Scand J Infect Dis, 1991, 23(3), 341 - 6 Antimicrobial therapy of septicemic patients in intensive care units before and after blood culture reporting; Rintala E et al.; 68 cases of positive blood cultures from 54 intensive care unit (ICU) patients were analyzed retrospectively . The empiric antimicrobial therapy was correct in 65% of the cases as judged by the species and sensitivity of the blood culture isolate . After initial Gram-staining results were known, coverage increased to 77% . After the final blood culture results the coverage was still only 81% . The bacteremia-related mortality was 13% . Although there was no significant difference between the occurrence of bacteremia-related and non-bacteremia-related deaths either in patients with correct or non-optimal empiric treatment, this study emphasizes the need for better utilization of culture reporting . A considerable part of the final blood culture results went unnoticed by the ICU physicians which stresses the importance of good communication between the laboratory and wards. Scand J Infect Dis, 1991, 23(3), 293 - 8 Short course of aerosol pentamidine as treatment of Pneumocystis carinii pneumonia in AIDS; Flamholc L et al.; Since July 1987, 20 HIV-positive patients with Pneumocystis carinii pneumonia (PCP) admitted to the Department of Infectious Diseases, Malmo General Hospital, Sweden have been treated with 10 consecutive days of aerosol pentamidine as sole antimicrobial therapy in a prospective open non-controlled trial . 16 patients (80%) responded to 10 days of 400 mg aerosol pentamidine daily . One patient responded after a prolonged treatment, one patient received simultaneous trimethoprim-sulfamethoxazole due to lack of improvement during aerosol therapy . Two patients died 26 and 41 days after initiation of treatment . No systemic side effects occurred . In conclusion, we found that 10 days of aerosol pentamidine may be a safe and effective treatment of PCP . Controlled studies are needed. J Microencapsul, 1991 Jan-Mar, 8(1), 29 - 36 Ampicillin-loaded liposomes and nanoparticles: comparison of drug loading, drug release and in vitro antimicrobial activity; Fattal E et al.; In this paper, we report the physico-chemical properties of negatively charged liposomes and of polyisohexylcyanoacrylate nanoparticles loaded with ampicillin . Although the carriers were of the same size (200 nm), drug-loading capacity was 20 times higher for nanoparticles than for liposomes . After freeze-drying or storage at +4 degrees C, no drug escaped from polymeric nanoparticles . On the other hand, in the same conditions, ampicillin leaked rapidly from liposomes . Drug release in foetal calf serum was gradual (of zero order) with nanoparticles, whereas it was rapid with liposomes . Finally, the antimicrobial activity of ampicillin-entrapped liposomes or nanoparticles was studied in vitro. Chemotherapy, 1991, 37 Suppl 2, 37 - 43 Intramuscular imipenem as adjuvant therapy for acute cholecystitis and perforated or gangrenous appendicitis; Yellin AE et al.; An open-label prospective study was performed employing intramuscularly administered imipenem as an adjunct to surgery in 20 patients with acute cholecystitis and 24 patients with perforated or gangrenous appendicitis . Three (12.5%) septic failures occurred in appendicitis patients and 2 (10%) failures in cholecystitis patients . There were no deaths . Adverse effects were minor, and there was no toxicity . Although failures were not associated with in vitro resistance, Pseudomonas spp . were recovered from 2 of 3 appendicitis failures . Intramuscular imipenem appeared to be an effective single-drug antimicrobial when used as an adjunct to surgery in patients with acute cholecystitis or perforated appendicitis . It should be a more cost-effective alternative to the current multiple-drug therapy frequently employed in patients with intra-abdominal sepsis. Schweiz Arch Tierheilkd, 1991, 133(4), 163 - 70 {Feed additives in whole milk fattening . Effect on production and health of fattening calves}; Wyss U et al.; In two fattening trials, each time 64 male calves of Simmental x Red Holstein cross breeds were used to investigate the influence of different commercial feed additives containing at the same time antimicrobial agents, minerals and vitamins on growth performance, feed intake, feed conversion and health condition . Calves whose milk diets were supplemented had, depending on products used, higher growth rates (9 to 28%) and better feed conversion rates (2 to 12%) compared to control calves which were fed only whole milk . This improved performance is primarily due to higher feed intakes . It is questionable how much the minerals and vitamins in addition to antimicrobial agents contributed to the improvement . The additional mineral supply caused after 8 weeks a statistically significant higher haemoglobin content, serum magnesium and glutathione peroxidase activity in erythrocytes compared to the exclusive whole milk feeding . Calves which were fed no additives refused feed intake more often as a result of disease incidence and required veterinary treatment more frequently. Clin Prev Dent, 1991 Jan, 13(1), 13 - 7 Staining and antimicrobial properties in vitro of some chlorhexidine formulations; Addy M et al.; Dietary staining studies have proved useful determinants of chlorhixidine activity in mouthrinse products, and results correlate with plaque inhibitory effects . This investigation compared the staining and antimicrobial action in vitro of two known and similarly effective, commercially available chlorhexidine mouthrinses with a reformulated 0.1% chlordexidine preparation . After adjustment for original concentration the 0.2%, 0.12% and reformulated 0.1% products had essentially similar, minimum inhibitory-dilution values against standard test organisms . The 0.1% preparation was more effective against Capnocytophaga ochracea, suggesting additional antimicrobial activity derived from an ingredient other than chlorhexidine . The staining in vitro of tooth and acrylic specimens was equivalent with the 0.2% and 0.12% products . By comparison with equivalent concentrations of the diluted 0.2% preparation, the 0.1% formulation produced less staining, particularly when diluted . The data suggest that the 0.1% formulation, when used in diluted form as recommended by the manufacturer, may have slightly reduced plaque-inhibitory effects by comparison to the 0.2% or 0.12% products . However, the results raise the question whether chlorhexidine solutions could be formulated to reduce side effects, in particular, tooth staining at the expense of some loss of antiplaque activity. Antimicrob Agents Chemother, 1991 Jan, 35(1), 164 - 9 Properties of plasmids responsible for production of extended-spectrum beta-lactamases; Jacoby GA et al.; The extended-spectrum beta-lactamases are believed to arise by mutations which alter the configuration around the active site of TEM- and SHV-type enzymes so as to increase their efficiency with otherwise nonhydrolyzable cephalosporins and monobactams . This hypothesis predicts that the genes for these new enzymes should be found on the same wide variety of plasmids that encode TEM-1, TEM-2, and SHV-1 beta-lactamases and that at least some of them should be mediated by transposons . Fifteen plasmids, each encoding an extended-spectrum beta-lactamase, were examined . Unlike the average TEM plasmid, all were large, ranging in size from 80 to 300 kb . All determined resistance to multiple antimicrobial agents, ranging from 5 to 11, and some conferred resistance to heavy metals and UV radiation as well . The plasmids belonged to a limited number of incompatibility (Inc) groups, including IncC, IncFI, IncHI2, and IncM . Because most of the mutations giving rise to extended-spectrum activity are G.C----A.T transitions and some of the mutant genes have as many as four base substitutions, a plasmid-determined mutator gene was searched for, but no such property was found . Several techniques were used to detect transposition of the extended-spectrum beta-lactamase genes, but a mobile genetic element could not be demonstrated even though eight of the plasmids hybridized with a DNA probe derived from the tnpR gene of Tn3 . The genesis of extended-spectrum beta-lactamases may not be as simple as has been supposed. J Periodontal Res, 1991 Jan, 26(1), 52 - 8 Suppression of human neutrophil functions by tetracyclines; Gabler WL et al.; Tetracycline inhibition of neutrophil-associated collagenolysis has been the focus of a number of investigations . Evidence has suggested that this inhibition results from the ability of this family of antimicrobial drugs to bind divalent cations such as Ca2+ and Zn2+, two cations that are required for full expression of activity of metalloproteinases such as collagenase and gelatinase . Data presented in this study demonstrate that tetracyclines can also inhibit neutrophil-mediated RBC lysis, superoxide anion synthesis, degranulation and migration . To some extent, tetracycline inhibition of neutrophil functions is mimicked by the Ca2+ binding agents, EDTA and TMB-8 . However, Ca2+ enrichment restored full function to EDTA- and TMB-8-treated cells but not to tetracycline-treated neutrophils . This suggests that Ca2+ binding plays a role but is not the critical effect leading to tetracycline suppression of neutrophil functions . It has been suggested that tetracyclines can suppress leukocyte-associated tissue damage . Host tissues are protected from neutrophil-mediated damage by two mechanisms: 1 . Neutrophil granule-associated enzymes are secreted in an inactive state; and, 2 . tissues are protected from these enzymes by a potent inhibitor shield . Neutrophils can bypass these protective elements by activating enzymes and by destroying the shield through the synthesis of oxygen radicals . Therefore, tetracyclines may suppress neutrophil-mediated tissue damage by inhibiting their migration and degranulation and, potentially more importantly, by suppressing synthesis of oxygen radicals.(ABSTRACT TRUNCATED AT 250 WORDS) J Med Chem, 1991 Jan, 34(1), 168 - 74 Synthesis, antibacterial activities, and pharmacological properties of enantiomers of temafloxacin hydrochloride; Chu DT et al.; Temafloxacin hydrochloride {(+/-)-7-(3-methylpiperazin-1-yl)-6-fluoro-1-(2,4-difluorophenyl)- 1,4-dihydro- 4-oxoquinoline-3-carboxylic acid hydrochloride} is a potent member of the 4-pyridone-3-carboxylic acid class of antibacterial agents and is currently under clinical development as a broad-spectrum antimicrobial agent . It is a racemate having a chiral center at the C3 of the 7-piperazin-1-yl group . The two enantiomers were synthesized and tested for their antibacterial activities . Although no difference in in vitro antibacterial activities was observed, a minor difference in in vivo antibacterial activities was observed . However, they both exhibited similar pharmacological profiles. Mem Inst Oswaldo Cruz, 1991, 86 Suppl 2, 227 - 30 Sesquiterpene lactones from Vernonia; Lopes JL; Some informations about the sesquiterpene lactones isolated from Brazilian species of Vernonia are described, as well the results of tests developed with such compounds with respect to their anti-feedant, molluscicide, antimicrobial and analgesic properties. Mem Inst Oswaldo Cruz, 1991, 86 Suppl 2, 189 - 91 Chemical and pharmacological investigation of Solanum species of Brazil--a search for solasodine and other potentially useful therapeutic agents; Barbosa-Filho JM et al.; A systematic search for solasodine, an important starting material for the partial synthesis of steroidal hormones as well as other potentially bioactive constituents of various Solanum species of Brazil has been undertaken . Thus, the fruits of S . paludosum, S . asperum, S . sessiliflorum and Solanum sp . were found to contain significant amounts of solasodine . The root bark of S . paludosum which showed curare like activity yielded tomatidenol and another yet unidentified alkaloid responsible for the biological activity . The fruits of S . asperum yielded a new spirosolane alkaloid, solaparnaine . The stem bark of S . pseudo-quina showed convulsive and excitatory activity from which (25S)-isosolafloridine was identified as the active principle . In addition, the latter alkaloid was also found to show antimicrobial activity. Ann Pharm Fr, 1991, 49(5), 278 - 85 {Additional contribution to the study of the antimicrobial activity and identification of lichenic substances in some lichens from southern Spain}; Rowe JG et al.; Antimicrobial activity in some lichens from south Spain has been studied . Some lichenical substances are also identified . A very hight activity has been observed in lichens with usnic acid. Perit Dial Int, 1991, 11(3), 252 - 60 Antimicrobial treatment of peritonitis associated with continuous ambulatory peritoneal dialysis; Millikin SP et al.; A multitude of therapeutic regimens have been proposed for the management of peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD) . There are, however, few clinical trials that have evaluated the efficacy of these proposed regimens in a prospective, comparative fashion . This retrospective report is a tabulation of the published data on antimicrobial treatment of CAPD-related peritonitis . The results are presented for combination and mono-drug therapies; Gram-positive bacterial, Gram-negative bacterial and fungal infections; intravenous, oral and intraperitoneal (i.p.) routes of drug administration; various dosages and dosing intervals; and clinical response and relapse rates . The apparent optimal combination regimen for empiric treatment of peritonitis is vancomycin administered in 1 dialysis exchange/week with ceftazidime . This regimen avoids the toxicity associated with the use of aminoglycosides while maintaining effectiveness. J Pharm Biomed Anal, 1991, 9(10-12), 1031 - 6 High-performance liquid chromatographic analysis of chlorhexidine phosphanilate, a new antimicrobial agent; Gadde RR et al.; Chlorhexidine phosphanilate (CHP) is analysed by two separate reversed-phase HPLC methods . CHP was found to be a non-stoichiometric compound with a phosphanilic acid to chlorhexidine ratio of 1.83 . By careful choice of solvents, solution pH and HPLC columns, loss of sample due to incomplete dissolution and adsorption to surfaces is avoided . Both methods are shown to be stability-indicating and accurate. Jpn J Ophthalmol, 1991, 35(4), 435 - 45 Effects of vancomycin and ofloxacin on rabbit ERG in vivo; Mochizuki K et al.; The retinal toxicity of vancomycin and ofloxacin was studied by electroretinogram (ERG) recorded before and after intravitreal injection in rabbits . A dose of 1.0 mg vancomycin caused no change in the ERG for at least 8 weeks after the injection . The ERG was nonrecordable during one to four weeks after an intravitreal injection of 10 mg vancomycin, with recovery of only the c-wave . A dose of 200 micrograms ofloxacin did not cause deterioration of the b-wave, the c-wave or the oscillatory potentials throughout the follow-up period of 8 weeks . Considering the individual susceptibility of the ERG components to these antimicrobial agents and taking into account the difference in vitreous volume between the rabbit and man, the results of this study indicate the recommended intravitreal doses of these antimicrobial agents for clinical use are as follows: vancomycin 1.0 mg/0.1 ml, and ofloxacin 200 micrograms/0.1 ml. Eur J Drug Metab Pharmacokinet, 1991, Spec No 3, 406 - 9 In vitro simulated pharmacokinetics profiles: forecasting antibiotic optimal dosage; Firsov AA; Sisomicin (SMN) and cefotaxime (CTX) antimicrobial effect (AME) kinetics were studied under in vitro stimulation the drug monoexponential pharmacokinetic profiles mimicking normal and impaired elimination of SMN or CTX administered in various doses to humans . Similar general shape of the AME intensity or duration vs the SMN and CTX AUC curves, i.e . the appearance of the "bacteriostatic" and "bactericidal" phases, was established irrespective of the antibiotic elimination rate . At the same time the AME vs AUC curves simulated normal and delayed drug elimination did not match . Thus, AME is defined not only the AUC value but also the peculiarities of the pharmacokinetic profile and, subsequently, the term of "antibiotic efficient concentration" is unseparable of the pharmacokinetic profile. Scand J Infect Dis, 1991, 23(6), 745 - 54 Effects of different types and combinations of antimicrobial agents on endotoxin release from gram-negative bacteria: an in-vitro and in-vivo study; Dofferhoff AS et al.; Total and free endotoxin release in time from cultures of Escherichia coli by different antibiotics was studied in vitro for 4 h in relation to the antibiotic effect on viable counts and morphological features of the test cultures . The most rapid fall in viable counts was seen after treatment with imipenem or the combination of imipenem with tobramycin, accompanied by an early, but minimal increase (1.8-fold) of the total (free plus cell-bound) endotoxin level at 1 h . Total endotoxin levels increased approximately 5-fold upon incubation with ceftazidime, tobramycin or the combination of tobramycin with cefuroxime, whereas incubation with cefuroxime or aztreonam alone caused a late 22-and 49-fold increase in total endotoxin, respectively, at 4 h . In chloramphenicol treated cultures there was still an increase in viable counts during therapy, resulting in an ultimately 78-fold increase of mean levels of total endotoxin . Free endotoxin levels increased approximately 6-fold within 1 h upon treatment with imipenem, alone or in combination with tobramycin, or ceftazidime as the result of rapid lysis of bacteria . Treatment with cefuroxime or aztreonam induced a relatively late but much higher release of free endotoxin (118-and 222-fold, respectively), which was due to the formation of long filamentous structures during the first 2 h of incubation and eventually cell lysis . Both tobramycin and the combination of tobramycin with cefuroxime caused a more gradual rise in free endotoxin, with a +/- 15-fold increase in free endotoxin at 4 h . In chloramphenicol treated cultures, as in the control cultures, the level of free endotoxin remained proportional to the amount of viable organisms . We also studied plasma endotoxin levels in 20 patients with septic shock . 10 out of these 20 patients had a detectable endotoxemia (greater than 5 ng/l) on admission . We describe the patterns of plasma endotoxin in these patients during the first 24 h of antibiotic treatment . We conclude that, in the in-vitro study, values of total endotoxin, free endotoxin, and the rate of release of endotoxin varies with the antibiotic used . We also demonstrate that in patients under treatment for septic shock endotoxin release can be related to the administration of antibiotics. Int J Clin Pharmacol Res, 1991, 11(3), 115 - 21 Pharmacokinetics of ofloxacin in healthy subjects and patients with varying degrees of renal impairment; Flor S et al.; The pharmacokinetics of the new fluoroquinolone antimicrobial ofloxacin were studied in 18 subjects with normal renal function or varying degrees of renal impairment, including patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and haemodialysis . Apparent total body and renal clearances declined and elimination half-life increased with decreasing creatinine clearance . CAPD and haemodialysis removed clinically insignificant fractions of ofloxacin body burden over the study period (6-15% and 9-11% of the dose, respectively) . The apparent volume of distribution, peak concentration, time to peak concentration, and non-renal clearance were not altered significantly by renal insufficiency . An extended dosing interval of 24-48 h is recommended, depending upon the degree of renal impairment, when creatinine clearance falls below 50 mL/min . In addition, supplemental doses would not appear to be necessary during CAPD and following haemodialysis. Chin J Biotechnol, 1991, 7(2), 135 - 43 Studies on breeding of antibiotic-producing strain 5102 by protoplast fusion . IV: Verification of fusant FR-008, and isolation and characterization of the new antimicrobial substance; Yuan DJ et al.; On the basis of the high performance liquid chromatography (HPLC) of Antibiotic 5102-1, the principal components of this antibiotic were isolated from the cultures of starting strain 10-22 and the fusant FR-008 . The result further verified that FR-008 was a recombinant of intraspecific fusion of Streptomyces hygroscopicus subsp . yingchengensis . A new antimicrobial substance was isolated and purified from the fermented product of fusant FR-008, which could not be produced by the starting strain . The color reactions of the new substance with concentrated sulphuric acid or concentrated hydrochloric acid and the UV-VIS absorptions indicated that it was a haptene macrolide antibiotic . The liquid chromatography for aromatic moiety showed that this antibiotic contained p-amino-acetophenone moiety . The amino acid analysis of the antibiotic revealed that it contained an aminosugar moiety, which was different from that in any other haptene macrolide antibiotic . The detailed chemical structure of the aminosugar moiety has yet to be identified. Rev Gastroenterol Peru, 1991, 11(1), 33 - 9 {Helicobacter pylori}; Ramirez Ramos A; Of great impact has been the studies of Helicobacter pylori and its association with illnesses of the stomach and duodenum . We have reviewed and outlined the pathological mechanisms by which H . pylori causes illness, the results of experiments in animals, the different methods of diagnosis (invasive and noninvasive) . We also have detailed the association of H . pylori infection in different gastric conditions such as chronic active gastritis and peptic ulcer disease and the results obtained after antimicrobial treatment . We also have reported the results of Peruvian patients studied over the last 6 years by the Gastrointestinal Working Group of the Universidad Peruana Cayetano Heredia and the Johns Hopkins University . These patients were of widely varying age, socioeconomic level and came from 3 different regions of Peru, we also have explained the result we have obtained in the treatment of this infection using regimens employing mono or triple therapy. Infection, 1991, 19 Suppl 6, S316 - 9 Anti-infective therapy in intensive care units; Shah PM; In intensive care units, treatment is primarily directed at the suspected pathogen . However, the risk of interaction with other concomitantly administered drugs, the possible accumulation when renal and, in particular, hepatic function are impaired, and the possible development of resistance play major roles when selecting a therapeutic regimen . Studies of interactions between the different antimicrobial substances and, in particular, interactions between the antibiotics and other drugs are urgently called for in the future. Chemotherapy, 1991, 37(4), 256 - 9 In vitro susceptibility of Ureaplasma urealyticum clinical isolates to new macrolides; Kanamoto Y et al.; Nine antimicrobial agents, the new macrolides, rokitamycin and midecamycin acetate, and seven other antibiotics, tetracycline, minocycline, doxycycline, josamycin, erythromycin, spiramycin, and norfloxacin, were studied for their antimicrobial activity against 100 strains of Ureaplasma urealyticum, using a microtiter broth dilution technique . The new macrolides, rokitamycin and midecamycin acetate, had the highest activity, with the MIC against 90% of isolates tested (MIC90) being less than or equal to 0.05 microgram/ml . MICs90 of erythromycin, josamycin, doxycycline, minocycline and tetracycline ranged from 0.1 to 0.78 micrograms/ml . Norfloxacin was least active, with a MIC90 of 12.5 micrograms/ml . Five of 100 strains tested were resistant (MIC greater than or equal to 12.5 micrograms/ml) to tetracycline, and two were resistant to minocycline and doxycycline; all of these were susceptible to rokitamycin and midecamycin acetate. Wien Med Wochenschr, 1991, 141(21), 501 - 4 {Dying kinetics of H . influenzae in fibrin clots under the influence of various antibiotics}; Guggenbichler JP et al.; Traditional test methods with determination of MIC values alone are not sufficient for the estimation of antimicrobial activity in tissues . Various other parameters like protein binding, the pH value of tissues and other yet unknown parameters influence bacterial killing under the influence of various antibiotics . In an in vitro model using fibrin clots kill kinetics of H . influenzae were determined . Concentrations of antibiotics were determined in fibrin clots . In these in vitro experiments the eradication of H . influenzae from fibrin clots was investigated under the influence of various antibiotics in different concentrations . The results demonstrate, that the relationship between MIC value and tissue concentration is of little value to determine the antimicrobial activity of beta lactam antibiotics and macrolide antibiotics of H . influenzae in fibrin clots . Macrolide antibiotics demonstrate a bactericidal mode of action. Epidemiol Rev, 1991, 13, 42 - 59 The epidemiology of Helicobacter pylori infection; Taylor DN et al.; The evidence that H . pylori causes gastritis in humans comes from both primary and secondary observations . The most important primary observations are the human volunteer studies, the animal models, and the treatment studies with antimicrobial agents . Supporting information comes from studies showing the specific association of H . pylori infection with type B gastritis and with gastric (but not intestinal) epithelial cells; the specific ultrastructural lesions, including adherence pedestals; the ubiquity and stability of the immune response; the response to bismuth treatment; and the association with epidemic gastritis and hypochlorhydria . It is important to note that all of Koch's postulates have been fulfilled, and despite nearly universal initial skepticism, no evidence exists against the hypothesis that H . pylori plays an etiologic role in type B gastritis . Therefore, it is reasonable to conclude that H . pylori is a pathogen in humans . The known features of H . pylori infection are listed in . Infection is chronic and common throughout the world, with a higher prevalence in developing countries than in developed countries . The prevalence of H . pylori infection increases with age in parallel with that of gastritis . Acquisition of H . pylori infection does not appear to have any seasonality, and infection is equally common among men and women . Without a significant animal or environmental reservoir for human strains of H . pylori, person-to-person contact appears to be the most likely mode of transmission . Exactly how the organism is transmitted from the stomach of one person to that of another remains unclear . Also unknown are the factors which determine who becomes ill after infection; why one person has gastritis alone while another person develops a duodenal ulcer; and how the traditional risk factors for ulcer disease, such as smoking, aspirin, and alcohol, interact with H . pylori infection . Finally, the long term neoplastic consequences of infection must be understood . Further elucidation of the natural history of H . pylori and the consequences of H . pylori infection is the most important goal for future study. Acta Otolaryngol, 1991, 111(6), 1006 - 12 Circadian rhythm dependent kanamycin-induced hearing loss in rodents assessed by auditory brainstem responses; Yonovitz A et al.; An antimicrobial agent, kanamycin, has been shown to produce as an untoward effect, ototoxicity . The purpose of this study was to investigate differential effects of kanamycin ototoxicity as a function of Rx timing with regard to circadian rhythms . Four groups of comparable weight Sprague-Dawley rats received a daily subcutaneous dosage of 225 mg/kg kanamycin sulfate with each receiving the antibiotic at a different time: 8 AM (8A), 2 PM (2P), 8 PM (8P), and 2 AM (2A) . The rats were housed in separate cages, in a room on a light-dark (12:12) illumination cycle with light between 6 AM and 6 PM . Hearing loss was assessed with the auditory brainstem response (ABR) using pure tone stimuli at 8, 16, 24, and 32 kHz . ABR measures were obtained before dosing began and 2, 4, and 6 weeks after the initial dosing . Kanamycin produced a hearing loss which reflected the total dosage given to each group . Significant differences in physiologic thresholds were observed for both timing of the daily dosage (p less than 0.05), and the 2, 4 and 6 week testings (p less than 0.001) . After 2 weeks, the 8A group showed an average hearing loss of 11.5 dB at 32 kHz, with the other timed treatment groups exhibiting minimal effects (3.0-6.5 dB) . For the 8A group at this frequency, the loss progressed at 4 (19.5 dB) and 6 (22.5 dB) weeks . The 2P group after 4 weeks exhibited similar losses as the 8A group for this frequency, with the loss at 6 weeks being even greater (34.0 dB) . The 8P and 2A groups exhibited only slight losses over all frequencies.(ABSTRACT TRUNCATED AT 250 WORDS) Ann Med, 1991, 23(5), 539 - 43 Infection as a risk factor for infarction and atherosclerosis; Valtonen VV; A growing amount of clinical and experimental evidence suggests a link between infection and atherosclerotic diseases including both myocardial and cerebral infarction . A prime example is a greatly increased risk of stroke in septicaemic patients with and without endocarditis . Controlled clinical studies have recently shown, however, that certain other milder bacterial infections are also a risk factor for infarction . A preceding febrile respiratory infection was a major risk factor for stroke in young and middle aged patients . In patients with acute myocardial infarction Chlamydia pneumoniae and dental infections seem to be risk factors according to one controlled clinical study . Several possible mechanisms could explain the observed association of infection and infarction . For instance, infection causes a hypercoagulable state which increases the risk of thrombosis . In addition, infection has profound and harmful effects on prostaglandin and lipid metabolism . Infection may also have some role in the atherosclerotic process itself by inducing damage and inflammation in vascular endothelium in the presence of hypercholesterolemia . So far, however, little clinical evidence is available to suggest that by controlling infection the risk of infarction or development of atherosclerotic lesions might be reduced except in patients with endocarditis, where the risk of thromboembolic complications rapidly diminished when the infection is controlled with antimicrobial therapy. Adv Exp Med Biol, 1991, 305, 89 - 96 Human neutrophil granule cationic protein CAP37 is a specific macrophage chemotaxin that shares homology with inflammatory proteinases; Morgan JG et al.; Cationic antimicrobial protein CAP37 (Mr = 37 kD) is derived from the azurophilic granules of human PMN . In vitro and in vivo studies demonstrate that CAP37 is a novel monocyte-specific chemoattractant . The N-terminal amino acid sequence of CAP37 shares significant homology with a number of inflammatory molecules with protease activity including elastase and cathepsin G . However, substitutions in the catalytic triad (serine for a histidine at position 41 and glycine for a serine at position 175), may account for its lack of serine protease activity . A full length cDNA for CAP37 was identified in an HL60 cDNA library screened with oligonucleotide probes designed from the N-terminal amino acid sequence . Sequencing of the cDNA reveals a protein of 225 amino acids with significant nucleotide homology to cathepsin G and human neutrophil elastase. Crit Rev Toxicol, 1991, 21(5), 315 - 28 Oral toxicity of formaldehyde and its derivatives; Restani P et al.; Formaldehyde (FA) has been commercially produced since the early 1900s . Its widespread use in a variety of applications is known to result in appreciable exposure of workers and of a section of the general population . Formaldehyde is a normal metabolite in mammalian systems . It occurs in air as a product of the natural photooxidation of automobile exhaust, combustion processes, incinerators; formaldehyde has been found in municipal and industrial effluents and is present in food either naturally (fruits and vegetables, in the order of parts per million), or as a result of its use as a food additive . The use of FA and its derivative, hexamethylenetetramine (HMT), which gradually decomposes to FA under acidic conditions as antimicrobial agents in food, raises questions about their potential chronic oral toxicity . Furthermore, since FA is a very reactive compound and reacts with different macromolecules such as proteins and nucleic acids, the safety evaluation of FA as a cheese additive must take into account the toxicity of the reaction products between FA and milk components . Biochemical aspects, acute and short-term toxicity studies including mutagenicity, multigeneration, and reproduction studies, long-term carcinogenicity studies after oral administration of FA and HMT are reviewed in this paper . The results of these studies indicate that repeated oral exposure of a relatively large amount of FA that could overwhelm the normal metabolic capacity of animals to convert FA into formiate, CO2, and water produces histopathological gastric changes . This paper correlates the hazard caused by the exposure to low levels of FA, as far as its carcinogenic potential by oral route is concerned per se or regarding its use as a food additive . Based on the evidence that FA is formed naturally in food and is a normal mammalian metabolite and that a threshold for carcinogenicity exists both after exposure by inhalation and oral administration, it may be deduced that FA is not carcinogenic at low levels of exposure. Ann Trop Paediatr, 1991, 11(3), 295 - 300 The impact of medical services on trachoma in a Gambian village: antibiotics alone are not the answer; Mabey DC et al.; We have measured the prevalence of active trachoma in children aged less than 15 years in the Gambian village of Keneba, which has had excellent free medical care and a continuous supply of antibiotics since 1974 . The prevalence was 13%, with the peak prevalence (20%) occurring in the 2 to 3-year age group . Of 71 cases diagnosed, only 23 (33%) had complained of ocular symptoms in the previous 3 months, in spite of the fact that 66 (94%) had attended the clinic . Only five had been diagnosed as having trachoma by the duty paediatrician (7%) . Compliance with treatment was poor, with only 29 subjects returning for continued treatment (41%), and at follow-up 16 months later 22 of 64 subjects still had active disease (34%) . We conclude that the widespread use of antimicrobial agents does not preclude the persistence of endemic disease . Socio-economic improvement or behavioural changes appear necessary for the control of trachoma in endemic areas . In the meantime there is a need for greater awareness of the disease both among clinicians in endemic areas and among the communities afflicted. Ann Trop Paediatr, 1991, 11(1), 99 - 102 A prospective study of some diarrhoeagenic Escherichia coli in infants with diarrhoea in Mosul, Iraq; Abbar F et al.; The incidence of diarrhoeagenic Escherichia coli was investigated in 304 infants with diarrhoea in Mosul, Iraq by using standard biological assays and reversed passive latex agglutination (RPLA) procedures . Enterotoxigenic E . coli (ETEC) were found in 12.8% of the cases--27 (8.8%) strains produced heat-labile toxin (LT) only, 8 (2.6%) heat-stable toxin (ST) only and 4 (1.3%) produced both toxins (LT-ST)--whereas enteropathogenic E . coli (EPEC) were responsible for about 13.8% of the incidence of diarrhoea in the community . Detailed analysis revealed that 12 serotypes were involved . A greater number of cases of acute enteritis were seen in infants aged 0-18 months than in those aged between 19 and 36 months . The data indicate a highly significant level of resistance to most common antimicrobial drugs among diarrhoeagenic E . coli isolated, but most were highly sensitive to nalidixic acid, cephalothin and gentamicin. J Nat Prod, 1991 Jan-Feb, 54(1), 92 - 7 New avarone and avarol derivatives from the marine sponge Dysidea cinerea; Hirsch S et al.; Six new avarol and avarone derivatives, 3'-hydroxyavarone {3}, 3',6'-dihydroxyavarone {4}, 6'-hydroxyavarol {5}, 6'-acetoxyavarol {6}, 6'-acetoxyavarone {7}, and 6'-hydroxy-4'-methoxyavarone {8}, are reported from the Red Sea sponge Dysidea cinerea . The structures of the new compounds were determined by spectroscopic data, mainly 1D and 2D nmr measurements . The absolute configurations of 5, 6, and 7, and most likely also of 3, 4, and 8, were established on the basis of cd measurements to be the same as that of avarol . Several of the new compounds are cytotoxic, possess antimicrobial activities, and have anti-HIV-1 reverse transcriptase activities; the most active is compound 8. Int J Immunopharmacol, 1991, 13(8), 1067 - 72 Enhancement of monocyte antimycobacterial activity by diethyldithiocarbamate (DTC); Hubner L et al.; Diethyldithiocarbamate (DTC) has been recently reported to significantly reduce the incidence of opportunistic infections in HIV-infected patients . The present study addresses the question whether DTC is capable of stimulating antimycobacterial activity of mononuclear phagocytes . We found that peripheral blood mononuclear cells (PBMC) of healthy subjects preincubated in vitro with 100-1000 ng/ml of DTC and thereafter infected with Mycobacterium tuberculosis H37Rv or Mycobacterium avium-intracellulare complex exhibited an enhanced antimycobacterial activity compared with control-incubated cells as assessed by the determination of mycobacterial colony-forming units . In subsequent experiments monocytes from healthy volunteers injected with 5 mg/kg body weight of DTC were tested ex vivo for antimycobacterial activity at various periods of time after injection . Injection of DTC resulted in a significant enhancement of antimycobacterial activity which was most evident 24 h after DTC injection . We conclude that DTC stimulates the antimicrobial function of mononuclear phagocytes both in vitro and in vivo . These results may explain the favourable clinical course observed in HIV-infected patients treated with DTC and may serve as a basis for treatment with DTC in patients with drug-resistant atypical mycobacteriosis. Chemotherapy, 1991, 37(5), 327 - 34 Direct virus inactivation of tachyplesin I and its isopeptides from horseshoe crab hemocytes; Murakami T et al.; Direct virus inactivation of tachyplesin I and related isopeptides, which are antimicrobial peptides isolated from the hemocytes of the horseshoe crab (Tachypleus tridentatus and Limulus polyphemus), was examined against several viruses . Vesicular stomatitis virus (VSV) was inactivated by incubation with tachyplesin I and its isopeptides . Influenza A (H1N1) virus was slightly inactivated by tachyplesin I, whereas herpes simplex virus 1 and 2, adenovirus 1, reovirus 2 and poliovirus 1 were resistant to inactivation . The inactivation of VSV by tachyplesin I depended on the concentration, the time and the temperature of incubation . Pretreatment of tachyplesin I with trypsin or lipopolysaccharide of gram-negative bacteria entirely abolished the antiviral activity . Electron microscopy of VSV treated with tachyplesin I showed naked and damaged virions . These data suggest that tachyplesin I directly inactivates the VSV by destroying its envelope subunits. Pediatrie, 1991, 46(5), 429 - 42 {Duration of antibiotherapy}; Rousseau C; Antibiotics have been used to treat various infectious since the second world war . Despite a thorough knowledge of the antimicrobial pharmacology, clinicians have less guidelines concerning duration of antibiotherapy . When assessing the length of time an infection should be treated, the physician must consider the following criteria: the antibiotics, the involved organisms and their susceptibility patterns, the infected site and the host. Acta Clin Belg, 1991, 46(5), 283 - 9 In vitro activity of commonly used oral antimicrobial agents against community isolates of respiratory pathogens; Struelens MJ et al.; The in vitro activity of ampicillin, amoxicillin/clavulanate, cefadroxil, cefaclor, cefuroxime (axetil), co-trimoxazole, doxycycline, ciprofloxacin, ofloxacin, erythromycin, and roxithromycin was tested against unselected isolates of S . pneumoniae (70), H . influenzae (93), and M . catarrhalis (46), cultured from clinically significant sputum samples of general practice patients . All isolates of S . pneumoniae were highly susceptible to ampicillin; cefadroxil and cefaclor were markedly less active on a weight basis; resistance was only observed with co-trimoxazole (4.3%), doxycycline (5.7%), and erythromycin (2.9%); however, ciprofloxacin and ofloxacin showed median MICs (MIC50), that were only one dilution below breakpoint . Beta-lactamase was detected in 14.0% of H . influenzae isolates; all isolates were susceptible to amoxicillin/clavulanate, cefaclor, and cefuroxime (axetil), although MICs were generally higher for cefaclor; the highest activity was exhibited by ciprofloxacin and ofloxacin; apart from cefadroxil, erythromycin, and roxithromycin, that showed only marginal activity, resistance was observed with co-trimoxazole (4.3%) and doxycycline (1.1%) . All (including 71.7% of beta-lactamase producing) isolates of M . catarrhalis were susceptible to amoxicillin/clavulanate, cefaclor and cefuroxime (axetil), although MICs were markedly lower for amoxicillin/clavulanate; ciprofloxacin and ofloxacin showed the lowest MICs; resistance was only observed with cefadroxil (2.2%) . In conclusion, the antimicrobial agents showing the most uniformly high in vitro activity against the 3 common community respiratory pathogens tested in the present study, were amoxicillin/clavulanate and, to a lesser extent, cefuroxime (axetil). Crit Rev Oral Biol Med, 1991, 2(3), 297 - 321 Tetracyclines inhibit connective tissue breakdown: new therapeutic implications for an old family of drugs; Golub LM et al.; Tetracyclines have long been considered useful adjuncts in peridontal therapy based on their antimicrobial efficacy against putative periodontopathogens . However, recently these drugs were found to inhibit mammalian collagenases and several other matrix metalloproteinases (MMPs) by a mechanism independent of their antimicrobial activity . Evidence is presented that this property may be therapeutically useful in retarding pathologic connective tissue breakdown, including bone resorption . The experiments leading to this discovery are described and possible mechanisms are addressed, including the specificity of tetracyclines' anti-collagenase activity, the role of the drugs' metal ion (Zn2+, Ca2+)-binding capacity, and the site on the tetracycline molecule responsible for this nonantimicrobial property . Of extreme interest, the tetracycline molecule has been chemically modified in multiple ways, generating a new family of compounds called CMTs (chemically modified tetracyclines) that lack antimicrobial but still retain anti-collagenase activity . The first of these CMTs, 4-de-di-methylaminotetracycline, was found not to produce a major side-effect of antimicrobial tetracycline therapy--its administration to experimental animals did not result in the emergence of tetracycline-resistant microorganisms in the oral flora and gut . Numerous examples of the clinical potential of this non-antimicrobial property of tetracyclines in the treatment of periodontal and several medical diseases (e.g., sterile corneal ulcers, rheumatoid arthritis, skin bullous lesions, tumor-induced angiogenesis and metastasis) are discussed. Toxicology, 1991, 68(1), 37 - 49 Cytotoxicity of myeloperoxidase-activated catechols: oxidative injury to the red blood cell; van Zyl JM et al.; The effects of two catechols (1,2-benzenediol and nordihydroguaiaretic acid) on the myeloperoxidase-Cl(-)-H2O2 antimicrobial/cytotoxic system of the human neutrophil were investigated . To determine the cytotoxicity of myeloperoxidase-generated oxygen metabolites (mainly chlorinated oxidants such as hypochlorite) and catechol oxidation products, the well characterized erythrocyte was used as a target . At relatively low concentrations (less than 10 microM), the catechols acted as redox catalysts by stimulating the generation of chlorinated oxidants . This is visualized as a promotion of haemolysis which reached a maximum and then decreased again with increasing concentrations of the catechol . In this respect, the dicatechol, nordihydroguaiaretic acid, was more potent . At higher concentrations, the catechols competed more effectively with Cl- as electron donors and the generation of chlorinated oxidants decreased with a consequent decrease in haemolysis . Above 200 microM nordihydroguaiaretic acid, complete haemolysis occurred which might be due to high membrane concentrations of the catechol due to its high lipid solubility . In contrast, high 1,2-benzenediol concentrations did not induce haemolysis . The catechols stimulated methaemoglobin formation in a concentration-dependent fashion with 1,2-benzenediol more potent than nordihydroguaiaretic acid . There was some correlation between membrane microviscosity and haemolysis which in turn did not correlate with haemoglobin oxidation . No direct correlation existed between intracellular methaemoglobin formation and the precipitation of haemoglobin oxidation products on the membrane . Disulphide crosslinks were not involved in the covalent polymerization of haemoglobin subunits. Life Sci, 1991, 49(4), 315 - 24 Interaction of berberine with human platelet alpha 2 adrenoceptors; Hui KK et al.; Berberine, an alkaloid, has been found to have a myriad of pharmacological effects including hypotensive, antisecretory, sedative, and antimicrobial effects, some of which are similar to those of clonidine, an alpha 2 adrenoceptor partial agonist . The interaction of berberine with human platelet alpha 2 adrenoceptor was investigated in this study . Berberine was found to inhibit competitively the specific binding of {3H}-yohimbine . The displacement curve was parallel to those of clonidine, epinephrine, norepinephrine, with the rank order of potency (IC50) being clonidine (0.4 microM) greater than epinephrine (7.5 microM) greater than norepinephrine (14.5 microM) = berberine (16.6 microM) . Increasing concentrations of berberine from 0.1 microM to 10 microM inhibited {3H}-yohimbine binding, shifting the saturation binding curve to the right without decreasing the maximum binding capacity . In platelet cyclic AMP accumulation experiments, berberine at concentrations of 0.1 microM to 0.1 mM inhibited the cAMP accumulation induced by 10 microM prostaglandin E1 in a dose dependent manner, acting as an alpha 2 adrenoceptor agonist . In the presence of L-epinephrine, berberine blocked the inhibitory effect of L-epinephrine behaving as an alpha 2 adrenoceptor antagonist . These properties are similar to those of clonidine on human platelets, suggesting that berberine is a partial agonist of platelet alpha 2 adrenoceptors . These findings may provide potential mechanisms for the hypotensive, antisecretory, and sedative effects of berberine. Biologicals, 1991 Jan, 19(1), 49 - 52 Heterogeneity in the reactivity of various groups of IgM antibodies with kaolin; Haukenes G et al.; Kaolin strongly adsorbed rheumatoid factor (RF) and mono-nucleosis antibodies, while cold agglutinins and some antimicrobial IgM antibodies were poorly adsorbed . Maximum adsorption took place at a pH of about 7 . The degree of adsorption also depended on the amount of kaolin . Rheumatoid factor could be eluted from kaolin at pH 11 after adsorption at pH 7 . The reported heterogeneity with regard to reactivity with kaolin is suggested to be due to hydrophobic interactions. Phytochemistry, 1991, 30(2), 708 - 10 An anthraquinone and three naphthopyrone derivatives from Cassia pudibunda; Messana I et al.; Chemical examination of the methanolic extract of the roots of Cassia pudibunda led to isolation of the new rubrofusarin-6-O-beta-D-glucopyranoside, quinquangulin-6-O-beta- D-apiofuranosyl-(1----6)-O-beta-D-glucopyranoside, quinquangulin-6-O-beta-D-glucopyranoside and chrysophanol dimethyl ether . Moreover the known chrysophanol, physcion, cis-3,3',5,5'-tetrahydroxy-4-methoxystilbene, trans-3,3',5,5' -tetrahydroxy-4-methoxystilbene, and cassiaside B were identified . The antimicrobial activity of some of these compounds is also reported. J Immunol, 1990 Dec 15, 145(12), 4290 - 7 Leishmania major amastigotes initiate the L-arginine-dependent killing mechanism in IFN-gamma-stimulated macrophages by induction of tumor necrosis factor-alpha; Green SJ et al.; Macrophages exposed to IFN-gamma and infected with amastigotes of Leishmania major develop the capacity to eliminate the intracellular pathogen . This antimicrobial activity of activated macrophages correlates with the initiation of nitrogen oxidation of L-arginine, yet other reports suggest that two signals are required for induction of this biochemical pathway for effector activity . In the present studies, macrophages treated with up to 100 U/ml IFN-gamma, or 100 ng LPS, or 10(7) amastigotes produced minimal quantities (less than 9 microM) of NO2- and failed to develop cytotoxic effector activities . In contrast, the combination of IFN-gamma and either LPS (greater than 0.1 ng) or amastigotes (10(6) induced high concentrations (much greater than 30 microM) of NO2- and macrophage cytotoxicity against intra- and extracellular targets . The induction of nitrogen oxidation by amastigotes could be dissociated from LPS-induced events by 1) performing the assays in the presence of polymyxin B (which blocked LPS effects, but not amastigote effects), 2) determining the threshold of IFN-gamma required to prime cells for subsequent trigger (1 U/ml for LPS trigger effects; 10-fold higher for amastigotes), and 3) determining the heat sensitivity of the two trigger agents (amastigote effects abolished at 100 degrees C; LPS effects unaffected at this temperature) . Further, culture fluids from amastigote-infected macrophages did not contain detectable LPS (less than 6 pg/ml) . Possible parasite and cell-associated factors that could contribute to the induction of nitrogen oxidation and cytotoxic activity of IFN-gamma treated macrophages were examined: only certain intact microorganisms, LPS from a variety of bacteria, and the cytokine TNF alpha were effective . Both NO2- production and intracellular killing were abolished by the addition of anti-TNF-alpha mAb in the assay . TNF-alpha was produced by amastigote-infected macrophages and IFN-gamma dramatically enhanced secretion of this cytokine; IFN-gamma alone had no effect . Endogenous TNF-alpha produced during infection of macrophages with L . major acted in an autocrine fashion to trigger the production of L-arginine-derived toxic nitrogen intermediates that killed the intracellular parasites. J Biol Chem, 1990 Dec 5, 265(34), 21350 - 4 Antimicrobial tachyplesin peptide precursor . cDNA cloning and cellular localization in the horseshoe crab (Tachypleus tridentatus); Shigenaga T et al.; The hemocytes of the horseshoe crab have been found to contain a new family of Arthropodous antibiotics, termed the "tachyplesin family." These peptides are composed of 17-18 amino acid residues with a carboxyl-terminal arginine alpha-amide . We report here the entire cDNA sequence coding for the tachyplesin precursors and their distribution in various tissues of the horseshoe crab . Sequence analysis of the cloned cDNAs revealed that the tachyplesin precursors consist of 77 amino acids with 23 residues in a presegment, and that there are two types of mRNAs corresponding to the isopeptides tachyplesins I and II . Both precursors contain a putative signal peptide, a processing peptide sequence and a carboxyl-terminal amidation signal "Gly-Lys-Arg" connected to the mature tachyplesin peptide . Moreover, an unusual acidic amino acid cluster, Asp-Glu-Asp-Glu-Asp-Asp-Asp-Glu-Glu-COOH, is present in the carboxyl-terminal portions of both precursors . These results suggest that the two types of tachyplesin precursors are first synthesized as preproproteins and are then incorporated into the intracellular organelle, accompanied by various processing events . Northern blot analysis on a total RNA from various tissues of the horseshoe crab revealed that the tachyplesin precursors are expressed mainly in hemocytes and cardiac and brain tissues . Tachyplesin was immunohistochemically localized in the smaller dense granules rather than the typical large granules present in abundance in the hemocytes. Clin Pharmacokinet, 1990 Dec, 19(6), 462 - 90 The effect of respiratory disorders on clinical pharmacokinetic variables; Taburet AM et al.; Respiratory disorders induce several pathophysiological changes involving gas exchange and acid-base balance, regional haemodynamics, and alterations of the alveolocapillary membrane . The consequences for the absorption, distribution and elimination of drugs are evaluated . Drug absorption after inhalation is not significantly impaired in patients . With drugs administered by this route, an average of 10% of the dose reaches the lungs . It is not completely clear whether changes in pulmonary endothelium in respiratory failure enhance lung absorption . The effects of changes in blood pH on plasma protein binding and volume of distribution are discussed, but relevant data are not available to explain the distribution changes observed in acutely ill patients . Lung diffusion of some antimicrobial agents is enhanced in patients with pulmonary infections . Decreased cardiac output and hepatic blood flow in patients under mechanical ventilation cause an increase in the plasma concentration of drugs with a high hepatic extraction ratio, such as lidocaine (lignocaine) . On a theoretical basis, hypoxia should lead to decreased biotransformation of drugs with a low hepatic extraction ratio, but in vivo data with phenazone (antipyrine) or theophylline are conflicting . The effects of disease on the lung clearance of drugs are discussed but clinically relevant data are lacking . The pharmacokinetics of drugs in patients with asthma or chronic obstructive pulmonary disease are reviewed . Stable asthma and chronic obstructive pulmonary disease do not appear to affect the disposition of theophylline or beta 2-agonists such as salbutamol (albuterol) or terbutaline . Important variations in theophylline pharmacokinetics have been reported in critically ill patients, the causes of which are more likely to be linked to the poor condition of the patients than to a direct effect of hypoxia or hypercapnia . Little is known regarding the pharmacokinetics of cromoglycate, ipratropium, corticoids or antimicrobial agents in pulmonary disease . In patients under mechanical ventilation, the half-life of midazolam, a new benzodiazepine used as a sedative, has been found to be lengthened but the underlying mechanism is not well understood . Pulmonary absorption of pentamidine was found to be increased in patients under mechanical ventilation . Pharmacokinetic impairment does occur in patients with severe pulmonary disease but more work is needed to understand the exact mechanisms and to propose proper dosage regimens. Prim Care, 1990 Dec, 17(4), 811 - 24 Lower respiratory tract infections; Billas A; Although lower respiratory tract infections are frequently diagnosed in a primary care setting, they are still associated with a significant morbidity and mortality, which warrants a careful approach to treatment . Knowledge of the most common cause based on the age of the patient, location where the infection was acquired, and clinical presentation helps to direct empiric treatment . A few basic laboratory studies, especially a sputum Gram stain, can allow for more specific treatment . Identification of patients at increased risk for virulent organisms should make the primary care physician consider inpatient treatment along with an aggressive diagnostic workup and broad-spectrum antimicrobial treatment . Prevention should always be considered. J Clin Microbiol, 1990 Dec, 28(12), 2765 - 9 Mycobacterium gordonae pseudoinfection associated with a contaminated antimicrobial solution; Tokars JI et al.; At Yale-New Haven Hospital, 46 specimens submitted for mycobacterial culture during an 8-week period in 1989 were positive for Mycobacterium gordonae, a nontuberculous acid-fast bacterium (AFB) of low pathogenicity . The specimens were submitted from 34 patients who came from various inpatient and outpatient services . Four patients were begun on antimycobacterial therapy on the basis of an AFB isolate which was later identified as M . gordonae . Isolation of M . gordonae was associated with use of the BACTEC TB system (BACTEC TB; Becton Dickinson Diagnostic Instrument Systems, Towson, Md.) and an antimicrobial solution, BACTEC PANTA PLUS (PANTA; Becton Dickinson Diagnostic Instrument Systems) . The manufacturer reported that two lots (B9K1 and C9K1) of PANTA kits containing a single production lot (N8C1) of PANTA, which had been shipped to 173 laboratories, had been contaminated with M . gordonae . A survey of mycobacteriology laboratories in the United States revealed that, during April to July 1989, the M . gordonae isolation rate was 5.8/1,000 AFB specimens processed at laboratories that did not use BACTEC TB, 11.4/1,000 AFB specimens at laboratories that used BACTEC TB but not the implicated lot of PANTA, and 23.5/1,000 AFB specimens at laboratories that used BACTEC TB and the lot of implicated PANTA . Intrinsic contamination of PANTA was attributed to ineffective sterilization of water used in the manufacturing process and was not detected prior to product shipment because cultures for AFB were not part of the quality control regimen . This episode emphasizes that clinical laboratories can detect pseudoepidemics promptly if they are alert to abrupt increases in isolation rates, especially of unusual or generally nonpathogenic organisms. J Am Vet Med Assoc, 1990 Dec 1, 197(11), 1487 - 8 Coliform myositis in a calf; Wallace LL et al.; Coliform myositis was diagnosed in a young calf with signs of pain, swelling, and edema of the right hind limb . Diagnostic methods included bacteriologic culture and antimicrobial susceptibility testing . The organism isolated was a gas-producing Escherichia coli . The infection responded to administration of trimethoprim/sulfadiazine, to which the organism was susceptible in vitro. J Exp Med, 1990 Dec 1, 172(6), 1709 - 15 Cloning of cDNA for proteinase 3: a serine protease, antibiotic, and autoantigen from human neutrophils; Campanelli D et al.; Closely similar but nonidentical NH2-terminal amino acid sequences have been reported for a protein or proteins in human neutrophils whose bioactivities is/are diverse (as a serine protease, antibiotic, and Wegener's granulomatosis autoantigen) but that share(s) several features: localization in the azurophil granules, a molecular mass of approximately 29 kD, reactivity with diisopropylfluorophosphate, and the ability to degrade elastin . We previously purified one such entity, termed p29b . Using a monospecific antibody, we have cloned from human bone marrow a cDNA encoding the complete p29b protein in its mature form, along with pre- and pro-sequences . The predicted amino acid sequence agrees closely with the NH2-terminal sequence obtained previously from purified p29b, as well as with sequences newly obtained from CNBr fragments . The primary structure is highly homologous to elastase, cathepsin G, T cell granzymes, and other serine proteases, and shares both the catalytic triad and substrate binding pocket of elastase . Hybridization of the full-length cDNA with restriction enzyme digests of human genomic DNA revealed only one fragment . This suggests that the closely related species described previously are the same, and can be subsumed by the term used for the first-described activity, proteinase 3 . Proteinase 3 is more abundant in neutrophils than elastase and has a similar proteolytic profile and specific activity . Thus, proteinase 3 may share the role previously attributed to neutrophil elastase in tissue damage, and has the potential to function as an antimicrobial agent. Todays OR Nurse, 1990 Dec, 12(12), 4 - 9 Maximizing wound healing with silver-impregnated porcine xenograft; Ersek RA et al.; 1 . Grossly contaminated or chronically infected wounds require adequate debridement of dead tissue and wound coverage or closure . 2 . Porcine xenograft is a temporary wound covering that prevents evaporation and thereby creates an environment for new cells to propagate instead of being sacrificed by desiccation . 3 . The addition of silver ions to the porcine xenograft provides a potent antimicrobial agent that is only active at the surface where it is needed, has no systemic effects, and allows epithelialization to proceed in half the time of uncovered or unsilvered methods . 4.Silver-impregnated porcine xenograft provides a temporary wound covering that is antimicrobial, physiologic, and allows even the most massive and chronically contaminated wounds of years duration to be healed by careful, consistent dressing changes without skin grafts or flaps. J Trauma, 1990 Dec, 30(12 Suppl), S30 - 3 Antibiotics and the postburn hypermetabolic response; Waymack JP; Severe burn injury has been documented to significantly increase resting metabolic energy expenditure . This increase in metabolic rate appears to be possibly correlated with the degree of burn wound colonization and infection with bacteria . Prevention of such colonization and infection through the use of topical antimicrobial agents appears to decrease the metabolic alterations resulting from burn injury . These findings indicate that appropriate use of topical antibacterial agents may decrease the metabolic demands seen in burned patients . Burn-induced translocation of intestinal bacteria has also been hypothesized to contribute to the postburn hypermetabolic response . Attempts at preventing this entity in a burned guinea pig model through the use of selective decontamination of the digestive tract by the administration of enteral antibiotics have failed to demonstrate any measurable effect. J Trauma, 1990 Dec, 30(12 Suppl), S100 - 6 Development and potential use of antibody directed against lipopolysaccharide for the treatment of gram-negative bacterial sepsis; Dunn DL; Gram-negative bacterial sepsis remains a major cause of lethality in hospitalized patients, despite routine therapy consisting of antimicrobial agents, hemodynamic monitoring and fluid resuscitation, and metabolic support . Because a large body of evidence supports the concept that Gram-negative bacterial lipopolysaccharide (endotoxin, LPS) is responsible for many of the direct and host mediator-induced deleterious effects, recent work has been centered on the development and use of anti-LPS antibody preparations in order to ameliorate lethality . Both polyclonal and monoclonal antibody preparations directed against the common deep core/lipid A region of LPS are cross-reactive in vitro and cross-protective in vivo against a wide range of challenge organisms and LPS, and preliminary clinical trials indicate that a reduction in lethality may be possible . The precise endotoxin epitope against which antibody should be directed in order to maximize protection, however, has not been established . This modality most probably will become a standard form of adjunctive therapy within the next several years for the treatment of Gram-negative bacterial sepsis. Urology, 1990 Dec, 36(6), 548 - 56 Tetracyclines in urology: current concepts; Cunha BA et al.; Tetracyclines have an unusually broad spectrum of antimicrobial activity . They are generally well tolerated, with relatively few side effects compared with alternative antibiotic choices . Tetracyclines also compare favorably with newer antimicrobials, i.e., oral quinolones, with respect to cost and microbial resistance . Doxycycline's and minocycline's spectrum of antibacterial activity, pharmacokinetic profile, and safety profile make them preferred drugs when tetracyclines are indicated in urologic infections. Clin Orthop, 1990 Dec, (261), 23 - 6 Newer concepts in antimicrobial therapy; Gentry LO; Advances in the treatment of infection have continued to increase both the length and quality of life . Unfortunately, many bacteria can readily adapt to their environment and develop a tolerance to the antimicrobial agents in widespread use . During the recent past, the consumption of cephalosporins has increased so dramatically as to parallel the initial acceptance of penicillin . Organisms that are resistant to the cephalosporins will no doubt continue to thrive, especially within the susceptible host . It is essential for the clinician to become familiar with the newest antimicrobial agents to more effectively treat modern infections. Plast Reconstr Surg, 1990 Dec, 86(6), 1059 - 64; discussion 1065 A randomized prospective study of topical antimicrobial agents on skin grafts after thermal injury; Livingston DH et al.; We prospectively studied 52 consecutive patients who were treated by early tangential excision and grafting following thermal injury . The usefulness of two topical antimicrobial agents--0.5% silver nitrate (Ag) and neomycin (1 gm/liter) plus bacitracin (50,000 units/liter) (NB)--was compared with the effectiveness of Ringer's lactate (RL) for prevention of autogenous skin-graft loss due to infection . Graft loss of 10 percent or more occurred in 17 patients (33 percent)--due to infection in 16 . Skin-graft loss was a minor problem in patients with less than 20 percent total body surface area (TBSA) burn (Ag: 0 of 6, NB: 1 of 6, RL: 1 of 5) . The use of either antimicrobial (Ag or NB) resulted in less graft loss (1 of 14) than RL (4 of 6; p less than 0.05) in the 20 to 40 percent TBSA burn group . Large burns (greater than 40 percent) had a very high incidence of at least 10 percent graft loss (67 percent) regardless of treatment . Infection in the area of graft loss was caused by antibiotic-resistant organisms or yeast in 50 percent of the Ringer's lactate group and the entire neomycin plus bacitracin group . No graft infections were caused by resistant organisms or yeast in the silver nitrate group . This study demonstrates that topical antimicrobial agents reduce infection-related skin-graft loss in patients with medium-sized (20 to 40 percent TBSA) burns and that neomycin plus bacitracin is associated with rapid emergence of drug-resistant organisms whereas silver nitrate is not. Biopolymers, 1990 Dec, 29(14), 1807 - 22 Analysis of side-chain conformational distributions in neutrophil peptide-5 NMR structures; Kominos D et al.; The side-chain conformations have been analyzed in the antimicrobial peptide, Neutrophil Peptide-5 (NP-5), whose structure was independently generated from nmr-derived distance constraints using a distance geometry algorithm . The side-chain and peptide dihedral angle distributions in the nmr structures were compared with those constructed from a data base of high-resolution protein crystal structures . The side-chain conformational preferences for NP-5 in solution are significantly different from those observed in the crystal structure data base . These results indicate that the side-chain conformations are quite disordered for many of the residues of NP-5 . The absence of a correlation between the width of the conformational distribution and surface accessibility suggests that the disorder may be due to limitations in the structural information extracted from the nmr data rather than to molecular motion . However, it is also observed that the degree of conformational disorder is only weakly correlated with the number of nuclear Overhauser enhancements to a given side chain . Possible reasons for this are discussed . Molecular mechanics refinement of these structures did not significantly change the side-chain populations . Anomolously wide distributions are observed for rotations about the peptide bonds and the disulfide bonds in the NP-5 distance geometry structures, which are improved by the refinement . The very high degree of order observed for the central dihedral angle of the disulfide bond in the high-resolution crystal data base suggests that the rotation about this bond in proteins is determined by the local potential. Proc Natl Acad Sci U S A, 1990 Dec, 87(24), 10048 - 52 Loss of DNA-membrane interactions and cessation of DNA synthesis in myeloperoxidase-treated Escherichia coli; Rosen H et al.; Neutrophils and monocytes employ a diverse array of antimicrobial effector systems to support their host defense functions . The mechanisms of action of most of these systems are incompletely understood . The present report indicates that microbicidal activity by a neutrophil-derived antimicrobial system, consisting of myeloperoxidase, enzymatically generated hydrogen peroxide, and chloride ion, is accompanied by prompt cessation of DNA synthesis in Escherichia coli, as determined by markedly reduced incorporation of {3H}thymidine into trichloracetic acid-precipitable material . Simultaneously, the myeloperoxidase system mediates a decline in the ability of E . coli membranes to bind hemimethylated DNA sequences containing the E . coli chromosomal origin of replication (oriC) . Binding of oriC to the E . coli membrane is an essential element of orderly chromosomal DNA replication . Comparable early changes in DNA synthesis and DNA-membrane interactions were not observed with alternative oxidant or antibiotic-mediated microbicidal systems . It is proposed that oxidants generated by the myeloperoxidase system modify the E . coli membrane in such a fashion that oriC binding is markedly impaired . As a consequence chromosomal DNA replication is impaired and organisms can no longer replicate. Pediatrics, 1990 Dec, 86(6), 848 - 55 Clinical role of respiratory virus infection in acute otitis media; Arola M et al.; The clinical characteristics of acute otitis media in relation to coexisting respiratory virus infection were studied in a 1-year prospective study of 363 children with acute otitis media . Respiratory viruses were detected using virus isolation and virus antigen detection in nasopharyngeal specimens of 42% of the patients at the time of diagnosis . Rhinovirus (24%) and respiratory syncytial virus (13%) were the two most common viruses detected . Adenovirus, parainfluenza viruses, and coronavirus OC43 were found less frequently . The mean duration of preceding symptoms was 5.9 days before the diagnosis of acute otitis media . Ninety-four percent of the children had symptoms of upper respiratory tract infection . Fever was reported in 55% and earache in 47% of cases . Patients with respiratory syncytial virus infection had fever, cough, and vomiting significantly more often than patients with rhinovirus infection or virus-negative patients . No significant differences were found in the appearance of the tympanic membrane and outcome of illness between virus-negative and virus-positive patients with acute otitis . Most patients respond well to antimicrobial therapy despite the coexisting viral infection . If the symptoms of infection persist, they can be due to the underlying viral infection, and viral diagnostics preferably with rapid methods may be clinically useful in these patients. Br J Haematol, 1990 Dec, 76 Suppl 2, 14 - 8 A clinical trial on efficacy and safety of teicoplanin in combination with beta-lactams and aminoglycosides in the treatment of severe sepsis of patients undergoing allogeneic/autologous bone marrow transplantation; Lang E et al.; Early institution of empiric therapy with a broad-spectrum antibiotic has markedly reduced the morbidity and mortality from infections complicating severe or prolonged cytopenia in patients receiving either an allogeneic or autologous bone marrow transplant . Ceftazidime in combination with an aminoglycoside, i.e . netilmicin, has been established as a combination schedule offering low or even avoiding therapy-related toxicity . We evaluated teicoplanin for suspected Gram-positive infections after inadequate response to initial beta-lactam and aminoglycoside combination therapy . All 11 patients so far included in this study received either an allogeneic (five patients) or an autologous (six patients) bone marrow transplant for acute myeloid leukaemia (AML), non-Hodgkin lymphoma (NHL, high grade) or other malignant diseases . All patients developing a primary septicaemia of unknown origin (10 patients) or a catheter related septicaemia (one patient) were treated with 400 mg teicoplanin, administered i.v . once daily in combination with a cephalosporin and an aminoglycoside (ceftazidime 2 g, i.v., t.i.d., netilmicin 400 mg once daily) . All 11 patients responded to therapy, 10 patients were clinically cured, one patient improved under therapy . The therapeutic regimen was well tolerated and adverse drug reactions did not occur . We have not observed any delayed take of prolonged neutropenia or thrombocytopenia with this therapeutic regimen when compared to other bone marrow transplant patients who did not receive this antimicrobial therapy . Our preliminary results suggest that teicoplanin is a potentially effective and well-tolerated antimicrobial agent in bone marrow transplant patients with infections not responding primarily to beta-lactams and aminoglycosides. Z Kinderchir, 1990 Dec, 45 Suppl 1, 5 - 7 A prospective randomised controlled trial of antimicrobial prophylaxis in hydrocephalus shunt surgery; Bayston R et al.; Despite attempts to reduce their incidence, shunt infections remain a major complication of the treatment of hydrocephalus . Various forms of antimicrobial prophylaxis are in use, but no controlled, statistically valid trial has been conducted to assess their efficacy . Such a trial was therefore carried out and its design is described here . After a 1-year retrospective and prospective study by members of the United Kingdom Hydrocephalus Group to establish feasibility and infection rates, a statistical study showed that at least 712 patients would be required . Six centres were enrolled to fulfil these requirements, and ethical committee approval was obtained at each . The chosen prophylactic regimen was 10 mg vancomycin administered into the ventricular system during surgery . Adults and children undergoing insertion or revision of ventriculoperitoneal shunts were included unless they were receiving therapeutic antimicrobials . Randomisation was by computer-generated numbers . Controls received the antimicrobial regimen, if any, currently used in that centre, the only difference between the two groups being intraventricular vancomycin in the test group . Diagnosis of shunt infection included accepted clinical and microbiological criteria reinforced by measurement of serum C-reactive protein levels . Follow-up was for at least six months . After 2.5 years only 158 patients had been enrolled in the trial, 80 controls and 78 tests . There were 5 preventable infections in the control group and 2 in the test group . In view of the small total the planned statistical analysis was not possible . Therefore, while no problems were encountered with toxicity, the trial failed to enroll enough patients to answer the question of efficacy of antimicrobial prophylaxis in shunt surgery and the reasons for this are discussed. Infect Immun, 1990 Dec, 58(12), 3893 - 8 Defect in the tissue cellular immune response: experimental visceral leishmaniasis in euthymic C57BL/6 ep/ep mice; Squires KE et al.; In BALB/c mice, successful defense against visceral leishmaniasis is T cell dependent, expressed by tissue granuloma formation, and probably mediated by macrophages activated by cytokines, including gamma interferon (IFN-gamma) . C57BL/6 ep/ep (pale ear) mice, which reportedly exhibit impaired IFN-gamma production, were challenged with Leishmania donovani to determine the outcome of infection in a euthymic host with an apparent defect in lymphokine secretion . In BALB/c and normal C57BL/6 mice, L . donovani liver burdens peaked at 2 weeks and were largely eliminated by 4 weeks . In contrast, in pale ear mice, infection progressed until after 4 weeks and persisted at high levels at 8 weeks . The failure to resolve hepatic infections was not related to deficiencies in (i) Thy-1+, L3T4+, or Lyt-2+ T cells; (ii) IFN-gamma secretion; (iii) liver tissue Ia expression; (iv) macrophage antimicrobial capacity; or (v) antileishmanial antibody production . However, despite the anticipated influx of mononuclear cells into livers, these cells were not properly focused on the parasitized Kupffer cells, the inflammatory infiltrate receded prematurely, and mature granulomas failed to develop . These results suggest that there is a cellular immune defect at the tissue level and emphasize the critical role of granuloma formation in successful resolution of systemic intracellular infections. Boll Chim Farm, 1990 Dec, 129(12), 314 - 6 New imidazolylpyrazoles of potential pharmaceutical interest; Lamartina L et al.; New imidazolylpyrazoles were synthesized and tested for antimicrobial activities . The compounds did not show any significant activity. Boll Soc Ital Biol Sper, 1990 Dec, 66(12), 1187 - 91 Studies on heterocyclic compounds: spiro {indole-3,2'-thiazolidine} derivatives . II . Antimicrobial activity of halogenated 3'-phenylspiro 3H-indole-3,2'-thiazolidine -2,4 (1H)-diones; Piscopo E et al.; The following polyhalogenated 3'-phenyl 3H-indole-3,2'-thiazolidine -2,4' (1H)-dione of general formula (A) were synthesized and screened for antimicrobial activity . (formula: see text) where: X = H (I, III, V, VII, IX, XI), CH3 (II, IV, VI, VIII, X, XII); Y = H (I, II), 2,4-F2 (III, IV), 2,4-Cl2 (V, VI), 3,4-Cl2 (VII, VIII), 2,6-Cl2 (IX, X), 2,4,6-Cl3 (XI, XII) . The general synthetic route involves the preparation of variously substituted isatin-3-imines, which are subjected to cyclocondensation with thioglycolic acid to give compounds I, III, V, VII, IX, XI, or thiolactic acid to give compounds II, IV, VI, VII, X, XII . The prepared compounds were screened against S . aureus, B . cereus, M . paratuberculosis, E . coli, Pr . mirabilis, Ps . aeruginosa, C . albicans, S . cerevisiae, A . niger by a disk-diffusion assay (Kirby-Bauer modified) . The results of the antimicrobial screening showed that the polyhalogenated derivatives of type (A) exhibited varying degrees of activity against Gram-positive, Gram-negative bacteria, and fungi . Compound (III) showed a significant activity toward A . niger, moreover compound (IV) was active toward C . albicans . Compound (IX) was very active toward S . typhi and Ps . aeruginosa . Compounds (VII), (IX) and (XII) were very active toward M . paratuberculosis. Boll Soc Ital Biol Sper, 1990 Dec, 66(12), 1181 - 6 Studies on heterocyclic compounds: spiro {indole-3,2'-thiazolidine} derivatives . Antimicrobial activity of monohalogenated 3'-phenylspiro 3H-indole-3,2'-thiazolidine-2,4' (1H)-diones; Piscopo E et al.; The following halogenated 3'-phenyl {3H-indole-3,2'-thiazolidine}-2,4'(1H)-dione of general formula (A) were synthesized and screened for antimicrobial activity . (formula: see text) where: X = H (I, III, V, VII, IX, XI, XIII, XV), CH3 (II, IV, VI, VIII, X, XII, XIV, XVI); Y = H (I, II), 3-F (III, IV), 2-Cl (V, VI), 3-Cl (VII, VIII), 4-Cl (IX, X), 2-Br (XI, XII), 3-Br (XIII, XIV), 4-Br (XV, XVI) . The synthetic approach involves the preparation of variously substituted Schiff-bases of indol-2,3-dione, which then are subjected to cyclocondensation with alpha-mercaptoalkanoic acids, to give spirothiazolidinones of type (A) . The prepared compounds were screened against S . aureus, B . cereus, M . paratuberculosis, E . coli, S . typhi, Pr . mirabilis, Ps . aeruginosa, C . albicans, S . cerevisiae, A . niger by a disk-diffusion assay (Kirby-Bauer modified . The results of the antimicrobial screening showed that the prepared compounds exhibited varying degrees of activity against Gram-positive, Gram-negative bacteria, and fungi . 3-Fluoro-derivative (III) showed inhibitory activity especially toward S . aureus and C . albicans . Chloroderivatives (VII) and (VIII) showed broad-spectrum "in vitro" antimicrobial activity, and were especially inhibitory toward S . aureus, E . coli, and S . Typhi . Fluoro-derivative (IV) and bromo-derivatives (XIII) and (XIV) possessed marked antimicrobial activity against M . paratuberculosis. Clin Oral Implants Res, 1990 Dec, 1(1), 33 - 40 Tissue integration of non-submerged implants . 1-year results of a prospective study with 100 ITI hollow-cylinder and hollow-screw implants; Buser D et al.; It has been postulated that the wound healing in a closed submerged location is one of the prerequisites for osseointegration of dental implants . The purpose of the present study was to evaluate the tissue integration of intentionally non-submerged titanium implants inserted by a one-stage surgical procedure . 100 ITI implants were consecutively placed in 70 partially edentulous patients . After a healing period free of masticatory loading for at least 3 months, the implants were examined . The clinical status showed for all implants neither detectable mobility nor signs of a peri-implant infection . Therefore, prosthetic abutments were inserted, and the patients were restored with fixed partial dentures . All patients were regularly recalled at 3-month intervals, and no patient dropped out of the study . Thus, all 100 implants were re-evaluated 12 months following implantation . Plaque- and sulcus bleeding indices, probing depth, clinical attachment level, width of keratinized mucosa, and periotest scores were assessed . In addition, standardized radiographs were analyzed for the presence of peri-implant radiolucencies and for the location of alveolar bone levels around the implants . Based on predefined criteria, the implants were classified as successful or failing . 98 implants were considered successful, and 1 implant failing . The remaining implant exhibited a peri-implant infection requiring local and systemic antimicrobial treatment . The results of this short-term study indicate that intentionally non-submerged ITI implants yield a high predictability for successful tissue integration. Oral Microbiol Immunol, 1990 Dec, 5(6), 315 - 9 Killing of oral, gram-negative, facultative bacteria by the rabbit defensin, NP-1; Miyasaki KT et al.; Oral, gram-negative, facultative bacteria, including Actinobacillus actinomycetemcomitans, Eikenella corrodens, and Capnocytophaga spp . have been associated with destructive periodontal infection . Neutrophils play a critical role in defending the periodontium against destructive infection . Defensins are antimicrobial peptides that have been isolated in human, rabbit, guinea pig, and rat leukocytes that may constitute an important nonoxidative mechanism of killing . The purpose of this study was to examine the sensitivity of a battery of oral, gram-negative, facultative bacteria to the bactericidal effects of the isolated rabbit peptide NP-1 . All species tested were killed by NP-1; however, there was strain-to-strain variation in sensitivity . The bactericidal effect was not dependent on net bacterial growth, although metabolic activity was evident as assessed by bacterial oxygen consumption . We conclude that bacteria are sensitive to the cidal mechanism involved in defensin-mediated bacterial killing and that the conditions of this assay system support the killing of bacteria by the defensin peptides. Semin Respir Infect, 1990 Dec, 5(4), 303 - 13 Pneumonia in the elderly: the hospital admission and discharge decisions; Fine MJ; Community-acquired pneumonia is both a common and a serious infection in the elderly population . The hospitalization and discharge decisions are among the most important management decisions physicians must make in caring for patients with this illness . Both of these decisions are important from a clinical, health services, and patient-oriented perspective . The hospitalization decision can be guided by a clinical algorithm that explicitly addresses five questions: (1) Does the patient have any life-threatening problems that require immediate stabilization (and de facto hospitalization)? (2) Does the patient have any prognostic factor(s) that increase the short-term risk of mortality? (3) Does the patient have any prognostic factor(s) that increase the short-term risk of morbidity or medical complications? (4) Does the patient have adequate functional skills or social support to allow care outside of the hospital? and (5) Does the patient require admission for a therapeutic modality or diagnostic evaluation? An affirmative response to any one of these questions indicates a need for hospitalization, whereas a negative response to all of the questions identifies potential candidates for outpatient care . The factors considered important in the hospitalization decision are also intimately related to the discharge decision . Before discharge, all acute physiological derangements should be corrected and laboratory abnormalities should be normalized or returning to baseline . All patients must be able to function socially outside of the hospital . Finally, treatment with an adequate course of antimicrobial therapy either must be completed or arranged on an ambulatory basis before discharge. Semin Respir Infect, 1990 Dec, 5(4), 276 - 94 Intensive care management of pneumonia in the elderly; Bell DD et al.; Arterial hypoxemia, hypercapnic respiratory failure, hypotension, and depressed level of consciousness are the usual reasons for admitting a patient with pneumonia to an intensive care unit (ICU) . Once the decision has been made to manage the patient in the ICU, age has little effect on the immediate goals of therapy, which include correction of hypoxemia, maintenance of adequate alveolar ventilation, and provision of sufficient blood pressure and cardiac output to support organ function until physiological homeostasis is restored as the pneumonia is controlled by appropriate antimicrobial therapy . Age-related decreases in physiological reserve are the major reasons specifically to consider ICU management of elderly pneumonia patients . These physiological changes increase the probability of major organ system failure with the development of pneumonia, and increase the likelihood that pneumonia will require ICU management . This has implications for the clinician regarding the selection and timing of therapeutic interventions . Unfortunately, the reduction of physiological reserve and the increased prevalence of coexistent chronic disease also result in significant mortality rates for elderly patients with pneumonia, potentially limiting the benefits of intensive care in this population . This raises a second issue: When, if ever, should intensive care not be used in the management of an elderly patient with severe pneumonia? A full discussion of the ethical issues surrounding this question is beyond the scope of this article, however, good medical ethics begin with sound medical judgment and are based upon solid clinical data . Accordingly, this article will also address the implications of age and underlying disease in the assessment of prognosis and use of the ICU in patients with pneumonia. Semin Respir Infect, 1990 Dec, 5(4), 260 - 8 Epidemiology of community-acquired pneumonia in the elderly; Marrie TJ; The attack rate for pneumonia increases with increasing age and with residence in a nursing home . The rate of hospitalization of Halifax County, Nova Scotia, Canada, residents with pneumonia was 1 in 1,000, while for nursing home residents it was 33 in 1,000 . The overall mortality rate for community-acquired pneumonia requiring hospitalization was 21.9% . Mortality was age-related: Seven percent of those 30 years of age or younger died, while 38% of those in the 81 to 90 year age group died . Comorbidities increased with increasing age from 0.73 +/- 0.81 for those 30 years old or younger to 2.75 +/- 1.47 for those 71 to 80 years of age . The most common comorbidities were chronic obstructive pulmonary disease, ischemic heart disease, hypertension, diabetes mellitus, malignancy, alcoholism, and neurological disease . The acquired immunodeficiency syndrome was a significant comorbidity among those 50 years of age or younger . Age-dependent trends were observed in the use of antimicrobial therapy: Cefamandole and aminoglycosides were prescribed more frequently with increasing age, whereas after the age of 61 years, the use of erythromycin declined . Penicillin usage was not age-dependent . Resource (hemograms, chest radiographs, blood chemistry, blood gases, and sputum culture) use peaked at the 50 to 60 year age group. J Chemother, 1990 Dec, 2(6), 348 - 50 In-vitro susceptibility of Borrelia burgdorferi and Borrelia hermsii to ten antimicrobial agents; Sambri V et al.; The in-vitro activity of ten antimicrobial agents against four strains of Borrelia burgdorferi originating both in the United States and Europe and against one isolate of B . hermsii was investigated . Ceftriaxone, erythromycin and roxithromycin were the most active drugs against both Borrelia species studied, with minimum bactericidal concentrations ranging from 0.015 micrograms/ml to 0.125 micrograms/ml. Med Hypotheses, 1990 Dec, 33(4), 241 - 4 Fever: thermodynamics applied to the leucocyte; Ngu VA; A fever, by raising the temperature of leucocytes, accelerates and so enhances their antimicrobial action against infections . This is in keeping with thermodynamic principles which apply to chemical and biochemical reactions . In keeping with the same thermodynamic principles, when the temperature of matter is raised, at certain critical temperatures its form and behaviour change dramatically and radically . Visible water, for example, boils at 100 degrees C into invisible steam . By analogy to such dramatic changes of behaviour it has been proposed as a hypothesis, that when the temperature of the leucocyte is raised in vitro to the extreme limit just before it dies, its behaviour will also change in a radical and dramatic manner to produce a totally new class of antimicrobial substances or antibiotics, called leucocyte derived antibiotics, LDA . The new LDA should have a wide spectrum of action against infecting micro-organisms including viruses that provoke a fever in the body . They should also have some anti-tumour effects in patients providing such leucocytes . Preliminary observations suggest that when the temperature of leucocytes is raised in vitro to the point of near cell death they can indeed produce new antimicrobial and antitumoral substances. Farmaco, 1990 Dec, 45(12), 1341 - 9 Synthesis of 1,3,4-thiadiazoles, imidazo{2,1-b}1,3,4-thiadiazoles and thiadiazolo{3,2-a}pyrimidines derived from benzimidazole as potential antimicrobial agents; Ashour FA et al.; Several new 1,3,4-thiadiazole, imidazo{2,1-b}1,3,4-thiadiazole and thiadiazole{3,2-al}pyrimidine derivatives of benzimidazole were synthesized . The compounds were obtained from 1-ethyl or benzyl 2-(2-amino-1,3,4-thiadiazol-5-yl)thiomethylbenzimidazole . The antimicrobial activity of the prepared compounds was studied. Antimicrob Agents Chemother, 1990 Dec, 34(12), 2300 - 3 Effects of colonial morphology and tween 80 on antimicrobial susceptibility of Mycobacterium paratuberculosis; Van Boxtel RM et al.; Smooth (Sm) and rough (Rg) colonial types of Mycobacterium paratuberculosis ATCC 19698 and two clinical isolates were tested to examine their growth responses in medium containing antimicrobial agents . Susceptibility tests were done in Middlebrook 7H12B medium with and without Tween 80 and one of the following antimicrobial agents: streptomycin, isoniazid, rifampin, ethambutol, ciprofloxacin, and penicillin G . Growth responses in the presence of antimicrobial agents led to the following observations . (i) In the absence of Tween, Rg colony types were more resistant than Sm colony types; (ii) the addition of Tween 80 significantly increased the susceptibility of both Sm and Rg colony types; however, the increase was greater with the Sm colony types . These studies showed that the antimicrobial susceptibility of M . paratuberculosis was significantly affected when Tween 80 was present in either the primary culture medium or the drug susceptibility test medium . In the absence of the perturbing influence of Tween 80, M . paratuberculosis was resistant to the antimicrobial agents tested. Postgrad Med J, 1990 Dec, 66(782), 1032 - 6 A review of typhoid fever in South African black children; Ellis ME et al.; Typhoid fever continues to escape swift diagnosis, even in an endemic country, and its multi-system nature led to delayed diagnosis in 25% of the patients in this study . This may have been an avoidable factor, leading to death in some patients through delay in instituting appropriate antimicrobial therapy . Neurological features and diarrhoea were particularly common in this paediatric population . Relative bradycardia has been shown to be a highly statistically significant finding for our group as a whole . Amoxycillin remains an effective and useful alternative to chloramphenicol . The mortality rate of 2.5% remains unchanged over the last 10 years . The relative inaccessibility to good primary health care, acceptable water supplies and sanitation that the black South African child encounters cannot be ruled out as a co-factor. J Antimicrob Chemother, 1990 Dec, 26(6), 841 - 6 Failure of prolonged treatment with ciprofloxacin in acute infections due to Brucella melitensis; Lang R et al.; A randomized prospective, pilot study was performed to compare the efficacy of oral ciprofloxacin (750 mg or 1000 mg bd) with standard oral antimicrobial therapy (rifampicin plus doxycycline) in the treatment of acute infection with Brucella melitensis . All antimicrobial drugs were administered for 42 days . Although all patients responded rapidly, five of the six patients receiving ciprofloxacin relapsed following cessation of therapy . There were no relapses among the patients who received doxycycline/rifampicin . Despite its in-vitro activity against B . melitensis (MIC 0.5 mg/l), ciprofloxacin, administered twice daily, does not appear to constitute adequate therapy for acute brucellosis. J Clin Microbiol, 1990 Dec, 28(12), 2722 - 5 Laboratory investigation of Acanthamoeba keratitis; Kilvington S et al.; Following the diagnosis of Acanthamoeba keratitis in a contact lens wearer, the antimicrobial susceptibility of the clinical isolate and the environmental source of the infection were investigated . Contrary to previous reports, in vitro antimicrobial testing showed that the infecting strain was inherently resistant to propamidine isethionate . Restriction endonuclease digestion analysis of Acanthamoeba whole-cell DNA of strains isolated from the patient's cornea, contact lens storage container, saline rinsing solution, and kitchen cold-water tap showed that the isolates were identical . This implicates, for the first time, domestic tap water as the source of Acanthamoeba sp . in this infection . It is therefore recommended that the use of homemade saline solutions and the rinsing of contact lenses in tap water be strongly discouraged. Agric Biol Chem, 1990 Dec, 54(12), 3093 - 7 Synthesis and antimicrobial activity of 2'-deoxypuromycin; Koizumi F et al.; 2'-Deoxypuromycin (2) was synthesized to learn the effect of the 2'-hydroxyl group on the biological activity . Acylated xylose 3 was condensed with silylated 6-chloropurine to give beta-D-xylofuranosyl-6-chloropurine derivative 4, whose 6-dimethylamination, 2'-deoxygenation and deprotection afforded 2'-deoxy-beta-D-xylofuranosyl purine analog 7 . The latter was converted to 2'-deoxypuromycin (2) in 8 steps . 2'-Deoxy analog 2 showed only weak antimicrobial activity compared with that of puromycin (1). Postgrad Med, 1990 Nov 15, 88(7), 33 - 6, 39-42, 47 Pneumococcal pneumonia . Recognizing and treating this persistent disease; Markowitz SM; Pneumococcal pneumonia remains a life-threatening disease despite the availability of many active antimicrobial agents and an effective vaccine . Dr Markowitz discusses why the disease persists, how it is diagnosed and treated, and what can be done to reduce its incidence. FEBS Lett, 1990 Nov 12, 274(1-2), 151 - 5 All-D-magainin: chirality, antimicrobial activity and proteolytic resistance; Bessalle R et al.; All-D-magainin-2 was synthesized to corroborate experimentally the notion that the biological function of a surface-active peptide stems primarily from its unique amphiphilic alpha-helical structure . Indeed, the peptide exhibited antibacterial potency nearly identical to that of the all-L-enantiomer . Being highly resistant to proteolysis and non-hemolytic all-D-magainin might have considerable therapeutic importance. J Biol Chem, 1990 Nov 5, 265(31), 18871 - 4 Amino acid sequences of two proline-rich bactenecins . Antimicrobial peptides of bovine neutrophils; Frank RW et al.; Bactenecins are highly cationic polypeptides of the large granules of bovine neutrophils, exerting in vitro a potent antimicrobial activity . Two bactenecins, with an approximate molecular weight of 7000 and 5000, called Bac7 and Bac5, are characterized by a high content of proline (greater than 45%) and arginine (greater than 23%) residues . Their complete amino acid sequences were determined by automated Edman degradation combined, in the case of Bac5, with plasma desorption mass spectrometry . Bac7 comprises 59 residues and includes three tandem repeats of a tetradecamer characterized by several Pro-Arg-Pro triplets spaced by single hydrophobic amino acids . Resolution of the primary structure of Bac5 required fragmentation with N-bromosuccinimide as well as digestion of the obtained C-terminal fragment with carboxypeptidases P and Y directly in the mass spectrometer . Bac5 comprises 42 amino acid residues with a repeated motif of Arg-Pro-Pro triplets also alternating with single apolar residues. Khirurgiia (Mosk), 1990 Nov, (11), 100 - 4 {Ultraviolet irradiation of blood in surgery}; Piksin IN et al.; The results of complex treatment of 81 patients with pyoinflammatory diseases with the use of blood ultraviolet irradiation are discussed . A marked clinical effect was noted, the terms of treatment reduced by 5-10 days, the outcomes improved, and the number of complications decreased . Irradiation of autologous blood by ultraviolet rays led to modulation of the indices of antimicrobial protection, increase of the intensity of the histochemical reaction to peroxidase up to 40-50%, and diminution of pH in the neutrophil phagosomes to 5.0 . The ultrastructure and ability of thrombocytes to store serotonin were restored, and intensity of their metabolic processes increased, the membrane phospholipid composition changed, and juvenile platelet forms appeared. J Antimicrob Chemother, 1990 Nov, 26 Suppl D, 31 - 44 Safety profile of the quinolones; Stahlmann R; The most important finding from preclinical evaluation of fluoroquinolones has been their arthropathogenic potential in young animals . This toxic effect is found with all quinolones known so far and has led to the decision not to use them in children and adolescents, despite the fact that the significance of the effect for humans is still unclear . The mutagenic potential of the drugs seems to be low although bacterial DNA-metabolism is a major target of their action . Newer in-vitro methods to study topoisomerases from bacterial and mammalian cells are suitable to detect differences in the derivatives with regard to their mutagenic potential . The major adverse effects observed clinically with the four most often used fluoroquinolones norfloxacin, ciprofloxacin, ofloxacin and enoxacin are gastrointestinal disturbances (1.8-5%), reactions of the central nervous system (0.9-1.6%) and skin reactions (0.6-1.4%) . Higher incidences have been noticed during the clinical evaluation of fleroxacin at doses of 400 mg or more . A comparison of the adverse reaction frequencies of fluoroquinolones with those of other antimicrobial agents can most closely be made with the results from double-blind studies . Such results show that in most cases fluoroquinolones have been tolerated as well as or better than conventional drugs . Clinically relevant drug interactions have been observed with some quinolones that are metabolized primarily in the liver: enoxacin and ciprofloxacin reduce the theophylline clearance . Also, interactions of quinolones with Mg2(+)-containing antacids, which result in tremendous loss of bioavailability, are of therapeutic importance . Overall, fluoroquinolones are well tolerated and the incidences of side effects are similar to those of other antibacterials. Can J Microbiol, 1990 Nov, 36(11), 760 - 4 Glucose oxidase as the antifungal principle of talaron from Talaromyces flavus; Kim KK et al.; Analysis of an authentic sample of the antifungal antibiotic talaron from the biocontrol fungus Talaromyces flavus indicated that approximately 40% of the solid sample was glucose oxidase . High-performance liquid chromatography elution profiles of the antimicrobial activity of talaron coeluted with those of glucose oxidase . Fluorescence emission and excitation wavelength maxima for talaron were similar to those of glucose oxidase from Aspergillus niger . The molecular weight of talaron was 152,000 with a subunit molecular weight of 71,000 . The isoelectric point of talaron was pH 4.2 . Mobilities of talaron on native, sodium dodecylsulfate, and isoelectric focusing polyacrylamide gels were identical with those of glucose oxidase produced by T . flavus . Furthermore, talaron had antimicrobial activity only in the presence of glucose . Hydrogen peroxide produced by the action of glucose oxidase is toxic to Verticillium dahliae . This study indicates that the antifungal activity of authentic talaron resulted from glucose oxidase produced by T . flavus. J Parenter Sci Technol, 1990 Nov-Dec, 44(6), 314 - 9 An evaluation of preservative adsorption onto nylon membrane filters; Guilfoyle DE et al.; Pharmaceutical drug products often contain antimicrobial agents as a preservative in their formulation . These excipients are required to destroy or impede the growth of microorganisms that inadvertently enter the product during manufacturing . Unfortunately, these preservatives may also interfere with microbiological assays used to determine product sterility or bioburden levels . The extent of interference by these preservatives can be quite significant, but varies depending on the method used . The most frequently used method for testing parenteral drug products is the membrane filtration technique . Membrane filters are composed of a wide variety of materials such as cellulose, polycarbonate, acrylic polypropylene, Teflon, and nylon . This study evaluated the adsorption characteristics that nylon filters, obtained from five different manufacturers, had on the filtration of solutions of four different antimicrobial compounds (phenol, methylparaben, propylparaben, and benzalkonium chloride) . The adsorption properties were determined using both HPLC and microbiological assay techniques . The data revealed that there was a wide range in the amounts of antimicrobial agent (2.3 to 94.1%) bound to the membrane filters when direct product filtration was used without a subsequent rinse step . However, when a rinse step is included, only propylparaben showed any significant "true" adsorption (less than 1 to 33.3%), but showed only marginal bacterial inhibition . Interestingly, the microbiological assays indicated that with a saline rinse step, only benzalkonium chloride was lethal for the two challenge organisms even though the percent adsorbed as measured by HPLC was below 1% . This discrepancy is significant because it demonstrates the analytical limitation when using HPLC to detect minimal concentrations of benzalkonium chloride that may be deleterious to microorganisms.(ABSTRACT TRUNCATED AT 250 WORDS) Am J Hosp Pharm, 1990 Nov, 47(11 Suppl 3), S6 - 10 Pathophysiology and treatment of gram-negative sepsis; DiPiro JT; The pathogenesis, clinical presentation, and complications of gram-negative bacterial sepsis are described, and the implications for therapy are reviewed . The sepsis syndrome is a clinically defined condition that involves the physiologic alterations and clinical consequences of the presence of microorganisms or their toxins in the bloodstream or tissues . Gram-negative bacteria produce sepsis and septic shock via the release of the cell-wall component known as endotoxin (lipopolysaccharide) . The lipid A moiety, common to gram-negative bacteria, is immunogenic and appears to account for many of the biologic effects of endotoxin . A variety of mediators, including tumor-necrosis factor, are released in response to endotoxin, with resultant diverse effects on host tissues, including organ dysfunction and shock . Adequate treatment requires prompt recognition of infection, especially endotoxemia and sepsis, and the early institution of appropriate therapy . Corticosteroids offer little benefit, and the efficacy of naloxone and nonsteroidal anti-inflammatory drugs has not been determined . Although suitable antimicrobial therapy is necessary to eliminate the offending organisms, antimicrobial agents do not inhibit the effects of the bacterial toxins that are present in sepsis . The outcome of sepsis may be favorably influenced in the future by the use of newer methods of detection and newer treatment modalities, including monoclonal antibodies directed against endotoxin or inhibitors of inflammatory mediators. Am J Hosp Pharm, 1990 Nov, 47(11 Suppl 3), S11 - 5 Role of monoclonal antibody therapy in the treatment of infectious disease; Chmel H; The past, present, and emerging roles of immunotherapy, including the use of monoclonal antibodies for diagnosis and treatment, are discussed . Although immunotherapy has been used for more than 100 years, it became less important when antimicrobial agents came into widespread use . In the 1970s investigators began to re-examine immunotherapy for potential use in gram-negative infections . Polyclonal antiserum against the J5 mutant of Escherichia coli (gram-negative lipid A) has been shown to be effective in treating patients with bacteremia and septic shock . The discovery of monoclonal antibodies and the creation of hybridoma technology by the fusion of immortal cells with antibody-producing cells have resulted in the production of large amounts of monoclonal antibodies of desired specificities . More recently, murine monoclonal antibodies have been used clinically for immunosuppression in renal-transplant patients (OKT3 antibody) and for prevention of septic complications in patients with suspected gram-negative infection and evidence of systemic response (E5 IgM antibody) . E5 antibody directed against gram-negative bacterial endotoxin has been reported to significantly reduce morbidity and mortality from gram-negative sepsis and to be well tolerated . The application of new treatment modalities such as monoclonal antibodies is expected to enhance the therapeutic options available to treat infectious diseases. Rinsho Byori, 1990 Nov, 38(11), 1226 - 31 {Infection with Pseudomonas pseudomallei}; Arakawa M; Melioidosis, a severe, often fatal disease caused by infection with Pseudomonas pseudomallei, has been thought to be a rare endemic disease relatively limited to the areas 20 degrees on either side of the equator . However, an increasing number of people travelling to these areas are reportedly suffering from this disease . It is timely to review this disease for doctors who are unfamiliar with this disease . P . pseudomallei, first discovered by Whitmore and Krishnaswami in 1912, is a gram-negative aerobic rod, motile due to polar flagella, isolated from soil and natural waters in endemic areas, and presumably transmitted to human beings through skin abrasion, ingestion and inhalation . Associated underlying conditions must be searched for, such as diabetes mellitus and chronic renal failure . Clinical classification ranges from disseminated septicemic melioidosis, the most serious form, to subclinical melioidosis, the least serious form . Disseminated septicemic type is associated with high fever, multiple organ lesions with septic shock and high fatality rate within a few days after symptoms develop . This type of infection requires prompt institution of antimicrobial therapy as well as surgical intervention such as drainage . Antimicrobial agents should be carefully selected according to the susceptibility results of the isolates . During the suspected stage, ceftazidime is a drug of choice . Subclinical melioidosis associated with positive serologic test alone should be closely followed up against the potential reactivation of dormant infection with P . pseudomallei . We must certainly be aware of melioidosis and diagnose melioidosis as early as possible by completing the initial routine diagnostic procedures to febrile patients. Rev Infect Dis, 1990 Nov-Dec, 12(6), 1109 - 26 Antibiotic-associated hypoprothrombinemia: a review of prospective studies, 1966-1988; Shevchuk YM et al.; Many antimicrobial agents have been associated with hypoprothrombinemia . The precise mechanisms are unknown, but alteration in vitamin K status or utilization is involved . The two postulated mechanisms implicate either direct inhibition of biosynthesis of the vitamin K-dependent clotting factors by the N-methylthiotetrazole (NMTT) moiety found in certain antimicrobial agents or eradication of vitamin K-producing intestinal microflora in patients with reduced oral intake of vitamin K . An English-language review of all prospective studies reported between 1966 and 1988 in which serial prothrombin times were monitored in adult patients revealed that the incidence of hypoprothrombinemia varied from 3.7% to 64% with NMTT-containing regimens and from 0% to 24% with non-NMTT-containing regimens . Detailed evaluation of t