Our results show that mgn2a forms a helix with an average length of less than 20 A upon binding to liposomes . At high concentrations (50 mg/mL) mgn2a spontaneously solubilizes phosphatidylcholine liposomes at temperatures above the gel-liquid-crystalline phase transition . Mgn2a appears to bind to the surface of liposomes made of negatively charged lipids without spontaneously penetrating the bilayer . Finally, mgn2a and PGLa interact together with liposomes in a synergistic way that enhances the helix content of one or both of the peptides and allows the peptides to more easily penetrate the bilayer . PGLa mixed with a small nonperturbing amount of magainin 2 amide is 25-43 times as potent as PGLa alone at inducing the release of carboxyfluorescein from liposomes . The results suggest that the mechanism of antimicrobial activity does not involve a channel formed by transmembrane helical peptides. Lancet, 1990 May 5, 335(8697), 1077 - 8 Sinus disease in patients with severe cystic fibrosis: relation to pulmonary exacerbation; Umetsu DT et al.; Four adult cystic fibrosis patients were selected for aggressive surgical management of sinus disease on the basis of severe pulmonary involvement, high frequency of hospital admission, chronic headache, and wheezing unresponsive to conventional treatment . They underwent bilateral Caldwell-Luc procedure with perioperative anti-Pseudomonas antimicrobials . There were substantial improvements in headache and respiratory symptoms and a significant reduction in the frequency of hospital admission after the operation . These findings suggest that sinus disease is associated with pulmonary exacerbation in patients with cystic fibrosis, and strengthens a similar observation in patients with asthma. Ann Acad Med Singapore, 1990 May, 19(3), 375 - 9 Spectrum of nocardiosis in renal patients; Kong NC et al.; Nocardiosis is an increasingly recognised opportunistic infection in immunologically incompetent hosts but diagnosis is often delayed . Between December 1975 to October 1988, our two Nephrology Units have encountered five cases of nocardiosis occurring in two post-renal transplant patients, two patients with systemic lupus erythematous (SLE) and one patient with mesangiocapillary glomerulo--nephritis . All were on immunosuppressants at the time . The first three patients presented with predominant pulmonary disease and were cured by combined trimethoprim-sulphamethoxazole (cotrimoxazole) and doxycycline therapy . The patient with limited skin involvement responded to cotrimoxazole alone . However, the last patient with lymphocutaneous disease initially responded to cotrimoxazole (+ chloramphenicol) but developed acute-on-chronic renal failure and relapsed with dose reduction of cotrimoxazole . Alternative treatment with amikacin and doxycycline was instituted with good response . We shall review potential clues that may suggest the diagnosis of nocardiosis and discuss other effective antimicrobial agents. Contact Dermatitis, 1990 May, 22(5), 257 - 61 Patch test sensitivity to the preservative Kathon CG in Spain; Hasson A et al.; Kathon CG is a very well studied preservative used in cosmetics and toiletries . It is effective in low concentrations (3 to 15 ppm active ingredients) and exhibits outstanding antimicrobial activity against gram-negative and gram-positive bacteria, yeasts and fungi . Although this biocide is not considered to pose a toxicological hazard at recommended use levels, the sensitizing potential of Kathon CG has been established . From November 1988 to June 1989, we patch tested 626 unselected contact dermatitis patients with Kathon CG solution containing 200 ppm active ingredients and obtained 22 (3.5%) positive reactions . Relevance was established in 7 of the 22 patients . Women were predominantly sensitized, the principal source of sensitization being cosmetics. Diagn Microbiol Infect Dis, 1990 May-Jun, 13(3), 277 - 9 Antibacterial activity of lomefloxacin against Brucella melitensis; Qadri SM et al.; The in vitro activity of lomefloxacin was tested against 114 clinical isolates of Brucella melitensis . Comparison was made with ciprofloxacin, tetracycline, gentamicin, rifampin, and trimethoprim-sulfamethoxazole . Lomefloxacin inhibited 113 (99.1%) of the 114 strains tested at less than or equal to 0.5 microgram/ml . It was comparable to ciprofloxacin, tetracycline and gentamicin in antimicrobial potency . One strain that was previously susceptible to ciprofloxacin and had become resistant after the patient was treated with ciprofloxacin showed cross-resistance to lomefloxacin. J Anim Sci, 1990 May, 68(5), 1318 - 22 Effect of chelated copper sources on performance of nursery and growing pigs; Stansbury WF et al.; Four experiments were conducted to determine the effect of Cu source and level and an antimicrobial agent on performance of nursery (6 to 25 kg) and growing (20 to 65 kg) pigs . Copper was fed either as CuSO4.5H2O (CS), inorganic chelated Cu (ICC) or organic chelated Cu (OCC) to provide 31.25 to 250 ppm supplemental Cu . In Exp . 1, 224 pigs were used to study Cu source and level added to nursery diets . No difference (P less than .05) among treatments was observed during the nursery period . Treatments were continued the first 56 d of the growing-finishing period . Regardless of the Cu source, pigs receiving 125 ppm added Cu gained faster (P less than .05) than pigs in other treatments . In Exp . 2, 216 pigs were used to determine the optimum level of CS and ICC in nursery diets . Pigs were less efficient (P less than .01) when Cu was added at 62.5 and 125 ppm than at 250 ppm (1.69, 1.72 and 1.59, feed/gain respectively) . In Exp . 3, no differences (P greater than .05) in performance between sources or among levels of Cu were found . In Exp . 4, 216 pigs were utilized to determine the combined effects of Cu source and an antimicrobial on performance . Pigs fed ICC were less efficient (P less than .01) than pigs fed either OCC or CS (1.99, 1.85 and 1.90, respectively) . The inorganic and organic chelated Cu compounds used in these studies were not more efficacious than CS for nursery or growing pigs. Decubitus, 1990 May, 3(2), 24 - 6 The perioperative antimicrobial management of pressure ulcers; Salzberg CA et al.; No clear data exist as to the efficacious use of antibiotics during the perioperative period for repair of pressure ulcers . Results of a survey from 50 university departments of plastic surgery and spinal cord injury centers revealed that 58% reported routine use of antibiotics for flap surgery with cephalosporins as the choice at 69% of the centers . Clinical experience with 35 patients perioperatively showed good results with a third generation cephalosporin. Jpn J Pharmacol, 1990 May, 53(1), 57 - 66 Effect of cysteine ethylester hydrochloride (Cystanin) on host defense mechanisms (V): Potentiation of nitroblue tetrazolium reduction and chemiluminescence in macrophages or leukocytes of mice or rats; Hisadome M et al.; L-Cysteine ethylester hydrochloride (Cystanin, ethylcysteine) at doses of 3-30 mg/kg, p.o., potentiated the reduction of nitroblue tetrazolium (NBT) by mouse peritoneal macrophages ex vivo . In in vitro experiments, this drug (30 microM) augmented NBT reduction of mouse peritoneal macrophages induced by opsonized zymosan (OZ) . At the same concentration, this drug accelerated the enhancement of the OZ-induced NBT reduction by the addition of concanavalin A, N-formyl-L-methionyl-L-leucyl-L-phenylalanine or phorbol myristate acetate . This enhancing effect of ethylcysteine was completely diminished by the addition of SOD, sodium azide and catalase . In ex vivo experiments, the OZ-induced chemiluminescence of rat peritoneal macrophages and white blood cells was enhanced by the administration of ethylcysteine at doses of 3-10 mg/kg (i.p.) and 3-30 mg/kg (p.o.) . In addition, this drug significantly enhanced the lumisphere-induced chemiluminescence of rat peritoneal leukocytes at 30 mg/kg (i.p.), but not the OZ-induced chemiluminescence . In in vitro experiments, this drug (30 microM) did not enhance the OZ-induced chemiluminescence response of rat peritoneal macrophages . These results suggest that ethylcysteine may enhance the intracellular generation of antimicrobial oxidants in macrophages and leukocytes. J Pharm Sci, 1990 May, 79(5), 447 - 52 Synthesis and biological activity of a series of aspartate transcarbamoylase inhibitors: N-substituted diethyl aspartates and N-substituted-3-oxo-1,4-piperazine-2-acetic acid esters; Dutta PL et al.; Series of N-substituted diethyl aspartates and N-substituted-3-oxo-1,4-piperazine-2-acetic acid esters were synthesized as potential inhibitors of aspartate transcarbamoylase . The aspartates were obtained by addition of substituted alkyl amines to diethyl maleate, or conversion of the hydroxy ethyl amino adduct to other functions . The 3-oxo-1,4-piperazine-2-acetic acid esters were prepared by addition of ethylene diamine to diethyl maleate, followed by cyclization . Addition of 1,2-diamino-2-methylpropane gave the corresponding 5,5-dimethyl-3-oxo-1,4-piperazine-2-acetic acid ester . N-Acyl derivatives in each series were obtained using the bromoacyl chlorides . A majority of the compounds in each series showed antimicrobial activity against five representative microorganisms, as well as significant activity against aspartate transcarbamoylase . Four of the compounds were found to have significant specificity against several tumor cell lines . A distance of two carbons between N and a reactive function was found to give the best activity for either antimicrobial, antienzyme, or tumor cell specificity activities, in either the open chain aspartates or cyclic piperazines . Little difference in anti-enzyme activity was found between the aspartates and piperazines, but introduction of the planar phenyl substituents lowered inhibitory activity. J Periodontol, 1990 May, 61(5), 300 - 4 Osseo-integrated implant treatment of a patient with rapidly progressive periodontitis . A case report; Malmstrom HS et al.; The case report presented describes placement of osseointegrated fixtures in a patient with a probable history of rapidly progressive periodontitis . A 12-year history is presented . The post-operative sequelae of placing fixtures in a fully edentulous maxilla and partially edentulous mandible were the worst seen by the Implant Team at Emory University . The hypothesis presented is that patients with aggressive forms of periodontal disease should be subjected to appropriate mechanical and antimicrobial therapy to produce a healthy oral flora before any implants are placed. Pediatr Res, 1990 May, 27(5), 432 - 5 Medical research in infants and children in the eighties: analysis of rejected protocols; Koren G et al.; We reviewed the 351 protocols dealing with research in infants and children in our institute between July 1982 and August 1988 to identify ethical issues that complicate the execution of pediatric research . Of the 16 rejected protocols (4.5%) 12 were drug studies, three dealt with the nature or course of disease states and one was in the area of behavioral sciences . Drug studies were significantly more likely to be rejected than all other studies . The most common reason for rejection (n = 10) were major scientific flaws that, according to the Committee, would result in inability of the study to answer the questions posed by the researchers . In nine cases the Committee judged a study to be physically invasive without a direct benefit to the involved infant/child . In three cases, the Committee rejected a study because patients with serious medical conditions might be randomized to receive placebo and not a drug that, based on current knowledge from adults, would possibly improve their condition . In three protocols, current antimicrobial therapy covered all pathogens causing the infection and the proposed new therapy could not improve the prognosis further but only be equal or inferior . Researchers who had more than one protocol rejected had significantly more protocols submitted (7.17 +/- 1.35) than those who had only one rejection (1.86 +/- 0.36, p less than 0.0005) or than the 10 researchers with the highest number of studies without a single rejection (4.2 +/- 0.4, p less than 0.05) . These numbers suggest that scientists who perform more research are more likely to stand at the front line of unresolved ethical issues. R I Med J, 1990 May, 73(5), 199 - 204 Traveler's diarrhea: methods of prevention and treatment; Opal SM et al.; Traveler's diarrhea can often be avoided by following safe food and water practices while traveling in developing countries . Prophylactic agents are generally not indicated in the prevention of traveler's diarrhea . Should traveler's diarrhea develop, fluid replacement is the principal therapeutic modality . Other useful treatments include bismuth subsalicylate or anti-motility agents such as loperamide or diphenoxylate . Early empiric use of antimicrobial agents including trimethoprim-sulfamethoxazole or quinolone agents offers an excellent means of treating traveler's diarrhea and preventing its potential complications . Travelers who develop dysentery, high fever, or prolonged diarrhea lasting more than 10-14 days should seek medical attention for specific diagnosis and appropriate antimicrobial therapy. J Am Acad Dermatol, 1990 May, 22(5 Pt 2), 956 - 9 Cutaneous zygomycosis in a diabetic HTLV-I-seropositive man; Clark R et al.; Zygomycosis, an invasive fungal infection, is usually seen in persons with diabetes, particularly in those with diabetic ketoacidosis . The infection most frequently occurs in the rhinocerebral region and rapidly spreads, causing a swift demise . Rarely, the infection is confined to the cutaneous tissues . We describe a 31-year-old man seropositive for human T lymphotropic virus type I who had diabetic ketoacidosis with zygomycosis confined to the right arm . The lesion was presumed initially to be a bacterial infection but did not respond to conventional antimicrobial therapy . The arm lesion was cultured, and Rhizopus arrhizus was isolated . The patient responded well to a combination of amphotericin B and extensive surgical debridements . Our case emphasizes the importance of maintaining a high index of suspicion of cutaneous zygomycotic infections in the impaired host, especially of those in patients with diabetes, who do not respond to initial antimicrobial treatment. J Pediatr, 1990 May, 116(5), 697 - 701 Respiratory virus infection as a cause of prolonged symptoms in acute otitis media; Arola M et al.; We studied respiratory viruses in 22 children with acute otitis media who had failed to improve after at least 48 hours of antimicrobial therapy . The mean duration of preenrollment antimicrobial therapy was 4.8 days . For comparison we studied 66 children with newly diagnosed acute otitis media . Respiratory viruses were isolated from middle ear fluid or from the nasopharynx, or both, significantly more often in the patients unresponsive to initial antimicrobial therapy than in the comparison patients (68% vs 41%, p less than 0.05) . Viruses were recovered from the middle ear fluid in 32% of the study patients and from 15% of the comparison group . Bacteria were isolated from the middle ear fluid of four (18%) children in the study group; one child had an isolate resistant to initial antimicrobial therapy . All four children with bacteria in the middle ear fluid had evidence of concomitant respiratory virus infection . Our results indicate that respiratory virus infection is often present in patients with acute otitis media unresponsive to initial antimicrobial therapy, and may explain the prolongation of symptoms of infection . Resistant bacteria seem to be a less common cause of failure of the initial treatment. Am J Epidemiol, 1990 May, 131(5), 905 - 16 Risk factors for wound infections after total knee arthroplasty; Gordon SM et al.; Wound infections are an infrequent but serious complication of total knee arthroplasty . Between January 1984 and November 1987, 20 of 243 (8.2%) patients at two affiliated hospitals developed surgical wound infections following 259 total knee arthroplasty procedures performed in clean-air operating rooms . Eighteen (90%) of the patients had deep infections; nine required removal of the prosthesis . A single surgeon (surgeon X) was associated with 18 of the procedures that had subsequent infection (risk ratio (RR) = 9.4, 95% confidence interval (CI) 2.2-39), and an investigation was carried out in an effort to explain the difference in infection rates between surgeon X and other surgeons . In a cohort study, stratified analyses identified a preoperative American Society of Anesthesiologists (ASA) physical status class greater than or equal to 3, surgeon X, and early postoperative use of a continuous passive motion device as risk factors associated with surgical wound infection following total knee arthroplasty procedures . Logistic regression analyses identified being a patient operated on by surgeon X with an ASA class greater than or equal to 3 as the only significant independent risk factor for total knee arthroplasty-associated surgical wound infections (RR = 9.3, 95% CI 2.8-31) . The effect due to surgeon X could not be explained by receipt or timeliness of administration of antimicrobial prophylaxis, type of prosthesis inserted, duration of operation, postoperative use of continuous passive motion, or underlying etiology of joint disease . The authors conclude that surgical technique and patient's severity of illness were the primary determinants of surgical wound infection after total knee arthroplasty . This study demonstrates the complexity of epidemiologic investigation of surgical wound infections and the importance of considering patient severity of illness when interpreting surgeon-specific infection rates. Jpn J Med, 1990 May-Jun, 29(3), 248 - 54 Clinical evaluation of 12 cases of antimicrobial drug-induced pneumonitis; Kohno S et al.; The diagnosis of drug-induced pneumonitis is generally difficult, and it is made clinically by Tamura's criteria . We experienced 12 cases (7 definite and 5 possible cases) of antimicrobial drug-induced pneumonitis (one of case was the first case caused by carbapenem) . Symptoms such as fever (11/12), cough (10/12) and dyspnea (10/12) and laboratory data such as eosinophilia (7/12), elevation of IgE (4/6) and hypoxia (11/12) were commonly seen in these patients, although they were not specific . Lymphocyte stimulation test (5/11) and provocation test (4/8) were quite suggestive of drug allergy . Bronchoscopy has been used for confirmation of pneumonitis . Transbronchial lung biopsy revealed alveolitis (4/9) or alveolar fibrosis (3/9), and bronchoalveolar lavage showed lymphocytosis (6/6) and depression of OKT4/T8 ratio (3/5) . The combination of bronchoscopic and immunological examinations were more confirmative for diagnosis. J Pharmacobiodyn, 1990 May, 13(5), 292 - 300 Sodium and pH dependent carrier-mediated transport of antibiotic, fosfomycin, in the rat intestinal brush-border membrane; Ishizawa T et al.; The mechanism of intestinal absorption of an antimicrobial agent, fosfomycin (FOM), was investigated in rats using small intestinal brush-border membrane vesicles (BBMV) . The uptake of {3H}FOM by BBMV was osmolarity- and temperature-sensitive and showed apparently saturable uptake kinetics consistent with the Michaelis-Menten equation, having Kt = 15.3 mM and Jmax = 7.78 nmol/30 s/mg protein at 37 degrees C . An overshoot uptake of FOM was observed in the presence of an inwardly direct Na+ gradient . The replacement of extravesicular Na+ with choline or mannitol significantly reduced the uptake . An addition of a protonophore, FCCP, significantly decreased the initial uptake of FOM in the absence of Na+ gradient but in the presence of a H+ gradient (pHin = 7.5, pHout = 6.0), whereas in the absence of a H+ gradient no significant difference was observed between the uptakes at an acidic pH (pHin = pHout = 6.0) and a neutral pH (pHin = pHout = 7.5) . An inside negative potassium diffusion potential induced by valinomycin enhanced significantly the uptake of FOM . The uptake of FOM in the presence of both Na(+)- and H(+)-gradients was significantly inhibited by phosphate, arsenate and phosphonoformic acid (PFA), which are specific inhibitors of phosphate transport, but not by D-glucose . Based on these results, it is concluded that FOM transport in the small intestine is partially shared with the Na(+)-phosphate cotransport system and in part occurs via a H(+)-gradient dependent carrier-mediated system. Lijec Vjesn, 1990 May-Jun, 112(5-6), 131 - 7 {Critical analysis of drugs in 1989}; Vrhovac B et al.; Changes and trends in the drug field in the world and in Yugoslavia in 1989 are presented and discussed . 1 . World . There appeared only a few new drugs all over the world, and new chemical entities (NCE) rather rarely represent a significant contribution to materia medica . Japan is the first in producing NCE (12) followed by United Kingdom and the USA (4 NCE each) . 2 . Yugoslavia . In Yugoslavia were 125 drugs discussed approval, new dose, new formulation or generic parallel . More than 84% of these have been related to generic or clinical ("me too") parallels; less than 9% of drugs had a certain contribution to materia medica, while, according to the authors, the number of drugs that contributed significantly to the materia medica and of those which should not have been approved was equal (3.2%) . Octreotide, erythropoietin, almitrine and flumazenil were placed in category A . Insulin appeared in the largest number of parallels (as many as 19) succeeded by cardiovascular, antimicrobial and gastrointestinal drugs . 3 . Drug formularies exist in all the developed countries and represent a way of limiting prescribing . Yugoslav list of drugs expenses of which will be covered by the Health Insurance will be prepared . 4 . The Federal Institute for Health Protection through its special committee for diagnostics, pharmacotherapy and side effects represents a useful activity in rationalizing drug use . 5 . Yugoslav publication of defined daily doses (DDD) is being prepared . 6 . A review of causes of deficient or inadequate drug supply in Yugoslavia, which still represents a major problem in this country, has been given at the end. J Med Assoc Thai, 1990 May, 73(5), 264 - 8 Liver abscess: a clinical study of 222 patients; Thamlikitkul V et al.; The medical records of 222 patients with liver abscess at Siriraj Hospital from 1978 to 1985 were analysed . Amoebic abscess was three times more prevalent than pyogenic abscess . In both groups middle aged males were affected more often than others . The main clinical manifestations were fever, right upper quadrant pain and hepatomegaly . History of colitis in the past, marked leukocytosis, elevation of alkaline phosphatase and a single abscess confined to the right lobe were suggestive of amoebic liver abscess . The presence of concurrent abdominal infection, marked anemia and jaundice were associated with pyogenic abscess . Patients with pyogenic abscess developed complications more often and the case fatality rate was greater than patients with amoebic abscess . Most of the patients were successfully treated with a combination of antimicrobials and drainage. Antibiot Khimioter, 1990 May, 35(5), 31 - 2 {Effects of a new derivative of 5-alkyl-3N-furanones on the colonization resistance of the intestine in albino mice}; Tomnikov AIu et al.; By its antagonistic function normal microflora provides the intestine with resistance to colonization with exogenic opportunistic and pathogenic microorganisms . The drug was effective in inducing a decrease in the intestine colonization resistance which in its turn leads to filling of free ecological ni