Antimicrobials

Pharmacotherapy, 1989, 9(3), 158 - 64
Prospective surveillance of antibiotic-associated coagulopathy in 970 patients; Grasela TH Jr et al.; N-methyl-thio-tetrazole (NMTT) has been proposed as a causative factor in antibiotic-associated coagulopathy . To evaluate this hypothesis, a nationwide surveillance program was initiated to determine the relative frequency of antibiotic-associated coagulopathy and the importance of specific risk factors . A total of 970 patients were studied, with 491 being treated for infections and 479 receiving antimicrobial surgical prophylaxis . The NMTT-containing antibiotic cefotetan was compared with non-NMTT-containing antibiotics, for example, cefoxitin and cefazolin (prophylaxis only), and an aminoglycoside-antianaerobic (AG + AA) combination . Prothrombin time (PT) and partial thromboplastin time (PTT) were measured for each patient prior to the start of antibiotics and within 24-96 hours after the conclusion of drug administration . The patient population was relatively young {mean (SD) age 51.0 (20) yrs} with good nutritional status . The overall frequency of hypoprothrombinemia (4.5%) and bleeding (1.7%) was very low, and was highest with the use of AG + AA (p less than 0.05) . No statistical differences were observed for the remaining antibiotic regimens in either the prophylaxis or treatment group . Logistic regression analysis identified treatment with the AG + AA combination, presence of liver disease, and renal dysfunction as factors associated with an increased risk of hypoprothrombinemia . In conclusion, this study suggests that the frequency of antibiotic-associated coagulopathy is low, regardless of antibiotic, in patients who are not critically ill and not malnourished.

Farmaco, 1989 Jan, 44(1), 89 - 95
Synthesis and antimicrobial activity of some pyrrole derivatives . IV--2-arylidenhydrazino-3-ethoxycarbonyl (or cyano) pyrrole derivatives; Cocco MT et al.; A new series of pyrrole derivatives obtained by heterocyclization of N1-aryliden-3-ethoxycarbonyl (or cyano) acetamidrazones with alpha-bromoketones was described . The in vitro microbiological investigation showed that none of the 2-arylidenhydrazinopyrrole derivatives presented any noteworthy activity.

Farmaco, 1989 Jan, 44(1), 51 - 63
{Substances with antibacterial and antifungal activity . VI . Synthesis and microbiologic activity of new derivatives of 1,5-diarylpyrrole and 1,4-pyrrolphenylene}; Porretta GC et al.; New 1,5-diarylpyrrole and 1,4-pyrrolphenylene derivatives were prepared to study influence on the microbiological activity of an unsubstituted pyrrole nucleus or of a double identical molecular structure . Antimicrobial data in comparision with antifungal antibiotic pyrrolnitrin showed that all tested compounds exhibited very poor antifungal and antibacterial activity . Only some derivatives showed a selective activity against strains of Candida sp . and against strains of gram-positive or gram-negative bacteria.

Eur Surg Res, 1989, 21 Suppl 1, 1 - 5
Short-term antimicrobial prophylaxis in surgery . The state of the art; Rodolico G et al.; The authors pointed out that contamination may be exogenous, as a result of invasive diagnostic techniques, patient preparation, surgery, catheter insertion and wound dressing, or endogenous, especially in patients with specific risk factors (age, metabolic disorder, malnutrition, immunodeficiency) and aspecific risk factors (anesthesia, blood transfusion, surgery) . Pharmacologic prophylaxis of infection may be unspecific (artificial nutrients, anticoagulants, immunomodulators) or specific (antibiotics) . Prophylaxis is indicated in clean-contaminated and contaminated surgery; antibiotic chemoprophylaxis is also indicated in risk patients and permanent prosthesis surgery . The authors emphasized that antibiotics are no substitution for careful surgery.

J Pediatr Gastroenterol Nutr, 1989 Jan, 8(1), 89 - 94
Functional capacity of colostral leukocytes from women delivering prematurely; Schlesinger L et al.; The phagocytic, bactericidal, and metabolic activity of colostral leukocytes from mothers delivering preterm infants was compared with that of colostral leukocytes from mothers of term infants . In addition, the proliferative capacity of colostral lymphocytes was compared . Preterm adherent colostral leukocytes had a significantly higher phagocytic index than term colostral adherent leukocytes . Mean +/- SEM values were 5.4 +/- 0.5 versus 2.7 +/- 0.2, respectively (p less than 0.001) . Bactericidal capacity against Escherichia coli and nitroblue tetrazolium reduction of preterm and term colostral leukocytes were comparable . Lymphocyte proliferative response was equivalent in preterm and term milk . We conclude that colostral leukocytes from preterm mothers are at least as functional in their antimicrobial activity and possibly phagocytose even better than the colostral cells of mothers of term infants.

Scand J Infect Dis, 1989, 21(1), 33 - 41
A new diagnostic approach to the patient with severe pneumonia; Sorensen J et al.; 36 patients with severe community-acquired pneumonia, treated in an intensive care unit (ICU), were examined in a prospective study using a comprehensive diagnostic program to establish an early etiological diagnosis . The resulting prompt and adequate antimicrobial therapy may have decreased the number of fatal cases . Special emphasis was placed on the use of a method incorporating fiberoptic bronchoscopy, together with protected brush sampling and bronchial lavage . An etiological diagnosis was established in 81% (29/36) of the cases . This etiological diagnosis was established within 48-72 h in 53% (19/36) of the patients, S . pneumoniae being the most frequent agent found (12 patients) . This information, however, was poorly utilized since in only 11/19 of these patients was the antimicrobial therapy changed from a broad-spectrum antibiotic to a more specific narrow spectrum agent . The overall mortality rate was 22% (8/36) . 7/8 patients who died had compromising factors . Most deaths in community-acquired pneumonia are still associated with pneumococcal infection . We conclude that fiberoptic bronchoscopy with brush samples via a plugged double lumen catheter provides the least misleading information concerning the etiological agent in pneumonia; sampling should be done as soon as possible after admission to the hospital, ideally before the need for ICU treatment; factors other than prompt antimicrobial therapy may influence the outcome of severe community-acquired pneumonia.

Padiatr Padol, 1989, 24(1), 49 - 61
{Diagnosis and therapeutic strategies in pneumonia in childhood}; Schmitzberger R et al.; Acute lower respiratory tract infections remain a major cause of morbidity in infants and children . In the majority of patients therapy is complicated by difficulties in securing a specific diagnosis and identification of the causative organism . Treatment is therefore largely based on experiential rather than experimental data . In our study we have tried in 722 patients with pneumonia to correlate the clinical findings with the causative agents . Age and a careful medical history give good clues towards the most probable aetiologic agent . Additional information is gained by the course of the illness . Physical examination, chest X-ray and few limited laboratory tests can also be of help to identify the most likely organism . Once the organism is identified, appropriate antimicrobial agent can be started . It is not only the choice of the antimicrobial substance, but also the choice of the proper total daily dose, dosage interval and mode of administration . By this management we had good results also in elimination of problem organism such as pseudomonas in CF.

Padiatr Padol, 1989, 24(1), 33 - 42
{Empirical antimicrobial therapy of infection and fever episodes in children and adolescents with neutropenia caused by cytotoxic chemotherapy}; Fink FM et al.; The experience with empirical antimicrobial therapy of septicemia and febrile episodes in pediatric neutropenic patients was analyzed retrospectively . Between January 1985 and March 1988 in 49 patients 77 episodes were observed . Bacteremia was found in 15 (20%), culture proven localized bacterial infection in 11 (14%) and clinically diagnosed bacterial infection was found in 7 (9%) of the febrile episodes . Thus, 33 (43%) documented bacterial infections were observed . For initial therapy a combination of aminoglycoside plus 2nd/3rd generation cephalosporin (60%) or aminoglycoside plus piperacillin (30%) was usually chosen . Both regimens were equally effective . 52% and 56%, respectively, were sufficiently treated with the initial regimen . 95% of all episodes resolved completely, the mortality rate was 5% . Central venous catheters remained in situ in 84% of the cases . The period of time necessary for recovery of granulopoiesis had an influence on the therapy success.

J Foot Surg, 1989 Jan-Feb, 28(1), 54 - 9
Antibiotic-impregnated bone cement: an in vitro comparative analysis; Heard GS et al.; This manuscript examines the in vitro antibacterial activity of eight different antibiotics when mixed with polymethyl methacrylate . Two different parameters are presented as being important considerations in the choice of antibiotic . One parameter is the bacterial inhibition created by the direct contact of the antibiotic-impregnated bone cement . The second parameter is the bacterial inhibition produced by diffusion of antibiotic from the bone cement into the surrounding liquid medium . These two experimental models were created to establish the contiguous and remote antimicrobial effects of antibiotic-impregnated bone cement.

Acta Microbiol Hung, 1989, 36(4), 425 - 32
Antimicrobial and immunomodulating effects of some phenolic glycosides; Molnar J et al.; Several phenolic glycosides, i.e . acteoside, desrhamnosyl acteoside, and purpureaside A, B and C, exerted weak antibacterial effects on Escherichia coli . Acteoside had antiplasmid effects, including F'lac plasmid elimination, and inhibited kanamycin resistance transfer in E . coli . Acteoside, desrhamnosyl acteoside and purpureaside A displayed antiviral effect on Aujeszky virus . All of the phenolic glycosides decreased some human leucocyte functions, including rosette formation, mitogen-induced blast transformation and phagocytic activity in vitro . The purpureaside C had significant proinflammatory action, however, other phenolic glycosides showed neither proinflammatory nor antiinflammatory effect on carrageenin-induced inflammation in vivo.

J Clin Dent, 1989 Spring, 1(4), 96 - 101
Antimicrobial action of sanguinarine; Godowski KC; Sanguinarine is a benzophenanthridine alkaloid derived from rhizomes of Sanguinaria canadensis L . (bloodroot) . It is a cationic molecule which converts from an iminium ion form at pH less than 6 to an alkanolamine form at pH greater than 7 . Sanguinaria extract is composed of sanguinarine and five other closely related alkaloids . The safety profile of both sanguinarine and sanguinaria extract provide a broad margin for their safe use in oral health products . Sanguinarine has broad antimicrobial activity as well as antiinflammatory properties . In vitro studies indicate that the anti-plaque action of sanguinaria is due to its ability to inhibit bacterial adherence to newly formed pellicle, its retention in plaque being 10-100 times its saliva concentration, and due to its antimicrobic properties . The MIC of sanguinarine ranges from 1 to 32 micrograms/mL for most species of plaque bacteria . Long term use of sanguinaria-containing toothpaste and oral rinse products does not predispose users to detrimental shifts in oral flora . Electron microscopic studies of bacteria exposed to sanguinarine demonstrate that bacteria aggregate and become morphologically irregular . Sanguinarine-containing slow release polymer systems are currently being developed for use in periodontitis treatment applications.

Drug Metabol Drug Interact, 1989, 7(1), 29 - 51
Interaction of amine oxides and quaternary ammonium salts with membrane and membrane-associated processes in E . coli cells: mode of action; Kopecka-Leitmanova A et al.; The antimicrobials (1-methyldodecyl)dimethylamine oxide and (1-methyldodecyl)trimethylammonium bromide affect the cytoplasmic membrane of E . coli . The interaction results in release of intracellular material (K+, 260nm-absorbing material), an effect on dehydrogenase enzyme activity and inhibition of respiration . The final effect of both substances is the same; they differ only in their dynamics . The effect of the membrane was correlated with parameters characterizing these surfactants i.e . critical micelle concentration (c.m.c.) minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) over the concentration range of 10(-4) to 10(-1) mmol/dm3 of active substance . The three stage mode of action model can be summarized as follows: 1-polar (coulombic) interactions, 2-polar and hydrophobic interactions, 3-hydrophobic interactions (extraction and solubilization) . The polar and hydrophobic interactions (1st and 2nd stage) are discussed also in relation to model membranes.

Postepy Hig Med Dosw, 1989, 43(1), 119 - 60
{New trends in studies of the pharmacologic activity of microbial metabolites}; Chmiel A; A new broad concept and novel approaches in the search for bioactive microbial metabolites are discussed . Methodology of the screening systems and assay techniques for the pharmacological and immunopharmacological activity of these products is presented . The value of the preliminary target-selective screening procedures is illustrated with a number of the pharmacologically active microbial products, among which the enzyme inhibitors are extremely important . Products with immunopharmacological activity are developed for organ transplantation and antitumor therapy . Another question discussed in the paper is non-antimicrobial and non-antitumor applications of the antibiotics.

ZWR, 1989 Jan, 98(1), 30 - 6
{Antibiotic therapy for odontogenic induced orofacial infections under office conditions}; Knoll-Kohler E; Due to the dominance of anaerobics in dentogen-induced orofacial inflammations the possibility of their treatment is restricted to a few groups of substances of different chemical structure (penicillins, lincosamides, nitroimidazoles, tetracyclins and macrolide antibiotics) for ambulant patients . The order of application for these different substances is determined by the local diagnosis and the pathophysiological state of the patient . The general anamnesis of disease, drugs and allergy as well as the knowledge of pharmacodynamics and pharmacokinetics of the substances to be applied are, therefore, indispensible for an optimal antimicrobial therapy.

Arch Androl, 1989, 23(3), 243 - 8
Chlamydial infection and male infertility: an epidemiological study; Custo GM et al.; Chlamydia-positive genitourinary infections are common causes of male and female infertility . Semen abnormalities are often associated with Chlamydia infections . A large population of male patients, admitted to our clinic for genitourinary infection, were examined for genitourinary pathogens, including Chlamydia, and for semen abnormalities . There were higher abnormalities semen in Chlamydia-infected patients than either non-Chlamydia-infected or healthy controls . Chlamydia therapy by antimicrobial agents improved semen characteristics . Chlamydia infection contributes to seminal fluid abnormalities and probably to male infertility . A search for chlamydial infection is warranted whenever semen abnormalities are noted . An antimicrobial therapy improves semen quality when effective in eradicating Chlamydia.

Ann Ital Chir, 1989, 60(3), 183 - 6; discussion 187
{Short-term antibiotic prophylaxis with ceftriaxone in general surgery}; La Rosa M et al.; The authors report their own experience on the efficacy of a short term antimicrobial prophylaxis involving a long-acting cephalosporin, ceftriaxone (Rocefin), in surgical patients . A study was carried out to evaluate the efficacy of a single dose of 1 or 2 g by i.v . administered 1 h . before elective surgery . 100 patients were admitted to study . Therapeutic success was achieved in 92 cases (92%).

Scand J Gastroenterol Suppl, 1989, 169, 70 - 80
Adverse reactions to furazolidone and other drugs . A comparative review; Altamirano A et al.; Furazolidone is a synthetic nitrofuran with a broad spectrum of antimicrobial action and has been widely used in the treatment of gastrointestinal infections . This article reviews the adverse reactions to furazolidone reported in the world literature . Of 10,443 adults and children who were treated with the drug, approximately 8.3% (864) experienced such reactions . Because some of these patients had more than 1 adverse reaction, 1178 reactions were reported in these studies . Nausea with vomiting, the commonest adverse reaction, was reported by 51% of the 864 patients who experienced adverse reactions . The authors compare the adverse reactions to furazolidone with those reported for other antimicrobial and antiprotozoal drugs that are frequently used to treat gastrointestinal infections.

Scand J Gastroenterol Suppl, 1989, 169, 24 - 7
Acute invasive diarrhea in the pediatric patient; Guerrero R; In acute invasive diarrhea, the pathogen penetrates the epithelial cells of the intestinal mucosa . Symptoms are produced by one or more of the following mechanisms: production of enterotoxins, increased synthesis of prostaglandins, and impaired reabsorption of fluids and electrolytes . The invasive process often results in dysentery, which is characterized by watery stools containing blood and mucus, accompanied by cramps, rectal burning, fever, and, sometimes, toxicity . Among the complications are bacteremia and toxic megacolon . Diagnosis is based on the patient's clinical condition and examination of stools . Microscopic examination of stools can rule out parasites and detect leukocytes, particularly polymorphonuclear leukocytes, a finding that suggests a bacterial origin for the disease . Because most patients are not severely dehydrated, rehydration is not the mainstay of treatment; in most cases, fluids can be replaced orally . Absorbents are ineffective, and antiperistaltic drugs should not be used routinely in children . Although often unnecessary in simple cases of invasive diarrhea, antimicrobials are useful when risk factors related to age, clinical condition, malnourishment, dehydration, or underlying disease are present . In such cases, antimicrobial therapy should begin when the clinical diagnosis has been made, to ensure the best clinical response.

J R Soc Med, 1989, 82 Suppl 17, 44 - 50; discussion 50-1
Treatment of severe malaria; Warrell DA; In the treatment of severe Plasmodium falciparum infection antimalarial drugs should, ideally, be given by controlled rate intravenous infusion until the patient is able to swallow tablets . In cases where infection has been acquired in a chloroquine resistant area, and where it has broken through chloroquine prophylaxis or where the geographical origin or species are uncertain, quinine is the treatment of choice . When access to parenteral quinine is likely to be delayed, parenteral quinidine is an effective alternative . A loading dose of quinine is recommended in order to achieve therapeutic plasma concentrations as quickly as possible . In the case of chloroquine sensitive P . falciparum infection, chloroquine, which can be given safely by slow intravenous infusion, may be more rapidly effective and has fewer toxic effects than quinine . There is limited experience with parenteral administration of pyrimethamine sulphonamide combinations such as Fansidar, and resistance to these drugs has developed in South East Asia and elsewhere . Mefloquine and halofantrine cannot be given parenterally . Qinghaosu derivatives are not readily available and have not been adequately tested outside China . Supportive treatment includes the prevention or early detection and treatment of complications, strict attention to fluid balance, provision of adequate nursing for unconscious patients and avoidance of harmful ancillary treatments . Anaemia is inevitable and out of proportion to detectable parasitaemia . Hypotension and shock ('algid malaria') are often attributable to secondary gram-negative septicaemia requiring appropriate antimicrobial therapy and haemodynamic resuscitation . Many patients with severe falciparum malaria are hypovolaemic on admission to hospital and require cautious fluid replacement . Failure to rehydrate these patients may lead to circulatory collapse, lactic acidosis, renal failure and severe hyponatraemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Eur J Cancer Clin Oncol, 1989, 25 Suppl 2, S9 - 16
Evaluation of fever in the patient with cancer; Pizzo PA; During the last decade, the survival of patients with fever and neutropenia has continued to improve . This is largely a reflection of the increasing repertoire of antimicrobial agents available to treat the fevers and infections that arise in this ever-increasing population of patients . Although it would be optimal if therapeutic decisions could always be made based on the microbial isolates and their sensitivity patterns, this is generally not possible in the cancer patient . Fever remains the predominant manifestation of infection, but the underlying microbial etiology is infrequently delineated . In spite of improved diagnostic tests, clinical acumen along with vigilant and repetitive patient assessment remain the cornerstone for evaluation of the cancer patient who becomes febrile . Indeed, strict adherence to simple principles can have a significant impact on improving the chances for survival of cancer patients who develop fever or infection.

Eur J Cancer Clin Oncol, 1989, 25 Suppl 2, S43 - 51
Empirical antibiotics for febrile neutropenic cancer patients; Hathorn JW; The empirical institution of broad spectrum antibiotics for febrile neutropenic cancer patients has become standard medical practice . Traditionally, the antibiotics consisted of a combination of agents selected to maximize activity against the most commonly isolated pathogens, and often employed agents with synergistic antimicrobial activity . Recent additions to the antibiotic armamentarium, however, have provided single agents with equivalent spectra of activity, thus potentially allowing a 'monotherapeutic' alternative to the combination regimens . The empirical utilization of antibiotics for the febrile, neutropenic episode is reviewed, with emphasis on recent clinical studies evaluating select monotherapeutic 'agents'.

Clin Pharmacokinet, 1989, 17 Suppl 1, 29 - 67
Clinical pharmacokinetics in infants and children . A reappraisal; Kearns GL et al.; A significant increase in the knowledge base in paediatric clinical pharmacology has occurred over the past 2 decades and has largely been the result of important scientific and sociological advancements pertaining to paediatric therapeutics . Although the data on drug disposition in infants and children have increased considerably over the past few years, pharmacokinetic-pharmacodynamic interactions, particularly the effect of development on pharmacodynamics, remain poorly understood . The impact of developmental physiology on drug absorption, distribution, metabolism and elimination in infants and children is reviewed and contrasted to the determinants of clinical pharmacokinetics in neonates . The most notable differences in drug disposition between infants and children when compared with neonates and young adults centre around alterations in body water and serum protein composition and the affinity/capacity for hepatic biotransformation of xenobiotics . As opposed to examining the effect of age on the disposition of specific compounds, the differences in developmental pharmacology are highlighted by the review of important and/or emerging pharmacokinetic-pharmacodynamic controversies in infants and children . These include the issues of altered drug distribution and metabolism in cystic fibrosis, pharmacokinetic determinants of successful antimicrobial therapy in bacterial meningitis and the pharmacokinetic determinants of immunosuppression treatment with cyclosporin . The pharmacological differences which are characteristic of development in both infants and children are also reviewed by examination of considerations for clinical pharmacokinetic evaluations such as specific routes and techniques for both drug administration and determination of sampling strategies . Clinical pharmacokinetics will continue to function as a bridge between the generation of new information and the practical application of this knowledge . Consequently, pharmacokinetics provides a pharmacological tool for use in research and clinical care . The clinical application of this tool is examined by a review of the pertinent assumptions and limitations, as well as useful mathematical techniques for use in paediatric patients . Additionally, 'non-traditional' uses of clinical pharmacokinetics (forensic application and use to evaluate organ function) in infants and children are discussed as are considerations for research use of clinical pharmacokinetic data.

Clin Pharmacokinet, 1989, 17 Suppl 1, 105 - 15
Antimicrobial therapy in neonates, infants and children; Brown RD et al.; Many antimicrobial medications may be administered to paediatric patients with a degree of impunity because they are relatively non-toxic and have a wide therapeutic margin . However, because of different pharmacokinetics from those in adults, the potential for toxicity exists with the use of some of these agents . Drug absorption in paediatric patients, either orally or parenterally, is generally similar to that in adults, except among neonates and, particularly, premature neonates . Similarly, in neonates, drug distribution is altered, plasma protein binding is decreased and hepatic metabolism and renal excretory capacity are limited by physiological immaturity . Thus, in neonates, only drugs that have pharmacokinetically derived dosage schedules should be used, and therapeutic monitoring of plasma drug concentrations is recommended during therapy with aminoglycosides, vancomycin and chloramphenicol . In older infants and children, the pharmacokinetics of antimicrobial drugs generally approximate those in adults, and recommended dosages have been determined relative to bodyweight . Therapeutic monitoring of plasma drug concentrations may be important in certain patients, such as those with major organ failure, and may be useful in cases of suspected noncompliance . Additional pharmacokinetic considerations concerning antimicrobial medication and paediatric patients are the extent to which drug therapy penetrates the cerebrospinal fluid in meningitis, and the potential for and implications of exposure of infants to antimicrobial medications excreted in breast milk.

Microbios, 1989, 60(242), 23 - 33
Antimicrobial activity of some 2-aminopyrimidines; Ghannoum M et al.; The minimum inhibitory concentration values for a group of pyrimidine derivatives were determined for Gram-positive and Gram-negative bacteria and yeast . The active compounds were further screened . The effect of these compounds on growth and morphology was tested, and their structural antimicrobial activity is discussed.

Chem Biol Interact, 1989, 71(2-3), 105 - 46
Structure-activity relationships among mycotoxins; Betina V; Relationships between structural features and biological effects of mycotoxins are reviewed . Structure-activity relationships are characterized at the molecular, subcellular, cellular, or supracellular level . Major chemical and physicochemical factors responsible for bioactivity of mycotoxins are stressed . A variety of chemical families of mycotoxins are then discussed from the point of view of structure-activity relationships . The structurally related families comprise small lactones, macrocyclic lactones, isocoumarin derivatives, aflatoxins and related compounds trichothecenes, anthraquinones, indole-derived tremorgens and selected amino acid-derived mycotoxins such as sporidesmins and cyclosporines . Biological effects of mycotoxins include acute and chronic toxicity, antimicrobial activity, mutagenicity and genotoxicity, carcinogenicity and biochemical modes of action.

Neurosurg Rev, 1989, 12(4), 333 - 40
Nocardial cerebral abscess cured with imipenem/amikacin and enucleation; Krone A et al.; A 72 year old female with cerebral abscess due to Nocardia farcinica is reported . Needle aspiration, antimicrobial therapy using a new combination of imipenem and amikacin, and, finally, surgical excision led to prompt and complete recovery . This is the oldest patient to survive cerebral nocardiosis reported in the literature . This infection, is usually regarded as opportunistic and is encountered with increasing frequency in immunocompromised conditions (organ transplantation, chemotherapy, underlying disabling disorder, acquired immunodeficiency syndrome, etc.) . The literature is extensively reviewed for various aspects of this disease including prognostic factors, recent developments in antibiotic therapy (imipenem, amikacin, minocycline etc.) and the essential role of surgery in the treatment strategy.

Rev Med Chir Soc Med Nat Iasi, 1989 Jan-Mar, 93(1), 175 - 7
{Pyridazinilides (XIV) . The action of p-phenyl-phenacyl bromide on 3-phenyl-pyridazine}; Caprosu M et al.; This time the synthesis of some new derivatives obtained by the quaternary substitution of one of the heterocyclic nitrogen atoms and by reactions of dipolar cycloaddition is presented . The results of the tests on their antimicrobial and antiinflammatory actions are discussed.

Respiration, 1989, 55 Suppl 1, 9 - 13
Role of leukocytes in lung defenses; Coonrod JD; Alveolar macrophages are the primary cells that protect the lung against inhaled or aspirated microbes . They kill microorganisms intracellularly by both oxidative and non-oxidative mechanisms . Alveolar macrophages secrete antimicrobial factors, including lysozyme, peptides, and transferrin, which are found in the bronchoalveolar lining fluid and may kill microbes extracellularly . Macrophage secretory products help initiate a controlled inflammatory response and a limited influx of granulocytes, which appears to be important for complete elimination of many bacterial pathogens from the lung.

Respiration, 1989, 55 Suppl 1, 60 - 7
Role of surfactant in alveolar defence against inhaled particles; Curti PC et al.; Alveolar surfactant molecules may concentrate on particulated matter (powders or microbes) with the formation of liposomes . In vitro the spraying of powders on a surfactant film causes the appearance of liposomes and consequent alterations in the tension/area diagram . In animals soon after inhalation of powders fine enough to be deposited in alveoli surfactant liposomes containing powder particles are observed in the alveolar spaces and later on along the airways . The powder content of liposomes collected through a T cannula in the trachea may be demonstrated by chemical or electronic microscopical analysis . Prolonged inhalation of powder may induce surfactant depletion and alveolar bronchiolar instability . In mice exposed for 5 months to silica dust a correlation has been found between surfactant depletion and silica retention in the lung with recruitment of phagocytic cells and increased serum and BAL-lysosomal enzyme activity . In animals treated with ambroxol, the clearance of silica is faster and longer lasting, and the pulmonary alterations are delayed and reduced . The first results of clinical trials with ambroxol in miners seem favorable . Microbes may also be incorporated as powder particles in alveolar surfactant liposomes . Using motile strains, bacteria struggling within a liposome may be observed with a telecamera . Preliminary observations suggest a direct antimicrobial action of ambroxol.

Hautarzt, 1989, 40 Suppl 9, 51 - 3
{Urea and urea combinations in ichthyoses}; Schnyder UW; The author recommends differentiated topical treatment of ichthyoses . At present, urea is the base curative for the five main types of this heterogenous group of diseases . Urea is not only effective as a keratolytic agent, but also in its ability to bind water . Whether the inhibition of proliferation, enhancement of penetration and the antimicrobial effects observed with urea are therapeutically important remains to be investigated . The combination of urea and tretinoin displays a beneficial effect on the clinical symptoms of nonerythematosus types of ichthyoses . The more severe the keratinization disorder, the sooner additional systemic treatment with retinoids is indicated.

Hautarzt, 1989, 40 Suppl 9, 23 - 6
{Biochemistry, pharmacology and toxicology of urea}; Raab W; In modern dermatology urea has two areas of application: --Applied topically urea is a pharmacologically active substance . It is moisturizing, keratolytic (in high concentrations only), desquamating, antipruritic, and antimicrobial . --Urea supplements and increases the effectivity of glucocorticoids, anthralin (dithranol) and tretinion . Urea-glucocorticoid combinations deserve special attention.

Infection, 1989, 17 Suppl 1, S14 - 8
{Enoxacin--comparative pharmacokinetics and tissue penetration}; Sorgel F et al.; The choice of an antimicrobial agent is primarily dependent on its antimicrobial activity and the pharmacokinetics in the host . The gyrase inhibitors differ in their antimicrobial spectrum as well as in their pharmacokinetics . In this review we compare key pharmacokinetic parameters of the most important 4-quinolones . Clearly, there are differences in their absorption, their sensitivity of the absorption process to food or di-or trivalent cations . On a weight basis enoxacin tends to have higher plasma levels then e.g . ciprofloxacin or norfloxacin and also tissue penetration of enoxacin as determined in the Body Fluid Model is superior to ciprofloxacin or norfloxacin . The elimination of enoxacin is mostly by the kidney (approximately 50-60% of dose) another 12-15% are metabolized in the liver . Renal failure therefore requires dose adjustments . The inhibitory effect of enoxacin on other compounds' metabolism has to be considered.

Annu Rev Microbiol, 1989, 43, 601 - 27
The evolution of fluorinated quinolones: pharmacology, microbiological activity, clinical uses, and toxicities; Siporin C; The fluorinated quinolones expand the spectrum of antimicrobial activity of the first-generation agents and offer more favorable pharmacokinetic and safety profiles than the older agents . Additionally, the need for only one daily administration of the third-generation quinolones may improve patient compliance . Data from clinical trials suggest that the oral fluoroquinolones provide cost-effective, outpatient therapy for infections previously treated in hospitals with parenteral antimicrobial agents (16) . The third-generation agents do not interfere with metabolism of theophylline, thus making fluoroquinolone treatment of patients receiving theophylline potentially more safe . Given the current focus on cost-containment strategies in health care, the fluorinated quinolones have become an attractive choice for therapy against a variety of bacterial infections . The future for antimicrobials and specifically quinolones looks especially bright with third-generation agents like lomefloxacin under development.

Yonsei Med J, 1989, 30(2), 111 - 7
Application of serologic diagnosis of tsutsugamushi disease (scrub typhus) in Korea where the disease was recently recognized to be endemic; Chong Y; In Korea, tsutsugamushi disease is a recently recognized infection . It has become clear that it is more prevalent than leptospirosis or hemorrhagic fever with renal syndrome . Accurate diagnosis of the disease is necessary for the selection of effective antimicrobial agents which can prevent fatalities and shorten the course . For the diagnosis, various serologic tests are used . Sensitivity and specificity of a test depend on various factors . In this report, microbiological aspects of the infection were briefly described and the Weil-Felix, indirect immunofluorescence and indirect immunoperoxidase tests were compared for their applicability in routine use and usefulness in the diagnosis . Their interpretations were also briefly discussed.

Pediatrie, 1989, 44(1), 27 - 9
{Cephalhematoma infection in neonatal septicemia}; Meignier M et al.; Most cephalhematomas resorb spontaneously; intervention by means of needle aspiration may introduce infection . In our case, a neonatal septicemia was associated with a large parietal cephalhematoma . The newborn was discharged after treatment of sepsis . Three days later, the diagnosis of infected cephalhematoma was apparent, associated with meningitis and septicemia . The authors discuss the physiopathology of the infection, antimicrobial therapy and careful aspiration when a serious infection is associated with cephalhematoma.

Chemotherapy, 1989, 35(5), 389 - 92
Treatment of various infections in an outpatient practice by intramuscular ceftriaxone: home parenteral therapy; Karachalios GN et al.; Ceftriaxone, a broad-spectrum third-generation cephalosporin with a long half-life, was administered intramuscularly to 23 outpatients who had a variety of infectious diseases . Cure was achieved in 21 of the patients (91%) . The results of this study indicate that ceftriaxone is an effective and well-tolerated antimicrobial agent when administered intramuscularly to outpatients with various infections.

Adverse Drug React Acute Poisoning Rev, 1989 Summer, 8(2), 73 - 88
Nephrotoxicity of aminoglycosides and cephalosporins in combination; Rankin GO et al.; Early clinical studies with combined cephaloridine and aminoglycoside therapy suggested that a synergistic nephrotoxic interaction was possible between agents in these two classes of antimicrobial drugs . The most compelling evidence supports a synergistic interaction between cephalothin and gentamicin or tobramycin . The documentation for interactions between other cephalosporin-aminoglycoside combinations is not as substantial as with cephalothin, but numerous case reports and clinical studies suggest the possibility of an enhanced nephrotoxic interaction with such regimens . Numerous factors may increase the likelihood of an apparent synergistic nephrotoxic aminoglycoside-cephalosporin interaction . In many cases where potentiation of drug-induced nephrotoxicity has been reported, patients were critically ill, and the underlying pathophysiological condition might have contributed to the resultant renal dysfunction . In addition, nephrotoxicity has been observed more frequently when very large doses of the cephalosporin were used in the combination therapy . Patients receiving cephalosporin-aminoglycoside therapy are also often being given other drugs that have the ability to damage the kidney (e.g . anticancer agents) or drugs that are known to enhance the nephrotoxic potential of the antimicrobial drugs (e.g . loop diuretics) . Therefore, attention must be given to numerous factors in order to minimize the possibility of renal dysfunction developing with combination therapy . The question as to which drug is potentiating the nephrotoxic potential of the other remains to be answered . Although some investigators have suggested that the cephalosporin potentiates the effects of the aminoglycoside, others feel that the reverse is true . Data from the rabbit tend to support aminoglycoside potentiation of cephalosporin-induced nephrotoxicity . Resolution of this problem may, however, have to await the development of a more suitable animal model of the interaction . In addition, a better understanding of the pharmacokinetic interactions between cephalosporins and aminoglycosides and a more precise description of the mechanisms of nephrotoxicity induced by these agents could help uncover the answers to many of these questions . The development of newer antimicrobial drugs with broader microbial coverage and a lesser nephrotoxic potential than agents currently in use may reduce the need for combining cephalosporins and aminoglycoside or provide safer drug combinations for many clinical situations.(ABSTRACT TRUNCATED AT 400 WORDS)

Pharmatherapeutica, 1989, 5(5), 312 - 9
Amoxycillin/clavulanic acid ('Augmentin') compared with a combination of aminopenicillin, aminoglycoside and metronidazole in the treatment of pelvic inflammatory disease; Cirau-Vigneron N et al.; A randomized, multi-centre trial was carried out in 152 hospitalized women with pelvic inflammatory disease to evaluate the efficacy and tolerability of amoxycillin/clavulanic acid compared with that of a standard regimen using three antimicrobial agents (aminopenicillin, an aminoglycoside and metronidazole) . Seventy patients initially received 3 to 4 intravenous doses per day of 1 g amoxycillin/200 mg clavulanic acid (mean 7.7 days) and then 4 to 6 tablets per day of 500 mg amoxycillin/125 mg clavulanic acid (mean 11.2 days) . The other group of 82 patients initially received parenteral therapy daily (mean 7.7 days) with a combination of 3 to 4 g amoxycillin or ampicillin, 160 mg gentamicin (or 150 mg dibekacin or tobramycin) and 1.5 g metronidazole, and then oral therapy with 2 to 3 g amoxycillin or ampicillin and 1 to 1.5 g metronidazole daily (11.1 days) . Clinical results, assessed at discharge from hospital (mean 10 days in both groups), were comparable in both groups, with 96% complete or partial response and no failures in the amoxycillin/clavulanic acid group, and 90% complete or partial successes and 5 failures with the triple therapy regimen . Both treatments were well tolerated and very few side-effects were reported.

J Oral Pathol Med, 1989 Jan, 18(1), 21 - 7
Recurrent aphthous stomatitis: current concepts of etiology, pathogenesis and management; Scully C et al.; Recurrent aphthous stomatitis (RAS) is a common oral disorder, however, despite detailed clinical, immunologic, hematologic and microbiologic investigation, the etiology of RAS remains unknown . At present, topical steroids and antimicrobial mouth rinses are the mainstays of treatment, but there is still no means of preventing recurrence of the oral ulceration.

Blood Purif, 1989, 7(2-3), 115 - 25
Antimicrobial therapy for CAPD-associated peritonitis; Winton MD et al.; Infectious peritonitis continues to be the leading cause of morbidity in patients on continuous ambulatory peritoneal dialysis (CAPD) . Optimum management of CAPD-associated peritonitis requires a concerted effort toward the establishment of the specific agent causing the episode . We have reviewed the current literature relating to the diagnosis and institution of antimicrobial therapy . Controlled comparative trials are needed to determine the efficacy of potentially less toxic therapeutic regimens for peritonitis, for definition of and treatment of exit-site infections, and timing of catheter replacement.

Eur Surg Res, 1989, 21 Suppl 1, 6 - 13
Use of a long-acting cephalosporin (ceftriaxone) for antimicrobial prophylaxis in abdominal and biliary surgery; Hell K; Present data available on ceftriaxone (Rocephin) dealing with microbiology, pharmacokinetics (long half-life, tissue penetration ability, tissue concentration present during vulnerable period, etc.), results of clinical trials, and world-wide experience seem to be in favor of ceftriaxone as the antimicrobial of choice for single-dose antibiotic prophylaxis in abdominal and biliary surgery . Single-dose surgical prophylaxis is cost-effective, has a low rate of adverse drug events, and so far does not increase danger of resistance.

Eur Surg Res, 1989, 21 Suppl 1, 25 - 32
Ceftriaxone as short-term antimicrobial chemoprophylaxis in orthopedic surgery: a 1-year multicenter follow-up . Preliminary results of a controlled multicentre study; Periti P et al.; In this multicentre study, 883 evaluable patients undergoing orthopedic surgery were randomly assigned to receive antiinfective prophylaxis with either ceftriaxone (Rocephin) or cefamandole . 25 patients in the ceftriaxone group and 29 patients in the cefamandole group (5.6 vs 6.5%) presented with infectious complications within the first 60 days after surgery . Delayed deep wound infections developed in only 1 of 435 patients in the ceftriaxone group compared with 4 of 413 patients in the cefamandole group . Both drugs were well tolerated . The infection rate was twice as high after surgery in conventional operating theatres than after treatment in hypersterile operating theatres (3.3 vs 6.5%); this difference is not statistically significant.

Chemotherapy, 1989, 35 Suppl 1, 81 - 8
Comparative study of aztreonam in gram-negative pneumonia versus a therapeutic regimen that includes an aminoglycoside . Spanish Study Group; Marco V et al.; Gram-negative pneumonia is a frequent complication in hospitalized patients, particularly in those with diminished defenses . The severity of the infections makes it necessary to start immediately an empirical antimicrobial therapy that usually combines a broad-spectrum beta-lactam antibiotic with an aminoglycoside (AMG), despite the potential toxicity of this regimen . We have compared the efficacy of a new beta-lactam antibiotic, aztreonam, which shows both a specific spectrum of activity against gram-negative bacteria and a very good diffusion into pulmonary tissue, with that of another antibiotic regimen including an AMG . Of a total of 69 patients, 43 were treated with aztreonam and the remaining patients with an AMG . Both groups were comparable with respect to the severity of infection and underlying pathology . Clinical efficacy was similar in the two regimens (81% aztreonam, 62% AMG) . However, antimicrobial efficacy was superior in the aztreonam group (88% aztreonam, 65% AMG), although differences disappeared in patients treated with the combination amikacin + cefotaxime or ticarcillin in the AMG group . Colonization/superinfection was also similar in both groups, although the selection of gram-negative bacteria occurred more frequently in the AMG group . Our results suggest that aztreonam, in monotherapy, may be a useful alternative for the treatment of gram-negative pneumonia.

Hinyokika Kiyo, 1989 Jan, 35(1), 159 - 65
{Clinical efficacy of ceftriaxone administered once daily against pyelonephritis}; Suzuki K et al.; Ceftriaxone (CTRX) was evaluated for clinical efficacy on uncomplicated and complicated pyelonephritis by administering 2 g once daily for 5 days to 16 female patients between 20 and 65 years old (average: 39.7 years); i.e., 3 with uncomplicated pyelonephritis and 13 with complicated pyelonephritis . The pathogens in all 3 cases of uncomplicated pyelonephritis were E . coli . All of them disappeared after the treatment . Twenty-two strains of 10 strains of bacteria were isolated from the 13 cases of complicated pyelonephritis . Twenty of the 22 (91%) strains disappeared . The clinical efficacy was evaluated according to the Criteria for Evaluation of Clinical Efficacy of Antimicrobial Agents on UTI Japan in 15 cases except for 1 case of the complicated type where the CTRX administration was discontinued after the initial dose due to an adverse event . The efficacy rate was 100% in the 3 uncomplicated cases; 'excellent' in 1 case and 'good' in 2, and 92% in 12 of the complicated cases; 'excellent' in 9, 'good' in 2 and 'poor' in 1 (infection was with multiple pathogens including P . aeruginosa) . No abnormal values were observed in any cases except for a slight increase in glutamic-pyruvic transaminase and alkaline phosphatase in one case and skin rash in another case which appeared following the initial dose and required the immediate withdrawal of the drug . CTRX is characterized by a long half-life and shows a strong antibacterial activity against GNRs, especially E . coli . The efficacy rate was high particularly following the initial dose in the acute stage of pyelonephritis.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagn Microbiol Infect Dis, 1989 Jan-Feb, 12(1), 93 - 9
Cefotaxime and desacetylcefotaxime in neonates and children: a review of microbiologic, pharmacokinetic, and clinical experience; Jacobs RF et al.; Over the past 5 yr, we have conducted two clinical and two pharmacokinetic investigations of cefotaxime (CTX) and desacetylcefotaxime (dCTX) in neonates, infants, and children . A total of 50 children with culture-proven bacterial meningitis were randomized to receive either 200 mg/kg/day of CTX (n = 23, mean age 24.4 mo) or standard doses of ampicillin (AMP) and chloramphenicol succinate (CAPS; n = 27, mean age 16.6 mo) . Results were similar between the CTX and Amp/CAPS groups for clinical/microbiological cures (100% versus 96%, respectively) and for survival without sequelae (78% vs . 77%, respectively) . All bacterial isolates were sensitive to CTX, and the comparison of the MIC/MBC values for CTX to the CSF bactericidal titers suggested antimicrobial activity for dCTX . In a second clinical trial, 20 infants (1 wk-3 mo) were treated with 200 mg/kg/day of CTX for Gram-negative enteric bacillary meningitis . Cultures of CSF obtained 24 hr after the initiation of treatment were sterile in all subjects . Survival and complication rates of 95% and 21%, respectively, were observed . This compared favorably to previously published experiences with alternate treatment regimens for Gram-negative meningitis in the newborn . In both meningitis studies, the safety profile for CTX was excellent.(ABSTRACT TRUNCATED AT 250 WORDS)

J Protozool, 1989 Jan-Feb, 36(1), 14 - 20
Novobiocin-induced ultrastructural changes and antagonism of DNA synthesis in Trypanosoma cruzi amastigotes growing in cell-free medium; Kerschmann RL et al.; The antimicrobial agent novobiocin, an inhibitor of the bacterial enzyme topoisomerase II (DNA gyrase), is known to antagonize Trypanosoma cruzi amastigotes growing in cell-free medium . To determine sites of antagonism of novobiocin, the effects of drug on parasite ultrastructure and incorporation of radiolabeled precursors of DNA, RNA and protein into macromolecules were determined . The predominant ultrastructural abnormality seen after exposure to 0.40 mM novobiocin for 24 h was the presence of electron-dense clumps in the mitochondrion-kinetoplast organelle in 95 of 257 (37%) of cells, in comparison to no clumps seen in 110 drug-free cells . In addition, in the nucleus, the karyosome was less distinct than in control cells and appeared to merge with the chromatin . In the radiolabeling studies, incorporation of thymidine was inhibited in a dose-dependent fashion by novobiocin (0.16-0.80 mM) in a range of drug concentrations that also inhibited parasite growth . For 0.16 and 0.24 mM novobiocin, incorporation of thymidine was inhibited up to 65% relative to drug-free control cells while uptake of uridine and leucine was unaltered . We interpret these ultrastructure and precursor-incorporation studies as suggesting that (i) the mitochondrion-kinetoplast and possibly the nucleus are sites of novobiocin antagonism of T . cruzi amastigotes and (ii) that novobiocin appears to antagonize DNA synthesis within these organisms . Whether the drug target is topoisomerase II, however, is as yet unknown.

Ann Pediatr (Paris), 1989 Jan, 36(1), 39 - 41
{Pleuropulmonary colibacillus infection in a 9-year-old boy leading to the diagnosis of Bruton agammaglobulinemia}; Seaume H et al.; A nine-year-old boy was hospitalized for pneumonia of the left lower lobe . A left pleural effusion developed 48 hours later . The same E . coli strain was recovered from five blood cultures, pleural fluid, and middle ear fluid . Recovery was achieved after two months . Pleural lavage was performed twice daily for the first 15 days and parenteral antimicrobial therapy was given for 45 days . Because E . coli is not usually responsible for ENT or lower respiratory tract infections, an immune deficiency was sought for . The index patient had a twin in whom a history of osteomyelitis at the age of 2 and pneumonia at the age of 8 was found . Recurrent otitis had been a problem in both twins from the age of 14 months . In both twins, immunoglobulin assays led to the diagnosis of Bruton agammaglobulinemia . These two children are now receiving intravenous infusions of human immunoglobulins every three weeks . Bruton agammaglobulinemia is infrequently diagnosed at so late an age.

Ann Ophthalmol, 1989 Jan, 21(1), 23 - 8
Uveitis in childhood--Part III . Posterior; Giles CL; Toxoplasma, nematodes, and cytomegalovirus are the most common causes of uveitis in children involving the posterior pole . Discussion of treatment and management is detailed . Rubella retinitis and subacute sclerosing panencephalitis are specific entities which are limited in their initial presentation in children . Panuveitis including sympathetic ophthalmia, Vogt-Koyanagi-Harada, and Behcet's syndromes, while relatively rare in their occurrence, demand early treatment intervention . Specific antimicrobial therapy and adrenocorticosteroids as well as therapeutic suggestions are also included . This is the last part of a three-part series of articles.

Bone Marrow Transplant, 1989 Jan, 4(1), 89 - 95
Oropharyngeal mucositis complicating bone marrow transplantation: prognostic factors and the effect of chlorhexidine mouth rinse; Weisdorf DJ et al.; Oral mucosal ulceration complicating bone marrow transplantation interferes with patients' comfort, nutrition and may lead to systemic infection derived from the mouth . The mucosal injury results from epithelial damage due to the cytotoxic effects of chemotherapy and radiation conditioning as well as from superficial oropharyngeal infection . Because chlorhexidine gluconate is a broad spectrum topical antimicrobial which has been demonstrably effective in preventing oral infection and gingivitis, we performed a randomized, placebo controlled, double-blind trial of chlorhexidine as a mouth rinse in BMT recipients to study the severity of oral mucositis and both oral and systemic infectious complications . One hundred patients were randomly assigned to receive either chlorhexidine gluconate 0.12% mouth rinse or placebo three times daily from the initiation (day -8) of chemoradiotherapy conditioning until day +35 post-BMT . Chlorhexidine use resulted in a trend toward improved oral hygiene index (reduced dental plaque) (p = 0.06) but did not modify the oral mucositis . Patients using chlorhexidine developed a maximum ulceration of 18 +/- 22% of their oral mucosa, while placebo patients ulcerated 25 +/- 31% of the mouth . Ulcerative mucositis was significantly worse in adults compared with children, in individuals who received methotrexate for graft-versus-host disease prophylaxis, and was most prominent on non-keratinized epithelium . Overall, there was no clinically demonstrable additional therapeutic advantage to the use of chlorhexidine in either reducing the mucositis, controlling oral pain, facilitating oral nutrition, shortening hospital stay, or reducing oral infection with herpes simplex virus . There was a trend toward diminished oral candidiasis in chlorhexidine users (p = 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)

Zentralbl Gynakol, 1989, 111(2), 65 - 77
{Chlamydia infections}; Hoyme UB; Chlamydia trachomatis is a pathogen with an intracellular developmental cycle . Sexually transmitted infection with serotypes D to K can lead to cervicitis, endometritis, salpingitis and urethritis, however, symptoms are commonly mild . Newborns of mothers with cervical infection or colonisation can acquire inclusion conjunctivitis and atypical pneumonia . An efficient prophylaxis is not available so far . Antimicrobial therapy should be initiated as soon as chlamydial infection is confirmed, e.g . with tetracyclines or erythromycin . Partner treatment is mandatory.

Rev Infect Dis, 1989 Jan-Feb, 11(1), 46 - 63
Infection due to Actinobacillus actinomycetemcomitans: 15 cases and review; Kaplan AH et al.; Actinobacillus actinomycetemcomitans is a small fastidious gram-negative coccobacillus that fails to grow on MacConkey's agar . Slow growth in broth may lead to delays in diagnosis . First described in 1912, A . actinomycetemcomitans has been recognized since 1962 as capable of causing serious infections in humans . Such infections include periodontal infection, soft tissue abscess (often in association with Actinomyces species), and systemic infection, most commonly endocarditis . Fifteen cases and a review of the English-language literature are presented to define the epidemiology and clinical features of infection due to A . actinomycetemcomitans . Therapy for infection due to A . actinomycetemcomitans has most commonly involved ampicillin or penicillin, often in conjunction with an aminoglycoside . However, resistance to penicillin or ampicillin is common . Antimicrobial agents with a high degree of in vitro activity included cefazolin, cefotaxime, cetriaxone, aminoglycosides, and chloramphenicol . Therapy should be guided by clinical response and in vitro susceptibility testing.

Dent Clin North Am, 1989 Jan, 33(1), 91 - 100
Factors influencing periodontal therapy for the geriatric patient; Greenwell H et al.; Anatomic changes in the periodontium occur with aging . There is no indication that these changes predispose to periodontal breakdown . In the United States, there is evidence that older individuals are retaining more teeth and that these teeth have less periodontal disease than previous generations of seniors . Studies comparing the healing of older and younger patients have clearly demonstrated that both groups of patients respond equally well to therapy . Proven methods of periodontal therapy include modified Widman surgery, pocket elimination surgery, or nonsurgical scaling and root planing . Surgical treatment may be used with confidence unless there are medical contraindications . In these cases, nonsurgical therapy may be preferred . If there are physical or mental disabilities that make effective home care difficult, antimicrobial agents, such as the extensively tested chlorhexidine rinse, may be valuable adjuncts . In the future, senior adults can look forward to the benefits of regenerative periodontal procedures that seek to regain lost periodontal support . Age alone should not diminish an individual's right to care because the practitioner has qualms about his or her longevity . Successful treatment of periodontitis by surgical and nonsurgical methods has been extensively documented . Senior patients can benefit from these treatments as much as younger patients, and age is not a barrier to effective periodontal therapy.

Medicine (Baltimore), 1989 Jan, 68(1), 38 - 57
Nocardial infections in renal transplant recipients; Wilson JP et al.; Upon review of the English literature and the patients at our hospital, we identified 94 renal transplant recipients with nocardiosis . These patients were further evaluated and compared to nonrenal transplant patients with nocardiosis . We found that these patients were similar in presentation, course, and therapeutic outcome to non-transplant patients . Survival was related to underlying disease, site of infection, rapidity with which the diagnosis was made and, especially, the inclusion of a sulfa compound in the antimicrobial regimen . Transplant centers with high rates of Nocardia infection should consider trimethoprim/sulfamethoxazole prophylaxis for at least the first year after transplantation.

Pediatr Hematol Oncol, 1989, 6(1), 17 - 22
Port-A-Cath in children during long-term chemotherapy: complications and outcome; al-Hathal M et al.; Complications related to Port-A-Cath were studied prospectively during a period of 32 months in 31 patients, aged 1-18 years, with leukemias and solid tumors . There were 34 Port-A-Cath inserted, and the cumulative time for these catheters kept in place was 5899 days . No complications occurred in 18 patients (19 catheters) kept in place for a cumulative time of 3998 days with an average duration of 210 days (12-550 days) . In 13 patients (15 catheters) there were 14 events of systemic infections; seven events were treated successfully with antibiotics, four events necessitated the extraction of the catheter (in one patient a combination of systemic and local infection), and in three events the catheters were kept unused, as the patients were in terminal stages . Nonsystemic complications occurred with five catheters; two local infections, two obstructions (catheters removed), and one local bleeding (catheter kept unused) . Appropriate antimicrobial treatment of systemic infections enables the immunocompromised child to keep the Port-A-Cath in place for a long time.

Rev Med Chil, 1989 Jan, 117(1), 10 - 7
{Gentamicin and amikacin nephrotoxicity: comparative study in patients with initially normal renal function}; Ballesteros J et al.; The purpose of this study was to compare the nephrotoxic potential of amikacin (AK) and gentamicin (GM) in patients (pts) with normal renal function at the beginning of the treatment (Tx) in an open comparative and prospective trial . Nephrotoxicity (NFTX) was defined as a blood creatinine (Cr) increase of at least 50% from the basal (normal) level, or an increase to higher than normal level during, at the end or after Tx . Peak and trough blood GM and AK levels were determined at 72 h of Tx to make proper adjustments in dosing . The two groups (GM, n = 27 and AK, n = 38) were similar in population composition, underlying pathology and infectious process requiring antimicrobials . Patients in the GM group tended to be older (mean age, 56 years) than the AK (mean age, 48 years) p NS; the latter had received more frequently aminoglycoside Tx (69 vs 11%) p less than 0.0005 . The GM group received a comparatively lower dose than the AK (x = 2.87 mg/k/d and 16 mg/k/d respectively) but duration of Tx was similar . Fifteen of 27 pts receiving GM (56%) and 7 of 38 receiving AK (18.2%) developed NFTX, p less than 0.004 . Five pts in the GM group (18.5%) and 2 in the AK (5.2%) had clinical NFTX . The difference in NFTX persisted after age adjustment . There were no intra or inter group significant differences between pts with or without NFTX . In conclusion, in pts with initial normal renal function gentamicin was significantly more nephrotoxic than amikacin.

Acta Vet Scand, 1989, 30(4), 409 - 23
Mycosis in the stomach compartments of cattle; Jensen HE et al.; During a period of 22 months, 9.7% (23 out of 238) of the cattle necropsied at the Department of Veterinary Pathology had mycotic affections in the stomach compartments . The various stomach compartments were affected in the following pattern: omasum: 15 cases, rumen: 10 cases, reticulum: 8 cases and abomasum: 6 cases . In 5 of the animals mycotic affection was also found in other organs of which the liver was most often involved . Out of the 23 cases described, a primary diagnosis of mycosis was only established in 5 cases . In the remaining 18 cases the mycotic infection was regarded as being of a minor importance in the total necropsy result . Macroscopically and histologically the mycotic processes could be grouped into acute, subacute or chronic affections . In 20 cases only one type of inflammation was present, in the remaining cases combinations were found . Identification of the infective agent was performed by immunological staining of hyphal structures in tissue sections . Members of the Zygomycetes were found to predominate as causative fungi . Aspergillus fumigatus was found to have a propensity for infecting the terminal gastric compartments, whereas the Zygomycetes were found regularly in all compartments . Candida spp . were only found in 1 case . Predisposing factors for developing systemic mycosis are discussed . Among these especially the use of antimicrobial drugs, other diseases, metabolic disturbances and stressors in the post parturient period seem to be important.

Acta Stomatol Croat, 1989, 23(2), 167 - 74
{Oral lichen ruber}; Cekic-Arambasin A et al.; As oral lichen ruber is quite frequently encountered in contemporary man, dental physicians should be familiar with the characteristics of the disease . Regardless of various forms of the disease, clinical features of lichen ruber may help in making the diagnosis . Recent research on the pathogenesis of the diseases has pointed to a local immune response . An individual diagnostic and therapeutic approach has been imposed by the complex etiology of the disease . In therapy, antimicrobial agents have resumed their place, along with the use of vitamins.

Bull World Health Organ, 1989, 67(6), 675 - 84
Monitoring selective components of primary health care: methodology and community assessment of vaccination, diarrhoea, and malaria practices in Conakry, Guinea . ACSI-CCCD team; Dabis F et al.; The Africa Child Survival Initiative-Combatting Childhood Communicable Diseases (ACSI-CCCD) Project is a primary health care activity that focuses on antenatal care, immunization, diarrhoeal disease control, and malaria control in children under 5 years of age . In order to gauge progress made in the project, a community-based health interview survey to measure simultaneously several prevention and treatment indicators was carried out in 1986 in Conakry, Guinea . A sample of 1415 caretakers and their 2048 children aged under 5 years was visited using a cluster sampling technique . The survey documented the levels of literacy and health education awareness of the caretakers, measured the vaccination coverage levels for children and women of childbearing age, and determined treatment practices for diarrhoea and malaria . Of the 637 women who reported having given birth in the previous 12 months, 96% had visited an antenatal clinic, but only 49% had had two or more doses of tetanus toxoid, and 13% took weekly chemoprophylaxis against malaria . The vaccination coverage for measles was 16% for children aged 12-23 months . Oral rehydration therapy (ORT) was given to 16% of children with diarrhoea; however, only 43% of those who were administered ORT at home were treated according to standard guidelines . Of children with diarrhoea, 51% were given antidiarrhoeal or antimicrobial drugs by caretakers . Fever was treated at home for 79% of the febrile children, and 43% of those with fever also visited health units . The use of injectable antimalarials and prolonged treatments with chloroquine were common . Combining findings from a population-based community study with an assessment of practices in health facilities can provide reliable information for the implementation and monitoring of selective components of primary health care.

Arch Inst Pasteur Madagascar, 1989, 56(1), 261 - 71
{Study of the antimicrobial action of various essential oils extracted from Malagasy plants . II: Lauraceae}; Raharivelomanana PJ et al.; The microbial growth inhibitory properties of some Lauraceae essential oils, Laurus nobilis, Cinnamomum zeylanicum (cinnamon) and Ravensara anisata were studied by the determination of their respective M.I.C . (Minimal Inhibitory Concentration) . Five bacterial strains, one fungi and two yeasts were used to evaluate the essential oils inhibitory capacities . These vegetable extracts, with decrease activity, were range also: C . zeylanicum--bark greater than R . anisata--bark greater than C . zeylanicum--leaves greater than L . nobilis greater than R . anisata--leaves . The essential oils extracted from cinnamon and R . anisata--bark were very interesting by their antifungic activities.

Drugs Exp Clin Res, 1989, 15(10), 465 - 76
Comparative antimicrobial activities of ribostamycin, gentamicin, ampicillin and lincomycin in vitro and in vivo; Inouye S et al.; The antimicrobial activity of ribostamycin, a unique aminoglycoside antibiotic possessing a neutral sugar component, was compared with those of gentamicin, ampicillin and lincomycin in vitro and in vivo . Ribostamycin showed comparable or slightly weaker in vitro activity than the reference antibiotics against Gram-positive bacteria . Against Gram-negative bacteria, ribostamycin was less active than gentamicin, but comparable to or more active than ampicillin . Lincomycin was less active or inactive to Gram-negative bacteria . Ribostamycin was active against some gentamicin-resistant bacteria, especially K . pneumoniae possessing the aminoglycoside-modifying enzymes AAC(3)-l and AAD(2") . The in vivo activity of ribostamycin was weaker than that of gentamicin, but comparable to that of ampicillin and lincomycin against Gram-positive bacteria, and superior to that of ampicillin against Gram-negative bacteria . The in vivo activity of ribostamycin was characterized by (i) and ED50 value not so affected by the challenge inoculum as that of ampicillin; (ii) a lower ED50 value by bolus administration than that by divided administration of the same dosage; and (iii) a lower ED50 value than that expected from the MIC value as compared with that of ampicillin and lincomycin . These characteristics are explained by the rapid and potent bactericidal activity of ribostamycin at high inoculum and high drug concentration, assisted by high serum concentration in mice.

Oper Dent, 1989 Spring, 14(2), 77 - 81
Antimicrobial properties of glass-ionomer cements and other restorative materials; Scherer W et al.; The antimicrobial properties of 14 different restorative materials, nine of which were glass-ionomer cements, were compared and observed in this study . The materials were mixed according to manufacturers' specifications and exposed to four types of bacteria commonly found in caries and plaque . Zones of bacterial inhibition were measured for all materials in millimeters . Glass-ionomer cement materials, materials containing zinc oxide, and amalgam produced measureable zones of inhibition.

Zentralbl Gynakol, 1989, 111(23), 1549 - 54
{Incidence, causes and follow-up of doubtful smear findings (Papanicolaou group III)}; Hofmann R et al.; Suspect smears of 622 patients from 1977-1986 were analysed for their causes and followed up until the definite cytologic or histologic result . In relation to the overall material of 97,963 cases the rate of suspect smears (group Pap . III) was between 1.18 and 0.27%, i.e . an average of 0.68% . The most frequent reasons for the classification "suspect" were inflammatory (42.4%), metaplastic or degenerative changes (16.1%) and doubtful pre-cancer (30.6%) . 58% of all cases became negative under cytological control and antimicrobial therapy or hormonal substitution; of these 91.4% converted into negative within 6 months . The histological examination carried out on 230 patients revealed pre-cancer (CIN I-III) in 201 cases; cancer was proved in 5 cases . Compared to the whole population that is a rate of 33.1% . 24 cases were to be found negative . 139 Multiparae (67.6%) were to be found in the group of the 206 histological positive cases . 151 women (74%) had taken hormonal contraceptives . The rate of suspect smears should not exceed one per cent.

Scand J Infect Dis, 1989, 21(6), 665 - 8
Dental procedures and endocarditis prophylaxis in patients with prosthetic heart valves: results of a questionnaire to 220 patients; Gutschik E et al.; 220 patients with prosthetic heart valves were surveyed regarding dental status, dental health, patient-dentist relationship, information on dental procedures and antimicrobial prophylaxis at the last visit to the dentist . The vast majority of these patients were on life-long anticoagulant treatment because of mechanical heart valve prostheses . Half of the patients had a regular dentist and customarily visited a dentist one or more times a year . One third of the patients were edentulous and 26.5% of the patients indicated dental disease, including chronic periodontitis . Only 30.4% of the patients received antimicrobial prophylaxis in connection with dental extraction and only 13.8% in connection with scaling . Maintenance of good oral health, routine dental checks and better information to the patients and the dentist are called for.

Klin Khir, 1989, (10), 1 - 3
{Antimicrobial polymers in surgery of the lungs}; Polous IuM et al.; Approved in the experiment and employed in 60 patients in atypical resection of a lung were the antimicrobial biocompatible absorbable polymers--"Capromed DC threads and ESBADCh film--in combination with MK-7 cyanoacrylate++ glue for formation of hermetic pulmonary suture . This facilitated good smoothing out of the lung remainder, sharp decrease of microbial colonization at the site, where the mentioned polymers were used.

Ann Med Interne (Paris), 1989, 140(7), 593 - 6
{Drug-induced pneumopathies (excluding cytostatic drugs)}; Akoun G et al.; Establishing the diagnosis of drug-induced pneumonitis is always difficult and requires that the following criteria be met: administration of the drug on a long-term basis; knowledge that the drug is able to induce pulmonary disorders; occurrence during therapy of interstitial pneumonitis with clinical, radiological and functional characteristics of this type of lung disease; exclusion of all other causes of interstitial pneumonitis (cardiac failure, infections, collagen vascular diseases, malignancies); bronchoalveolar lavage specimen, revealing lymphocytosis with an inverted CD4/CD8 lymphocyte ratio, isolated or associated with neutrophil and/or eosinophil alveolitis; finally, full recovery within several weeks or months after drug withdrawal unless irreversible pulmonary fibrosis has occurred . Certain specific characteristics correspond to the therapeutic class of the drug, i.e . antimicrobial, cardiovascular, antiinflammatory, neurological, metabolic, antiallergy or some other drugs.

Pharmacology, 1989, 39(4), 213 - 23
Effects of 2(3)-tert-butyl-4-hydroxyanisole pretreatment on cefpiramide binding to mouse glutathione S-transferases; Nishiya H et al.; Binding of cefpiramide (CPM) and other beta-lactam antimicrobial agents to 2(3)-tert-butyl-4-hydroxyanisole (BHA)-induced liver glutathione (GSH) S-transferases (EC 2.5.1.18) from CD-1 mice was studied . A marked induction of hepatic GSH S-transferase from mice fed BHA was observed . Gel chromatography of liver cytosol from mice fed BHA showed an increased binding of CPM, cefotetan and cefazolin to BHA-induced GSH S-transferases . The extent of their binding to GSH S-transferase seemed to be correlated with the extent of their excretion into the bile . Binding of CPM to the GSH S-transferase fraction was inhibited by both indocyanine green, which is known to bind liver GSH S-transferases intensively, and by cefoperazon, which is mainly excreted into the bile . This study suggests that GSH S-transferases are the main binding proteins of CPM in the liver cytosol fraction and play an important role as carrier proteins of CPM and some antimicrobial agents in mouse liver.

Pediatr Radiol, 1989, 20(1-2), 76 - 9
Physeal involvement in chronic recurrent multifocal osteomyelitis; Manson D et al.; Chronic recurrent multifocal osteomyelitis is a recently recognized disease characterized by remissions and exacerbations of multiple bone lesions which radiographically and pathologically have the appearance of hematogenous osteomyelitis . No consistent etiology can be identified, and antimicrobial agents seem to have no beneficial effect . A review of the appearances on imaging modalities and the clinical and pathologic manifestations is undertaken in seven cases of CRMO . No therapeutic regimen resulted in consistent clinical or radiographic improvement . We suggest the sequelae of this process are not as benign as previously reported.

Arch Oral Biol, 1989, 34(7), 499 - 506
Relationships between human parotid saliva lysozyme lactoferrin, salivary peroxidase and secretory immunoglobulin A in a large sample population; Rudney JD; Saliva antimicrobial proteins may interact in a common system for host defence . This study applied multivariate analysis as a means of describing inter-person variation in that system . Samples of stimulated parotid saliva were obtained from 198 subjects . Flow rate was determined, and assays run for total protein, lysozyme, lactoferrin, salivary peroxidase and secretory IgA . Correlation and principal components analysis were used to define the relationships between proteins; cluster analysis was used to identify persons with similar protein concentration profiles . All proteins were significantly correlated at p less than 0.002 (r = 0.20-0.52) . Principal components analysis identified a major axis of common variation, defined by lysozyme and salivary peroxidase, and a second axis, defined by secretory IgA . Lactoferrin was associated with both axes . Seven major groupings were obtained by cluster analysis; these were significantly different at p less than 0.001 . Such groupings may prove useful in comparing the antimicrobial properties of saliva samples.

Ter Arkh, 1989, 61(8), 113 - 6
{The efficacy of the natural antibacterial preparation chlorophyllypt in the combined treatment of acute lung abscesses}; Nikitin AV et al.; The complexity of the treatment of acute suppurative pulmonary diseases has been aggravated recently by the growth of microbial resistance to antibiotics and enhancement of the allergy incidence among the population . This circumstance restricts the use of antibiotic on a broad scale in clinical practice and makes the researchers go in studies of adequate substitutes . In the given case, use was made of chlorophyllipt . It was given to patients by intravenous drip in the form of a 0.25% solution based on saline twice a day . To increase local deposition of the administered antimicrobial drug in the affected area, interstitial electrophoresis was employed . In the patients' group on chlorophyllipt, the clinico-laboratory and x-ray parameters returned to normal earlier . Chlorophyllipt was noted to produce an immunocorrective action characterized by the normalization of the absolute count and percentage of E-RFC and theophylline-resistant-RFC . This action could not be observed in the patients' group receiving only antibiotics.

Adv Perit Dial, 1989, 5, 103 - 10
Ca++ and 1,25(OH)2D3 enhance peritoneal macrophage (PMPhi) antimicrobial functions in CAPD; Carozzi S et al.; Ca++ has been proposed as an intracellular second messenger for the activation of immune cells . An immune regulatory role for 1,25(OH)2D3 has also been suggested . We therefore evaluated the role of Ca++ and 1,25(OH)2D3 in the depressed antibacterial functions of 8 CAPD patients with relapsing bacterial peritonitis by evaluating in vitro the effects of escalating concentrations of 1,25(OH)2D3 and/or Ca++ on: 1 . peritoneal macrophage (PMO) cytoplasmic Ca++; 2 . PMO superoxide generation; 3 . PMO leukotriene B4 release, 4 . PMO bacterial killing . Results showed a dose-dependent increase in all parameters for Ca++ concentrations from 500 to 3,000 microM while with both a CA(++)-free medium and with Ca++ concentrations of 5,000 microM of medium all the aforementioned functions were abrogated . Addition of low doses of 1,25(OH)2D3 strongly potentiated the stimulatory effect of Ca++ on cell functions, while high doses were inhibitory . These in vitro data underline the importance of Ca++ and 1,25(OH)2D3 in PMO antibacterial functions in CAPD patients, and may be useful in the prophylaxis and therapy of peritonitis.

Acta Derm Venereol, 1989, 69(3), 223 - 6
Cutaneous drug reactions: clinical types and causative agents . A five-year survey of in-patients (1981-1985); Alanko K et al.; We collected a 5-year series of drug eruptions . There were 225 cases, 128 of them verified by a positive provocation test . The most common types of clinical reaction were fixed drug eruptions, exanthematous eruptions and urticarias . The drugs most often responsible for the eruptions were antimicrobial agents and antipyretic/anti-inflammatory analgesics . Comparing this series with our three previous series from the same hospital, the total number of drug eruptions proved to have decreased over the last 30 years . The main groups of drugs causing skin reactions have remained the same, but in recent years the proportion of sulphonamides has diminished.

Gan To Kagaku Ryoho, 1989 Jan, 16(1), 1 - 8
{Anti-tumor natural products isolated from marine organisms}; Kitagawa I et al.; Marine organisms comprise over half a million species . Due to their unusual living environment as compared with terrestrial organisms, marine organisms produce a variety of metabolic substances which often have various unprecedented chemical structures . In recent years, an increasing number of marine natural products have been reported to exhibit various biological activities such as antimicrobial, physiological, and pharmacological ones . Some metabolites have also been noted by their significant toxicities . The effort to find out anti-tumor substances from marine organisms has been also undertaken in recent years, and several novel compounds (e.g . peptide, polyether, alkaloid, prostanoid etc.), with anti-tumor activities, have been isolated from marine sponges, octocorals, marine algae, tunicates, nudibranchs, bryozoans, and so on . In this article, those chemically clarified anti-tumor compounds isolated from marine organisms were reviewed.

Bull Hosp Jt Dis Orthop Inst, 1989 Spring, 49(1), 107 - 10
Nocardia asteroides infection of an Austin-Moore hemiarthroplasty in a nonimmunocompromised host . A case report; Robinson D et al.; A case of Nocardia asteroides infection of a hip prosthesis in a nonimmunocompromised patient is presented . The infection developed soon after the operation, and did not respond to empiric treatment by multiple antimicrobial drugs . Reoperation and removal of the prosthesis was necessary . The authors found no previous cases of nocardiosis complicating arthroplasty reported in the literature.

Fortschr Ophthalmol, 1989, 86(2), 164 - 6
{The peroxidase content of human tears}; Buchberger W et al.; The peroxidase-(POD)-thiocyanate-hydrogenperoxide-system is a well-known antibacterial system, which has been demonstrated to exist, for example, in milk and saliva . Earlier investigations by van Haeringen et al . established a POD level in human tears of 10(3) units/l, yet the thiocyanate concentration was only about 0.2 mmol/l . Therefore van Haeringen et al . excluded the existence of a POD-thiocyanate-hydrogenperoxide antibacterial system in human tears because of the insufficient amount of thiocyanate in the tears examined . Instead of thiocyanate halides such as J- can also complete the POD hydrogen peroxide system as electron donors . Sufficient amounts of iodide can be expected after the application of iodine-containing eye drops or after local treatment with iodine-containing brine, as done in Bad Hall in Austria . Therefore, the above mentioned antibacterial system may be of importance if the POD-level is high enough (greater than 250 units/l) . We investigated 22 tear samples from healthy persons: the POD levels were below 20 units/l in 19 cases; in 3 cases the POD concentration was found to be between 20 and 50 units/l . Therefore, in normal human tear fluid, not only the amount of thiocyanate but also the concentration of POD is too low for effective antimicrobial activity of the peroxidase-thiocyanate-hydrogenperoxide system . It is so far not known whether this system is effective under pathological conditions.

Antibiot Khimioter, 1989 Jan, 34(1), 20 - 4
{Structural and functional investigation of polymyxins . Structure and biological properties of polymyxin M analogs}; Trakhanova MN et al.; The effect of proteinases of plant and microbial origin on polymyxin M was studied . It was shown that this antibiotic was absolutely stable to the effect of papain and ficin . On hydrolysis with subtilisin there formed polymyxin decyclized analogs not described earlier . Their isolation, purification and biological activity are described . The structure of these compounds was assessed by one- and two-dimensional 1H NMR spectroscopy . The role of various functional groups, their space orientation and impact on antimicrobial activity of the compounds are discussed.

Biochem Pharmacol, 1989 Jan 1, 38(1), 161 - 5
The inhibitory effect of acetaminophen on the myeloperoxidase-induced antimicrobial system of the polymorphonuclear leukocyte; van Zyl JM et al.; Acetaminophen binds via its acetamido side chain to purified myeloperoxidase in a pH-dependent manner and maximum binding occurred around pH 6 . The H2O2-dependent myeloperoxidase-catalysed polymerization products of acetaminophen had excitation maxima at 304 nm and 334 nm in acid and alkaline solutions, respectively, and an intense blue fluorescence maximum at 426 nm . Acetaminophen can compete effectively with Cl- as myeloperoxidase substrate and thus HOCl formation is suppressed while HOCl, nevertheless present, can be scavenged by the drug . In this way the microbicidal action of the myeloperoxidase-H2O2-Cl- system can be seriously limited in the presence of high concentrations of acetaminophen . To study the effect of acetaminophen on peptide bond splitting in the myeloperoxidase antimicrobial system, thyroglobulin was used as a model peptide . Peptide bond splitting was inhibited at acetaminophen concentrations below the accepted toxic range for plasma values.

Acta Derm Venereol Suppl (Stockh), 1989, 143, 14 - 9
Pharmacology and toxicology of azelaic acid; Topert M et al.; The results of general pharmacological studies on metabolism, smooth muscles, renal function, cardiovascular and neurotropic effects do not contra-indicate the specific surface use of azelaic acid . From specific pharmacologic studies it is assumed that azelaic acid exerts its therapeutic effect in acne by an antimicrobial, probably bacteriostatic, effect on acne-relevant microorganisms such as Propioni bacerium acnes and, in addition, by a strong comedolytic effect . In numerous studies it has been demonstrated that azelaic acid is not toxic.

Zahn Mund Kieferheilkd Zentralbl, 1989, 77(2), 128 - 30
{Experimental research on the genotoxicity of various root canal antiseptics in the SOS chromotest}; Klimm W et al.; The genotoxicity of the endodontic antiseptics chlorhexidine digluconate, chloramine and sodium hypochlorite was determined by SOS chromotest using Bioscreen Analyzer Systems (Labsystem OY) . All antiseptics did not show a genotoxic effect . Chlorhexidine digluconate was the most efficient antimicrobial agent against E . coli PQ 37.

J Antimicrob Chemother, 1989 Jan, 23(1), 37 - 41
Susceptibility of Legionella pneumophila to eight antimicrobial agents including four macrolides under different assay conditions; Liebers DM et al.; A comparison of agar dilution and microdilution susceptibility testing for eight antimicrobial agents, including roxithromycin, was performed against 48 isolates of Legionella pneumophila . For agar dilution tests, charcoal free agar (BSYE) and charcoal supplemented agar (BCYE) were used . In general, BSYE agar produced lower MICs than BCYE agar, except for imipenem . Microdilution testing data fell between the data obtained for the two agar media . The MBCs were two to sixteen fold higher than the MICs . Prolongation of the incubation time from 48 h to 72 h or growth in 5% CO2 did not influence the results . As tested by the microdilution method, an increase in the inoculum from 10(5) to 10(7) was associated with a two-fold increase in the MIC . Roxithromycin and two other investigational macrolides (A-56268 and rosaramicin) demonstrated better in-vitro activity than erythromycin.

J Periodontal Res, 1989 Jan, 24(1), 75 - 80
The effect of a dentifrice containing zinc citrate and Triclosan on developing gingivitis; Saxton CA et al.; A partial mouth experimental gingivitis model was employed to establish the potential efficacy of a dentifrice containing a zinc salt and the antimicrobial agent Triclosan to prevent or delay the development of gingivitis over a period of 28 days . Initially, gingival health was established in 34 subjects following a 6-week period of professional tooth cleaning and oral hygiene instruction . A toothshield was constructed to fit 4 posterior mandibular teeth . Undiluted test or placebo dentifrice was applied to the experimental teeth via the toothshield, which also prevented plaque removal from these teeth during habitual brushing of the remainder of the dentition . The presence of plaque, bleeding after probing and visual signs of inflammation were independently assessed . Plaque accumulated rapidly and gingivitis developed in both groups . At the 2-wk assessments, lower mean plaque scores were recorded for the group using the test dentifrice . At the 4-wk assessment a significantly lower level of gingivitis was recorded for the test group . It is concluded that (a) the model can be used to establish the potential efficacy of a dentifrice to maintain gingival health, (b) the dentifrice containing zinc citrate and Triclosan was efficacious and (c) the Gingival Index possibly overestimates the proportion of healthy gingival sites.

Cell Immunol, 1989 Jan, 118(1), 229 - 33
Aging and immunity to tuberculosis: prolonged survival of old mice infected with Mycobacterium tuberculosis by adoptive immunization with memory-immune T lymphocytes; Orme IM; This study shows that memory immune T lymphocytes, harvested from young (3-month-old) mice infected intravenously with Mycobacterium tuberculosis and then exposed to protracted chemotherapy with isoniazid, are capable of adoptively protecting old (24 month) mice from a subsequent fatal challenge infection . Survival of such adoptively protected animals was prolonged, but did not extend beyond the mean survival time of uninfected old control mice . During this time the passively transferred memory T cell population retained their functional capacity to protect against subsequent tuberculosis infection . These data indicate, therefore, that reconstitution of decayed cell-mediated antimicrobial immunity in old mice in vivo with memory T cells is technically feasible, although the life span of the animal is not extended over that of control animals . They indicate, moreover, that the memory T cells remain functional in what some reports have considered a suppressive environment and show further that the macrophages with which the infused T cells interact in the aged host remain functionally able to express acquired resistance.

G Batteriol Virol Immunol, 1989 Jan-Dec, 82(1-12), 165 - 73
{Evaluation of in vitro antibiotic sensitivity: critical features of the MIC}; Malcangi A et al.; Current methods for the "in vitro" study of antibiotic activity, as minimum inhibitory concentration, expose bacteria to constant concentrations of antibiotics . The "in vivo" situation is significantly different, since the antibiotic concentration changes with time . Pharmacokinetic models are "in vitro" experimental systems that seek to simulate conditions of exposure of bacteria to antimicrobial agents that exist in blood and tissues . All of these systems are complicated constructions . A new simple "in vitro" kinetic model, based on solid phase growth, is described.

Braz J Med Biol Res, 1989, 22(9), 1127 - 9
Antimicrobial activity of kaurenoic acid derivatives substituted on carbon-15; Davino SC et al.; The antibacterial and antifungic activities of two kaurenic acids, ent kaurenoic acid and cinnamoylgrandifloric acid isolated from a hexane extract of aerial parts of Mikania laevigata, were investigated and compared with the activities of other kaurenic acid derivatives substituted on carbon-15 . Only acetylgrandifloric acid (ent-kaur-16-en-15 alpha-acetyloxy-19-oic) and its epimer xylopic acid (ent-kaur-16-en-15 beta-acetyloxy-19-oic) displayed significant antibacterial activity at concentrations greater than or equal to 250 micrograms/ml, the 15 alpha epimer being the most active.

Acta Pol Pharm, 1989, 46(4), 337 - 42
{Synthesis of phosphobetaine--a derivative of long-chain tertiary aliphatic amine with epichlorohydrin}; Marcoin W; Synthesis of a new surface active agent, a phosphobetaine derivative of tertiary amines with C12-22 long chains and sodium 3-chloro-2-hydroxypropyl phosphate has been elaborated . The reactants were applied at the molar ratio of 1:1.3 . The obtained compounds was found to possess high surfactant and antimicrobial activities.

Eur J Clin Microbiol Infect Dis, 1989 Jan, 8(1), 40 - 50
Nosocomial pneumonia in the intubated patient: role of gastric colonization; Craven DE et al.; A high rate of nosocomial pneumonia exists among intubated patients receiving mechanical ventilation . Retrograde colonization of the oropharynx and trachea with bacteria from the stomach is not widely appreciated in the pathogenesis of pneumonia . Gastric colonization is affected by age, malnutrition, antibiotics, disease of the gastrointestinal tract, and changes in pH . The widespread use of antacids and/or histamine type 2 blockers as prophylaxis against stress bleeding in the ventilated patient may also increase gastric pH and the risk of colonization in the upper gastrointestinal tract . Migration of bacteria between the stomach, oropharynx and trachea in the intubated patient may be a dynamic system involving large numbers of bacteria . The high fatality rate of mechanically ventilated patients with pneumonia, which persists despite treatment of these patients with appropriate antimicrobial therapy, underscores the need for effective measures of prevention . Preventive measures include the appropriate use of antibiotics, proper decontamination of respiratory therapy equipment, the cautious use of drugs that alter the natural gastric acid barrier, or, possibly, the selective use of antibiotics to prevent or reduce gastric, oropharyngeal and tracheal colonization.

Eur J Clin Microbiol Infect Dis, 1989 Jan, 8(1), 35 - 9
Diagnosis of nosocomial pneumonia in intensive care unit patients; Chastre J et al.; The optimal technique for diagnosing nosocomial bacterial pneumonia in critically ill patients cared for in the intensive care unit remains unclear, especially in the subgroup of patients requiring mechanical ventilation . An important advance has been the development of the protected specimen brush technique . We and others have demonstrated that secretions obtained using this technique and evaluated by quantitative cultures are useful in distinguishing patients with and without pneumonia . However, this procedure has important limitations in that results are not available immediately and in that a few false negative or false positive results may be observed . Recently, the use of bronchoalveolar lavage has been suggested to be of value in establishing the diagnosis of pneumonia, since the cells and liquid recovered can be examined microscopically immediately after the procedure and are also suitable for quantitative culture . We believe that microscopic identification of bacteria within cells recovered by lavage may provide a sensitive and specific means for early and rapid diagnosis of pneumonia in this setting and that the lavage technique can be conveniently incorporated into a protocol along with the quantitative culture of samples obtained using the protected specimen brush . This combination will probably improve the overall accuracy of diagnosis while allowing the administration of prompt empiric antimicrobial therapy in the majority of patients with pneumonia.

JPEN J Parenter Enteral Nutr, 1989 Jan-Feb, 13(1), 92 - 8
Treatment of an infected silicone right atrial catheter with combined fibrinolytic and antibiotic therapy: case report and review of the literature; Lewis JA et al.; Tunnelled silicone rubber right atrial catheters are commonly used to administer long-term total parenteral nutrition (TPN), cancer chemotherapeutic agents, and antimicrobial agents . The indwelling devices potentiate platelet-fibrin thrombi formation, providing a nidus for infection . Although many episodes of sepsis associated with thrombotic tunnelled catheters respond to antimicrobial therapy alone, a significant number require catheter removal . Evidence from case studies and small clinical trials suggests that fibrinolytic agents may increase the response rate and prevent removal of the device when combined with antimicrobial therapy . We present the first case reported of bacterial sepsis secondary to a thrombotic indwelling Hickman catheter for long-term TPN successfully treated with a combination of streptokinase and antibiotic therapies.

Chin J Biotechnol, 1989, 5(3), 161 - 6
Interspecific protoplast fusion of Streptomyces hygroscopicus var . yingchengenisis with Streptomyces qingfengmyceticus and biological characterization of their recombinants; Zhou XF et al.; The frequency of recombination between Streptomyces hygroscopicus var . yingchengensis and Streptomyces qingfengmyceticus as a result of interspecific protoplast fusion was 4.5 x 10(-4) . Characterization of biological properties revealed differences in spore mass color, drug resistance, antimicrobial activity, and antibiotic production capacity between the recombinants and their parents . Two recombinant strains, FL-42 and FL-48, exhibited production of the antibiotics originally elaborated by the two parents individually . They also produced two compounds with antimicrobial activity that their parents could not synthesize.

G Batteriol Virol Immunol, 1989 Jan-Dec, 82(1-12), 92 - 6
{Various biotypes of Escherichia coli: their correlation with antibiotic resistance}; Molinari GL et al.; The antimicrobial susceptibilities of 572 strains of Escherichia coli were evaluated . The strains were divided according to the biotypes and the differences between the strains towards various antibiotics were examined . We found a correlation between biotype and antibiotype . This correlation lead us to think of a possible existence of more resistant biotypes than others . Now we are doing other studies in order to show if this correlation is constant during time and if similar differences are present for other microorganisms, as well.

J Pharm Biomed Anal, 1989, 7(9), 1011 - 32
Advances in liquid chromatography and related methodologies for therapeutic drug monitoring; Wong SH; In this article the merits of current liquid chromatography (LC) columns and techniques are reviewed, to include the following topics: (1) a brief introduction to rational therapeutic drug monitoring (TDM) to justify drug measurements; (2) selected recent survey results from the College of American Pathologists (CAP) to establish the current utilization pattern of LC for TDM in the USA; (3) LC analyses of major classes of drugs--antiarrhythmics, antidepressants, antiepileptics, antimicrobials, cyclosporine, and others--with emphasis on analysis of these drugs in human serum or plasma, by focusing on the less usual, reversed-phase functional groups such as CN and phenyl, and by the use of "mini" columns, silica and polymeric columns, the emphasis being reduced on the well-established C-18 columns; (4) high-speed LC; (5) various approaches of direct sample analysis--solvent extraction, automated sample processing, column switching, micro-injections, micellar chromatography, electrochemical detection with photolytic derivation, and the internal surface reversed-phase column of Pinkerton; (6) microbore LC drug analysis; (7) clinical chiral separation; and (8) overall conclusions.

Lens Eye Toxic Res, 1989, 6(1-2), 59 - 85
An in vitro method which assesses corneal epithelial toxicity due to antineoplastic, preservative and antimicrobial agents; Lazarus HM et al.; We developed an in vitro model for studying the cytotoxicity of pharmacologic agents on corneal epithelium employing 3H-thymidine incorporation . Primary rabbit corneal epithelial cell cultures were established, and the cells plated prior to each experiment . 3H-thymidine incorporation was measured after the addition of drug or vehicle to these confluent cells, and dose-response curves were generated . Marked inhibition of 3H-thymidine incorporation was reached at chemotherapeutic concentrations achieved clinically for cytosine arabinoside (10(-7) M), methotrexate (10(-3) M), and 5-fluorouracil (10(-6) M) . A 10(-4) M concentration of 2-deoxycytidine, a naturally occurring competitive inhibitor of cytosine arabinoside, protected cells up to a concentration of 10(-5) M . We utilized these data to undertake an in vivo prophylaxis study in 13 leukemia patients receiving high-dose iv cytosine arabinoside . Topical deoxycytidine 10(-4) M and 1% prednisolone phosphate, given 12 hours prior to the start of antileukemic therapy, were effective in reducing symptoms and signs of keratitis; both were better than historical placebo-treated eyes . Ophthalmic preservatives were studied in vitro at concentrations used clinically: benzalkonium chloride (BAC) (0.004-0.02%) was the most toxic, thimerosal (TMS) (0.001-0.004%) intermediate, and chlorobutanol (CHB) (0.2-0.5%) the least toxic . Antiviral agents (final concentration) included: trifluridine (TFT) (1.0%), ethyldeoxuridine (EDU) (2.0%), and idoxuridine (IDU) (0.1%) . Dose but not time-dependent concentrations of these 3 agents were noted to cause toxicity; however, (E)-5(2-bromovinyl)-2'-deoxyuridine (BVDU) (0.1%) was non-toxic . Similarly, tobramycin and amikacin were significantly less toxic than gentamicin and neomycin in this system . These in vitro cytotoxicity data correlate well with previous in vivo and pre-clinical corneal epithelial toxicity studies . Our model may be useful in the toxicologic study of future topical ophthalmic agents.

Acta Paediatr Scand Suppl, 1989, 361, 31 - 43
Iron-binding proteins; Brock JH; The structure and properties of the iron-binding proteins transferrin, lactoferrin and transferrin are reviewed . Transferrin and lactoferrin are structurally similar, consisting of a single polypeptide chain and reversibly binding two iron atoms per molecule . Transferrin is found mainly in serum, whereas lactoferrin is found in neutrophils and in external secretions . Transferrin functions mainly as a donor of iron to cells, but there is no established iron-transport role for lactoferrin . Both these proteins may have antimicrobial activity as a result of their ability to sequester iron . Lactoferrin may act principally as a scavenger of iron in conditions where transferrin may not bind iron well, e.g . at low pH . Ferritin is a multisubunit protein capable of binding up to 4,000 iron atoms and serves principally as an iron-storage protein, though it may also serve to detoxify iron . In iron-rich tissues ferritin is largely degraded and the iron is converted to haemosiderin.

Int J Biochem, 1989, 21(5), 463 - 8
Effect of pisiferic acid and its derivatives on cytotoxicity macromolecular synthesis and DNA polymerase alpha of HeLa cells; Kobayashi K et al.; 1 . Seventy-seven derivatives of pisiferic acid (2), an antimicrobial diterpenoid, were tested for cytotoxicity against HeLa cells and 9 derivatives were found to show cytotoxicity at less than 2 micrograms/ml dose (IC50) . 2 . Hydrophobicity was revealed to be an important factor for cytotoxicity of the derivatives . 3 . Compound 2 inhibited predominantly DNA synthesis in HeLa cells as compared with RNA and protein synthesis . 4 . No direct interaction between 2 and nucleic acid bases was indicated by a u.v . spectral method . 5 . Several of the pisiferic acid species showed inhibitory action on HeLa DNA polymerase alpha, and the inhibitory activity was about 1/20 of aphidicolin.

J Leukoc Biol, 1989 Jan, 45(1), 29 - 34
Interferon-induced indoleamine 2,3-dioxygenase activity in human mononuclear phagocytes; Carlin JM et al.; Interferon (IFN)-induced tryptophan degradation, catalyzed by indoleamine 2,3-dioxygenase (IDO), has been shown to mediate antimicrobial activity in epithelial cells . IDO activity has also been augmented in peripheral blood mononuclear cells (PBMC) treated with IFN or interleukin-2 (IL-2) . The effector cells in this population have now been further characterized . PBMCs were isolated from normal donors, separated into monocyte and lymphocyte populations by plastic adherence, treated with IFN or IL-2, and cultivated in medium supplemented with {3H}tryptophan . Culture supernatants were collected after a 48-h incubation and fractionated by high-performance liquid chromatography; radioactivity was determined in fractions corresponding to tryptophan and its metabolites . IFN-gamma and IFN-beta induced IDO activity only in monocytes (plastic-adherent, nonspecific esterase-positive PBMCs) . The induction of IDO activity by IL-2 required both monocytes and lymphocytes . Interaction was required between these populations for induction of IDO by IL-2, due to production of IFN-gamma by T lymphocytes, with subsequent IFN-gamma-mediated induction of IDO in monocytes . A number of myeloid cell lines as well as monocyte-derived macrophages were also tested for their ability to be induced to degrade tryptophan in response to IFN treatment . Monocyte-derived macrophages were found to retain their capacity to be induced by IFN-gamma and IFN-beta to degrade tryptophan after differentiation, and to possess seven times more IDO activity per cell than IFN-induced monocytes . However, the presence of lipopolysaccharide (LPS) in the culture medium was required for the maximum induction of IDO activity by IFN-beta . Furthermore, higher concentrations of LPS were sufficient to induce IDO activity in macrophages in the absence of exogenous IFN.

Z Gesamte Inn Med, 1988 Dec 15, 43(24), 713 - 4
{Principles of modern antibiotic therapy in the general practice and clinic . Discussion of the contribution by Walter Siegenthaler and Gertrude Siegenthaler-Zuber published in Z . gesamte inn . Med . 42 (1987) 614-618}; Tauchnitz C et al.; W . Siegenthaler's and G . Siegenthaler-Zuber's opinion, according to which in the majority of infections in practice an etiological (microbiological) diagnosis may be renounced and the guiding slogan "before therapy the gods have placed the diagnosis" should be relativized for the situation in the practice in contrast to the situation in the clinic, is opposed . Microbiological findings represent an unrenouncable basis for a rational antimicrobial chemotherapy in practice and clinic . In the individual case this does not exclude a calculated chemotherapy on account of a clinical and microbiological tentative diagnosis made by the physician in charge . But at the latest when the empiric therapy fails an efficient microbiologic diagnostics must be at our disposal.

Hosp Pharm, 1989 Jan, 24(1), 26 - 9, 32
Pharmacy-laboratory interactions: a unique method to control antibiotic costs; Goff D et al.; Because a large percentage of hospital antibiotic use is regarded as inappropriate, hospital pharmacists must investigate ways of decreasing such usage . A unique approach was evaluated for its impact on cost-effective antibiotic therapy . By functioning as a team, the pharmacy and laboratory departments implemented the following steps: cost-code index on antimicrobial susceptibility and organism identification reports; suppression of cost-ineffective antibiotics within the same pharmacologic group from the antimicrobial susceptibility reports; design of minimum inhibitory concentration panels to conform to the hospital formulary; daily delivery of the antimicrobial susceptibility reports to the pharmacy . Of the 1078 documented therapeutic interventions by the clinical pharmacist, 100 were randomly selected for review, 62% of which involved direct interaction with the laboratory . Estimated cost savings due to these interactions were $8214; annual savings were $88,554 . The results of this study show the importance of pharmacy departments forming and maintaining lines of communication with the hospital laboratory department.

Hosp Formul, 1989 Jan, 24(1), 41 - 4, 46
Impact of a two-stage intervention program on cefazolin usage at a major teaching hospital; Gupta S et al.; To reduce antimicrobial drug costs associated with the administration of cefazolin, a two-stage therapeutic intervention--employing persuasive (informational) and power (therapeutic interchange) strategies--was initiated at this 1,000-bed major Canadian teaching hospital . The target of the intervention was to extend the dosage interval of cefazolin to q8h . During a 12-week preimplementation period, 32% of orders specified 8-hour dosage intervals . This percentage increased to 58% after the 3-week, initial informational stage of the intervention . When therapeutic interchange was employed, the percentage of orders for extended intervals rose to an average of 97% over a 32-week postimplementation period . An estimated annual cost savings of $58,000 resulted from this intervention . Manpower requirements to implement and maintain this program were minimal and prescriber antagonism was not encountered.

Mech Ageing Dev, 1988 Dec, 46(1-3), 29 - 32
An age-related loss of the isogeneic barrier to the successful passive cell transfer of antimicrobial immunity in mice; Orme IM; The results of this study show that an isogeneic barrier to the successful adoptive immunotherapy of Mycobacterium tuberculosis infected mice is progressively lost as these animals age . This was shown in this study by the demonstration that increasing levels of transferred acquired specific resistance could be conferred on normal old recipients of greater than 22 months of age, whereas in young recipients such transfers were unsuccessful without the prior exposure of recipients to sublethal levels of whole-body ionizing gamma irradiation . These data indicate that strategies of adoptive immunotherapy in the elderly may not have to overcome the age-related isogeneic physiological barrier to this procedure.

Chemioterapia, 1988 Dec, 7(6), 369 - 72
Antibiotics and immunity: effects of antibiotics on mitogen responsiveness of lymphocytes and interleukin-2 production; Ibrahim MS et al.; The immunomodulating properties of antimicrobial drugs may have important implications in prescriptive practice . This is particularly so for patients whose immune system has been compromised . In this study, tetracycline, cephalothin, rifampicin, polymyxin B and nitrofurantoin reduced mitogen responsiveness of both B and T lymphocytes of mouse spleen cells and human peripheral blood lymphocytes in vitro in a dose-dependent fashion . Ampicillin, chloramphenicol, gentamicin, streptomycin and erythromycin had no effect . In the in vivo study none of the antibiotics affected mouse spleen cell transformation in response to mitogen . The addition of interleukin-2 (IL-2) did not prevent the effect of the antibiotics tested on human lymphocytes in vitro . Cephalothin, chloramphenicol and gentamicin decreased IL-2 production by mouse spleen cells in vitro.

Farmaco {Sci}, 1988 Dec, 43(12), 951 - 60
Synthesis and antimicrobial activity of some pyrrole derivatives . III--2-(4-arylpiperazino)-3-ethoxycarbonyl-5-aryl-pyrrole derivatives; Cocco MT et al.; The synthesis of 3-ethoxycarbonyl-5-aryl-pyrrole derivatives with an arylpiperazine group in position 2 is described . The in vitro biological investigation showed that compound (XVIII) had considerable antibacterial activity against gram-positive microorganisms and antifungal activity against Candida rugosa, while the other compounds did not show any significative activity.

Pharmacol Res Commun, 1988 Dec, 20 Suppl 5, 33 - 6
Antibacterial activity of some African medicinal plants; Forestieri AM et al.; The antimicrobial activity of some drugs utilized in traditional African medicine and selected on the basis of medicinal folklore reports, have been studied, within a screening program . The distribution of the antimicrobial activity among gram-positive, gram-negative bacteria, yeasts and mycoplasma is reported.

Antimicrob Agents Chemother, 1988 Dec, 32(12), 1891 - 2
Decrease in antimicrobial susceptibility of Bordetella bronchiseptica caused by antigenic modulation and phase variation; Ishikawa H et al.; The susceptibilities to 20 antimicrobial agents of Bordetella bronchiseptica variants in C mode and degraded phases were compared with those of their parents in X mode . Increases in MICs of 4- to 32-fold were observed for ampicillin, carbenicillin, erythromycin, novobiocin, rifampin, chloramphenicol, nalidixic acid, and oxolinic acid.

J Pharm Sci, 1988 Dec, 77(12), 1062 - 5
Reversed-phase liquid chromatographic separation of enantiomeric and diastereomeric bases related to chloramphenicol and thiamphenicol; Gal J et al.; The important antimicrobial agents chloramphenicol and thiamphenicol are N-acylated amines whose chemical structures include two chiral centers . Each drug is the single enantiomer of R,R configuration . The N-deacylated bases of the drugs are important intermediates in their synthesis and optical resolution . In this report, reversed-phase HPLC methods are described for the separation of enantiomeric and diastereomeric bases of the two drugs and of two closely related bases used in some syntheses of the drugs . The stereoisomeric bases were derivatized with a homochiral isothiocyanate and the resulting diastereomeric thioureas were separated on C18 columns with methanol:water mixtures as mobile phases and detection at 254 nm . The four stereoisomeric bases of chloramphenicol and those of its unnitrated analogue were thus separable after derivatization with 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl isothiocyanate . This reagent also allowed the separation of the D-threo isomer of the p-mercaptomethyl analogue of thiamphenicol base from its stereoisomers . The stereoisomers of thiamphenicol base were similarly separated with (R)-alpha-methylbenzyl isothiocyanate as the derivatizing agent . The diastereomers of chloramphenicol base and of thiamphenicol base were chromatographically separable after derivatization with the nonchiral reagent benzyl isothiocyanate . The procedures developed may be useful in the determination of the stereoisomeric composition of the drugs in research and in quality control, and may be applicable to other similar agents whose chemistry and pharmacology are receiving considerable attention.

J Antimicrob Chemother, 1988 Dec, 22(6), 857 - 61
In-vitro activity of seventeen antimicrobial compounds against seven species of mycobacteria; Collins CH et al.; Within attainable serum concentrations, quinolones, especially ciprofloxacin, inhibited strains of Mycobacterium tuberculosis, M . xenopi, M . kansasii, M . fortuitum and M . marinum; vancomycin inhibited M . tuberculosis, the M . avium-intracellulare-scrofulaceum complex . M . kansasii, M . xenopi and M . chelonei; erythromycin was active against M . kansasii, M . xenopi and M . fortuitum, minocycline against M . kansasii and M . marinum and netilmicin and cefuroxime against M . xenopi . Aztreonam showed some activity against M . tuberculosis but little or no effect was shown by five cephalosporins or imipenem.

J Pediatr Surg, 1988 Dec, 23(12), 1204 - 9
Successful treatment of Candida-infected caval thrombosis in critically ill infants by low-dose streptokinase infusion; Lacey SR et al.; Chronic central venous catheters are an important component in the management of chronically ill infants and children . Sepsis and thrombosis are common complications of these catheters . When the combination of Candida sepsis and caval thrombosis occurs, the prognosis is very poor . Lysis of the thrombus is critical to effective therapy and allows preservation of vascular access . We report the successful treatment of four critically ill infants with Candida-infected caval thrombosis treated with low-dose infusion of streptokinase combined with standard antimicrobial therapy . All four infants survived, and in all cases thrombolysis was complete and Candida sepsis resolved . Each of the infants required continued central venous access, which was made possible by resolution of the caval thrombosis . There were no hemorrhagic or other complications of the therapy.

Chemioterapia, 1988 Dec, 7(6), 400 - 5
Economic implications of oral treatment replacing parenteral therapy in antimicrobial chemotherapy; Leigh DA; The cost of antimicrobial chemotherapy is a major part of the total hospital pharmacy cost . Parenteral administration is considerably more expensive than oral and until recently was the only available therapy for nosocomial and resistant bacterial infections . Apart from the cost of the antimicrobial agent itself, many other factors such as the infusion sets, catheters and cannulae, monitoring of blood to avoid toxicity and other laboratory investigations will influence the costs . The introduction of ciprofloxacin, a new quinolone, with a wide range of bacterial activity which can be prescribed orally, will have economic advantages in the treatment of hospital infections.

Chemioterapia, 1988 Dec, 7(6), 387 - 92
The pattern of antimicrobial use in general hospitals in Egypt; el-Teheawy MM et al.; This work was carried out to study the pattern of use of antimicrobial agents in Egypt . 2034 files were selected from two general hospitals by a systematic random sampling method, and the data concerning the antimicrobials were collected from each file . The results of this study showed that there was misuse of these agents both in therapy and prophylaxis . Antibiotics were prescribed to 80.17% of admitted patients . In most of the cases they were prescribed without documented proof of infection and were prescribed for conditions in which antimicrobial use is not justified for either therapy or prophylaxis . Among patients who received antibiotics, 30.8% received repeated courses, in most of whom there was no reasonable indication.

J Reprod Med, 1988 Dec, 33(12), 939 - 44
Single-dose antimicrobial prophylaxis at abdominal hysterectomy . Cefamandole vs . cefotaxime; Hemsell DL et al.; Two hundred twenty-three women were given a single, 1-g, intravenous dose of cefamandole or cefotaxime at elective abdominal hysterectomy in a multicenter, prospective, randomized, blind clinical trial of efficacy and safety . The demographic, surgical, efficacy and safety variables were statistically similar . Prior to discharge from the hospital, 12 women (5.3%) developed major postoperative pelvic infections that required parenteral antimicrobial therapy; no wound infections occurred . There was no correlation between a depressed antimicrobial development of significant postoperative infection . An expanded spectrum of antibacterial activity and a longer serum half-life did not improve clinical efficacy, and single-dose intravenous cephalosporin prophylaxis before abdominal hysterectomy was associated with a low incidence of pelvic infection.

APMIS, 1988 Dec, 96(12), 1079 - 84
Synergy between a non-neuroleptic thioxanthene stereo-isomer and penicillin in vivo; Kristiansen JE et al.; Some neuroleptic drugs of the phenothiazine and thioxanthene groups have an antimicrobial effect in vitro . This is also true for neuroleptically inactive stereo-isomeric analogs of the thioxanthenes e.g . trans(E)-clopenthixol (t-CPT) . In a murine pneumococcus peritonitis model t-CPT demonstrated a slight, but non-significant antibacterial effect in doses of 0.3-0.9 mg per mouse, while higher doses seemed to enhance the bacterial virulence . If combined with subtherapeutic doses of penicillin, a significantly higher survival rate was obtained compared with either drug given alone . In vitro studies demonstrated a similar synergistic effect . These results indicate that at least one non-neuroleptic thioxanthene stereo-isomer has an antibiotic potential also in vivo . The mechanism of action is not known.

J Vet Pharmacol Ther, 1988 Dec, 11(4), 390 - 6
Pharmacokinetic estimation for therapeutic dosage regimens (PETDR)--a software program designed to determine intravenous drug dosage regimens for veterinary applications; Riviere JE et al.; Pharmacokinetic estimation for therapeutic dosage regimens (PETDR) is a soft-ware program used to design individualized intravenous dosage regimens, determine concentration-time profiles, predict serum concentrations at a specific time after intravenous dosing and predict the time after the last dose to achieve a specified concentration of drug . The reference pharmacokinetic parameters may be based on an individual animal's pharmacokinetic disposition of drug or on FARAD (Food Animal Residue Avoidance Databank) mean population kinetic parameters . An individual animal's kinetic parameters may be input for predetermined analysis or the program can calculate these values by input of raw serum concentration-time data . The program allows the user to specify certain parameters of the dosage regimen, then calculates the other parameters (given desired maximum and minimum serum concentrations, dose and interval are calculated; given desired maximum serum concentration and interval, dose is calculated, etc.) . Given the kinetic parameters, the dose and dosing interval, the program calculates and plots the serum concentration-time profile of the drug for that animal . The time and the number of doses to reach steady state can be calculated as well as the determination of loading dose . The percentage of the time of a dosing interval at steady state that the serum concentration is above a specific minimum inhibitory concentration (MIC) allows evaluation of efficacy of an antimicrobial regimen . Similarly, the time to reach a specific concentration (e.g . residue tolerance) or the MIC of a drug can be calculated . Legal tissue tolerances can be accessed from FARAD to aid in predicting for what period of time illegal residues will remain in the animal.(ABSTRACT TRUNCATED AT 250 WORDS)

Farmaco {Sci}, 1988 Dec, 43(12), 979 - 88
S-Aryl(tetramethyl)isothiouronium salts as possible antimicrobial agents--III; Tait A et al.; A series of S-Aryl(tetramethyl)isothiouronium salts were prepared and evaluated in vitro for antimicrobial activity . Some compounds revealed interesting inhibiting action on Gram-positive bacteria which is noteworthy in view of the large number of strains antagonized and of the low MIC values . The possible influence of decomposition kinetics to the corresponding mercaptoderivatives was intestigated and compared with those of salts previously studied.

Zentralbl Bakteriol Mikrobiol Hyg {B}, 1988 Dec, 187(2), 166 - 79
Effects of disinfectants on bacterial metabolism evaluated by microcalorimetric investigations; Allerberger F et al.; The technique of microcalorimetry allows uninterrupted observation of the effects of antimicrobial agents on bacterial metabolism; bacteriostasis and bacterial death can be distinguished from one another directly from the thermal output, without the necessity of inactivating the antimicrobial drugs . In contrast to the traditional methods, microcalorimetry assesses the thermal activity of bacteria rather than their multiplication; the microcalorimetrical results correlate with those of traditional test methods as far as MIC (minimal inhibitory concentration) and MBC (minimal bactericidal concentration)_ are concerned . Microcolarimetry permits a clear differentiation between disinfectants and antibiotics/chemotherapeutics, except in the case of polymyxins which, like the tested disinfectants, show a rapid fall to the zero-line of the power-time-curve at bacteridical concentrations . At sub-bactericidal concentrations, however, each of the disinfectants tested produced an individually characteristic microcalorimetrical curve pattern . This leads us to suspect that the various disinfectants attack at different points in bacterial metabolism . Although the technique of microcalorimetry does not replace standard evaluation, it provides additional insight into the mode of action of disinfectants.

Geriatrics, 1988 Dec, 43(12), 43 - 6, 49
Prescribing antibiotics in home health care: problems and prospects; Brown RB; The elderly represent an increasing percentage of the population, and an important group of users of intravenous antibiotics . Therapy at home can provide a cost-effective means of treating many infectious diseases . Special problems to be anticipated include those related to reimbursement, possibility of adverse drug interactions, non-compliance, and need for venous access . Choice of antimicrobial agent is dependent upon ease of administration, safety, efficacy, and cost . Careful patient selection, availability of appropriate home health care services, and diligent physician follow-up can allow many elderly patients to receive long-term intravenous antibiotic therapy outside the hospital.

Pharmazie, 1988 Dec, 43(12), 827 - 9
Historical aspects and applications of barbituric acid derivatives . A review; Guillen Sans R et al.; This review considers the pharmacological and other applications of barbituric and 2-thiobarbituric acid derivatives . A chronological description about the discovery, structural studies and first clinical assays are given . Therapeutic expectations as anticonvulsant, antimicrobial, spasmolytic, antiinflammatory, antitumoral and some other effects of 5,5-disubstituted barbituric acids and alkylidene- or arylidenebarbituric acids are overviewed . A considerable amount of these types of compounds have been proposed as industrial dyes and pigments, photosensitizers and thermosensitive materials.

Antimicrob Agents Chemother, 1988 Dec, 32(12), 1776 - 9
Antimicrobial susceptibility patterns of Nocardia asteroides; Wallace RJ Jr et al.; Testing of the susceptibility to 12 antimicrobial agents, including beta-lactams, aminoglycosides, ciprofloxacin, and erythromycin, was performed by broth microdilution on 78 consecutive clinical isolates of Nocardia asteroides . Surprisingly, a limited number of patterns of susceptibility were identified that included all drug classes, with 95% of isolates exhibiting one of five patterns . One group (17%) exhibited resistance to the broad-spectrum cephalosporins, one group (18%) was susceptible to both ampicillin and erythromycin, one group (17%) was susceptible to ampicillin and carbenicillin but intermediate in susceptibility to imipenem, and the most common group (35%) was resistant to ampicillin but susceptible to the broad-spectrum cephalosporins and imipenem . The most active parenteral agents were amikacin (95%), imipenem (88%), ceftriaxone (82%), and cefotaxime (82%), while the most active oral agents were the sulfonamides (100%), minocycline (100%), and ampicillin (40%) . Additional studies are needed to determine whether differences in beta-lactamases relate to varying beta-lactam resistance and whether taxonomic differences that correlate with the different susceptibility groups can be identified.

Biosci Rep, 1988 Dec, 8(6), 609 - 18
Seminalplasmin: a protein with many biological properties; Shivaji S; Proteins present in the seminal plasma of mammals are known to influence functions associated with ejaculated spermatozoa such as motility, capacitation, acrosome reaction and fertilising ability . The proteins isolated and characterised so far influence only one of the above functions of spermatozoa . Seminalplasmin, a protein isolated from the seminal plasma of bull is exceptional in that it influences many of the above spermatozoal functions . It is also a potent antimicrobial protein and capable of lysing microbial and mammalian cells . The physiological function of seminalplasmin as nature's own antifertility agent is discussed.

Pathol Biol (Paris), 1988 Dec, 36(10), 1204 - 10
{In vitro measurement of the inhibitory effect of macrolides, lincosamides and synergestines on the growth of Toxoplasma gondii}; Derouin F et al.; The in vitro inhibitory effect of macrolides, synergestines and lincosamides on Toxoplasma gondii was evaluated using an enzyme immunoassay performed directly on the infected cultures . Antimicrobial agents were tested at various concentrations, and regression models were used to quantify the relationship between optical density values (correlated to Toxoplasma count in the cultures) and drug concentrations in the cultures . A significant inhibitory effect was observed with the macrolides (erythromycin, roxithromycin, midecamycin, spiramycin, josamycin and oleandomycin) for concentration of 0.1 to 4 micrograms/ml . This effect progressively increased with increasing concentration of drug in the cultures and reached its maximum value for concentrations of 40 to 250 micrograms/ml . Similarly, clindamycin was found to have a significant inhibitory effect for concentration ranging from 0.5 ng/ml to 100 micrograms/ml . Only a partial inhibitory effect was noted with virginiamycin, pristinamycin and lincomycin . The concentrations giving a 50% inhibition of Toxoplasma growth in the culture were determined from regression models and ranged between 0.15 and 12 micrograms/ml according to the drug . This results confirm that macrolides, lincosamides are effective against Toxoplasma gondii in vitro, and can be proposed for treatment of toxoplasmosis because of their large diffusion, their good tolerance and their concentration in tissues such as lung and placenta.

Infect Control Hosp Epidemiol, 1988 Dec, 9(12), 559 - 61
The problem of selecting antimicrobial agents before (or without) the results of susceptibility testing; Stratton CW; The appropriate selection of an antimicrobial regimen depends upon more factors than merely the results of susceptibility testing . It is a task more difficult today because of the recent development of many new antimicrobial agents . Clinicians who prescribe antibiotics need to invest time and energy beyond reading a package insert in order to gain familiarity with antimicrobial agents . Understanding the antimicrobial and pharmacologic properties of a few agents from each class of antimicrobial agents will help make the selection of empiric regimens less difficult . Essential to empiric therapy is frequent and habitual reassessment of antimicrobial regimens with possible application of cost-effective modifications kept in mind . Once the pathogen is isolated, the empiric regimen can be modified . The very last factor that is used in modification of the antimicrobial regimen is the result of susceptibility testing . Prior to (or without) this information, the clinical outcome of serious infections most often will depend upon the early institution of appropriate empiric therapy.

Int J Lepr Other Mycobact Dis, 1988 Dec, 56(4), 588 - 91
Inhibition of phenolic glycolipid-I synthesis in extracellular Mycobacterium leprae as an indicator of antimicrobial activity; Harris EB et al.; The effects of 22 antimicrobial agents on the incorporation of {U14C} palmitic acid ({U14C} PA) into the unique phenolic glycolipid-I (PGL-I) antigen of Mycobacterium leprae were studied . Nude-mouse-propagated M . leprae were incubated in a modified Dubos medium in the presence of antimicrobial agents for 4 days . {U14C} PA was then added and incubation was continued for 8 days . The antileprosy agents dapsone, rifampin, and clofazimine (2 micrograms/ml each) caused a significant reduction in {U14C} PA incorporation into PGL-I . Among other agents, the most active were erythromycin, chloramphenicol, and cerulenin . Low concentrations of ethionamide, tetracycline, and minocycline stimulated label incorporation . This system may prove useful in the evaluation of antileprosy agents.

Immun Infekt, 1988 Dec, 16(6), 220 - 5
{Antimicrobial therapy with nitroheterocyclic compounds, for example, metronidazole and nitrofurantoin}; Hof H; Nitroheterocyclic compounds, such as metronidazole and nitrofurantoin, are widely used in medical practice for the treatment of infectious diseases . Indeed, they exhibit a strong antimicrobial effect, which is directed not only against several groups of bacteria but also against certain protozoa and even worms . The nitrogroup coupled onto a heterocyclic structure, for example an imidazole, a thiazole or a furan ring, represents the proper site of effect . A priori the nitrogroup is, however, inactive . It has to be activated by microbial nitroreductases after penetration into the microbial cell . Those microorganisms which possess an anaerobic metabolism exhibit marked nitroreductase activity . The intracellularly produced intermediate products attack the chromosomal DNA of the target cell . Consequently, diverse mutations may occur . Partially, these chromosomal damages can be compensated by an SOS repair mechanism, which is under the control of the uvrB, lexA and polA genes . SOS repair-deficient mutants are much more susceptible to nitrocompounds than repair-proficient strains . Principally, the genotoxic activity of nitrocontaining compounds can also be expressed in eukaryotic cells of human or animal origin . This virtual property does not, however, prohibit clinical use, since until now no evidence of increased cancer incidence has been observed after rational therapy with nitrocompounds.

Clin Pharm, 1988 Dec, 7(12), 878 - 88
Effect of antimicrobial therapy on bowel flora; Hooker KD et al.; The known patterns and functions of gastrointestinal flora and antimicrobial effects on flora are described, and the clinical implications of altered bowel flora are described . A major role of the normal endogenous intestinal flora is to inhibit gastrointestinal colonization and overgrowth by potentially pathogenic bacteria . Serious disruption of this protective mechanism may occur after the administration of various antimicrobial agents . Alteration of bacterial flora by antimicrobials is often the result of incomplete absorption after oral administration or of high concentrations in saliva, bile, or secretions from the intestinal flora . Suppression of endogeneous microflora after antimicrobial administration may permit overgrowth of pathogenic strains in the gastrointestinal tract, development or selection of antimicrobial-agent-resistant strains, and disruption of colonization resistance . The disruption of normal bowel flora can result in diarrhea, pseudomembranous colitis, and systemic infections or sepsis in immunocompromised patients . Agents that are well absorbed and have minimal biliary excretion should minimize the detrimental effects from altered flora . The choice of an antimicrobial agent that has a narrow spectrum, is specific for the infection, is not appreciably excreted in the bile, and is completely absorbed if given orally appears to be the most appropriate practice for preventing or minimizing alteration of bowel flora.

Surg Gynecol Obstet, 1988 Dec, 167(6), 474 - 84
Infection and rejection of primary hepatic transplant in 93 consecutive patients treated with triple immunosuppressive therapy; Ascher NL et al.; Ninety-three consecutive patients who underwent primary orthotopic hepatic transplantation were treated, after transplantation, with prophylactic immunosuppressive therapy consisting of cyclosporine, prednisone and azathioprine . Weekly percutaneous biopsies were performed to diagnose rejection rapidly . Rejection was treated using a sequential multidrug therapeutic approach based on histologic findings . Mild rejection was initially treated with steroids; moderate to severe rejection was initially treated with steroids; moderate to severe rejection was treated with Minnesota antilymphoblast globulin (mALG) or OKT3 monoclonal antibody (Orthoclone, Ortho Pharmaceutical Corp.), or both . The one year actuarial survival rate for adults was 80 per cent and for children, 70 per cent . The incidence of biopsy-proved rejection was 75 per cent in adults and 80 per cent in children; however, the rejection was relatively easily reversed in both groups using biopsy-guided multimodal therapy . In 21 of 22 patients treated with steroids alone, rejection was reversed . Forty-one patients with moderate to severe rejection required treatment with mALG or OKT3, or both; in 38, rejection was resolved, and in three, chronic rejection required retransplantation . The incidence of bacterial, fungal and viral infections was high after transplantation and was further exacerbated by antirejection therapy requiring mALG Or OKT3, or both . Although the rate of infections was high, most were easily treated with antimicrobial agents . Thus, triple drug immunoprophylaxis followed by biopsy-guided antirejection therapy provided effected treatment of rejection without promoting fatal infections.

Am J Infect Control, 1988 Dec, 16(6), 253 - 66
Guideline for use of topical antimicrobial agents; Larson E; This Guideline is based on published data available at the time of writing . The ideal means for comparing performance of various antimicrobial agents is through the conduct of carefully designed, large-scale clinical trials . Recommendations contained in this Guideline are subject to modification as additional data become available . It particularly should be noted that the implementation of universal precautions or body substance isolation has resulted in marked increase in the use of gloves for direct patient contact . Whether there is an additional cost-benefit rationale for handwashing with an antimicrobial agent remains to be studied.

J Biol Chem, 1988 Nov 15, 263(32), 16709 - 13
Tachyplesin, a class of antimicrobial peptide from the hemocytes of the horseshoe crab (Tachypleus tridentatus) . Isolation and chemical structure; Nakamura T et al.; A cationic peptide, designated tachyplesin, was isolated from acid extracts of horseshoe crab (Tachypleus tridentatus) hemocyte debris . It consists of 17 residues and the structure determined by Edman degradation is: (formula; see text) The carboxyl-terminal end of this peptide was identified as arginine alpha-amide, and the whole sequence including the alpha-amide was also confirmed by fast atom bombardment mass spectrometry, indicating a mass value of 2263 . Tachyplesin inhibits growth of both Gram-negative and -positive bacteria at low concentrations and formed a complex with bacterial lipopolysaccharide . Tachyplesin seems likely to act as antimicrobial peptide for self-defense in the horseshoe crab against invading microorganisms.

S Afr Med J, 1988 Nov 5, 74(9 Suppl), 1 - 8
Imipenem-cilastatin . A new dimension; Quality control of individual components used in Middlebrook 7H10 medium for mycobacterial susceptibility testing; Microbial Diseases Laboratory, California Department of Health Services, Berkeley 94704The acceptability of different lots of commercial components which constitute our basal medium for susceptibility testing of mycobacteria was evaluated . The basal medium consisted of Middlebrook 7H10 agar supplemented with 10% oleic acid-albumin-dextrose-catalase and 0.5% glycerol . Studies were performed by using three separate microbiologic assays, and results were compared with parallel tests on previously standardized and acceptable lots of media . Components were rejected if comparison with standardized medium showed a major change in growth support or susceptibility status of any reference strain to any antimicrobial agent tested . Of the components tested in such a manner, 7 of 23 (30%) lots of 10% oleic acid-albumin-dextrose-catalase, 2 of 13 (15%) lots of Middlebrook 7H10 agar, and 0 of 5 lots of glycerol were found to be unacceptable . This study demonstrates that individual lots of components of this basal medium may vary significantly in their suitability for susceptibility testing, and failure to detect such variation may dramatically affect susceptibility profiles.

Pediatr Infect Dis J, 1988 Nov, 7(11 Suppl), S137 - 40
Current management of chronic suppurative otitis media in infants and children; Bluestone CD; Most children who have chronic suppurative otitis media require: (1) a thorough examination of the external canal and tympanic membrane with the otomicroscope (under general anesthesia, if necessary); (2) a Gram stain and culture obtained directly from the middle ear; (3) thorough aspiration of the ear canal and, if possible, the middle ear, i.e . "aural toilet"; (4) treatment with an orally administered antimicrobial agent and an ototopical medication, if the organisms are susceptible; and if the suppurative process is unresponsive to this management, hospitalization and the parenteral administration of an antimicrobial agent . Parenteral antimicrobial therapy should be selected following microbiologic assessment of the discharge . If the infection can be eliminated using the methods described above, prevention of recurrence can be achieved by the following options: (1) prophylactic antimicrobial therapy; (2) removal of the tympanostomy tube; or (3) surgical repair of the tympanic membrane defect . The choice of these options depends on the age of the child and the status of the function of the eustachian tube . Middle ear and mastoid surgery should be reserved for those children who fail to respond to intensive medical therapy.

Res Vet Sci, 1988 Nov, 45(3), 324 - 31
Development of periodontal disease in a single flock of sheep: clinical signs, morphology of subgingival plaque and influence of antimicrobial agents; Spence JA et al.; The clinical development of broken mouth over a single reproductive year and the effect of two broad spectrum antibacterial agents upon it was followed in 72 Scottish Blackface ewes aged between two and three years . Using a number of dental health indices especially developed for the purpose, the amount of gingivitis, tooth movement, gum recession and pocketing were quantified and graphed for both the whole population and each group in the drug trial . All clinical features except movement fluctuated significantly with time, the fluctuations often being associated with nutritional or other environmental factors . Despite the extended use of large doses of two antimicrobial agents no significant reduction in the amount of clinical gingivitis or pocketing was evident.

J Antimicrob Chemother, 1988 Nov, 22(5), 623 - 9
In-vitro susceptibility testing of Nocardia spp . and its taxonomic implication; Boiron P et al.; By disc diffusion, 28 clinical isolates of four species of Nocardia were tested against 16 antimicrobial agents . Among the drugs included in the study, only a few exhibited in-vitro activities . A species difference in susceptibility was noted for amoxicillin + clavulanic acid, kanamycin, gentamicin, chloramphenicol, minocycline and erythromycin, which was of clinical and taxonomic interest . All six N . brasiliensis and six N . otitidis-caviarum were susceptible to gentamicin and minocycline, while all 15 N . asteroides were not . In addition, N . otitidis-caviarum was susceptible to kanamycin and chloramphenicol, while the sensitivity of N . farcinica was less predictable . The only antibiotic to which members of all of the Nocardia species tested were susceptible was amikacin, which therefore appears to be a good candidate for the treatment of all forms of nocardial infections.

J Antibiot (Tokyo), 1988 Nov, 41(11), 1575 - 9
A new macromolecular antitumor antibiotic, C-1027 . I . Discovery, taxonomy of producing organism, fermentation and biological activity; Hu JL et al.; Strain C-1027, an actinomycete isolated from a soil sample collected in China, was found to produce the new antibiotic, C-1027 . From taxonomical studies on its morphological, cultural and physiological characteristics, this antibiotic-producing strain was identified as Streptomyces globisporus C-1027 . Antibiotic C-1027 has antimicrobial activity against most Gram-positive bacteria but not against Mycobacterium sp . or Gram-negative bacteria . This antibiotic shows remarkable activity in spermatogonial assay and potent cytotoxicity against KB carcinoma cells in vitro, and exhibits inhibition on transplantable tumors in mice.

APMIS, 1988 Nov, 96(11), 997 - 1001
Factors influencing the biological inactivation of high protein bound beta-lactam antibiotics in vitro; Henning C et al.; Unpredictable inactivation of antimicrobial agents may cause erratic results in pharmacokinetic studies . In this study we followed the inactivation of the high protein bound beta-lactams flucloxacillin, dicloxacillin and ceftriaxone in vitro . The antibiotics were added to pools of human and rabbit sera, ultrafiltrates of these pools, rabbit interstitial fluid, phosphate buffered saline (PBS), rabbit albumin in PBS and sodium dodecyl sulphate (SDS) treated preparations of human sera . Ceftriaxone was relatively stable but different serum pools varied significantly in their flucloxacillin and dicloxacillin inactivating capacity . The dominating inactivation took place within five minutes after the addition of antibiotics to serum . The inactivating factor was heat stable at 56 degrees C, 0.5 h, of relatively high molecular weight, and not related to albumin . The inactivating capacity could be diminished by SDS-treatment of serum suggesting a lipoprotein nature.

J Am Acad Dermatol, 1988 Nov, 19(5 Pt 2), 965 - 8
Altered gentamicin disposition in a child with a cavernous hemangioma; Gillespie JB et al.; Physiologic third spacing can cause an increase in the volume of distribution of certain drugs, such as aminoglycosides, which results in a decrease in the serum concentration . The case reported here, that of a child with a large cavernous hemangioma, demonstrated this phenomenon . To obtain adequate serum and tissue concentrations, alteration of antimicrobial dosing may be needed in similar cases.

Clin Pediatr (Phila), 1988 Nov, 27(11), 532 - 7
Serious bacterial infections . C-reactive protein as a serial index of severity; Peltola H et al.; The clinical course of 72 septicemic episodes or focal severe bacterial infections was monitored by daily measurements of serum C-reactive protein (CRP) in 59 children beyond the neonatal period, 19 of whom were immunocompromised . CRP was determined quantitatively by an immunoturbidimetric method from a finger prick sample until either clinical recovery occurred and antimicrobial therapy was discontinued or until the death of the patient . The primarily elevated CRP levels (greater than or equal to 20 mg/l) usually increased about for a day but then decreased rapidly, provided the patient recovered uneventfully . If not, CRP remained at a high level or reincreased after transient decrease . Behaviour of CRP was not affected by the immunologic status of the patient . This property makes CRP especially useful in immunocompromised patients in whom other commonly used laboratory parameters may fail.

Arch Surg, 1988 Nov, 123(11), 1389 - 93
Protective capacity of polyclonal and monoclonal antibodies directed against endotoxin during experimental sepsis; Dunn DL et al.; Both monoclonal antibody (MAb) and polyclonal antibody (PAb) directed against the shared core/lipid A region of lipopolysaccharide (LPS) (endotoxin) provide protection during experimental gram-negative bacterial sepsis . Although these preparations have not been compared, clinical trials administering either preparation to septic patients have been instituted . The core/lipid A region of LPS represents an antigenic domain common to many, if not all, gram-negative microbes, and thus represents an ideal target site for antibody binding . We sought to determine (1) the protective capacity of similarly reactive IgG anti-core LPS/lipid A MAbs and PAbs, (2) whether the timing of administration was important, and (3) whether either would act additively with antimicrobial agents . Antibody was administered intravenously to outbred mice, and Escherichia coli 0111:B4 was then administered intravenously or intraperitoneally with hemoglobin . Monoclonal antibodies and PAbs were equally protective, and protection was maximized by pretreatment, although the effect extended to four hours after bacterial challenge . Both MAbs and PAbs acted in concert with gentamicin hydrochloride to further reduce lethality . We concluded that MAbs and PAbs were equally protective and that clinical utility may eventually be dictated by ease and cost of antibody production.

Crit Care Med, 1988 Nov, 16(11), 1087 - 93
Prevention of colonization and infection in critically ill patients: a prospective randomized study; Kerver AJ et al.; In a prospective randomized study to determine whether prevention of colonization of Gram-negative bacteria results in prevention of Gram-negative bacterial infections, 96 intensive care patients were randomly allocated into a control group and a study group . The study group received oral nonabsorbable antimicrobial agents (i.e., tobramycin, amphotericin B, and polymyxin E) in addition to parenteral antibiotics . Colonization with Gram-negative microorganisms in the oropharynx, and respiratory and digestive tracts increased in the control group during their stay, while the study group did not tend to colonize with Gram-negative bacteria . In the control group, 107 nosocomial infections were diagnosed, vs . 42 nosocomial infections in the study group . Nosocomial infections caused by Gram-negative bacteria were significantly less frequent in the study group . Mortality due to an acquired infection was significantly less frequent in the study group . We conclude that colonization, infection, and subsequent mortality by nosocomial Gram-negative bacteria can be prevented by a regime of topically applied nonabsorbable antibiotics.

J Antibiot (Tokyo), 1988 Nov, 41(11), 1561 - 7
Thrazarine, a new antitumor antibiotic . I . Taxonomy, fermentation, isolation and biological properties; Kameyama T et al.; Thrazarine, O-{(3R)-2-diazo-3-hydroxybutyryl)}-L-serine, is a new antitumor antibiotic produced by Streptomyces coerulescens MH802-fF5 . Thrazarine was isolated from culture filtrate by Sephadex LH-20 column chromatography and reversed phase HPLC . Thrazarine induced cytolysis of tumor cell lines co-cultured with nonactivated macrophages . This effect was tumor specific because the nontumorigenic cells were not lysed by macrophages in the presence of thrazarine . Thrazarine inhibited DNA synthesis and growth of tumor cells directly . It showed neither antimicrobial activity nor the inhibition of transamidation reactions in contrast to azaserine . Toxicities of thrazarine were much weaker than those of azaserine.

Arch Intern Med, 1988 Nov, 148(11), 2421 - 7
A cost-effectiveness comparison of the use of antimicrobial agents for treatment or prophylaxis of travelers' diarrhea; Reves RR et al.; We conducted a decision analysis to compare the cost-effectiveness of antimicrobial agents used for treatment with their use for prophylaxis of travelers' diarrhea . Estimates of the likelihood and the cost of various outcomes were obtained from a panel of experts using the Delphi group opinion technique . Treatment with sulfamethoxazole-trimethoprim for three days was compared with daily prophylaxis with sulfamethoxazole-trimethoprim or doxycycline . The cost-effectiveness of prophylaxis with either agent (75% to 83%) was greater than that of treatment (38%) . Treatment would become more cost-effective than prophylaxis when the cumulative risk of acquiring travelers' diarrhea was less than 0.05 episodes per person per week or if the effectiveness of prophylaxis fell below 35% for doxycycline and 46% for sulfamethoxazole-trimethoprim . The most important contributor to the mean cost of travelers' diarrhea in this analysis was the cost associated with a day of incapacitation due to illness . On the basis of the results of this decision analysis, we conclude that prophylaxis of travelers' diarrhea is an option that should be considered for individual situations and recommend further studies of its cost-effectiveness.

Antibiot Khimioter, 1988 Nov, 33(11), 831 - 3
{Antimicrobial activity of polyhydroxynaphthoquinones from sea urchins}; Stekhova SI et al.; Antimicrobial activity of polyhydroxynaphthoquinones from sea urchins was studied . 6-Ethyl-2,3,5,7,8-pentahydroxy-1,4-naphthoquinone (equinochrome A) containing the beta-ethyl functional group was found to be the most active substance . Methylation of beta-hydroxyls markedly increased the inhibitory effect of the derivatives as compared to that of the initial quinones.

J Hand Surg {Am}, 1988 Nov, 13(6), 953 - 6
Eikenella corrodens in human mouth flora; Rayan GM et al.; The incidence of Eikenella corrodens in the human mouth was studied in 229 individuals . Six (2.6%) had positive cultures . The incidence of positive cultures for the saliva group was 0.6% and for the tooth-scraping group it was 8.2% . When 11 isolates were tested against 33 antimicrobials by disc-agar diffusion, 82% were susceptible to penicillin, cephalothin, and cefoperazone . Susceptibility to the remaining second- and third-generation cephalosporins studied was 100% . We suggest that the use of a second- or third-generation cephalosporin only is appropriate empiric therapy for human bite injuries.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1988 Nov, 270(1-2), 171 - 99
Side effects of antibiotics on immune response parameters and their possible implications in antimicrobial chemotherapy; Gillissen G; Antibiotics may influence immune response by quite different ways . By screening the multitude of publications on this subject, the aim of this overview was to arrive at a basic generalizing statement on the relationship between chemical structure or mode of action of antibiotics and the effect on immune response and to get an indication on whether certain in vitro and/or ex vivo parameters could represent comparable effects under clinical conditions . - The influence of antibiotics on immune response may arise by direct effects on immunocompetent cells, i.e . in the absence of microorganisms, or indirectly by changes in structure or metabolic products of germs induced by subminimal inhibitory concentrations (subMIC's) . In the former case, stimulatory and inhibitory effects have been observed on phagocytosis and intracellular killing activity, on antibody production including IgE, on different parameters of cellular immunity (e.g . foodpad swelling reaction, MIF-production, mitogen/antigen induced lymphocyte proliferation and delayed type hypersensitivity skin reaction), on mediator production as interleukins or prostaglandins and the expression of corresponding receptors on immunocompetent cells as well as on the course of experimental infections with primary resistant microorganisms . - Indirect effects are related to the influence of subMIC's of antibiotics on the morphology and structure of microorganisms, on their antigenicity/immunogenicity or on their serosensitivity and enzyme and toxin production . - This overview shows that - according to the actual knowledge - antibiotics may exhibit immunological side effects which, however, can not strictly be attributed to certain chemical structures or to a certain mode of action . - It has to be considered that a literary study comparing the results of different authors is rendered difficult by the often nonhomogeneity of experimental procedures and the fact that little is known yet about immunological side effects of antibiotics in man, i.e . under clinical conditions.

J Burn Care Rehabil, 1988 Nov-Dec, 9(6), 602 - 5
Use of 5% sulfamylon (mafenide) solution after excision and grafting of burns; Lee JJ et al.; In previous reports, 5% sulfamylon solution has been utilized on unexcised burns and granulation tissue . We prospectively evaluated 67 burn patients to determine graft take and the incidence of side effects with use of sulfamylon solution dressings after excision and grafting . Of patients excised and grafted, the mean graft take for a total of 100 procedures was 86% . Rash occurred in 18% of patients and sulfamylon was discontinued with no sequelae . Twenty-five percent had at least one positive fungal wound culture, yet only 3% required treatment for candidemia . Those patients who developed a rash and fungal colonization had a significantly larger percent burn and were treated with sulfamylon for a longer period of time . Pain intensity was rated on a Visual Analog Scale with a mean score of 2.4; in no case was the pain considered severe enough by the patient to terminate treatment . Acidosis was present in 3% of patients but felt to be unrelated to the sulfamylon treatment . As an antimicrobial agent, 5% sulfamylon solution is a viable alternative for fresh autografts with excellent graft take and acceptable side effects.

Vet Clin North Am Small Anim Pract, 1988 Nov, 18(6), 1141 - 65
Treatment of gram-negative infections; Brown SA; The armamentarium of antimicrobial agents for treatment of gram-negative infections has increased tremendously over the past 10 to 15 years . This article considers the characteristics of gram-negative bacteria . Also discussed are the mechanism of action, spectrum of activity, toxicity, disposition, and drug interactions of various antimicrobial agents, including the aminoglycosides, beta-lactam antibiotics, quinolones, tetracyclines, chloramphenicol, and the polymyxins.

Heart Lung, 1988 Nov, 17(6 Pt 1), 612 - 6
Antibiotic dosing in patients with renal insufficiency or receiving dialysis; Cunha BA et al.; Many patients are admitted to the hospital with renal insufficiency or renal insufficiency develops during their hospital stay . Many of these patients have bacterial infections requiring antimicrobial therapy . Antibiotic dosing in patients with varying degrees of renal insufficiency or hepatic failure is a therapeutic challenge to the clinician . The physician must be aware of the pharmacokinetics of the antibiotic in renal insufficiency as well as with intact renal function . Most antibiotics are eliminated via either hepatic or renal mechanisms, and the clinician should use this knowledge to select an antibiotic with the proper spectrum for the patient . This article presents practical guidelines for patients with hepatic insufficiency or various degrees of renal failure as well as for patients receiving peritoneal dialysis or hemodialysis . The guidelines presented provide the clinician with an approach that is easy to use and remember for determining the appropriate dose and dosing interval in patients with impaired hepatic or renal dysfunction.

Heart Lung, 1988 Nov, 17(6 Pt 1), 608 - 11
Fever in the neurosurgical patient; Cunha BA et al.; Patients with central nervous system trauma frequently have fevers while in the neurosurgical intensive care unit . Temperature elevations in the neurosurgical patient often cause much diagnostic confusion, and little is written that assists the critical care team in arriving at a proper etiologic diagnosis for the fever . This article discusses the common causes of temperature elevations in neurosurgical patients, such as central fever, wound infection, nosocomial pneumonia, posterior fossa syndrome, line sepsis, urosepsis, and drug fever . The recognition of central fevers, posterior fossa syndrome, and drug fevers is particularly important in neurosurgical patients to avoid inappropriate and potentially dangerous treatment with unnecessary antimicrobial therapy . Clinical and laboratory clues provide the clinician with a diagnostic approach to fever in the neurosurgical intensive care setting.

J Pharmacol Exp Ther, 1988 Nov, 247(2), 439 - 44
Nitrofurantoin-stimulated proteolysis in human erythrocytes: a novel index of toxic insult by nitroaromatics; Novak RF et al.; Nitrofurantoin is an antimicrobial agent that causes nonimmune hemolytic anemia in susceptible populations and produces oxidant stress and cellular damage by mechanisms that differ from those associated with oxidants such as phenylhydrazine, which has been shown to stimulate proteolysis in red cells (Goldberg and Boches, 1982) . Thus a study of the effects of nitrofurantoin on proteolysis in normal human red cells and red cell hemolysate has been conducted . Nitrofurantoin produced greater than a 3- and an approximately 5-fold increase in the rate of tyrosine release from red cells at 100 and 800 microM, respectively, compared with untreated red cells . In hemolysates nitrofurantoin also effectively increased proteolysis with a 2.4- and 4.0-fold increase in the rate of tyrosine release monitored at 100 and 800 microM, respectively, relative to controls . Stimulation of proteolysis by nitrofurantoin occurred linearly with time and with hematocrit over the range 5-25% . The rate of nitrofurantoin-stimulated proteolysis varied with glucose concentration in the incubation medium with a 2-fold increase in activity monitored between 2 and 10 mM glucose . Inhibitors of flavoprotein activity (electron transport), such as 2'-AMP and NADP, decreased nitrofurantoin-enhanced proteolysis in red cells to control levels, whereas methylene blue provided only a slight increase in proteolysis and an anaerobic environment (N2) stimulated significantly the rate of tyrosine production . Although N-acetylcysteine protected against the stimulation of proteolysis produced by 10 microM nitrofurantoin, this protective effect was diminished at higher concentrations of drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Pept Res, 1988 Nov-Dec, 1(2), 81 - 6
The Magainins: sequence factors relevant to increased antimicrobial activity and decreased hemolytic activity; Cuervo JH et al.; The Magainins, two antimicrobial peptides found in the skin of the frog Xenopus laevis, and 50 Magainin analogs were synthesized by the method of simultaneous multiple peptide synthesis (SMPS) . This series of peptides was prepared in order to examine the effects of omitting individual amino acids on antimicrobial activity . The series consisted of 22 Magainin 1 omission analogs having a C-terminal carboxyl (M1-C) and 23 Magainin 2 omission analogs having a C-terminal amide (M2-A), as well as both the C-terminal amide and carboxyl forms of Magainin 1 and Magainin 2 . These peptides were tested against E . coli (Gram negative), S . epidermis (Gram positive) and C . albicans (yeast) . Amino acid omissions in the N-terminal region (residues 1-14) resulted in the complete loss of antimicrobial activity in both Magainin series . These analogs also had very low hemolytic activity against human erythrocytes . However, analogs with omissions in the C-terminal region, especially residues alanine-15, glycine-18 or glutamic acid-19, while having equal or increased antimicrobial activity relative to the original Magainin 1 or Magainin 2 forms, had variable hemolytic action . Thus, both Magainin 1 and Magainin 2 with the glutamic acid 19 omission had equal activity against E . coli and increased activity against S . epidermis, while having lower hemolytic activity than the original sequences . The amide form of Magainin 2 with glycine 18 omitted had equal antimicrobial activity, but significantly increased hemolytic activity . The C-terminal carboxyl form of Magainin 1, however, showed equal antimicrobial activity, but substantially decreased hemolytic action.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Metab Dispos, 1988 Nov-Dec, 16(6), 804 - 12
Virginiamycin metabolism in cattle rumen fluid; Gottschall DW et al.; The antibiotic virginiamycin (VM) was extensively metabolized in cattle rumen fluid in vitro . The antimicrobial activity of VM decreased rapidly with an initial half-life of approximately 8 hr . In contrast, in buffer at near neutral pH, VM maintained its full activity for at least 24 hr . Four metabolites were isolated and identified using a combination of spectral techniques including FAB MS-MS, LC-MS, and 500 MHz NMR . The metabolites were all derived from reduction of the major component of virginiamycin, factor M . The minor component, factor S, was not metabolized in cattle rumen fluid . The metabolic pathways involved included C = C and C = O reduction as well as dehydroxylation . All metabolites were found to have less antimicrobial activity than the parent factor M . In addition to the metabolites, two factor M decomposition products were isolated after incubation of VM in buffer alone . These two products resulted from the dehydration of factor M and were shown to interconvert at room temperature.

S Afr Med J, 1988 Oct 15, 74(8), 390 - 2
Imipenem/cilastatin in the treatment of severe nosocomial pneumonia; Potgieter PD et al.; Imipenem/cilastatin (Tienam 500; Logos) 1 g, administered intravenously every 8 hours, was evaluated in an open clinical trial in 35 patients with severe nosocomial pneumonia . In 84.4% of cases there was a favourable clinical response; microbiological success was achieved in 63.3% and partial success in 20% of patients . The majority of Gram-negative and Gram positive organisms were sensitive to imipenem, including those resistant to the aminoglycosides . Although colonisation was frequent, superinfection was uncommon . Imipenem was well tolerated in these critically ill patients, many of whom had renal and other organ failure . The wide spectrum of antimicrobial activity and minimal side-effects made it a useful agent in patients with severe nosocomial pneumonia.

Hosp Formul . 1988 Nov;23(11):909.
DUE (drug usage evaluation) of ticarcillin and clavulanate potassium: determining appropriate and cost-effective therapeutic options; Lomaestro BM et al.; The initial 46 patients who were prescribed the combination drug ticarcillin disodium and clavulanate potassium in a 640-bed teaching hospital were evaluated to determine the potential usefulness of the drug in the institution . The review revealed frequent use of the drug for inappropriate indications and in situations for which less expensive antimicrobials were appropriate . The results demonstrate that an increase in costs can occur when an agent that is being considered for formulary addition--because of its cost-saving potential--is not used as expected . In order to optimally utilize the clinical or cost advantages of newer antimicrobials, a program of prescriber education, drug use controls or guidelines, and a concurrent monitoring program may be required and should be implemented at the time of initial drug use within an institution.

Clin Pharm, 1988 Oct, 7(10), 760 - 5
Postinfusion phlebitis after intravenous push versus intravenous piggyback administration of antimicrobial agents; Garrelts JC et al.; The incidence and severity of phlebitis associated with the i.v . push method versus the i.v . piggyback method of administration of antimicrobial agents were evaluated . All patients admitted to two nursing units of an 886-bed, tertiary-care hospital from March through June 1987 who received intravenous cephalosporins or extended-spectrum penicillins were considered for inclusion in the study . The method of administration, either i.v . push or i.v . piggyback, was randomly assigned . Each patient's catheter site was evaluated every 24 hours according to standardized definitions of phlebitis and patency . Information on each patient and venipuncture site also was collected . A total of 319 catheter sites were studied in 155 patients . There was no significant difference in the incidence or severity of postinfusion phlebitis between the i.v . push and the i.v . piggyback groups (41% versus 47%) . When studying only those catheter sites discontinued because of phlebitis, the time until development of phlebitis averaged 45 +/- 20.5 hours in the i.v . push group, compared with only 36.2 +/- 17.6 hours in the i.v . piggyback group; this difference was significant . The fact that the catheter sites lasted significantly longer in the i.v . push group, combined with elimination of the cost of syringe infusion pumps or i.v . tubing and minibags, suggests that use of the i.v . push method may result in substantial cost savings . Other advantages associated with the i.v . push method include time savings for nursing personnel and patients and greater ease in scheduling doses of multiple antimicrobial agents.(ABSTRACT TRUNCATED AT 250 WORDS)

HNO, 1988 Oct, 36(10), 423 - 5
{Antimicrobial effectiveness of azlocillin in cholesteatoma in parenteral administration}; Mertens J et al.; Azlocillin has a broad spectrum particularly against pseudomonas and should therefore be useful for preoperative parenteral treatment of infected cholesteatomas in those cases which cannot be controlled by local therapy . To determine the efficacy in treatment of cholesteatoma the concentration of azlocillin in separate tissue fractions of cholesteatoma matrix, cholesteatoma debris and granulation tissue surrounding cholesteatoma was determined . In 9 cases 2 g azlocillin was injected and in 5 cases 4 g . The concentration drop between the different tissue fractions was equal in all cases . However, as clinical experience has shown, differing high levels of azlocillin were found in comparable tissue fractions of the 14 cholesteatomas . In some of the cases the minimal antibacterial activity was not attained in the cholesteatoma fractions.

Antibiot Khimioter, 1988 Oct, 33(10), 767 - 71
{Study of the combined action of an antibiotic and an immunostimulator using mathematical modeling}; Churnosov EV et al.; A mathematical model of antibiotic and immunostimulator (IMS) combined effect on various elements of the immune system and general state of patients with infectious diseases is described . The model was constructed as a system including 6 usual differential equations of the 1st order . With the use of this model and a computer many diverse variants of infection development under conditions of treatment with IMS at the background of antibiotic therapy were modeled . Ii was shown that IMS-antibiotic complexes markedly improved the indices of antibiotic therapy as compared to the use of the antibiotics alone . In combined use of IMS and antibiotics it was possible to lower the antibiotic doses without lowering the antimicrobial effect . The use of IMS at the optimal period led to balanced activation of the host specific and nonspecific resistance factors at the background of antibacterial therapy . The results of the mathematical modeling corresponded to the data on protective effect of salmozan (IMS) and doxycycline (antibiotic) combination in animals (albino mice) . It was concluded that the described mathematical model was adequate for validation and optimization of schemes for combined use of IMS and antibacterial agents.

Jpn J Antibiot, 1988 Oct, 41(10), 1550 - 6
{In vitro activity of minocycline against Chlamydia trachomatis clinical isolates and clinical efficacy of minocycline to C . trachomatis associated nongonococcal urethritis}; Kato N et al.; The in vitro activity of minocycline (MINO) against Chlamydia trachomatis and its efficacy in the treatment of C . trachomatis-associated nongonococcal urethritis were investigated . Six isolates of C . trachomatis were inhibited at 0.06 micrograms/ml of MINO and 5 isolates at 0.03 micrograms/ml . All cases received oral MINO twice daily for 7 or more days in doses of 100 mg . In 5 of 31 cases, 2 g of spectinomycin was intramuscularly administrated together with MINO only once . C . trachomatis was eliminated in all cases tested . Excellent results were obtained in 26 cases (84%); urethral discharge and polymorphonuclear cells (PMN) disappeared or decreased to normal levels (3 cells/hpf or less) in these cases . Ureaplasma urealyticum was isolated from 8 cases, 7 of which became free of ureaplasmal infection . MINO seemed to be less effective on the decrease of PMN in the urethral smear in cases infected coincidentally with C . trachomatis and U . urealyticum than in cases infected with C . trachomatis alone . No subjective side effects were observed in any of the 31 cases studied . In conclusion, MINO was a useful antimicrobial agent for the treatment of C . trachomatis- and U . urealyticum-associated nongonococcal urethritis.

Antimicrob Agents Chemother, 1988 Oct, 32(10), 1571 - 5
In vitro displacement of bilirubin by antibiotics and 2-hydroxybenzoylglycine in newborns; Wadsworth SJ et al.; Hyperbilirubinemia is frequently observed in neonates, and serious neurological complications such as kernicterus can be precipitated when the concentration of unconjugated bilirubin is abnormally increased . The administration of drugs which bind to albumin and compete with bilirubin can increase the possibility of such a complication . To test the bilirubin-displacing activity of pharmacological agents that are used with newborns, 52 antimicrobial agents were investigated in vitro . A glycine conjugate of salicylate, 2-hydroxybenzoylglycine, which is known to be present at elevated levels in newborns and has a potent bilirubin-displacing property, was used as a positive control agent . Pooled cord serum was used as a source of hyperbilirubinemic serum . A centrifugal ultrafiltration method with semipermeable cones was employed to determine the effects of potential bilirubin-displacing agents on the levels of total bilirubin . 2-Hydroxybenzoylglycine was demonstrated to be the most potent bilirubin-displacing agent . Antibiotics could be classified into four groups: high-level displacers (sulfisoxazole, sulfamethoxazole, dicloxacillin, cefoperazone, and ceftriaxone), intermediate-level displacers (moxalactam, nafcillin, and 14 others), low-level displacers (aztreonam, carbenicillin, and 11 others), and nondisplacers (mezlocillin, cefuroxime, kanamycin, and 15 others) . It is concluded that the ultrafiltration method is a rapid and readily reproducible for the determination of bilirubin displacement and that antibiotics with a tendency to displace bilirubin should be avoided in jaundiced newborns whenever appropriate alternatives are available.

J Am Acad Dermatol, 1988 Oct, 19(4), 737 - 41
Comparison of preoperative skin preparations for the face; Dzubow LM et al.; Antiseptic preparation of the skin before dermatologic surgical procedures should provide maximal reduction of cutaneous microflora for the duration of the operation . No data currently exist concerning the efficacy of topical antimicrobials on the most common site of cutaneous surgery, the face . In this study the potency and temporal characteristics of three antimicrobials were tested on the faces of 14 volunteers . A 10-second wipe of 70% isopropyl alcohol was as effective in reducing aerobic microflora at the 5-minute postoperative period as a 60-second alcohol wipe or a 60-second povidone-iodine or chlorhexidine tincture application . At 60 minutes after the application, aerobic bacterial reduction possibly was better maintained by the povidone than by the 10- or 60-second alcohol preparation . None of the antiseptics tested were capable of a profound reduction of the anaerobic flora present on the sebaceous facial regions.

Epidemiol Infect, 1988 Oct, 101(2), 411 - 7
Pneumococcal carriage amongst children in Adelaide, South Australia; Hansman D et al.; Amongst 1267 healthy children 6 months to 4.5 years of age in Adelaide, the pneumococcal carriage rate from a single nasal swab sampling was 29% in the period 1980-1 . Of 269 children, sampled monthly on five occasions, 91% carried a pneumococcus on one or more occasions: 55% carried a single type, 33% carried two types, 2% carried three types and 1% carried four types; 18% carried a pneumococcus on either 4 or 5 occasions . The commonest types encountered were types 6, 19 and 23 in that order, and these three types constituted 57% of the total: other common types (greater than 5% of the total) were types 14, 15 and 11, and the six commonest types constituted 77% of the total . Of these, types 6, 14, 19 and 23 commonly cause systemic disease in children; on the other hand types 11 and 15 cause disease infrequently . The number of strains showing antimicrobial drug resistance was low: on quantitative testing 0.7% of 291 isolates examined showed relative resistance to benzylpenicillin and 0.7% were resistant to tetracycline; 10.9% of 230 isolates examined showed resistance to co-trimoxazole; dual or multiple drug resistance was not detected, and all isolates tested were susceptible to chloramphenicol, erythromycin, lincomycin and rifampicin.

Laryngoscope, 1988 Oct, 98(10), 1116 - 23
Antimicrobial prophylaxis in ear surgery; Jackson CG; The purpose of this research was to assess the efficacy of prophylactic antibiotic administration in ear surgery over a wide range of cases . Additional objectives include the assessment of the relative effect of patient age, duration of operation, preoperative condition, and the success of tympanoplasty . Prospectively, in a controlled study, 4,000 patients were studied employing cephalosporin and oxacillin as prophylactic antimicrobials . No statistically significant difference in postoperative otologic infection rates was observed . This conclusion was unaltered by the operative duration, patient age, or preoperative condition . Grafting success was not improved.

Food Chem Toxicol, 1988 Oct, 26(10), 815 - 22
Influence of water activity and reaction temperature of ribose-lysine and glucose-lysine Maillard systems on mutagenicity, absorbance and content of furfurals; Cuzzoni MT et al.; The effect of water activity (aw 0.98, 0.84 and 0.60) and reaction temperature (100, 120, 140 and 160 degrees C) on the mutagenic activity of the Maillard reaction products in heated ribose-lysine and glucose-lysine model systems, was investigated . In the ribose-lysine system, heated at 100 degrees C, the mutagenic activity of the mixture increased as the water activity was lowered . On the contrary, no dependence between mutagenic activity and water activity was observed in the glucose-lysine system . At higher temperatures, in both systems, the presence in the browned mixtures of an antibacterial activity interfering with the bacterial mutagenicity assay was observed . Under all the conditions tested, the ribose-lysine system turned out to be the most reactive by producing higher levels of mutagens . Furthermore, in this system, the antimicrobial interference was more easily detectable . In the model systems used, the browning reaction mixtures were analysed for their absorption spectrum between 200-460 nm, and for the accumulation of furfurals . The results obtained showed that, at temperatures between 120 and 140 degrees C there is a correlation among reaction temperature, absorbance at 420 and around 280 nm, mutagenic activity of the mixture and the level of furfurals . Changes in the levels of furfurals can be related to changes in mutagenicity of the browned mixtures.

J Antimicrob Chemother, 1988 Oct, 22 Suppl D, 49 - 54
Inhibition of Legionella pneumophila multiplication within human macrophages by fleroxacin; Pohlod DJ et al.; The susceptibility of Legionella pneumophila to a new quinolone, fleroxacin, was studied in both an extra- and an intracellular system . The activity of fleroxacin was compared with that of erythromycin, cefoxitin, and rifampicin . In the extracellular system, erythromycin inhibited while cefoxitin killed the organism . Extracellularly, fleroxacin performed similarly to cefoxitin . Rifampicin was initially bactericidal for L . pneumophila but resistant bacteria emerged at 48 h . The Horwitz monocyte model was used for studies of intracellular antimicrobial activity . At ten times the MIC, cefoxitin did not inhibit intracellular L . pneumophila . Fleroxacin was as active as erythromycin and rifampicin in inhibiting intracellular L . pneumophila . No intracellular, rifampicin-resistant L . pneumophila emerged . Addition of rifampicin to cefoxotin, erythromycin or fleroxacin provided neither synergy nor antagonism.

J Infect Dis, 1988 Oct, 158(4), 831 - 47
Correlation of antimicrobial pharmacokinetic parameters with therapeutic efficacy in an animal model; Vogelman B et al.; Current antimicrobial dosing regimens are designed to maintain active drug levels for most of the dosing interval and are based on 40-y-old observations . With use of numerous multiple-dosing regimens in an animal model, this study is the first to successfully minimize the interdependence between pharmacokinetic parameters and thereby determine, by stepwise multivariate regression analysis, that the time that serum levels exceeded the minimum inhibitory concentration (MIC) was the most significant parameter determining efficacy for beta-lactams and erythromycin against various pathogens, whereas the log area under the curve was the major parameter for aminoglycosides . Optimal dosing intervals were no greater than the time that serum levels exceeded the MIC plus the duration of the postantibiotic effect . Careful application of these concepts should allow other investigators to use more optimally dosed regimens than those previously used in preclinical trials and to design studies to improve on current dosing regimens for humans.

Dermatol Clin, 1988 Oct, 6(4), 497 - 520
Oral antibiotic therapy of dermatologic conditions; Reboli AC et al.; Oral antibiotics that may be useful in dermatology can be classified as beta-lactams (penicillins and cephalosporins), tetracyclines, macrolides, or quinolones; other options are clindamycin, trimethoprim-sulfamethoxazole, rifampin, and metronidazole . Proper understanding of the mechanisms of action and resistance, pharmacology, antimicrobial spectra, and adverse effects of these drugs will enable the clinician to obtain the best results.

Pharmazie, 1988 Oct, 43(10), 701 - 3
Parabens as antimicrobial preservatives in creams; Turakka L et al.; Antimicrobial effectiveness of methylparaben and a mixture of methyl- and propylparabens in an oil-in-water cream was studied . How the number of microbes and inclusion of nutrients into the cream affect the effectiveness of these compounds were also investigated, as well as the survival of test microbes in the cream without preservatives . Survival of microbes and antimicrobial effectiveness of parabens against the microbes in the cream were dependent on the species and number of microbes present and also on the amount of nutrients available for the microbes . In spite of the large amount of water, the cream studied did not readily support microbial growth unless the number of microbes was large or nutrients were added . Parabens were not effective antimicrobial agents against the yeast studied . The bacterial species showed different sensitivities to parabens . A mixture of methyl- and propylparabens was more effective than the methylester alone.

Can J Vet Res, 1988 Oct, 52(4), 484 - 7
Colitis in calves: natural and experimental infection with a verotoxin-producing strain of Escherichia coli O111:NM; Schoonderwoerd M et al.; Verotoxin-producing Escherichia coli O111:NM were isolated from two five week old Holstein calves with dysentery . On necropsy both calves had pseudomembranous ileitis, mucohemorrhagic colitis and proctitis . Large numbers of E . coli O111:NM were isolated from the colon and lesions typical of attaching-and-effacing E . coli were evident . The isolates from both calves had identical biochemical reactions and antimicrobial resistance patterns . Oral inoculation of a four day old colostrum deprived calf with 1 x 10(10) organisms of E . coli O111:NM produced a mild, focal colitis with typical attachment and effacement lesions . We conclude that the strain of E . coli O111:NM isolated from the clinical cases has the ability to produce colitis characterized by attachment and effacement of the colonic mucosa.

Antimicrob Agents Chemother, 1988 Oct, 32(10), 1521 - 7
Effect of clindamycin on neutrophil killing of gram-negative periodontal bacteria; Baker PJ et al.; Periodontal diseases are infections of the tissues supporting the dentition . Recognition that relatively specific microfloras are associated with distinct clinical forms of periodontal disease has prompted the use of antimicrobial agents as adjuncts in periodontal therapy . Clindamycin is one of several antibiotics known to concentrate in bioactive form in neutrophils and to potentiate phagocyte bactericidal activity against certain bacteria . Neutrophils appear to play a key role in host defense against periodontopathic gram-negative bacteria . In the present study, we evaluated the effect of preincubation of neutrophils with therapeutically achievable concentrations of clindamycin upon subsequent in vitro bactericidal activity against three species of gram-negative periodontal bacteria, including Actinobacillus actinomycetemcomitans, Eikenella corrodens, and Capnocytophaga ochracea . In each instance, clindamycin neither enhanced nor inhibited the kinetics of bactericidal activity at low bacterium-neutrophil multiplicities . Further, this antibiotic had no demonstrable effect upon neutrophil bactericidal capacity, as assessed at bacterium-neutrophil ratios as high as 50:1 . Our results indicate that clindamycin does not potentiate neutrophil bactericidal activity against the species of gram-negative periodontal organisms tested.

Vet Hum Toxicol, 1988 Oct, 30(5), 431 - 43
Pharmacology and toxicology of doxycycline; Riond JL et al.; Doxycycline, a structural isomer of tetracycline, has been used in human medicine since 1966 . The molecule, obtained semi-synthetically from oxytetracycline or methacycline, is highly lipophilic permitting excellent penetration into tissues . In vitro antimicrobial activity of doxycycline is superior to that of the older tetracyclines (chlortetracycline, oxytetracycline, tetracycline) . In laboratory animals, the protective dose for 50% of the subjects (PD50) demonstrates a better in vivo activity than that of all other members of the tetracycline family . Clinical use in human medicine has confirmed the efficacy of doxycycline for a variety of infectious conditions . High lipophilicity results in a large volume of distribution, substantial binding to plasma proteins, and reabsorption in the renal tubules and gastrointestinal tract, thereby conferring a long elimination half-life to the drug . Excellent absorption after oral administration allows small oral doses and minimizes the known side effects of tetracyclines on the gastrointestinal tract--irritation and suprainfection . The contrast to the other tetracyclines, doxycycline does not accumulate in renal failure due to a compensatory gastrointestinal secretion . The pharmacology, toxicology and therapeutics of doxycycline in laboratory animals and man indicate that this drug may be a valuable antimicrobial for use in veterinary medicine.

J Clin Microbiol, 1988 Oct, 26(10), 2006 - 12
Characterization of Escherichia coli serotype O157:H7; Ratnam S et al.; A total of 174 strains of Escherichia coli serotype O157:H7 representing human isolates obtained from outbreaks and sporadic cases of hemorrhagic colitis, hemolytic-uremic syndrome, and nonbloody diarrheal illnesses as well as from asymptomatic carriers across Canada and the United States were examined . E . coli serotype O157:H7 possessed distinct biochemical markers, a 100% negative reaction for beta-glucuronidase and sorbitol, and a 100% positive reaction for raffinose and dulcitol; all strains otherwise were biochemically typical of E . coli . The vast majority (97%) of the strains were susceptible to commonly used antimicrobial agents . All strains produced readily detectable levels of Verotoxin; however, with polymyxin extraction, nearly 50% of the strains showed up to a 10-fold increase in the toxin level . None were found to mediate hemagglutination of human group A erythrocytes with or without D-mannose . The majority (approximately 70%) of the strains showed localized and diffuse adherence to HEp-2 cells and Henle 407 cells, and the adherence patterns were not very different from those observed among other E . coli strains . Twenty phage types were recognized, with phage types 1 and 2 accounting for 65% of the test strains . Plasmid analysis indicated three basic plasmid profiles: profile I was characterized by 68.7- and 4.2-megadalton (MDa) plasmids (62% of strains), profile II was characterized by 66.2- and 1.8-MDa plasmids (20% of strains), and profile III was characterized by a 62.5-MDa plasmid (18% of strains) . A small number (19%) of the strains carried at least one additional plasmid over the basic complements, and these could be considered to constitute a miscellaneous category . None of the above-described characteristics of E . coli serotype O157:H7 could be directly correlated with one another, with the nature of infection, or with the geographical distribution of strains.

Am Fam Physician, 1988 Oct, 38(4), 125 - 34
New antibiotics: carbapenems, monobactams and quinolones; Amin NM; New beta lactams and the quinolone class of antibiotics represent major improvements in the therapy of moderate to severe infections . These newer antibiotics have an extended spectrum of antimicrobial activity, excellent pharmacokinetic properties and low toxicity . The beta lactams include carbapenems, represented by imipenem-cilastatin, and monobactams, represented by aztreonam . Norfloxacin and ciprofloxacin are potent quinolones.

J Med Chem, 1988 Oct, 31(10), 1997 - 2000
Oral absorption of cephalosporin antibiotics . 3 . Synthesis and biological properties of 7 alpha-methoxy-7 beta-(arylacetamido)-3-chloro-3-cephem-4- carboxylic acids; Pfeil-Doyle J et al.; A series of 7 alpha-methoxy-7 beta-amido-3-chloro-3-cephem-4-carboxylic acids was prepared and evaluated for biological activity . When compared with the parent 7-non-methoxy analogues, these new 7 alpha-methoxy-3-chloro cephalosporins displayed diminished antimicrobial activity.

Pediatr Infect Dis J, 1988 Oct, 7(10), 698 - 703
Monitoring serum aminoglycoside concentrations in children with amphotericin B nephrotoxicity; Goren MP et al.; We prospectively studied the effect of amphotericin B therapy on aminoglycoside clearance in 20 consecutive children during the remission-induction phase of chemotherapy for acute myelocytic leukemia . Increases (greater than 50%) in the half-life for aminoglycoside excretion were not associated with antileukemic or aminoglycoside therapy alone but occurred in 12 of 17 children when amphotericin B was added to the antimicrobial regimen . Seven children had impaired aminoglycoside clearance without increases (greater than 50%) in serum creatinine; hence the resulting adjustments in aminoglycoside dosage would not have been made had we relied solely on serial measurements of serum creatinine . Evidence for increased excretion of the renal enzymes N-acetyl-beta-D-glucosaminidase and alanine aminopeptidase during amphotericin B therapy suggested that damage to proximal tubular cells may contribute to the renal impairment that has been associated with this drug . Our findings underscore the value of monitoring serum aminoglycoside concentrations in children being treated with amphotericin B.

Am J Obstet Gynecol, 1988 Sep, 159(3), 779 - 84
Repair of old complete perineal lacerations; Given FT Jr et al.; Our subjects were 32 patients whose old complete perineal lacerations were repaired in the 10 hospitals in the South Hampton Roads Metropolitan area over a 20-year period . The layer technique of repair (26 patients) and the Warren flap procedure (6 patients) were used . Function improved in 24 of 26 patients (92%) with adequate follow-up . Function was completely restored in 22 of 26 patients (85%) . The use of a careful mechanical and antimicrobial bowel prep is emphasized, as is the debatable use of the paradoxical incision (Miller).

Invest Ophthalmol Vis Sci, 1988 Sep, 29(9), 1397 - 401
Pharmacokinetics and safety of transcorneal iontophoresis of tobramycin in the rabbit; Rootman DS et al.; Transcorneal iontophoresis of tobramycin in normal eyes of New Zealand white rabbits was compared to an eye cup control and application of fortified topical drops . Iontophoresis was performed with 25 mg/ml of tobramycin at 0.8 mAmps for 10 or 5 min . The eye cup with 25 mg/ml of tobramycin was placed on the eye for 10 min without current . Topical fortified drops (13.6 mg/ml) were applied every half hour for 4 hr . Epithelium, stroma, and aqueous humor were assayed separately at 1, 4, 8 and 16 hr after treatment . The eyes were examined using the slit-lamp biomicroscope before and immediately after the treatment, and prior to sacrifice . Two eyes were examined by light and scanning electron microscopy 5 and 10 min after iontophoresis . Iontophoresis yielded significantly higher tobramycin concentrations than the eye cup or fortified topical drops at 1 hr and 4 hr after treatment (P = 0.001) . In all treated eyes, iontophoresis resulted in epithelial edema and mucous discharge, which resolved by 24 hr after the treatment . Histologically there was evidence of epithelial disruption in the superficial layer after 5 min of iontophoresis and in all layers of the epithelium after 10 min of iontophoresis . Iontophoresis is a relatively safe, effective method to deliver medications to ocular tissues and may be useful alone or as an adjunct to current modes of antimicrobial chemotherapy.

Antimicrob Agents Chemother, 1988 Sep, 32(9), 1323 - 6
Effects of antimicrobial agents on growth and chemotaxis of Trichomonas vaginalis; Sugarman B et al.; The motility of viable Trichomonas vaginalis organisms is readily demonstrable in a clinical wet mount or cultured specimens . We attempted to determine whether migration is a dynamic process such that the organisms move to avoid exposure to toxic antimicrobial agents . With the use of axenic cultures of T . vaginalis that were radiolabeled and assayed for chemotaxis in plastic multiwelled plates with a membrane filter inserted to trap organisms, the response of clinical isolates to various antimicrobial agents was studied . Chemotaxis was readily demonstrable and dependent upon factors including time of incubation, media used, and viscosity of media . Nitroimidazoles (e.g., metronidazole) which readily inhibited the growth of these organisms also caused significant chemorepulsion after minutes of exposure . The antifungal imidazoles ketoconazole and miconazole inhibited growth nearly as readily and caused chemorepulsion, but to a lesser degree . The spermicide Nonoxynol-9 also inhibited growth and caused significant chemorepulsion . The minimal concentrations of many compounds which inhibited growth were very similar to those which caused significant chemorepulsion . Imidazole and antibiotics (e.g., penicillin) which did not inhibit growth did not induce any chemotactic effects . Chemotaxis of T . vaginalis is an active and dynamic process, and the organisms display chemorepulsion shortly after exposure to toxic antimicrobial agents, well before toxicity can be demonstrated.

Farmaco {Sci}, 1988 Sep, 43(9), 665 - 76
{A substance with antibacterial and antifungal activity . IV . Synthesis and microbiological activity of new 1,5-diarylpyrrole derivatives}; Scalzo M et al.; The synthesis and antifungal activities of new 1,5-diarylpyrrole derivatives are reported . Antimicrobial data in comparison with pyrrolnitrin show that only carboxamide derivatives exhibit satisfactory antifungal activity . By contrast all tested compounds show very poor antibacterial activity . The displacement of NO2 group from para to meta or ortho position of the aryl at C5 of the pyrrole ring affects the antimicrobial activity.

Antibiot Khimioter, 1988 Sep, 33(9), 666 - 71
{Study of general toxic properties and side effects of polymethylsiloxane and gentamicin immobilized on it}; Kaban AP et al.; A long-acting dosage form for local use of gentamicin immobilized on polymethylsiloxane, a silicon organic adsorbent was developed . It combined the antimicrobial spectrum of gentamicin and the local sorption-detoxication action of the matrix . In acute and chronic experiments on 5 species of laboratory animals it was shown that polymethylsiloxane had no general toxic action on the animals, no damaging action on their internal organs, did not affect their functions and the state of the biological fluids, had no pyrogenic or allergenic effect . During gentamicin immobilization on polymethylsiloxane there was observed no increase in the antibiotic toxicity as compared to the nonimmobilized dosage form of the antibiotic . Further study of the immobilized dosage form of gentamicin is advisable.

Pediatr Res, 1988 Sep, 24(3), 367 - 72
Effects of antimicrobial agents used for therapy of CNS infections on dissociated brain cell cultures; Schaad UB et al.; The prediction, measurement, and monitoring of neurologic toxicity of antibacterial agents is an exceedingly difficult matter . In this study we investigated if in vitro exposure of cultured brain cells to antibacterial drugs could predict neurotoxicity in man . Effects of antibiotics used for therapy of bacterial CNS infections on growth and differentiation in dissociated rat brain cell cultures were studied over 24 days in culture, the drugs being added from 10 to 17 days in culture, the main differentiation phase of rat CNS cells . Our results demonstrated a reversible inhibition of cerebral sulfate transferase activity (p less than 0.001 or less than 0.01) and to a lesser extent (p less than 0.001 or NS) of DNA synthesis in brain cell cultures by the highest concentrations studied of amikacin, cefuroxime, and ceftazidime which correspond to peak cerebrospinal fluid values attained by intraventricular therapy in patients . Accumulation of DNA reflects brain cell growth whereas cerebral sulfate transferase activity parallels brain cell differentiation . Our findings indicate that intraventricular therapy could be more toxic with amikacin, cefuroxime, and ceftazidime than with penicillin, chloramphenicol, or ceftriaxone . Thus, this brain cell culture model might become a supplement, complement, or even alternative technique for neurotoxicity assessment of antibiotics with proven or potential value for therapy of CNS infections.

J Int Med Res, 1988 Sep-Oct, 16(5), 386 - 93
Ciprofloxacin in elderly patients with underlying chronic diseases; Bianchi W et al.; Age is not as important in predisposing to infections as are the associated problems peculiar to certain age groups . Factors such as the advanced age of the patients combined with the presence of chronic disease reduce their resistance to infection . This study comprises 212 elderly patients (aged 65-98 years) who were treated with 500-1000 mg/day ciprofloxacin for 1-18 days . Despite the high incidence of associated chronic diseases, microbiology showed that infections were eradicated in 88.5% . Clinical resolution occurred in 75.5% of patients and clinical failure occurred in 6.1% . Treatment was well tolerated, with clinical side-effects reported in only seven patients . Ciprofloxacin may be considered an effective and safe antimicrobial agent for the treatment of infections in the elderly.

Antimicrob Agents Chemother, 1988 Sep, 32(9), 1435 - 6
In vitro activities of the newer beta-lactam and quinolone antimicrobial agents against Pseudomonas pseudomallei; Ashdown LR; Imipenem was highly active and bactericidal against all 100 strains of Pseudomonas pseudomallei tested, followed in activity by piperacillin, carumonam, ceftazidime, cefotaxime, and ceftriaxone . The addition of clavulanic acid significantly increased the activities of both amoxicillin and ticarcillin . Ciprofloxacin and norfloxacin showed poor activity against test strains.

Antimicrob Agents Chemother, 1988 Sep, 32(9), 1392 - 5
Antimicrobial synergism against Mycobacterium avium complex strains isolated from patients with acquired immune deficiency syndrome; Yajko DM et al.; Pairs of 11 antimicrobial agents were tested in vitro for their ability to act synergistically against three strains of Mycobacterium avium complex isolated from patients with acquired immune deficiency syndrome . From the combinations tested, four drugs (ethambutol, rifampin, ciprofloxacin, and erythromycin) were selected for more extensive study against 20 strains of M . avium complex . The inhibitory and killing synergism obtained with combinations of two, three, or four drugs was assessed by determining the fractional inhibitory concentration index and fractional bactericidal concentration index . Inhibitory synergism occurred against 90 to 100% of the strains for all drug combinations in which ethambutol was included . Killing synergism occurred against 85 to 95% of the strains when ethambutol was used in combinations which included either rifampin or ciprofloxacin . However, killing synergism occurred against only 45% of the strains when drugs were tested at concentrations that can be obtained in patient serum . In other experiments, rifabutin (Ansamycin) gave results that were comparable to those obtained with rifampin . Clofazimine did not show synergistic killing activity at a concentration that is achievable in serum for any of the drugs tested . Our results indicate that there is considerable variability in the antimicrobial susceptibility of M . avium isolates obtained from patients with acquired immune deficiency syndrome . This variability could have significant impact on the clinical response to various therapies.

J Antibiot (Tokyo), 1988 Sep, 41(9), 1205 - 11
Arizonins, a new complex of antibiotics related to kalafungin . I . Taxonomy of the producing culture, fermentation and biological activity; Karwowski JP et al.; The arizonins, a novel complex of antibiotics related to kalafungin, were discovered in the fermentation broth of Actinoplanes sp . AB660D-122 . Comparative taxonomic studies indicated that the culture is a new species and therefore has been designated Actinoplanes arizonaensis sp . nov . Two members of the complex, arizonins A1 and B1, exhibit moderate to potent in vitro antimicrobial activity against pathogenic strains of Gram-positive bacteria.

Eur J Epidemiol, 1988 Sep, 4(3), 357 - 9
Chemoprophylaxis in the surgical ward: results of a national survey in Italy; Mozzillo N et al.; As part of a national program for the control of hospital acquired infections, a survey on the use of antibiotic chemoprophylaxis was conducted in 1050 public hospitals in Italy (95% of the total number of hospitals in the country) . In each hospital, the chief of the general surgery ward was interviewed by means of a standard mail questionnaire . Answers were obtained from 479 surgeons (45.6%) after two mailings . More than 60% of these reported that they used chemoprophylaxis in clean surgery (mastectomy, splenectomy, hernioplasty) . More than 80% used antibiotic prophylaxis in surgery in which antimicrobial prophylaxis is facultative (i.e . elective cholecystectomy, gastric resection), and 97.1% used antibiotic prophylaxis in large bowel surgery . The authors recorded starting times and duration of chemoprophylaxis . Cephalosporins were found to be the most commonly used antibiotics followed by penicillin.

Tijdschr Diergeneeskd, 1988 Sep 1, 113(17), 921 - 32
{Considerations on the sense and nonsense of sensitivity determinations for veterinary practice}; van den Bogaard AE Jr; The parameter most frequently used as a basis for antibiotic therapy is the minimum inhibitory concentration (MIC) . This is a valid, standardised and comparative parameter for evaluating the effectiveness of a drug under laboratory conditions . The results of this test are considerably affected by changes in the standard laboratory conditions, which differ widely from the varying in vivo situations . The most common methods used in sensitivity testing, which are based on MIC values and pharmacokinetic data are discussed . The minimum antibiotic concentration (MAC) is much less affected by laboratory manipulations than is the MIC . The MAC is the lowest concentration having a barely measurable effect on the bacterium, whatever method is used . Although the MAC has not yet been standardised, it is a very informative test . The MAC is usually much lower than the MIC and it clearly shows that the MIC is an underestimation of antibacterial activity, particularly in animals with a reasonably functioning natural resistance . However, antimicrobial therapy should not be evaluated by microbiological and pharmacological methods alone, but also by clinical parameters, as the clinical response to antibacterial treatment may be influenced by many factors, which cannot be calculated as yet . Until he or she initiates treatment, particularly in life-threatening situations, a veterinary practitioner cannot wait for laboratory results . However, by carefully evaluating the clinical symptoms, and as a result of training and experience, he or she should be able to determine the causative organism in the majority of cases . Making and evaluating Gram-stained smears may be extremely helpful . The species of the suspected causative organism will suggest the antibiotic treatment of choice . Prospective sensitivity testing and resistance monitoring of pathogenic bacterial species, which may readily become resistant, at regular intervals is likely to be more effective, than culturing and testing alone in the event of failure of therapy.

Zhonghua Ya Yi Xue Hui Za Zhi, 1988 Sep, 7(3), 105 - 12
{A clinical evaluation of antimicrobial effectiveness of EDTA as an endosonic irrigant}; Lee LW et al.; Recently the chelating agent EDTA has gained increasing attention by dentists, in view of the facts that it does not produce deleterious or corrosive effect when used as an irrigant for root canal debridement . However, the efficacy of EDTA as an irrigant in clinical practice is still not clear . Therefore, in this study EDTA was adopted as an irrigant alone to evaluate its antimicrobial effect as a reference for subsequent clinical application . One hundred single-root teeth were selected and evenly divided into 4 groups . The root canals were prepared with conventional hand filing or ultrasonic filing respectively and the canals were rinsed singly with either EDTA or distilled water for contrast . The contents of each root canal before and after debridement were cultured in an incubator . The results showed that EDTA with hand filing in 48 hours and with endosonics in both 48 hours and one week had better antimicrobial effect than did distilled water . The results also indicated that EDTA combined with endosonics manifested the best antimicrobial effect among the four groups in this experiment . The above-mentioned differences were statistically significant at the level of p less than 0.05 by Fisher's exact test.

Antimicrob Agents Chemother, 1988 Sep, 32(9), 1441 - 2
In vitro susceptibilities of Mycobacterium tuberculosis to 10 antimicrobial agents; Byrne SK et al.; After preliminary in vitro screening of 10 antimicrobial agents against Mycobacterium tuberculosis, the MICs of the 6 most promising agents against 27 clinical isolates were determined by agar dilution . The two quinolone compounds tested (difloxacin and A-56620) were the most active, each inhibiting 50% of the strains at concentrations of 4 micrograms/ml . M . tuberculosis strains previously shown to be resistant to isoniazid, streptomycin, rifampin, or ethambutol were as susceptible to these quinolone compounds as susceptible strains.

Arch Intern Med, 1988 Sep, 148(9), 2001 - 7
Use of antimicrobial agents in a university teaching hospital . Evolution of a comprehensive control program; Hirschman SZ et al.; A comprehensive control program for utilization of anti-microbial agents in a large tertiary university teaching hospital regulates both dosage and duration of therapy and requires the prior approval of an infectious disease specialist for utilization of restricted antimicrobial agents . Benefits of the program include more cost-effective antimicrobial therapy and increased physician education in the use of these drugs . Gross savings in pharmacy costs for antibiotics during the first year of the program (1985) amounted to +483,032 for an average monthly savings of +40,252 . Gross savings for 1986 were +211,786 with monthly savings of +17,648 . The control of the use of one agent may lead to overuse of another agent . Antimicrobial prescribing patterns of physicians are quickly influenced by changing regulations of the program . An ongoing surveillance and review program of in-hospital utilization of antimicrobial agents is necessary to maintain effective and flexible controls.

J S Afr Vet Assoc, 1988 Sep, 59(3), 169 - 72
Practical small animal dermatology . III: Bacterial disease; Briggs OM; Bacterial infection is often overlooked as an aetiological factor in small animal dermatology . The misuse of glucocorticoids may result in immunosuppression in the patient . Pyoderma may then become refractory to all forms of therapy . The impression smear is a simple technique to confirm a pyoderma . Empirical selection of antimicrobial agents is acceptable for initial therapy of uncomplicated pyoderma . Appropriate antibiotics must be used at therapeutic doses for extended periods . Primary pyoderma is caused by pathogenic bacteria alone . The underlying cause in secondary pyodermas must be eliminated in order to prevent recurrence.

Antimicrob Agents Chemother, 1988 Sep, 32(9), 1350 - 3
Rapid determination of MICs of 15 antichlamydial agents by using an enzyme immunoassay (Chlamydiazyme); Bianchi A et al.; An enzyme immunoassay (EIA), Chlamydiazyme (Abbott Laboratories), was evaluated for its determination of MICs of 15 antimicrobial agents against Chlamydia trachomatis (MRC-1, LB, TRIC/GB/MRC-1 Gf {ATCC VR-1}) . The inoculum size, incubation time, and enhancers were defined for the assessment of chlamydial antigen synthesis in HeLa 229 cells seeded as monolayers in 96-well plates . MICs were determined and defined as the lowest antibiotic concentrations required to inhibit, after 24 or 48 h of incubation, antigen production as determined by the EIA . The MICs (after 48 h) were similar to those determined by the peroxidase-antiperoxidase staining of inclusions . MIC determinations after 24 h were suitable for screening the activities of quinolones, but less so for measuring the susceptibility of C . trachomatis to macrolides and tetracyclines . MIC determination by EIA was rapid, appropriate for standardization, and less cumbersome than determination by quantification of inclusions.

J Periodontol, 1988 Sep, 59(9), 557 - 64
Use of antimicrobial containing acrylic strips in the treatment of chronic periodontal disease . A three month follow-up study; Addy M et al.; Local antimicrobial therapy has been considered for use in the treatment of chronic periodontal disease . This study evaluated chlorhexidine, metronidazole, and tetracycline delivered into periodontal pockets in an acrylic resin vehicle and compared the results with root planed and untreated sites over a three-month follow-up period . One site per patient where pocketing greater than or equal to 6 mm associated with a single rooted tooth was randomly allocated to one of the five possible regimens . Baseline and follow-up measurements included probing depth, loss of attachment, bleeding on probing, crevicular fluid flow, and dark-field microscopy of a subgingival plaque sample . Intratreatment evaluations revealed no significant changes in any parameter for untreated sites . Significant improvements in many parameters occurred with all four therapies although the magnitude and duration were greater in metronidazole and root planing groups . The more important intertreatment comparisons indicated that most treatments produced significant benefits compared with the control group; however, again these were greater with metronidazole and root planing . Furthermore, significantly greater effects were noted for metronidazole and root planing compared with tetracycline and more particularly chlorhexidine . It is concluded that some locally delivered antimicrobials alone may be useful in the treatment of chronic periodontal disease . However, at this time local antimicrobial therapy should be considered as adjunctive to conventional debridement techniques.

J Clin Periodontol, 1988 Sep, 15(8), 511 - 6
Mouthrinses in "experimental gingivitis" studies; Wennstrom JL; The experimental gingivitis study design is a frequently used clinical model for the evaluation of the effects of antimicrobial agents on developing plaque and gingivitis . In individuals who at the start of the experiment have clean teeth and healthy gingivae and who use a mouthrinse containing the test agent as the only tooth cleaning measure during a period of 14-21 days, the anti-plaque and anti-gingivitis potential of the agent can be properly evaluated . The present paper describes different designs of experimental gingivitis studies for the evaluation of chemotherapeutic agents used to control supragingival plaque formation . Findings reported in the literature with respect to the effects obtained by various antimicrobial compounds are also reported.

Eur J Epidemiol, 1988 Sep, 4(3), 306 - 9
Antimicrobial resistance patterns and plasmids of enteropathogenic Escherichia coli isolated in Nigeria; Olukoya DK et al.; In an epidemiological study of enteropathogenic Escherichia coli, 102 strains were isolated from patients seen at the University Teaching Hospital in Lagos . The most common serotype encountered was 055 followed by 026 . Antimicrobial susceptibility testing and plasmid profiling of the strains were done . All the strains were sensitive to colistin, nalidixic acid, nitrofurantoin, cefotaxime, amikacin, and augmentin . Of the 102 strains, 47 (46%) were resistant to one or more of the following antimicrobial agents: Co-trimoxazole, tetracycline, ampicillin, streptomycin, sulphonamide and a combination of ampicillin with sulbactam . All the strains that were resistant to any antimicrobial agents were also resistant to tetracycline . Seventy-two strains (70.6%) harbored plasmid whose molecular weights ranged from 0.8 to 120 x 10(6) daltons . The majority of the plasmid were smaller than 6 x 10(6); 90% of strains carrying plasmid ranging in size from 2 to 6 x 10(6) daltons and 50 to 70 x 10(6) daltons were resistant to one or more antimicrobial agents . Transformation and conjugation experiment showed that about 57% of the resistant strains carried R plasmid . Plasmid-determined resistance to tetracycline, ampicillin, streptomycin and sulphonamide was found.

Clin Pharmacokinet, 1988 Sep, 15(3), 133 - 64
Clinical pharmacokinetics of enzyme inhibitors in antimicrobial chemotherapy; Watson ID et al.; The effectiveness of some antimicrobial agents can be enhanced by using them in combination; such combinations are termed synergistic . Where one compound potentiates the effect of a second drug they may be coformulated . Inhibition of the bacterial degradation of an active antimicrobial is the basis of clavulanate and sulbactam-potentiated penicillin combinations, and inhibition of degradative pathways in the host is the rationale behind imipenem/cilastatin therapy . Trimethoprim/sulphonamide combinations depend on the maintenance of an effective ratio for synergistic action . In order to achieve potentiation the coformulated drugs should have similar pharmacokinetics . Trimethoprim was originally matched with sulphamethoxazole, since these two drugs have similar elimination half-lives, but the significantly poorer penetration of sulphonamides, their greater non-renal clearance, the emergence of resistance, and the adverse reactions attributable to them argue against the rationale that underlies their coformulation . Time-dependent inhibition of bacterial beta-lactamases by clavulanic acid and sulbactam has extended the use of penicillins which are highly susceptible to beta-lactamase inactivation . The beta-lactamase inhibitors must penetrate to the same extent as the penicillin used with them, and be present long enough to effect inhibition; thus, rapid penetration, similar or slower elimination and equivalent volume of distribution are necessary . These requirements are met for amoxycillin/clavulanic acid, ticarcillin/clavulanic acid and ampicillin/sulbactam combinations . Clavulanic acid is absorbed orally and is given with amoxycillin . However, since sulbactam is labile by this route, the combination of sulbactam with ampicillin to form the prodrug sultamicillin has been necessary to enable an oral form to be developed . Imipenem is metabolised by renal brush-border dehydropeptidases, and may cause proximal tubular necrosis . Cilastatin was designed to inhibit this metabolism, which it effectively does, thereby both potentiating the effect of imipenem and avoiding toxicity . Appropriate matching of the kinetics of coformulated drugs is intended to maximise potentiation and minimise the risk of emergent resistance . The kinetics of the above combinations are discussed in the light of these requirements and the effects of age and disease.

Gastroenterol Clin North Am, 1988 Sep, 17(3), 587 - 98
Infectious diarrhea in human immunodeficiency virus infection; Smith PD et al.; Gastrointestinal symptoms, particularly diarrhea, are common in patients with AIDS . Recent evidence indicates that enteric pathogens can be identified in most of these cases . Appreciating the clinical features caused by protozoal, fungal, bacterial, and viral pathogens will assist the clinician in effectively evaluating the gastrointestinal symptoms . Antimicrobial agents now are available for many of these pathogens.

Med Clin North Am, 1988 Sep, 72(5), 1067 - 89
Diagnosis of pulmonary infections in immunocompromised patients; McCabe RE; In an immunocompromised patient with fever and pulmonary infiltrates, it frequently is difficult to decide which invasive procedure, if any, to use to obtain a definitive diagnosis . Because most lung infiltrates in immunosuppressed patients are caused by bacteria and sputum usually is readily available for examination, empiric therapy with potent, safe, broad spectrum, antibacterial drugs often is successful . Invasive procedures that prove a diagnosis may result in substantive changes in therapy in perhaps as few as 10 to 20 per cent of patients, and the procedure itself may harm the patient . In a unique study in which patients with acute pneumonitis without neutropenia were randomized to either empiric antibiotic treatment or treatment based on results of open lung biopsy, patients with open lung biopsy had a worse outcome, possibly related to morbidity of open lung biopsy . Furthermore, no diagnoses were provided by open lung biopsy that were not treated by the empiric regimen . A missed treatable disease may be tragic, however . A thoughtful clinician must evaluate each patient with careful consideration of the history in light of the underlying disease and its treatment, rapidity of clinical course, physical examination, and laboratory data, particularly the chest radiograph, sputum examination, and bleeding parameters . Fiberoptic bronchoscopy with washings and brushings is very safe; the addition of transbronchial biopsy adds diagnostic power at the price of some complications . Bronchoalveolar lavage is a very promising technique that probably will find widespread use . However, none of the foregoing techniques is completely sensitive . When no diagnosis is established and bronchoscopy studies are negative, open lung biopsy must be considered, especially when the chest radiograph or computed tomography scan suggests focal disease or lymphadenopathy . Needle aspiration can be used, particularly if local experience is favorable and lung disease is peripheral . When evaluating a procedure, local experience must be considered rather than reliance on published diagnostic yields and complication rates . New diagnostic and therapeutic developments may change decision analysis in the near future . At present, cultures for viruses and fungi and serologic techniques have little application at most medical centers, and decisions on data from invasive procedures pivot on interpretation of histology and smears . Development of assays for antigen (for example, Aspergillus) and rapid culture techniques (for example, cytomegalovirus and the shell vial method), coupled with new, effective antimicrobials, may demand maximum effort for a definitive diagnosis in every patient.

Tubercle, 1988 Sep, 69(3), 187 - 92
Comparative in vitro and in vivo activity of rifabutin and rifampicin against Mycobacterium avium complex; Saito H et al.; In vitro antimicrobial activity of rifabutin and rifampicin against various mycobacteria, including the Mycobacterium avium complex, was evaluated by the agar dilution method, using 7H10 agar medium . The activity of rifabutin based on MIC50 and MIC90 was higher than that of rifampicin, against all the acid-fast organisms tested . Microbicidal activity of rifabutin against the M . avium complex phagocytosed in mouse peritoneal or alveolar macrophages was greater than that of rifampicin . Both rifabutin and rifampicin had therapeutic effects against murine infections induced by M . avium complex . Rifabutin was somewhat more effective than rifampicin in mice.

FEBS Lett, 1988 Aug 29, 236(2), 462 - 6
Synthetic magainin analogues with improved antimicrobial activity; Chen HC et al.; Based on modifications to enhance the alpha-helical structure of the broad spectrum antibiotic magainin 2, a series of analogues have been synthesized which display an increase up to two orders of magnitude in antimicrobial activity and, in the most favorable case, no appreciable increase in hemolytic activity over magainin 1 at the concentrations tested.

Biochem Pharmacol, 1988 Aug 15, 37(16), 3109 - 17
Nitrofurantoin-mediated oxidative stress cytotoxicity in isolated rat hepatocytes; Rossi L et al.; Freshly isolated rat hepatocytes were used to study the mechanism(s) of toxicity of the antimicrobial drug nitrofurantoin . This 5-nitrofuran derivative stimulated hepatocyte oxygen uptake in the presence of the mitochondrial respiration inhibitors KCN or antimycin A . This could indicate the formation of O2- and H2O2, following intracellular nitrofurantoin reduction . Addition of nitrofurantoin to suspensions of isolated rat hepatocytes produced a dose- and time-dependent decrease of cell viability . H2O2 probably plays a significant role in the cytotoxic effects of nitrofurantoin as the catalase inhibitors azide or aminotriazole markedly enhanced cytotoxicity . The loss of cell viability was preceded by glutathione (GSH) depletion and a concomitant and nearly stoichiometric formation of oxidised glutathione (GSSG) that did not occur in hepatocytes lacking glutathione peroxidase activity isolated from rats fed a low-selenium diet . This indicates that H2O2 and the seleno-enzyme glutathione peroxidase are responsible for GSH oxidation . Furthermore, addition of nitrofurantoin to isolated rat hepatocytes produced a reversible inactivation of hepatocyte glutathione reductase activity and explains the maintenance of high GSSG levels . The compromised hepatocytes were also highly susceptible to H2O2 . The hepatocyte toxicity of nitrofurantoin may, therefore, be attributed to oxidative stress caused by redox-cycling mediated oxygen activation.

J Am Vet Med Assoc, 1988 Aug 15, 193(4), 470 - 3
Changes in the susceptibility of Actinobacillus pleuropneumoniae to antimicrobial agents in Quebec (1981-1986); Vaillancourt JP et al.; An important reduction in the in vitro efficacy of spectinomycin and chloramphenicol was recorded between 1981 and 1986 against the causal agent of porcine pleuropneumonia Actinobacillus . Antimicrobial susceptibility tests were carried out by use of Kirby-Bauer disk diffusion technique on a total of 723 isolates of Actinobacillus pleuropneumoniae . Results did not agree with those of other reports in which a constant susceptibility to any of the antimicrobial agents tested was reported with serotype 2 isolates . The ability to acquire drug resistance may differ from one serotype to another.

BMJ, 1988 Aug 13, 297(6646), 445 - 7
Use of drugs by children; Rylance GW et al.; To obtain information on the use of prescribed and non-prescribed drugs in the general population of children 1590 children were surveyed in 1984-5 by weekly questionnaires filled out by parents . Drugs were taken in 13% of the 26 weeks studied and on 9% of the 182 days . Use in the summer and winter was similar . More than half (56%) of all drugs were taken on Saturdays and Sundays . Boys took drugs on 11% of days and girls on 8% of days . Almost half (45%) of drugs taken were not prescribed . Drugs acting on the respiratory tract and on coughs accounted for 42.2% of the drugs used . Analgesics were taken on 14.0% of days and antimicrobials on 12.5% . Aspirin accounted for 14.9% of all drugs used in any one week and for 31.7% of drugs obtained without prescription . Aspirin, paracetamol, triprolidine-pseudoephedrine (Actifed), ampicillin or amoxycillin, and salbutamol were the drugs most frequently used . The widespread use of drugs obtained without prescription suggests that community pharmacists and parents would benefit from further education on the choice of treatment in relation to symptoms . Doctors should be aware of the extent of treatment with non-prescription drugs and consider playing a greater part in advising on its indications.

APMIS, 1988 Aug, 96(8), 720 - 2
A comparison between Bactec aerobic resin and hypertonic blood culture media; Sjoberg L et al.; The presence of antimicrobial agents in patients' blood is thought to represent an important source of false-negative blood cultures . This has led to the incorporation of agents with inhibitory effects on antimicrobial drugs into culture medium . In the present study, Bactec aerobic resin-containing blood culture medium was compared with Bactec hypertonic blood culture medium . 504 patients receiving cytostatic and/or antibiotic treatment were studied . Sensitivity calculations on detection of bacteremia in these patients gave 0.91 for the resin medium and 0.79 for the hypertonic blood culture system and showed a significant difference (p = 0.016) . In addition, the resin-containing system more rapidly detected positive cultures than the hypertonic system.

J Med Chem, 1988 Aug, 31(8), 1631 - 41
Synthesis and evaluation of tylosin-related macrolides modified at the aldehyde function: a new series of orally effective antibiotics; Kirst HA et al.; Modification of the aldehyde group in tylosin and related macrolide antibiotics dramatically enhanced the oral efficacy of the derivatives against experimental infections caused by susceptible bacteria in laboratory animals . A large number and wide variety of aldehyde-modified macrolide derivatives were prepared, utilizing the Mitsunobu reaction and other chemical transformations . Evaluation of in vitro and in vivo antimicrobial activity indicated that derivatives of demycarosyltylosin (desmycosin) combined the broadest spectrum of antimicrobial activity with the best efficacy and bioavailability after oral administration.

Chest, 1988 Aug, 94(2 Suppl), 115S - 120S
Pharmacokinetics of antimicrobial drugs in cystic fibrosis . Beta-lactam antibiotics; Lietman PS; The pharmacodynamics and pharmacokinetics of beta-lactam antibiotics in patients with cystic fibrosis are discussed . A hypothetical dosing regimen based on these principles is considered . The usual dosing regimens may be suboptimal . New dosage regimens should be studied using prospective, controlled, randomized and blinded clinical trials.

J Neurosurg, 1988 Aug, 69(2), 216 - 20
Results of a randomized trial of vancomycin prophylaxis in craniotomy; Blomstedt GC et al.; A single prophylactic dose of vancomycin was given in 143 supratentorial craniotomies with a bone flap and 26 suboccipital craniotomies . No antimicrobial agents were given to two similar groups of patients: 172 with supratentorial craniotomy and 19 with suboccipital craniotomy . The infection rate in the vancomycin groups was significantly lower (p less than 0.013), and bone-flap infections alone, the most common infection after supratentorial craniotomy, were significantly fewer (p less than 0.042) . Antimicrobial prophylaxis is recommended only for selected high-risk groups . Since a bone flap is devascularized, its resistance to infection is reduced and, once infected, it usually requires surgical removal . Patients undergoing craniotomy with a bone flap therefore form a high-risk group, and antimicrobial prophylaxis is justified.

Emerg Med Clin North Am, 1988 Aug, 6(3), 391 - 402
Prostatitis; Stewart C; Prostatitis is a poorly defined group of syndromes with multiple causes, some of which are not yet determined . Although treatment of acute prostatitis is well defined and almost uniformly successful, chronic prostatitis, either of bacterial or undetermined etiology, remains a perplexing problem in both diagnosis and treatment . Identification of the etiologic agent of chronic "nonbacterial" prostatitis, if one exists, has not yet been accomplished . Undoubtedly, more than one organism may be responsible for these cases . Treatment is ineffective for a high percentage of patients with chronic prostatitis, both from proven bacterial and nonbacterial causes . Few drugs penetrate the prostatic tissues well, and few of those that do have an appropriate antimicrobial spectrum . An excellent, or even adequate, antibiotic for chronic prostatic infections has yet to be developed . Prostatodynia remains as a "wastebasket" syndrome of miscellaneous pains, aches, and pelvic discomforts . With this collection of symptoms, no easy approach to diagnosis or treatment is possible . Only when more detailed diagnosis has been developed can one hope for better therapy of this condition.

J Antimicrob Chemother, 1988 Aug, 22(2), 257 - 60
Rational use of antimicrobial agents and diagnostic microbiology facilities; Sturm AW; During a two month period doctors' motives for prescribing antimicrobial chemotherapy were studied . Of the 1775 patients admitted, 374 (21%) received antimicrobial agents for 384 infective episodes . In 44 (11.5%) no infection could be subsequently proven . Of the remaining 340, drug selection was based on a susceptibility report in 120 (35%), on the advice of a medical microbiologist with the aid of a Gram stain in 66 (19%), and without this assistance in 51 (15%) . In 103 (30%) episodes the clinician selected the agent without advice and laboratory tests . Infection was proven in 237 of 238 episodes in which therapy was started following a known susceptibility result or the advice of the microbiologist . Four (1.7%) of these later required a change of therapy, compared with 22 (21%) of the 103 courses started without such help (P less than 0.0005) . This study has shown that the use of the laboratory and consultation with a medical microbiologist improves the rational prescribing of antimicrobial chemotherapy.

Chemioterapia, 1988 Aug, 7(4), 233 - 6
Clinical and pharmacokinetic study of cefotetan in biliary tract infections: preliminary report; Cristiano P et al.; Twelve hospitalised patients, affected by biliary tract infections, were treated with cefotetan at dosages ranging between 4 and 6 g daily i.v . In only 11 patients was the aetiological agent identified . Eleven patients (91.67%) completely recovered from their infections and the pathogens were eradicated; the treatment failed in only 1 patient (8.33%) . Furthermore, determinations were made of cefotetan concentrations in serum, gallbladder bile, gallbladder wall and gallstones of 14 patients undergoing cholecystectomy: in 7 patients after only 1 injection i.v . of 2 g and in 7 patients after 7 injections i.v . of 2 g at intervals of 12 h . The levels recorded were several times higher than the minimum inhibitory concentrations against bacteria that are most often responsible for biliary infections . Cefotetan is a promising and effective antimicrobial agent in the therapy of biliary tract infections.

J Clin Microbiol, 1988 Aug, 26(8), 1590 - 1
Fatal infection caused by a multiply resistant type 3 pneumococcus; Lawrenson JB et al.; The most virulent pneumococcal serotype (type 3) has not to date been associated with multiple antimicrobial resistance . We report an unusual gastrointestinal presentation of fatal septicemia caused by a multiply resistant type 3 pneumococcus in a setting of increasing prevalence of multiple resistance, including resistance to erythromycin, clindamycin, and tetracycline.

Eur J Clin Microbiol Infect Dis, 1988 Aug, 7(4), 524 - 5
Successful treatment of chronically infected wounds with sugar paste; Tanner AG et al.; A sugar and polyethylene glycol paste is introduced which has marked antimicrobial activity and is available in thick and thin forms . The paste was used to treat 20 patients with chronically infected abdominal and perineal wounds that had failed to respond to conventional forms of treatment . Complete healing was achieved in 19 patients . The paste was especially effective in the treatment of large abscess cavities with small external openings . It was inexpensive, and easy and painless to apply.

J Inorg Biochem, 1988 Aug, 33(4), 285 - 95
Antimicrobial and anticancer activity of tetrahedral, chelated, diphosphine silver(I) complexes: comparison with copper and gold; Berners-Price SJ et al.; Tetrahedral, bischelated Ag(I) diphosphine complexes {Ag(P-P)2}NO3, where P-P is Ph2P(CH2)2PPh2 (dppe), Et2P(CH2)2PPh2 (depe), and cis-Ph2P(CH = CH)PPh2 (dppey), are potently cytotoxic to B16 melanoma cells in vitro (IC50 4 microM) and exhibit good activity against ip P388 leukemia in mice . The complex {Ag(dppe)2}NO3 is active against M5076 reticulum cell sarcoma . The antibacterial and antifungal activities of Ag(I) diphosphine and related Cu(I) and Au(I) complexes were assessed . The complexes {Au(dppey)2}Cl, {Au(dppp)2}Cl and (CuCl)2(dppe)3 show modest activity against three of the 12 bacterial strains tested, but all complexes exhibit antifungal activity against three strains of C . albicans in a "defined" medium, {Ag(depe)2}NO3 and {Au(dppp)2}Cl having comparable activity to fungizone . Antifungal activity of the complexes is reduced in Sabouraud's broth medium, and lost altogether for the Ag(I) complexes . Reactions of some of the Ag(I) complexes with glutathione and blood plasma were studied by 31P NMR.

J Infect Dis, 1988 Aug, 158(2), 392 - 7
Susceptibility of lymphokine-resistant Leishmania to cell contact-mediated macrophage activation; Sypek JP et al.; Lymphokine-mediated activation of macrophages is considered an important host defense mechanism against Leishmania . Recently we identified an additional mechanism of T cell-mediated macrophage activation of defense against Leishmania that is apparently lymphokine-independent and cell contact-dependent but not cytotoxic to host cells . In the present study we determined that strains of Leishmania mexicana that are not susceptible to the antimicrobial effects that result from lymphokine activation are nonetheless susceptible to antileishmanial effects resulting from T cell contact-mediated macrophage activation . Lymphocytes capable of activating macrophages by the cell contact-dependent mechanism appeared transiently in C57BL/6 mice infected with one of these L . mexicana strains . Our findings provide further evidence for fundamental distinctions between lymphokine- and contact-mediated antileishmanial defense . The results suggest that in addition to resistance to lymphokine-mediated effects, suppression of cell contact-mediated defense may account for chronicity in these infections.

Am J Orthod Dentofacial Orthop, 1988 Aug, 94(2), 117 - 22
Effects of cold disinfectants on the mechanical properties and the surface topography of nickel-titanium arch wires; Buckthal JE et al.; The effects of disinfectants on the mechanical properties and surface topographies were determined for 0.017 x 0.025-inch Nitinol and Titanal wires . Three disinfectants approved by the American Dental Association were tested at maximum antimicrobial concentrations: 2% acidic glutaraldehyde, chlorine dioxide, and iodophor . Bending and tensile tests were evaluated to determine whether the stiffness, strength, or range of the wires changed after disinfectant treatment . Laser spectroscopy was used to detect surface changes from corrosion or tarnish after treatment . No detrimental changes were detected in the mechanical properties or surface topography of either wire product after disinfectant treatment . Nitinol was found to be stronger and stiffer than Titanal . On average, Titanal exhibited five times more specular reflectivity than Nitinol.

J Immunol, 1988 Aug 1, 141(3), 890 - 6
Regulation of activated macrophage antimicrobial activities . Identification of lymphokines that cooperate with IFN-gamma for induction of resistance to infection; Belosevic M et al.; Macrophages exposed to lymphokines (LK) before exposure to parasites develop the capacity to resist infection with amastigotes of Leishmania major . Activity of LK for induction of this activated macrophage effector function is abrogated by depleting the LK of IFN-gamma, yet IFN-gamma is incapable of inducing the activity by itself . To identify the factors in LK that serve as second signals for induction of resistance to infection, we exposed macrophages to the following cytokines available as recombinant or highly purified reagents: CSF-1, granulocyte/macrophage colony-stimulating factor (GM-CSF), IL-1, -2, -3, -4, and -5, and IFN-alpha/beta . None of these factors induced resistance to infection by themselves or in combination with each other; in the presence of 50 U/ml IFN-gamma, three cytokines were active: GM-CSF, IL-2, and IL-4 . IFN-gamma was an essential component of the activation cascade but was insufficient by itself to induce the effector reaction . Cytokines that act as cofactors with IFN-gamma worked directly on macrophages and not through another cell in the peritoneal cell (PC) cultures . Activation of PC depleted of Thy-1.2+ cells (85 +/- 5% macrophages) and bone marrow-derived macrophages (100% macrophages) showed that 50% maximal doses of GM-CSF, IL-2, and IL-4 for these macrophage-enriched populations were not different than for untreated PC . Unlike other effector reactions of activated macrophages, bacterial LPS did not synergistically enhance the activity of any of the cytokines, alone or in combination with IFN-gamma . Antibody depletion of the active cytokines from LK, singly or in combination, failed to alter the dose response of the active factors in whole LK for induction of resistance to infection . Thus, multiple factors can provide the second signal for IFN-gamma in the induction of resistance to infection, namely, GM-CSF, IL-2, IL-4, and at least two additional undefined factors in whole LK . Resistance to infection may be the first example of an activated macrophage effector reaction that has an absolute requirement for more than one endogenous signal for its induction.

Chest, 1988 Aug, 94(2 Suppl), 150S - 156S
Antibiotic therapy in cystic fibrosis . Evaluation of efficacy; Levy J; Eradication of the bacterial pathogen, resolution of the local and systemic inflammatory signs, and recovery of organ function are the main criteria by which antibiotic treatment is evaluated . In cystic fibrosis (CF) the pathogen is seldom eradicated and systemic markers of inflammation are not always present . The main criterion for assessing the results of antimicrobial therapy in CF is therefore clinical improvement . The use of clinical scoring systems and double-blind design in therapeutic trials can reduce bias in evaluation of outcome . Assessment of the contribution of antibiotic therapy to the outcome requires greater knowledge of the role of bacterial infection in the pathogenesis of pulmonary exacerbations and could be improved by the development of quantifiable markers in respiratory secretions for inflammation.

Behring Inst Mitt, 1988 Aug, (83), 139 - 44
Potential role of granulocyte-macrophage colony stimulating factor in patients with HIV infection; Mitsuyasu RT et al.; Abnormalities in leukocyte number and function contribute to the high incidence of infection in patients with HIV infection . Leukopenia is a frequent occurrence in patients with AIDS and AIDS-related diseases and is a major dose limiting factor in the treatment of HIV infected individuals with antiviral compounds and chemotherapy . Granulocyte-macrophage colony stimulating factor (GM-CSF) is a hematopoietic hormone that stimulates the growth and differentiation of myeloid progenitor cells in vitro and enhances the function of mature monocytes and neutrophils . Studies on the effects of this agent in patients with AIDS, indicate that GM-CSF causes increased production of neutrophils, monocytes, and eosinophils in a dose dependent fashion . Leukocytes produced in response to GM-CSF function normally as judged by in vitro tests . The effects of GM-CSF on HIV replication and expression in vivo are uncertain . Studies of the use of GM-CSF alone and in combination with antiretroviral, antimicrobial, antineoplastic agents or other hematopoietins and cytokines will help define its ultimate clinical utility in patients with HIV infection.

Antimicrob Agents Chemother, 1988 Aug, 32(8), 1187 - 91
Endogenous active efflux of norfloxacin in susceptible Escherichia coli; Cohen SP et al.; Escherichia coli was shown to have an energy-dependent reduced uptake of the fluoroquinolone antimicrobial agent norfloxacin . Studies of everted inner membrane vesicles suggested that this reduced accumulation involved a carrier-mediated norfloxacin active efflux generated by proton motive force with an apparent Km of 0.2 mM and a Vmax of 3 nmol min-1 mg of protein-1 . Other hydrophilic, but not hydrophobic, quinolones competed with norfloxacin for transport . Porin (OmpF)-deficient E . coli cells were twofold less susceptible to norfloxacin and showed twice as much energy-dependent reduction in drug uptake . However, active efflux assayed in everted vesicles from the OmpF strain was unchanged compared with that in the parental strain . These findings suggest that in the OmpF mutant decreased outer membrane permeability, combined with active efflux across the inner membrane, in some manner results in decreased steady-state uptake of norfloxacin and lowered drug susceptibility.

Antimicrob Agents Chemother, 1988 Aug, 32(8), 1113 - 8
Association between early inhibition of DNA synthesis and the MICs and MBCs of carboxyquinolone antimicrobial agents for wild-type and mutant {gyrA nfxB(ompF) acrA} Escherichia coli K-12; Chow RT et al.; Quinolone antimicrobial agents are known to interact with DNA gyrase, but the mechanism by which bacterial cell death occurs is not fully understood . In order to determine whether there is a correlation between quinolone-induced inhibition of early (i.e., 10 to 15 min) DNA synthesis and potency (MICs and MBCs), we measured the rate of DNA synthesis in log-phase Escherichia coli K-12 by using {3H}thymidine incorporation . Three quinolones (ciprofloxacin, norfloxacin, and difloxacin) were selected based on their decreasing activity against reference strain KL16 . All three quinolones caused an early 50% inhibition of DNA synthesis which was proportional to MICs and MBCs (r greater than 0.99) . Furthermore, 50% inhibition of DNA synthesis and MICs were nearly identical for mutant strains with an altered quinolone target (gyrA) or with decreased {nfxB(ompF)} or increased (acrA) permeability . There were significant differences (P less than 0.001) between individual quinolones in the degree of DNA synthesis inhibition in nalidixic acid-resistant gyrA and nfxB(ompF) mutant strains . The comparison of the three mutants with the wild-type strain permitted an in vivo examination of the effects of alterations of the drug target or entry on the activity determined by DNA synthesis inhibition and MICs.

J Clin Microbiol, 1988 Aug, 26(8), 1492 - 5
Novel application of video image processing to biochemical and antimicrobial susceptibility testing; D'Amato RF et al.; ALADIN (Analytab Products, Plainview, N.Y.) is an automated instrument that uses video imaging (computer-assisted guided video camera) for the determination of biochemical and antimicrobial susceptibility test reactions . This collaborative investigation compared video-generated results obtained with ALADIN with visually determined findings . Both approaches were used to view identical reactions . Overall agreement for biochemical and antimicrobial susceptibility tests was greater than 95% . This study demonstrates that video imaging is an acceptable approach for determining microbial responses to biochemical and antimicrobial agents and may provide, with appropriate computer modifications, more accurate and reproducible results than are possible by visual scrutiny.

Surg Clin North Am, 1988 Aug, 68(4), 823 - 35
Management of associated soft-tissue injury; Rodgers CM et al.; Initially, soft-tissue injuries associated with vascular trauma require management according to the general surgical principles of wound care . Antimicrobial prophylaxis should be instituted . The mechanism and extent of injury must be determined, and debridement and irrigation should be completed in the operating room with the intent to preserve vital structures, decrease bacterial contamination, and render the wound free of devitalized tissue . Prompt coverage of exposed vascular repairs is vital in order to minimize the chance for infection and to protect the repair from desiccation and subsequent trauma . Early primary closure of heavily contaminated wounds can have disastrous results . Therefore, questionable wounds should be managed by delayed primary closure after repeated irrigation and debridements, with the definitive decision as to the timing of wound closure being based on quantitative cultures . The plastic and reconstructive surgeon can aid the vascular surgeon in the primary or secondary closure of such wounds by bringing healthy, vascularized muscle to cover the vascular repair . Vascularized muscle has proved superior in the coverage and healing of contaminated wounds . If conditions permit, this can be most readily accomplished by transfer of local muscle . Musculocutaneous flaps are of special value in cases that require increased durability or where extended coverage is necessary . With either of these flap techniques, the surgeon must be thoroughly familiar with the anatomy, blood supply, and function of the local muscles . Free-tissue transfer is to be utilized when local tissue is severely damaged in a way that precludes the use of adjacent muscle or myocutaneous flaps . Strict adherence to the principles and techniques of microsurgery, thorough evaluation of the zone of injury and recipient blood vessels, and understanding of the principles governing local muscle transfer are essential for a successful outcome.

Am J Obstet Gynecol, 1988 Aug, 159(2), 522 - 6
Vitamin B12 R-binder localization in the human uterus: an immunohistochemical study; Kim YC et al.; The localization of vitamin B12 R-binder in the uterus was studied by use of an immunoperoxidase technique . Positive staining by anti-R-binder antiserum was observed in the columnar epithelium of the endocervix (18/18 cases) and in the surface epithelium of the endometrium (8/21 cases) . Staining was usually seen in the apical portion of the epithelium; cytoplasmic staining in the endocervical columnar epithelium was intense . The secretory products in the endocervical glands showed positive staining . The endometrial glandular epithelium did not stain (0/24 cases) . Metaplastic squamous epithelium of the endocervix showed positive staining (3/18 cases) . The native squamous epithelium as well as the stromal components of the cervix, endometrium, and myometrium were negative for R-binder . This study shows that R-binder is localized in the uterus, especially in the endocervical glands . The R-binder in the endocervix may have antimicrobial activity in the uterus as in other organs, such as the intestines and mammary glands.

Plast Reconstr Surg, 1988 Aug, 82(2), 281 - 4
The antifibrinolytic activity of sulfamylon solution; Aldridge JH et al.; Sulfamylon (mafenide) solution, a potent experimental topical antimicrobial, is used in our burn unit to treat burn wounds both before and after skin grafting . The importance of fibrin to early graft adherence prompted this in vitro study of the effect of Sulfamylon upon fibrin clot . Assessing fibrinolysis by in vitro proteolysis of {125I} fibrin monomers, Sulfamylon, at relevant clinical concentrations, produced dose-related inhibition of streptokinase-mediated fibrinolysis . In addition, Sulfamylon had no intrinsic fibrinolytic activity . This antifibrinolytic property of Sulfamylon solution may, in vivo, protect against early graft loss when used on burn wounds and other potentially contaminated graft sites.

Antimicrob Agents Chemother, 1988 Aug, 32(8), 1149 - 53
Activities of amikacin, roxithromycin, and azithromycin alone or in combination with tumor necrosis factor against Mycobacterium avium complex; Bermudez LE et al.; The effect of amikacin and two new macrolides (roxithromycin and azithromycin) used either alone or in combination with recombinant tumor necrosis factor (TNF) to inhibit or kill Mycobacterium avium complex in human macrophages was examined in vitro . Macrophage monolayers infected with M . avium complex (strain 101, serotype 1) were treated with antibiotics or TNF by using three different protocols: (i) antibiotics or TNF was added to the monolayers immediately after infection and washed out after 24 h, (ii) antibiotics or TNF was replenished daily for 4 dys, or (iii) infected macrophage monolayers were treated with antibiotics plus TNF for 4 consecutive days . The number of viable intracellular bacteria was determined after 2 and 4 days of treatment by lysing cultured macrophages . Treatment for 24 h resulted in an inhibition of growth, as determined by macrophage lysis at day 4, for all three antimicrobial drugs and killing of 22% of intracellular bacteria after treatment with TNF . After treating the monolayers with amikacin, roxithromycin, or azithromycin for 4 consecutive days and replenishing the drug concentration daily, we observed 18 +/- 6, 20 +/- 4, and 22 +/- 1% killing, respectively . TNF (100 U/ml) was added daily to the monolayers, which resulted in 54 +/- 5% killing after 4 days . Combinations of antibiotics with TNF were associated with 62 +/- 3% killing with TNF-azithromycin, 73 +/- 6% killing with TNF-roxithromycin, and 56 +/- 4% killing of intracellular M . avium complex with TNF-amikacin after 4 days . The mycobactericidal effect was enhanced (91 +/- 4% killing by roxithromycinamikacin) . Combinations of antimicrobial agents with immunomodulators like TNF may be useful for treatment of M . avium complex infection.

J Antibiot (Tokyo), 1988 Aug, 41(8), 1093 - 105
Enzymatic and chemical modifications of lipopeptide antibiotic A21978C: the synthesis and evaluation of daptomycin (LY146032); Debono M et al.; The novel lipopeptide antibiotic A21978C complex is active against Gram-positive organisms . This complex consists of a common peptide nucleus with various lipid acyl groups at the N-terminus characteristic of each individual factor . The fatty acid acyl group is removed by incubation of the A21978C complex with Actinoplanes utahensis to give the peptide nucleus . This peptide nucleus has the same amino acid sequence as A21978C . New analogs of A21978C were synthesized by acylation of the N-terminus of a tert-butoxycarbonyl (tert-BOC)-protected nucleus and subsequent deprotection . 1H NMR showed that the newly introduced acyl group was at the desired N-terminus . Three major groups of analogs were synthesized bearing fatty acid acyl, amino-aroyl and extended peptide side chains . Each analog was evaluated for antimicrobial activity and acute toxicity . Of these analogs, the n-decanoyl analog of A21978C (LY146032) gave the best survival in the mouse acute toxicity test at a high dose of 1,000 mg/kg, iv and was chosen for further study . This analog has been named daptomycin.

Am J Med, 1988 Jul 25, 85(1A), 9 - 16
Cefoperazone in the treatment of infections in cancer patients; Klastersky J; Cefoperazone appears to be one of the cephalosporins with the most promise in granulocytopenic patients, regardless of whether it is used in combination or as monotherapy . It has the broad spectrum of antimicrobial activity necessary to inhibit the organisms commonly encountered in patients with cancer, as well as the ability to achieve high serum levels for sustained periods of time . Administration of cefoperazone should provide effective therapy in the overall management of most infections encountered in patients with neoplastic diseases.

Ann Intern Med, 1988 Jul 15, 109(2), 127 - 42
Neutrophils and host defense; Lehrer RI et al.; Neutrophils, the predominant phagocytes of circulating blood, are the first cells to arrive at sites of infection . Although neutropenia has long been recognized to predispose to infection, recently other syndromes marked by frequent infections have been shown to be caused by an underlying neutrophil dysfunction . Efforts to define the molecular pathology of such disorders have helped delineate the molecular basis of normal neutrophil function . Advances have been made in defining the roles of the neutrophil's varied receptors in recognition, movement, and adhesive phenomena . Progress in establishing the pathogenesis of chronic granulomatous disease has provided important insights into the enzymatic machinery that normal neutrophils use to produce antimicrobial oxidants . The identification and precise characterization of antimicrobial components, such as defensins, have outlined the potential roles of "natural antibiotics" in neutrophil-mediated host-defense functions . These areas of neutrophil function will be reviewed and placed in a clinical context to guide physicians in evaluating children and adults with frequent or unusual infections.

Hosp Formul, 1988 Aug, 23(8), 654 - 7
The role of the microbiology laboratory in guiding formulary decisions; Stratton CW; Typically, P & T Committee antibiotic selection criteria have included such factors as cost, pharmacokinetics, side effects profile, spectrum of activity, and relative activity against specific pathogens . The microbiology laboratory can provide the P & T Committee with other useful information to help guide them in making even more appropriate and cost-effective formulary decisions . This information includes specific susceptibility data (including prevalence of pathogens, source of infection {community or nosocomial}, anatomical site of isolates, specific unit or service where isolated, type of culture specimen, total number of pathogens in the hospital), resistance trends data, an evaluation of microbiologic data presented in published studies, further data regarding an antimicrobial's spectrum of activity and activity against specific pathogens, and the relevance and limitations of in vitro data . With this information in hand, P & T Committee should be in a much better position to optimize formulary decision-making.

Can J Hosp Pharm, 1988 Aug, 41(4), 195 - 99, 214
Drug usage review of cefamandole at a teaching hospital; Zaremba CD et al.; A drug usage audit of cefamandole was conducted at a 900-bed teaching hospital . Health records of all in-patients receiving cefamandole during a three-month period (November 1, 1985 to January 31, 1986) were retrospectively reviewed . Treatment of lower respiratory tract infections accounted for 35 (44%) of the 79 treatment courses examined . Surgical antimicrobial prophylaxis for cardiovascular procedures involved 26 (33%) courses of therapy and 15 (19%) courses were associated with biliary tract procedures . The three remaining treatment courses (4%) included therapy for septicemia, orthopedic surgery prophylaxis, and a leg ulcer . Twenty-eight percent of all treatment courses were deemed to be appropriate . Thirty-two percent were considered controversial, and 40 percent inappropriate . The majority of the suboptimal use identified involved prescribing cefamandole for cardiovascular surgery prophylaxis . The role of cefamandole in the acute hospital setting is reviewed with reference to other available first, second and third-generation cephalosporins . General recommendations for its use are outlined.

Clin Pediatr (Phila), 1988 Jul, 27(7), 339 - 43
Necrotizing fasciitis as a complication of chickenpox; Falcone PA et al.; Necrotizing fasciitis is a rapid, potentially fatal soft tissue infection . Chickenpox is a common childhood illness not usually associated with severe complications . We present the case of an 8-year-old girl with necrotizing fasciitis of the upper back arising from superinfection of varicella skin lesions . Necrotizing fasciitis may have devastating sequelae, including septic shock, which mandate vigorous fluid resuscitation, appropriate antimicrobial therapy, and early aggressive surgical debridement.

Postgrad Med, 1988 Jul, 84(1), 163 - 6, 169-70
Update on traveler's diarrhea; Strum WB; Traveler's diarrhea affects a substantial number of travelers to high-risk areas of the world . The key to controlling this troublesome disease is prevention . The most important preventive measures depend on educating patients to consume only safe foods and pure water . Physicians cannot overemphasize the importance of avoiding high-risk foods and of boiling water if a safe water supply is not available . Prophylactic medications are a secondary consideration and should be prescribed with discretion . In most cases, diarrhea is mild and self-limited, requiring only fluid and electrolyte replacement and perhaps an antidiarrheal agent . In moderate to severe cases, the addition of an antimicrobial agent may be of benefit . Until an efficacious polyvalent vaccine is developed, caution and common sense, together with discretionary dietary and hygienic practices, are the best defenses against traveler's diarrhea . The ultimate solution is greatly improved sanitation and personal hygiene, especially in high-risk countries . However, only dreamers will consider waiting for this transformation to occur.

Mutat Res, 1988 Jul, 196(1), 1 - 16
Chloramphenicol: magic bullet or double-edge sword?
Rosenkranz HS.
The genetic and genotoxic potentials of chloramphenicol are reviewed and analyzed . Although this widely used antimicrobial agent appears to cause chromosomal effects in somatic cells, in view of the consistent absence of other genetic effects, these cytogenetic abnormalities are ascribed to non-genotoxic causes . It is pointed out that despite its widespread use in human medicine, chloramphenicol has not been systematically tested for genotoxicity.

J Dent Assoc Thai, 1988 Jul-Aug, 38(4), 153 - 62
{Antibacterial effects of CMCP, Cresophene, and formocresol as root canal medications}; Timpawat S et al.; This clinical and laboratory study was to compare the antimicrobial effects of camphorated monoparachlorophenol, Cresophene and formocresol . Root canals of anterior teeth with 3-5 mm . rarefied area were instrumented and irrigated until they were ready to be filled . The patients returned every 7 days . Intracanal medicaments were changed until negative culture was obtained . The number of visits was recorded . The comparative effectiveness of the three medicaments were analysed . Results showed no statistical differences of the three medicaments (p greater than 0.1) . The antimicrobial activity against bacteria from positive root canal culture of these three antiseptics were assayed by disc diffusion method . The inhibition zone of camphorated mono-parachlorophenol and Cresophene were nearly the same size, but that of formocresol had greater diameter . Using Gram's staining procedure, the majority of bacteria obtained from root canals was identified as gram positive cocci (94.74%).

J Antimicrob Chemother, 1988 Jul, 22 Suppl A, 73 - 86
Antimicrobial susceptibility testing: a critical evaluation; Isenberg HD; Antibiotic susceptibility test results must be interpreted cautiously . There are important differences between the laboratory and natural environments . There are also important differences between disc and dilution tests, and between laboratories . Laboratory tests can demonstrate antagonism and synergy . Because beta-lactamases can be induced, beta-lactam susceptibility may have to be monitored during therapy . Increases in the incidence of drug resistance are particularly important in nosocomial infections.

Antimicrob Agents Chemother, 1988 Jul, 32(7), 1078 - 9
In vitro susceptibilities of Nocardia species to newer antimicrobial agents; Berkey P et al.; The in vitro activities of various quinolones, two newer cephalosporins, and imipenem against 23 strains of Nocardia asteroides, 4 strains of Nocardia brasiliensis, and 4 strains of Nocardia caviae were determined by an agar dilution method . PD-117558, a newer carboxyquinolone, and imipenem were the most active agents tested, inhibiting 90% of N . asteroides isolates at an MIC of 2 micrograms/ml . Of the 23 strains of N . asteroides, 15 were susceptible to cefpirome and 10 were susceptible to ciprofloxacin . The N . brasiliensis and N . caviae strains were very susceptible to PD-117558 (MIC, less than or equal to 1 microgram/ml), moderately susceptible to ciprofloxacin, and resistant to most of the other tested drugs.

J Antimicrob Chemother, 1988 Jul, 22(1), 51 - 60
A mouse model for simultaneous pharmacokinetic and efficacy studies of antibiotics at sites of infection; Renneberg J et al.; Tissue penetration may be an important pharmacokinetic determinant to achieve the chemotherapeutic efficacy of antimicrobial agents . We describe a mouse model for the simultaneous study of antibiotic kinetics and efficacy at the site of infection . With the doses tested there was no difference in drug penetration into healthy tissue and tissue at the site of acute bacterial infection . Ampicillin and netilmicin levels over the minimal inhibitory concentration (MIC) were needed to produce significant bacterial killing . During the 6 h observation period susceptible Gram-positive bacteria were eradicated whereas Gram-negative bacteria were reduced in number but not eradicated, even though the antibiotic concentrations exceeded minimal bactericidal concentration (MBC) three times.

Can J Vet Res, 1988 Jul, 52(3), 315 - 8
Minimal inhibitory concentrations of antimicrobial agents against Actinobacillus pleuropneumoniae; Nadeau M et al.; Forty-five isolates of Actinobacillus pleuropneumoniae were tested for susceptibility to 12 antimicrobial agents using a microdilution method for the minimal inhibitory concentration determinations . These results confirmed the high prevalence of A . pleuropneumoniae strains resistant to antibiotics as reported earlier using the disc diffusion method (Kirby-Bauer method) . While 36% of the isolates were resistant to the penicillins, 47% were resistant to chloramphenicol and 68% were resistant to tetracycline . Minimal inhibitory concentrations for the resistant isolates were approximately 32 times higher than those for the susceptible isolates to the above antibacterial agents . The isolates were in general weakly susceptible or resistant to spectinomycin, lincomycin, tiamulin and spiramycin whereas most of them were susceptible to gentamicin, trimethoprim and erythromycin . The susceptibility pattern was similar throughout the 1980 to 1984 period . The 14 serotype 5 isolates were more resistant to tetracycline but less resistant to chloramphenicol and the penicillins than the 28 serotype 1 isolates.

J Am Dent Assoc, 1988 Jul, 117(1), 179 - 82
Cleaning and disinfectant properties of dental surface disinfectants; Molinari JA et al.; The appropriate use of disinfectants for operatory surfaces constitutes a major component of a routine infection control protocol . Both the cleaning and the disinfection abilities of the various available products are important to consider when selecting a surface disinfectant . This study shows the importance of initial surface cleaning as a mandatory first step in surface asepsis . All manufacturers emphasize this in their written directions by stating that the products should be used on precleaned surfaces . Based on the inability to remove dried organic material and a lack of effective antimicrobial activity in the presence of accumulated bioburden, preparations containing high concentrations of alcohols (greater than or equal to 70%) should not be used as the sole agent for routine precleaning and disinfection . Properly diluted iodophor, sodium hypochlorite, and complex phenol preparations are superior in comparison with other disinfectants in accomplishing the initial precleaning of surfaces.

J Burn Care Rehabil, 1988 Jul-Aug, 9(4), 389 - 90
The burned hemophiliac; Smith AA et al.; Reports of the care of burned hemophiliac patients requiring cutaneous autografting are rare . A 28-year-old white male with classic hemophilia A sustained a 30.5% total body surface area burn . The patient received standard topical antimicrobial therapy and the majority of his burn wound healed . While undergoing therapy, multiple tooth extractions were recommended . On postburn day 25 the patient underwent multiple tooth extractions plus excision and grafting of his unhealed burn after preoperative infusion of cryoprecipitate . Despite a maximum factor VIII concentration of only 23%, no remarkable bleeding occurred from the excision sites, the skin graft donor site, or the tooth extraction wounds . Preoperative infusion of cryoprecipitate does not appear to be required for split-thickness skin graft harvest or excision of burns within the dermis.

Zentralbl Bakteriol Mikrobiol Hyg {B}, 1988 Jul, 186(4), 360 - 7
Suitability of a propanolic PVP-iodophor preparation as preoperative skin disinfectant: germicidal activity and chemical stability; Grunig HM et al.; The preparation Solutio Betadini propanolica 3% w/w, used as a pre-operative skin disinfectant was examined for its germicidal activity and its chemical stability . The additive activity of iodine and propanol resulted in a wide range of antimicrobial activity against bacteria, including bacterial spores, and fungi, with a rapid onset and sustained duration of action . The solution is easily manufactured and analyzed, its stability is guaranteed for 6 months . Because of its staining property, there is no need of coloured additives to mark the disinfected area . In addition, no skin irritations by the disinfectant were observed so far . Thus, the preparation fulfills the essential requirements for preoperative skin disinfectants and is suitable for the preparation and the compounding in hospital pharmacies.

J Antimicrob Chemother, 1988 Jul, 22 Suppl A, 37 - 44
Induction of beta-lactamases; Eliopoulos GM; Inducible beta-lactamases can significantly affect the activities of both beta-lactamase-stable and beta-lactamase-sensitive antibiotics . beta-Lactam antibiotics vary in their ability to induce beta-lactamases . Strong inducers can antagonize the antimicrobial activity of other beta-lactams.

J Ethnopharmacol, 1988 Jul-Aug, 23(2-3), 127 - 49
Screening methods for natural products with antimicrobial activity: a review of the literature; Rios JL et al.; Diffusion and dilution methods have been employed to study the antimicrobial activity of medicinal plants . A number of modifications have been made in the technique in order to obtain better results . Since some factors (culture medium composition, microorganisms tested, extractive method, pH, solubility of the sample in the culture medium, etc.) can change results, it is difficult using these methods to standardize a procedure for the study of antimicrobial plants . Bioautography is another method for studying antimicrobial activity . With it, previously chromatographed principles are diffused to the agar . The results can also change according to the method employed . All the various techniques are reviewed here and, in order to unify the different criteria and parameters, standard methods to study the antimicrobial activity of medicinal plants are proposed.

Rev Infect Dis, 1988 Jul-Aug, 10 Suppl 2, S450 - 6
Human neutrophil antimicrobial activity; Thomas EL et al.; Polymorphonuclear neutrophilic leukocytes (PMNs) take up opsonized microorganisms into phagosomes that fuse with secretory granules in the PMN cytoplasm to form phagolysosomes . Killing and digestion of microorganisms take place within phagolysosomes . Antimicrobial activities in phagolysosomes are divided into two classes . Oxygen (O2)-dependent mechanisms are expressed when PMNs undergo the "respiratory burst." An NADPH oxidase in the phagolysosome membrane is activated and reduces O2 to superoxide (O2-) . O2 reduction is the first step in a series of reactions that produce toxic oxidants . For example, .O2- dismutases to hydrogen peroxide (H2O2), and the azurophil granule enzyme myeloperoxidase catalyzes the oxidation of Cl- by H2O2 to yield hypochlorous acid (HOCl) . The reaction of HOCl with ammonia and amines modulates the toxicity of this oxidant . O2-independent antimicrobial mechanisms include the activities of lysosomal proteases, other hydrolytic enzymes, and proteins and peptides that bind to microorganisms and disrupt essential processes or structural components . For example, the bactericidal/permeability-increasing protein, cathepsin G, and the defensins are released into phagolysosomes from the azurophil granules . Proposed mechanisms of action of neutrophil antimicrobial agents, their range of microbial targets, and their possible interactions within phagolysosomes are discussed.

Anticancer Res, 1988 Jul-Aug, 8(4), 581 - 7
Induction of antimicrobial activity by antitumor substances from pine cone extract of Pinus parviflora Sieb . et Zucc; Harada H et al.; Pretreatment with two distinct antitumor substances extracted from pine cone of Pinus parviflora Sieb . et Zucc . protected mice from the lethal effects of E . coli infection . Intraperitoneal administration of these fractions transiently induced differentiation-inducing factor (DIF) with a peak at 1-2hr . The rapid decay of DIF activity from the peritoneal cavity was followed by polymorphonuclear cell (PMN) accumulation and enhancement of superoxide generation (assayed with luminol-dependent chemiluminescence (LDCL} by peritoneal exudate cells . The superoxide generation by adherent cells was similarly enhanced by pretreatment, but was only 10-20% of that of the peritoneal exudate cells . Fractions that showed comparable antitumor/antimicrobial activity were also obtained from seed shells and cones of other pine trees of Japanese and foreign origin . On the other hand, a neutral polysaccharide fraction from Pinus parviflora Sieb . et Zucc . that lacked any of these activities did not induce PMN accumulation, DIF activity or LDCL generation . The results suggest a significant role in PMN activation for the expression of antimicrobial activity induced by pine cone extracts.

Am J Hosp Pharm, 1988 Jul, 45(7), 1540 - 4
Compliance with a restricted antimicrobial agent policy in a university hospital; Volger BW et al.; Compliance with a policy for use of antimicrobial agents that requires both oral approval from the infectious diseases service and completion of a restricted antimicrobial agent use form was evaluated in a 950-bed teaching hospital . The charts of patients for whom a restricted antimicrobial agent was ordered during four one-week periods between January 1987 and April 1987 were audited to determine whether completed use forms had accompanied orders for restricted antimicrobial agents . The validity of the information on completed forms was determined by comparing the information on the form with notes in patients' charts and through discussions with infectious diseases physicians . Two infectious diseases physician reviewers evaluated the appropriateness of prescribing of piperacillin and ceftazidime by analyzing data collected by pharmacists . Forms were submitted with 132 of 154 orders written for restricted agents; incomplete forms were received and accepted by pharmacists for 39 courses of therapy . The infectious disease service had not been contacted to approve use of a restricted agent in 25 cases . Eight of the 48 courses of piperacillin or ceftazidime therapy were deemed inappropriate despite initial infectious diseases approval . Compliance with a formal antimicrobial agent restriction policy at this institution has been good, but periodic re-education and follow-up monitoring appear to be necessary to ensure optimal use of restricted agents.

Microbiologica, 1988 Jul, 11(3), 225 - 30
Enhanced antimicrobial activity of lactoferrin by binding to the bacterial surface; Dalmastri C et al.; In order to elucidate the mechanisms involved in the antibacterial activity of lactoferrin, quantitative determinations of siderophore production and lactoferrin adsorption on various bacterial species were performed . The binding of lactoferrin took place both on Gram-positive and Gram-negative species and occurred with bacterial cells grown in stress or in excess of iron . The different degrees of sensitivity to lactoferrin observed could not be directly related to the type and amount of siderophores produced . However, it was possible to find a correlation between the capacity of some strains to bind lactoferrin and their sensitivity to this protein . These data suggest that the binding of lactoferrin on the cell surface can result in an antibacterial activity additional to iron witholding.

Antimicrob Agents Chemother, 1988 Jul, 32(7), 1086 - 9
In vitro cleavable-complex assay to monitor antimicrobial potency of quinolones; Walton L et al.; Seven quinolones were evaluated to determine whether their ability to generate the DNA gyrase-mediated cleavable complex correlated with their ability to inhibit the catalytic activity of purified DNA gyrase and inhibit the growth of Escherichia coli . The rank order of potency of these drugs in the cleavable-complex assay was essentially the same as in the DNA supercoiling-inhibition assay . It required 2- to 10-fold-lower drug concentrations to generate the cleavable complex than to inhibit E . coli DNA gyrase . With the newer fluoroquinolones, a 25- to 100-fold-greater concentration was required for DNA gyrase inhibition than for cell growth inhibition, suggesting a more subtle interaction between these inhibitors and DNA gyrase than mere enzyme inhibition.

FEBS Lett, 1988 Jun 20, 233(2), 282 - 8
Relationship of promagainin to three other prohormones from the skin of Xenopus laevis: a different perspective; Hunt LT et al.; We observed a striking sequence similarity between precursors for promagainin and procaerulein type I (excluding the caerulein peptide region) . Additional comparisons of the promagainin precursor with those of other procaeruleins, proxenopsin, and peptide-Gly-Leu-amide revealed that all possess one or more copies of a structurally similar spacer module, from which an amphiphilic spacer peptide is cleaved . Promagainin yields the magainins, spacer peptides with antimicrobial activity; we suggest other spacer peptides may have similar activity . We propose that the genes for the four kinds of hormones were derived from a common ancestral gene through gene and exon duplications and that the procaerulein and proxenopsin genes are mosaic genes in which the original 3'-ends were replaced by exon shuffling.

J Chromatogr, 1988 Jun 17, 442, 289 - 99
Formation of polychlorinated dibenzo-p-dioxins upon combustion of commercial textile products containing 2,4,4'-trichloro-2'-hydroxydiphenyl ether (Irgasan DP300); Kanetoshi A et al.; Commercial textile products containing 2,4,4'-trichloro-2'-hydroxydiphenyl ether (Irgasan DP300) as an antimicrobial agent gave dichlorodibenzo-p-dioxin(s) (di-CDD) upon combustion . The extent of conversion of Irgasan DP300 into di-CDD(s) reached 19-43% at 600 degrees C . Upon bleaching the textile products with sodium hypochlorite, Irgasan DP300 was chlorinated to 2',3,4,4'-tetrachloro-2-hydroxydiphenyl ether, 2',4,4',5-tetrachloro-2-hydroxydiphenyl ether and 2',3,4,4',5-pentachloro-2-hydroxydiphenyl ether . These chlorinated derivatives were converted into trichlorodibenzo-p-dioxins and tetrachlorodibenzo-p-dioxin upon combustion, which are more toxic than di-CDD(s) . These results suggest that the bleaching and incineration of textile products containing Irgasan DP300 result in environmental pollution by PCDDs.

Thromb Haemost, 1988 Jun 16, 59(3), 440 - 4
Mafenide (Sulfamylon) inhibits plasmin fibrinolytic activity; Weisdorf DJ et al.; Inflammatory fibrinolysis by plasmin or phagocyte proteases is a major cause of skin graft failure on burn wounds where the primary adherent attachment of the skin grafts is due to the glue-like action of fibrin . We investigated the potential of mafenide acetate solution, an experimental topical antimicrobial used in treating grafted burn wounds, to modify plasmin fibrinolytic activity in vitro and, thus, its potential to alter or modify the integrity of the fibrin glue critical for skin graft viability . Immobilized 125I-fibrin monolayers were used to assay fibrinolytic activity from plasmin or from plasma activated by streptokinase or urokinase and modified by the presence of mafenide or epsilon-aminocaproic acid (EACA) . While streptokinase-activated plasma lysed 52.7 +/- 3.9% of the 125I-fibrin, this plasmin activity was more than 80% inhibitable by EACA . Mafenide acetate had no intrinsic fibrinolytic activity (1.5 +/- 0.3%) nor activated plasma fibrinolytic potential (2.4 +/- 0.5%), but produced significant and dose-related reduction in fibrinolytic activity (p less than 0.001) . Other sulfonamide analogues lacking a para-methylamino reactive group had 10-100 fold less antifibrinolytic potency while lysine, like mafenide, able to compete for plasmin binding sites, could potently block fibrinolysis . Mafenide did not qualitatively alter activation of plasminogen or affect generation of complexes with alpha 2 antiplasmin complexes . Adding mafenide only minutes following streptokinase-activated plasma or plasmin with the fibrin substrate reduced antifibrinolytic activity, supporting the conclusion that mafenide, like EACA, can modulate the interaction between fibrin and the plasmin reactive sites and thus prevent close plasmin/fibrin apposition.(ABSTRACT TRUNCATED AT 250 WORDS)

Am J Hosp Pharm, 1988 Jun, 45(6), 1338 - 42
Multidisciplinary program for promoting single prophylactic doses of cefazolin in obstetrical and gynecological surgical procedures; Smith KS et al.; A multidisciplinary cost-containment program for promoting the use of single prophylactic doses of cefazolin for obstetrical and gynecological surgical procedures is described . Following a one-month review of patient charts to identify the antimicrobial regimens used most frequently for prophylaxis in obstetrical and gynecological surgical procedures, the department of pharmacy services, with the cooperation of the pharmacy and therapeutics (P&T) committee and the departments of obstetrics and gynecology and infectious diseases, implemented an educational program to promote the use of single doses of cefazolin for surgical prophylaxis . The program included inservice education and distribution of letters of support and a therapeutics newsletter . Drug stocking patterns in the operating and delivery rooms were changed to make cefazolin more accessible, and the P&T committee formally restricted the use of prophylactic antimicrobial agents in obstetrical and gynecological surgical procedures to single doses of cefazolin unless a consulting infectious-disease physician recommended otherwise . Compliance with the program increased as each step was implemented; data collected 16 months after the program was initiated demonstrated a compliance rate of 78.8% . Based on comparison of data collected before initiation and six months after initiation of the program, an actual cost savings of +7,125 was realized, which extrapolates to +14,250 annually . No apparent adverse effects on patient care were noted . The multidisciplinary approach to promoting the use of single doses of cefazolin was effective.

J Antibiot (Tokyo), 1988 Jun, 41(6), 741 - 50
Actinoplanones C, D, E, F and G, new cytotoxic polycyclic xanthones from Actinoplanes sp; Kobayashi K et al.; Our previous finding of strong cytotoxic polycyclic xanthones, actinoplanones A (1) and B (2), in the culture broth of Actinoplanes sp . R-304 stimulated us to isolate further five new cytotoxic polycyclic xanthones which were named actinoplanones C (3), D (4), E (5), F (6) and G (7) from the broth . Actinoplanones C (3) and G (7) showed very strong cytotoxicity against HeLa cells at less than 0.00004 microgram/ml dosage (IC50) . The structures of 3-7 were varieties of 1 for the N-2 and C-4 substituents . All or several actinoplanones showed strong antimicrobial activities against bacteria and the rice blast fungus . Actinoplanone A (1) was tested for cytotoxicity against various tumor cells and for inhibitory effect on HeLa cell macromolecular synthesis, and 1 exhibited strong cytotoxicity against the cells and inhibitory action on DNA synthesis.

J Reprod Med, 1988 Jun, 33(6 Suppl), 588 - 90
Prophylactic antibiotics for cesarean section and surgical procedures; Gilstrap LC 3rd; Although prophylactic antibiotics are used frequently on women undergoing pelvic surgery, including cesarean section, they should be reserved for patients who have a significant risk of infection . Among such patients are those who have undergone vaginal hysterectomy or cesarean section after having been in labor with ruptured membranes . Prophylaxis should be limited to one to three doses of antibiotic, with the newer broad-spectrum antibiotics and combination antimicrobial agents reserved for more serious, established infections.

Pediatr Clin North Am, 1988 Jun, 35(3), 465 - 83
Herpes simplex virus encephalitis in children; Kohl S; Herpes simplex encephalitis (HSE) is an uncommon disease, yet 25 to 30 per cent of cases involve children . The initial clinical findings are nonspecific (fever, altered mental status), but most cases evolve to demonstrate focal neurologic signs and symptoms . The CSF is abnormal in over 90 per cent of cases . The EEG, CT, and MRI will further help in detecting focal encephalitis . The clinician caring for a child with focal encephalitis should institute broad-spectrum antimicrobial therapy plus acyclovir, pending definitive diagnosis by ancillary tests or brain biopsy, which is positive for HSE 33 to 55 per cent of the time and is diagnostic for other treatable conditions 10 to 20 per cent of the time . Acyclovir is the drug of choice for HSE and substantially reduces mortality and morbidity . The management of HSE in a child requires an experienced team of specialists and laboratory support in a tertiary intensive care setting.

Infect Immun, 1988 Jun, 56(6), 1615 - 7
Endotoxin-induced shedding of viable uroepithelial cells is an antimicrobial defense mechanism; Aronson M et al.; ICR mice were infected intravesically with a virulent (7343) or a nonvirulent (U+) Escherichia coli strain . The U+ strain induced considerably more shedding of uroepithelial cells than did the 7343 strain . The stimulus for this shedding was shown to be associated with lipopolysaccharide and was abrogated by pretreatment with aprotinin . Desquamation commenced within 1 h postinjection, and the cells that were shed proved to be viable . Comparison of C3H/HeJ and C3H mice revealed that only the latter responded to shedding inducers . However, C3H/HeJ mice succumbed to a systemic infection on injection of 10(6) U+ cells intravesically, whereas other mouse strains required a 100-fold dose of bacteria for this effect . Since the first stage of a bacterial infection entails adherence of the microbes to epithelial cells, inducible shedding is an antimicrobial defense mechanism.

Hinyokika Kiyo, 1988 Jun, 34(6), 1091 - 5
{Combined treatment of chronic prostatitis with sulfamethoxazole-trimethoprim and hachimi-ji-oh-gan}; Kaneko S et al.; Treatment of chronic prostatitis is difficult and many antimicrobial drugs have been tried . Although these drugs showed good permeability into prostatic fluid in experimental studies, they have limited value in clinical use and development of more effective drugs has been anticipated . A study was performed on the effect of Hachimi-ji-ji-oh-gan, a traditional Chinese medicine, for the treatment of chronic prostatitis . Symptoms were improved in 53% of the patients treated with sulfamethoxazole-trimethoprim alone for two weeks and in 84% of those treated with Hachimi-ji-oh-gan in addition to sulfamethoxazole-trimethoprim for two weeks . Since Hachimi-ji-oh-gan has no antimicrobial effect, the drug may change the characteristics of the prostatic tissue or prostatic fluid providing a favorable condition for antimicrobial agents to penetrate into the prostatic fluid . Further examination is necessary to disclose the machanism of Hachimi-ji-oh-gan on the effect of prostatitis.

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