Bactericidal

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 these and other studies suggests that certain risk factors, including malnutrition, hepatic and renal dysfunction, older age, and severity of illness, may be the major determinants of hypoprothrombinemia . The hypothesis that the NMTT side chain is primarily responsible for hypoprothrombinemia may not be justified . We conclude that patients at high risk for coagulopathy should be carefully monitored and that serious consideration should be given to the use of prophylactic vitamin K in such cases.

Clin Pediatr (Phila), 1990 Nov, 29(11), 634 - 9
Once-daily intramuscular ceftriaxone in the outpatient treatment of severe community-acquired pneumonia in children; Leibovitz E et al.; Ceftriaxone, a broad spectrum third-generation cephalosporin with a half-life of six to eight hours, was evaluated prospectively in 147 children with severe community-acquired bacterial pneumonia during the period 11/15/88-5/15/89 . Thirty-nine of the children had been unsuccessfully treated with vanous oral antibiotics prior to admission {corrected} . All the patients were initially hospitalized and started on once a day intramuscular ceftriaxone . Mean duration of ceftriaxone therapy was five days . Pathogens were recovered from blood cultures of 17 (11.6%) patients and included S . pneumoniae (13 patients), H . influenzae (three, all resistant to ampicillin) and S . viridans (1) {corrected} . All isolates were sensitive to ceftriaxone . An additional patient had L . pneumophila diagnosed by serology . Cure was achieved in 142 (96.6%) patients; improvement was usually observed within 24-48 hours . After 48 hours, 121 (82.2%) children could be discharged and continued the therapy on ambulatory basis . Based on previous experience we estimated that 383 hospitalization days were saved . No serious side effects were observed . Five patients were considered therapeutic failures; two of them developed empyema and one of them required repeated drainage procedures . A third patient experienced a relapse of pneumonia shortly after completion of therapy . The other two remained febrile for more than seven days; their subsequent improvement was unrelated to the antibiotic therapy, suggesting a viral or mycoplasmal syndrome . Our data suggest that once daily intramuscular ceftriaxone can be successfully used for the outpatient treatment of most community-acquired severe bacterial pneumonias in children . In our opinion it represents the treatment of choice for patients who failed treatment with other antimicrobials and are clinically stable enough not to require hospitalization.

J Clin Periodontol, 1990 Nov, 17(10), 698 - 701
The effect of triclosan, stannous fluoride and chlorhexidine products on: (II) Salivary bacterial counts; Jenkins S et al.; A previous study demonstrated that triclosan and stannous fluoride containing oral hygiene products reduced plaque regrowth compared to saline but were not more effective than a conventional commercial fluoride/anionic detergent toothpaste . To further understand these results, this study measured the persistance of antimicrobial activity of the same products by recording the duration of salivary bacterial count reductions following a single exposure to each product . Comparison was also made with a chlorhexidine rinse as the positive control . From a panel of 16 volunteers, in an 8-cell randomised cross-over designed study, salivary bacterial counts were recorded at baseline and to 420 min . All test and control products were significantly more effective than saline and significantly less effective than chlorhexidine at suppressing bacterial counts . Unlike chlorhexidine, evidence of bacterial recovery was apparent after the 30-min sampling time . There were essentially no significant differences between the test and control products, although the stannous fluoride toothpaste performed marginally better than other products . The findings are consistent with the plaque regrowth results previously obtained and again demonstrate to date that it is difficult to surpass the antimicrobial and plaque inhibitory properties of conventional commercially available toothpastes by the addition of antimicrobial agents such as triclosan and metal salts.

J Anim Sci, 1990 Nov, 68(11), 3642 - 8
Antimicrobial supplementation of growing pigs: the effect of porcine sera fractions on in vitro muscle cell proliferation; Hathaway MR et al.; Sera obtained from pigs before and after subtherapeutic levels of ASP250 supplementation (pre and post serum pools) have been subjected to comparative fractionation by using gel filtration and affinity chromatography on immobilized Cibacron Blue F3G-A . Comparable serum fractions obtained from pre- and post-ASP250 blood sera were assayed in muscle cell culture bioassays designed to measure their effect on proliferation . Pre- and post-ASP250 sera were subjected to gel filtration and divided into the following fractions: fraction 1, Kav less than .17; fraction 2, Kav = .17 to .41; fraction 3, Kav = .41 to .59 . Post-ASP250 fractions 2 and 3 increased proliferation rate in cultured muscle cells to a greater extent than comparable pre-ASP250 fractions (P less than .001) . Chromatography of fraction 3 on immobilized Cibacron Blue F3G-A showed that both pre- and post-ASP250 fraction 3 contained a putative inhibitor of myogenic cell proliferation as well as mitogenic factors . However, negative growth factor activity was greater in pre-ASP250 fraction 3 than in post-ASP250 fraction 3 (P less than .05) . Additionally, positive growth factor activity was lower in pre-ASP250 fraction 3 than in post-ASP250 fraction 3 (P less than .05) . These data suggest that levels and(or) activities of both positive and negative muscle growth factors in serum may be altered by the addition of antimicrobials to the diets of growing pigs.

Infect Control Hosp Epidemiol, 1990 Nov, 11(11), 595 - 9
Importance of neutralizers in the stripping fluid in a simulated healthcare personnel handwash; Benson L et al.; The Food and Drug Administration (FDA) healthcare personnel handwash procedure allows for the use of a non-neutralizing stripping fluid after washing with an antimicrobial handwash product . The antimicrobial in the handwash product can remain active up until the time of neutralization or plating . A modified healthcare personnel handwash procedure using a pigskin substrate and a 4% chlorhexidine gluconate handwash product was used to demonstrate the need for a neutralizer in the stripping fluid . When tests were run with and without neutralizers in the dilution blanks, but with adequate neutralizers in the stripping fluid, there were no significant differences (p greater than .05) between results obtained after five washes or after each wash . When tests were run with a non-neutralizing stripping fluid, significant differences were noticed in the first and the fifth wash (p less than .05), and in the presence or absence of neutralizers in the dilution blanks (p less than .05) . The data generated indicate that in order to determine the true activity of an antimicrobial handwash product, an adequate neutralizer should be incorporated into the stripping fluid and not just the dilution media . They also suggest that neutralizer carry-over from the stripping fluid is not a valid concern.

J Periodontol, 1990 Nov, 61(11), 663 - 9
Clinical and microbiological effects of subgingival and gingival marginal irrigation with chlorhexidine gluconate; Jolkovsky DL et al.; Recent interest in the local delivery of antimicrobial and anti-inflammatory agents has stimulated interest in the efficacy of various treatment regimens . Chlorhexidine gluconate (CHX) delivered daily by home-applied marginal irrigation as a 0.04% solution in combination with a single professional irrigation of 0.12% CHX was tested over a 3-month period . Sixty periodontal maintenance patients each having at least 2 pockets greater than or equal to 4 mm probing depth, and bleeding on probing were assigned to either Group 1: one professional subgingival 0.12% CHX (Peridex) irrigation (Perio Pik) followed by adjunctive daily home marginal 0.04% CHX irrigation (Pik Pocket); Group 2: one professional subgingival 0.12% CHX irrigation followed by adjunctive daily home marginal water irrigation; Group 3: one professional subgingival water irrigation followed by adjunctive daily home marginal water irrigation; or Group 4: control . At baseline and 3 month visits, subgingival plaque samples were taken from 2 sites per patient . Cultural microbiological analysis was performed using non-selective and selective media . Plaque Index, Gingival Index, pocket probing depths, and gingival recession were assessed . Scaling and root planing (supportive periodontal treatment) was provided for each patient followed by subgingival irrigation as outlined above . At 3 months the Gingival Index and pocket probing depths were both significantly reduced (P less than .05) in all irrigation groups compared to baseline . There were no significant changes in clinical parameters in the control group from baseline to 3 months . In Group 1 the GI was significantly reduced (P less than .05) compared to Group 4 at 3 months.(ABSTRACT TRUNCATED AT 250 WORDS)

J Clin Microbiol, 1990 Nov, 28(11), 2570 - 2
Osteomyelitis and synovitis produced by Mycobacterium marinum in a fisherman; Clark RB et al.; We report a case of osteomyelitis and synovitis produced by Mycobacterium marinum in the left index finger of a fisherman . A combination of surgical intervention and antimicrobial therapy with minocycline, rifampin, and ethambutol was efficacious.

J Pediatr Health Care, 1990 Nov-Dec, 4(6), 297 - 303
Pharmacologic treatment of otitis media and sinusitis in pediatrics; Zenk KE et al.; Otitis media and sinusitis are common diseases of childhood whose treatment is essential to long-term health . This article presents an update on the microorganisms involved in these two conditions and the selection and appropriate use of antimicrobial drugs for treatment . The issues of prophylaxis of recurrent otitis media and potential vaccines are discussed . In addition, approaches to increase patient compliance are presented, and the role of the nurse in educating parents about the condition and its treatment is discussed.

J Hered, 1990 Nov-Dec, 81(6), 428 - 33
Rheumatic fever susceptibility in four ascertainments: regressive segregation on a geometric ascertainment pattern; Sit KH; On resolving the ascertainment biases of the observed data in the geometric continuum vaffected-1 x P(sibship), where 0 less than v----infinity, four published ascertainments of rheumatic fever show excellent conformation with Mendelian recessive segregation, even in multiplex sibships . In two surveys in which ascertainment bias is near or a little above random sampling (v = 1), this conclusion is further corroborated by classical segregation analysis . The other two surveys have bias trends declining (v less than 1) very much below random sampling . Such levels of ascertainment bias, if defined through the ascertainment probability parameter pi, would be out of range because the range is from single ascertainment, where pi----0 to random sampling where pi = 1 and probability cannot exceed unity . Highly successful antimicrobial measures that would reduce the number of diseased sibs independent of the distribution of susceptible sibs could produce a dissociation of the gene-to-"rheumatic" relationship and thus explains the declining ascertainment bias.

Am J Surg, 1990 Nov, 160(5), 473 - 80
Algorithm for assessing renal dysfunction risk in critically ill trauma patients receiving aminoglycosides; Boucher BA et al.; A recent retrospective study proposed that the following screening criteria be used in identifying critically ill trauma patients receiving aminoglycosides who are at significant risk to develop renal dysfunction: (1) post-admission shock, (2) minimum serum concentration more than 2 mg/L, and (3) diagnosis of septicemia . The major purpose of the present study was to validate these criteria and design a corresponding algorithm for clinical use . All patients admitted to a trauma intensive care unit and receiving an aminoglycosides was also studied . All patients studied over a 7-month period . A control group not receiving aminoglycosides was also studied . All patients were evaluated for the presence of renal dysfunction (i.e., serum creatinine increase greater than or equal to 0.5 mg/dL) . Univariate and multivariate statistical analyses were used to compare potential associated risk factors . The overall renal dysfunction incidence was 10% in the treatment patients (n = 93) versus 5% in the control patients (n = 199) (p = 0.13) . Sensitivity and specificity of the screening criteria were 67% and 92%, respectively . The predictive values of a positive and negative test relative to correctly labeling patients at high risk or low risk to develop renal dysfunction were 46% and 96%, respectively . Major risk factors associated with renal dysfunction in the treatment group were post-admission shock, minimum serum concentration more than 2 mg/L, and liver dysfunction . Use of three major risk factors has excellent predictive value in identifying severely traumatized patients at low risk for developing renal dysfunction while receiving aminoglycosides . The modest predictive value of a positive test results in conservative management of patients by avoidance of aminoglycosides, i.e., use of alternative antimicrobial agents.

Am J Obstet Gynecol, 1990 Nov, 163(5 Pt 1), 1580 - 91
Cervicovaginal microflora and pregnancy outcome: results of a double-blind, placebo-controlled trial of erythromycin treatment; McGregor JA et al.; Available information suggests that some instances of preterm birth or premature rupture of membranes are associated with clinically unrecognized infection and inflammation of the lower uterine segment, decidua, and fetal membranes . Various cervicovaginal microorganisms have been recovered from these sites . Many of these microorganisms produce factors that may lead to weakening of the fetal membranes, release of prostaglandins, or both . This study evaluated the presence of various lower genital tract microflora and bacterial conditions in 229 women enrolled in a double-blind, placebo-controlled trial of short-course erythromycin treatment at 26 to 30 weeks' gestation to prevent preterm birth . Demographic, obstetric, and microbiologic parameters were prospectively evaluated . Premature rupture of membranes occurred less frequently (p less than 0.01) among women who received erythromycin (6%) versus placebo (16%) . Preterm premature rupture of membranes also occurred less frequently, although not significantly (p = 0.3) in patients who received erythromycin (2%) versus placebo (5%) . Erythromycin treatment significantly decreased the occurrence of premature rupture of membranes among women who were initially positive for Chlamydia trachomatis infection . Logistic regression analysis demonstrated that C . trachomatis (p = 0.05; odds ratio, 9), vaginal wash phospholipase C (p = 0.08; odds ratio, 6) and prior preterm birth (p = 0.007; odds ratio 17) were associated with increased risk of preterm birth . Bacterial vaginosis, Mycoplasma hominis, Ureaplasma urealyticum were not significantly associated with increased risk of preterm birth or preterm rupture of membranes . These findings support a role for selected lower genital tract microflora in preterm birth and premature rupture . Large controlled treatment trials of specific infections or conditions associated with preterm birth and premature rupture of membranes are required to confirm the value of antimicrobial treatments in prevention of microbial-associated preterm birth.

Urology, 1990 Nov, 36(5 Suppl), 13 - 7
Diagnosis and treatment of prostatic infections; Schaeffer AJ; The diagnosis and management of prostatitis and pelviperineal pain is a challenge to the clinician . Careful examination of the prostatic fluid and bacteriologic cultures to differentiate bacterial from nonbacterial prostatitis are essential . Antimicrobial therapy is effective in the majority of men with acute or chronic bacterial prostatitis . Nonbacterial prostatitis is the most common type of prostatitis . The etiology is unknown and treatment with repeated antimicrobial therapy is ineffective . Alpha-blocking agents may relieve symptomatology . Pelviperineal pain may be of prostatic origin but other nonprostatic causes should be sought.

Surgery, 1990 Nov, 108(5), 847 - 50
Hyperbaric oxygen therapy for necrotizing fasciitis reduces mortality and the need for debridements; Riseman JA et al.; Twenty-nine patients with necrotizing fasciitis were treated from 1980 to 1988 . This study evaluates how the addition of hyperbaric oxygen (HBO) therapy to surgical treatment has affected mortality and the number of debridements required to achieve wound control in these patients . Two groups of patients were viewed: group 1 (n = 12) received surgical debridement and antibiotics only; group 2 (n = 17) received HBO (90 minutes at 2.5 atm, average 7.4 treatments) in addition to surgery and antibiotics . Both groups were similar in age, race, sex, wound bacteriology, and antimicrobial therapy . Body surface area affected was similar, however, perineal involvement was more common in group 2 (53%) than in group 1 (12%) . The admitting conditions of patients in group 1 (non-HBO) were diabetic, 33%; white blood cell count more than 12,000, 50%; and shock, 8% . The admitting conditions of patients in group 2 (HBO) were diabetic, 47%; white blood cell count more than 12,000, 59%; and shock, 29% . Although group 2 patients receiving HBO were more seriously ill on admission, mortality was significantly lower (23%) compared to group 1 (66%) (p less than 0.02) . In addition, only 1.2 debridements per group 2 patient were required to achieve wound control versus 3.3 debridements per group 1 patient (p less than 0.03) . The addition of HBO therapy to the surgical and antimicrobial treatment of necrotizing fasciitis significantly reduced mortality and wound morbidity (number of debridements) in this study, especially among nonclostridial infections . We conclude that HBO should be used routinely in the treatment of necrotizing fasciitis.

Medicine (Baltimore), 1990 Nov, 69(6), 392 - 8
Extrapulmonary pneumocystosis: clinical features in human immunodeficiency virus infection; Northfelt DW et al.; Pneumocystis carinii infection is reported with increasing frequency as a cause of disease outside of the respiratory tract in patients with human immunodeficiency virus (HIV) infection . Extrapulmonary pneumocystosis is not limited to patients in any discrete risk group for HIV infection . Patients with HIV infection who develop extrapulmonary pneumocystosis frequently do not have concurrent P . carinii pneumonia . Signs and symptoms of extrapulmonary pneumocystosis are nonspecific but when present are frequently referable to the tissues or organs involved . Extrapulmonary pneumocystosis can be diagnosed by examination of tissue biopsies from affected sites using standard histologic techniques . Therapy with antimicrobial agents used to treat P . carinii pneumonia has been effective in some patients . An association between use of aerosolized pentamidine for prevention of P . carinii pneumonia and development of extrapulmonary pneumocystosis has been suggested but remains unconfirmed . Other factors such as the use of zidovudine and duration of immunodeficiency may also be important to the pathogenesis of extrapulmonary pneumocystosis . Further studies are needed to better identify risk factors that may predispose patients to the development of extrapulmonary pneumocystosis.

J Med Chem, 1990 Nov, 33(11), 3086 - 94
Synthesis and structure-activity relationships of new 9-N-alkyl derivatives of 9(S)-erythromycylamine; Kirst HA et al.; A series of new 9-N-alkyl derivatives of 9(S)-erythromycylamine has been synthesized by reductive alkylation of erythromycylamine with aliphatic aldehydes and sodium cyanoborohydride . Alternative syntheses employing hydrogenation methods have also been developed . These new 9-N-alkyl derivatives possess excellent antimicrobial activity in vitro and in vivo, especially when administered orally to treat experimental infections in mice . From structure-activity studies, 9-N-(1-propyl)erythromycylamine (LY281389) was selected as the most efficacious derivative . These methods have also been extended to the synthesis of some 9-N,N-dialkyl derivatives of erythromycylamine.

Crit Care Med, 1990 Nov, 18(11), 1239 - 42
Prevention of nosocomial lung infection in ventilated patients: use of an antimicrobial pharyngeal nonabsorbable paste; Rodriguez-Roldan JM et al.; A comparative, prospective study was made of the incidence of infection in the lower airway (purulent tracheobronchitis and pneumonia) in long-term patients who were mechanically ventilated due to respiratory failure of noninfectious origin . Twenty-eight patients were randomly allocated into a study group (A, n = 13) in which a nonabsorbable paste containing 2% tobramycin, 2% amphotericin B, and 2% polymyxin E was administered locally to decontaminate the oropharynx, and a control group (B, n = 15) in which a paste without antibiotics was also applied to the oropharynx . We studied the effectiveness of the prophylactic technique in decontaminating the oropharynx and trachea of organisms potentially pathogenic for the respiratory system . Decontamination was successful in ten of 13 patients in group A vs . one of 15 patients in group B (p less than .001) . The results demonstrated a lower rate of infection in the lower respiratory tract in the study group (three patients with tracheobronchitis and no pneumonias) than in the control group (three patients with tracheobronchitis and 11 with pneumonia), the difference between both being highly significant (p less than .001) . Two (15%) patients in group B developed sepsis of pulmonary origin . None of the patients on prophylactic treatment developed this complication . Although the overall mortality was similar in both groups (group A, 30% vs . group B, 33%), we believe that infection contributed to a great extent to the death of two of five patients in group B . We conclude that nosocomial pneumonia, which is a frequent complication in critically ill patients on mechanical ventilation, could be prevented by local application of nonabsorbable antibiotics to the oropharynx.

Clin Geriatr Med, 1990 Nov, 6(4), 747 - 69
Foot ulceration and infections in elderly diabetics; Lipsky BA et al.; Foot lesions occur commonly among patients with diabetes, particularly the elderly and those with sensory neuropathy . Because of serious or recurrent infections and impaired healing processes, initially trivial lesions may progress to chronic nonhealing wounds, gangrene, or untreatable infections that can lead to limb amputation . Strategies to prevent amputation depend on understanding the multifactorial nature of diabetic foot disease; providing effective ongoing preventive care, including patient education; and prompt and aggressive treatment of foot lesions when they occur . The approach to treatment of infections depends on many factors, including the severity of the soft tissue infection, whether or not underlying bone or joints are involved, the types of infecting organisms, the patient's social situation, and his other medical problems . Proper diagnostic studies followed by appropriate antimicrobial therapy and local wound care can usually lead to resolution of these potentially serious infections.

J Histochem Cytochem, 1990 Nov, 38(11), 1531 - 4
Magainin-like immunoreactivity in human submandibular and labial salivary glands; Wolff A et al.; Magainins, antimicrobial peptides secreted by granular glands of frog skin, may be related to the high resistance to infections of this epithelial surface . The oral mucosa of healthy individuals is another tissue in which infection is not frequent, probably owing to the activity of potent salivary and mucosal defense mechanisms . To investigate if magainin-like factors are a component of these oral defense mechanisms, human and animal minor (mucosal) and major salivary glands were examined by immunohistochemistry, using a polyclonal rabbit anti-magainin antibody . Cryostat sections of (para) formaldehyde-fixed tissues were incubated with the antibody and then stained with fluorescein-complexed anti-rabbit IgG . Specific staining was observed in the apical portion of the cytoplasm of ductal epithelial cells of human submandibular and labial salivary glands . Diffuse staining was present in submandibular acinar cells . Bovine, rat, hamster, and mouse tissues were unreactive . The presence of magainin-like substances in human salivary gland duct cells is consistent with reports of the occurrence of other biologically active substances in salivary gland ducts.

J Periodontal Res, 1990 Nov, 25(6), 321 - 30
Low-dose doxycycline therapy: effect on gingival and crevicular fluid collagenase activity in humans; Golub LM et al.; Tetracyclines are now recognized to have non-antimicrobial properties with therapeutic potential--for example, these agents can inhibit pathologic collagenolysis by blocking mammalian collagenases and other matrix-degrading metalloproteinases . In the current study, adult human subjects with moderate chronic periodontitis were administered specially formulated capsules of doxycycline, containing lower-than-usual amounts of this semi-synthetic tetracycline, on a daily basis for 2 weeks prior to a full-thickness flap procedure; control subjects were administered placebo capsules . The gingiva excised during this surgical procedure were extracted, the extracts partially purified and analyzed for collagenase activity using {3H-methyl} collagen as substrate and the techniques of SDS-PAGE/fluorography or liquid scintillation spectrometry . In the absence of any drug pre-treatment, or after a 2-wk regimen of placebo capsules, the gingival extracts exhibited pathologically-excessive mammalian collagenase activity . The 2-wk regimen of low-dose doxycycline capsules reduced this activity by approximately 60-80% (p less than 0.05 and less than 0.01, respectively); in vitro exposure of the gingival extract to doxycycline also inhibited its collagenase activity . Collagenase activity in the crevicular fluid of periodontal pockets of an additional group of subjects was also significantly reduced, as was the severity of inflammation at the same gingival sites . The results suggest that a regimen of low-dose doxycycline capsules may provide a safe (other studies indicate that this regimen may not induce tetracycline resistance in the subgingival plaque) and effective adjunct to instrumentation therapy in the management of pathologic collagenolysis in the periodontal patient . However, further studies are necessary to confirm this hypothesis.

Rozhl Chir, 1990 Nov, 69(11), 774 - 80
{An effective and achievable system of ultrashort antimicrobial prophylaxis in colorectal surgery}; Korcek J et al.; The authors describe their own system of ultrashort antimicrobial prophylaxis in colorectal surgery . They give an account of two years' experience with their system of ultrashort antimicrobial prophylaxis and demonstrate its effectiveness, feasibility and economic advantages on a group of 113 patients . They implement the prophylaxis of wound infection in colorectal surgery by antibacterial substances which are available in all health facilities in Czechoslovakia . In a group of 113 patients after elective operations of the colon and rectum they recorded, when using their system of ultrashort antimicrobial prophylaxis, 7.07% wound complications.

Farmaco, 1990 Nov, 45(11), 1193 - 205
Synthesis of 3-(1,3,4-thiadiazol-2-yl)pyrazolo{1,5-a} pyrimidine derivatives as potential antimicrobial agents; Auzzi G et al.; The synthesis of some 3-(1,3,4-thiadiazol-2-yl)pyrazolo{1,5-a}-pyrimidine derivatives is performed by reacting 2-(3-amino-1,2-dihydro-5-oxo-5H-pyrazol-4-il)-1,3,4- thiadiazoles with 2,4-pentanedione, ethyl 3-oxobutyrate and diethyl ethoxymethylenemalonate . The antimicrobial activity of the synthesized compounds is reported.

Otolaryngol Head Neck Surg, 1990 Nov, 103(5 ( Pt 2)), 876 - 8; discussion 878-9
Therapeutic approach to sinusitis: antiinfectious therapy as the baseline of management; Winther B et al.; Although acute sinusitis is an infectious disease in which several bacterial species play a major etiologic role, there is an important interaction between the respiratory viruses (common cold viruses) and the bacteria in the pathogenesis of acute community-acquired sinusitis . The relative inaccessibility of the sinus cavities makes special techniques of sampling necessary to acquire specimens that accurately reflect disease conditions in the sinuses . Bacterial etiology of sinus infection has therefore been determined by sinus puncture studies, chiefly of the maxillary sinus, several of which are reviewed here . Because the bacteria causing acute sinusitis have not changed in many years, puncture is not often necessary for clinical diagnosis . Patients with acute, community-acquired sinusitis can usually be treated empirically, on the basis of previous studies, unless complications are suspected . In that case, and in other patients with hospital-acquired sinusitis, puncture of the involved sinus and aspiration of sinus fluid for Gram's staining and quantitative microbial cultures and sensitivities are required for appropriate antimicrobial management.

Infect Control Hosp Epidemiol, 1990 Nov, 11(11), 578 - 83
Changing surgical antimicrobial prophylaxis practices through education targeted at senior department leaders; Everitt DE et al.; Prescribing antibiotics for perioperative prophylaxis in common surgical procedures presents an ideal target for educational intervention . In this situation, antibiotics are often used inappropriately, with consequent excess expense and risk of morbidity . We developed an educational intervention aimed at the choice and appropriate dosing of antibiotics for the prophylaxis of cesarean sections . Person-to-person educational messages targeted at authoritative senior department members were supplemented by brief reminders on a structured antibiotic order form . Time-series analyses were conducted on 34 months of antibiotic use data for 2,783 cesarean sections to estimate the trend of magnitude and significance of discontinuities associated with the start of the program . Prior to the intervention, 95% of sections receiving prophylaxis were given cefoxitin and 3% were given cefazolin . After the intervention, these proportions were reversed, with the shift in use occurring immediately after the intervention (p less than .001) . Two years after the intervention, virtually all patients undergoing cesarean sections who receive antibiotic prophylaxis are given cefazolin . Savings from this change alone accounted for over $26,000 each year, or $47.36 per patient-day of prophylaxis . Substantial changes in prescribing practices for routine procedures can be accomplished through the implementation of a coordinated educational program that enlists influential senior staff members in a department in which policy-making is highly centralized, coupled with a structured educational ordering system . Lasting improvements in clinical practices may be brought about by means that are noncoercive, inexpensive and well-accepted by medical staff.

APMIS, 1990 Nov, 98(11), 1039 - 44
Antimicrobial susceptibility and beta-lactamase characterization of Branhamella catarrhalis isolates from 1983/1984 and 1988; Christensen JJ et al.; Branhamella catarrhalis isolates from lower respiratory tract specimens collected in 1983/84 (n = 50) and 1988 (n = 30) were examined for beta-lactamase production . The percent of beta-lactamase-producing strains increased from 25% to 63% from 1983/84 to 1988 . beta-lactamases from 30 strains could be typed, and of these 28 were of the BRO-1 type and two the BRO-2 type . The two beta-lactamase inhibitors, clavulanic acid and brobactam were very active against beta-lactamase extracts whether of the BRO-1 or the BRO-2 type . Susceptibility to a number of antimicrobial agents or combinations of agents was determined by a plate dilution method (MICs) and by a tablet diffusion method . The penicillin tablet (Rosco Neo-Sensitabs) was found to be useful in discriminating between beta-lactamase-producing and non-beta-lactamase- producing strains of B . catarrhalis.

Med Clin North Am, 1990 Nov, 74(6), 1353 - 66
Gonorrhea; Judson FN; During a 10-year period from 1976 to 1985, N . gonorrhoeae demonstrated remarkable genetic resiliency in developing clinically important antimicrobial resistance through a variety of chromosomal mutations and by acquiring either entire plasmids or resistance determinants on plasmids from other species . Gonococcal resistance is widespread, and few communities will be spared all types . None of the newer diagnostic technologies has provided any performance or cost advantages over traditional Gram-stained smears and cultures . The two most important components of a control program are (1) the National Gonococcal Isolate Surveillance project and (2) treatment with ceftriaxone, 125 or 250 mg intramuscularly, which is active against all known types of resistance and will cure all forms of uncomplicated gonorrhea, including the more difficult-to-treat infections of the pharynx and anorectum . Fear of AIDS has had a powerful motivating effect on sexual behavior, and in the United States has been associated with an overall reduction in incidence of gonorrhea in homosexual men of over 95% . After peaking in 1985, incidence of gonorrhea in white heterosexual men and women has declined as well . A diagnosis of gonorrhea in 1990 implies recent high-risk behavior for acquiring HIV infection . The gonorrhea epidemic in the United States is rapidly contracting down around poor urban minorities; although this is not good, at least it tells us where to target our resources.

Mikrobiol Zh, 1990 Nov-Dec, 52(6), 79 - 82
{The antimicrobial activity of desoxon-5 in the disinfection of plastics used in dental practice}; Flis PS et al.; The disinfecting effect to the new preparation--desoxon-5 when decontaminating plastics, used in stomatology, plastic removable {correction of demountable} dentures and orthodontic, apparatus, infected by test microbes has been studied . One of the results of the work is the determination of desoxon-5 concentrations, causing the death of test microbes on the surface of plastic objects . It is proposed to include the use of desoxon-5 as an active decontaminating preparation into the number of means on looking after removable {correction of demountable} plastic dentures.

Farmaco, 1990 Nov, 45(11), 1207 - 18
Synthesis of certain thiosemicarbazide and triazole derivatives as potential antimicrobial agents; Ashour FA et al.; Two novel series of thiosemicarbazide derivatives were synthesized: 2-{4-(substituted thiocarbamoylhydrazinocarbonyl) phenoxymethyl}-1H-benzimidazoles and 1-benzyl-2-{4-(substituted thiocarbamoylhydrazinocarbonyl) phenoxymethyl}-1H-benzimidazoles, and cyclised to 2-{4-(4-substituted-4H-1,2,4-triazole-5-thion-3-yl)phenoxymethy }-1H-benzimidazoles and 1-benzyl-2-{4-(4-substituted-4H-1,2,4-triazole-5- 5-thion-3-yl)phenoxymethyl}-1H-benzimidazoles, respectively . The antimicrobial activity of the prepared compounds was tested.

Am J Hosp Pharm, 1990 Nov, 47(11 Suppl 3), S16 - 9
Selecting patients for monoclonal antibody therapy; Fant WK; The role of the pharmacist in defining and implementing criteria for selection of patients who are most likely to benefit from monoclonal antibody therapy is discussed . The introduction of new biotechnology products has raised concerns about rationing of health-care services, particularly in view of the costs of drug research and development . Traditional antimicrobial therapy has not reduced morbidity and mortality from gram-negative sepsis . Early clinical trials indicate that immunotherapy with new agents that supplement the host immunological response to these infections may be effective . Criteria must be developed to identify patients who will obtain maximum benefits from these newer interventions . Severity-stratification systems (e.g., the APACHE II scoring system) have been used to classify disease and monitor treatment outcome . These techniques have been applied in clinical trials assessing E5 monoclonal antibody therapy in patients with gram-negative sepsis and in others evaluating the use of imipenem versus tobramycin and clindamycin in the treatment of intraabdominal infection . Pharmacists with a knowledge of infectious-disease processes and pharmacotherapeutics can play a major role in developing criteria for identifying patients who are most likely to benefit from the products of biotechnology and thereby ensuring the cost-effective use of these products.

Z Gesamte Hyg, 1990 Nov, 36(11), 622 - 4
{Use of disinfectant solutions at a university clinic}; Muhlhausen C et al.; As part of complex checkups of the antimicrobial regimen the application of disinfecting solutions (Fesia-form, Kombinal asept, Wofasept, Fesia-pin, peracetic acid-spirit SR, and Wofasteril) was studied at 12 institutions of the clinical centre of the medical school of the Friedrich Schiller University Jena from May 1986 to February 1988 . It was the aim of the studies to show how properly the disinfecting solutions were applied and whether their concentrations was correct . Despite several discussions and intensive instruction at the workplace the criticized institutions showed positive changes, clearly but not yet satisfactorily, only after the third follow-up inspection . Our results demonstrate a wide gap between theoretical knowledge and application in practice . Possible reasons for that and ways for improvement of the objective and subjective components leading to an incorrect application of disinfectants are discussed.

FEMS Microbiol Lett, 1990 Nov, 60(3), 281 - 4
Seminalplasmin, an antimicrobial protein from bovine seminal plasma, inhibits peptidoglycan synthesis in Escherichia coli; Chitnis SN et al.; Seminalplasmin, an antimicrobial protein from bovine seminal plasma, inhibited peptidoglycan synthesis in Escherichia coli in a concentration-dependent manner . The inhibition of peptidoglycan synthesis appears to be a cause rather than a consequence of growth inhibition as it was observed soon after the addition of the antibiotic even in E . coli cells whose growth was totally inhibited by chloramphenicol.

Arch Pharm (Weinheim), 1990 Nov, 323(11), 901 - 4
Synthesis and antimicrobiological activity of N-aryl-substituted 2-methyl-3-carbethoxy-5-pyrrolinone derivatives; Lovren F et al.; We describe the synthesis of N-aryl-2-methyl-3-carbethoxy-5-pyrrolinones benzylidene derivatives, their condensation with azomethines and substitution with aniline . The compounds have been tested for antimicrobial and fungicide activity: they have better fungicidal than bactericidal activity.

Vopr Med Khim, 1990 Nov-Dec, 36(6), 13 - 6
{Lysosomal cationic proteins in neutrophilic granulocytes during phagocytosis and inflammation}; Kokriakov VN; Literature and experimental data are reviewed on functional properties of cation proteins in neutrophil granulocytes under conditions of phagocytosis and inflammation . These proteins are not only effective antimicrobial agents but they regulate a lot of protective-adaptational reactions responsible for development of human and animal unspecific resistance.

Antimicrob Agents Chemother, 1990 Nov, 34(11), 2133 - 6
Comparative in vitro and in vivo susceptibilities of the Lyme disease spirochete Borrelia burgdorferi to cefuroxime and other antimicrobial agents; Johnson RC et al.; The in vitro and in vivo susceptibilities of the Lyme disease pathogen Borrelia burgdorferi to cefuroxime were compared with those of several other antibiotics commonly used to treat this disease . Cefuroxime demonstrated a higher MBC in vitro (1.0 microgram/ml) than ceftriaxone (0.08 microgram/ml) or erythromycin (0.32 microgram/ml), but the MBC was similar to that of amoxicillin (0.8 microgram/ml) and doxycycline (1.6 micrograms/ml) . B . burgdorferi was considerably less susceptible to tetracycline (3.2 micrograms/ml) and penicillin G (6.4 micrograms/ml) . Of the three other Borrelia species tested, two (Borrelia turicatae and Borrelia anserina) also demonstrated susceptibility to cefuroxime, while the third (Borrelia hermsii) was less susceptible . Results obtained with four antimicrobial agents in the in vivo hamster model parallel the antibiotic susceptibilities in the in vitro study . The three antibiotics with similar MBCs in vitro, i.e., cefuroxime, doxycycline, and amoxicillin, demonstrated comparable activities in preventing borreliosis in B . burgdorferi-challenged hamsters (50% curative doses = 28.6, 36.5 and 45.0 mg/kg, respectively) . Penicillin G, which demonstrated the highest MBC in vitro, had very weak protective activity in the hamster model system . These results indicate that the in vitro and in vivo activities of cefuroxime against B . burgdorferi are comparable to those of several oral antibiotics currently being used in the treatment of early Lyme disease and suggest that the oral form of this cephalosporin may be an effective alternative therapy for this disease.

Antimicrob Agents Chemother, 1990 Nov, 34(11), 2128 - 32
Disk elution method for MICs and MBCs; Wilson E et al.; A MIC macrodilution broth method in which routine antimicrobial susceptibility testing disks were used as a source of antibiotic was compared with the M7A reference method of the National Committee for Clinical Laboratory Standards for accuracy and reproducibility over five test runs . Gentamicin, piperacillin, and oxacillin were tested by using American Type Culture Collection quality control strains and laboratory isolates for which the MIC of each agent was known . An optimum time for elution of 1 h was first determined by timed elution in broth, confirming levels determined by the TDX method (Abbott, North Chicago, Ill.) for gentamicin and bioassay for piperacillin and oxacillin . MICs determined by the disk elution method demonstrated a reproducibility rate of 97% as well as 97% agreement with the reference method to within +/- 1 dilution; MBCs showed 93% agreement . The disk elution method is reproducible and provides a reliable test system that can be used by any laboratory in which disk susceptibility testing is performed.

J Clin Invest, 1990 Nov, 86(5), 1589 - 94
Cephalosporin-induced alteration in hepatic glutathione redox state . A potential mechanism for inhibition of hepatic reduction of vitamin K1,2,3-epoxide in the rat; Mitchell MC et al.; Hypoprothrombinemia is a serious adverse effect of antimicrobial therapy that occurs after administration of some second- and third-generation cephalosporins which contain the methyltetrazole-thiol (MTT) group . Previous studies have shown that in vitro MTT directly inhibits microsomal gamma-carboxylation of a synthetic pentapeptide . Since MTT is a thiocarbamide, a type of compound that can increase oxidation of glutathione, the present studies were carried out to determine whether alterations in hepatic glutathione redox state might interfere with vitamin K metabolism . Dose-related increases in biliary efflux and hepatic concentration of oxidized glutathione (GSSG) occurred after intravenous administration of MTT or MTT-containing antibiotics to rats . This finding suggested that these compounds could alter the hepatic glutathione redox state in vivo . Microsomal reduction of vitamin K epoxide occurred in the presence of 100 microM dithiothreitol (DTT), but was inhibited by preincubation with GSSG at concentrations as low as 10 microM . At higher concentrations of DTT (1.0 mM) inhibition by GSSG persisted, but higher concentrations were required, suggesting that the thiol/disulfide ratio, rather than the absolute concentration of GSSG was important . By contrast, GSSG did not effect microsomal gamma-carboxylation of a pentapeptide, using either vitamin K1 or its hydroquinone as a cofactor . These findings suggest a novel mechanism for the hypoprothrombinemia occurring after administration of MTT-containing antibiotics.

N Y State Dent J, 1990 Nov, 56(9), 37 - 9
Oral mucositis . A complication of radiotherapy; Rider CA; Oral mucositis is a complication of head and neck radiotherapy . It is understood what causes the inflammation and what biological tissue changes occur, however, a definite cure for oral mucositis has not yet been found . Supportive treatments, analgesics, antimicrobials and anti-inflammatory agents have been prescribed, none of which has been a thorough measure of treatment . An effective cure for oral mucositis is still in the midst of scientific research . In the interim local palliative treatments will help to alleviate the patients', debilitating symptoms.

Agric Biol Chem, 1990 Nov, 54(11), 2875 - 81
New pyrrolobenzodiazepine antibiotics, RK-1441A and B . I . Biological properties; Osada H et al.; Streptomyces griseus and bacteriophage B were used for an assay system detecting anti-bacteriophage antibiotics . Streptomyces sp . RK-1441 was found to produce antibacteriophage antibiotics, RK-1441A and B, which are pyrrolo{1,4}benzodiazepine group antibiotics related to neothramycin . Both RK-1441A and B had antibacteriophage activity . The former showed antimicrobial activity on a hypersensitive strain of E . coli for antitumor antibiotics, but the later did not show the activity . Restriction enzyme assay suggested that RK-1441A formed adducts with guanine residues in DNA strands . RK-1441B was not active in vitro, but it might be converted to the active form in host organisms.

J Immunol Methods, 1990 Oct 19, 133(2), 175 - 9
The use of diphenylene iodonium, an inhibitor of NADPH oxidase, to investigate the antimicrobial action of human monocyte derived macrophages; Robertson AK et al.; Diphenylene iodonium is an inhibitor of the respiratory burst-generating NADPH oxidase of phagocytes . The effect of this compound on human monocyte-derived macrophages and its usefulness in exploring the antimicrobial mechanisms of phagocytes was examined . 1 microM diphenylene iodonium inhibited hydrogen peroxide production by human macrophages and the activity of these cells against Toxoplasma gondii . At this concentration macrophage degranulation was unaffected.

Med J Aust, 1990 Oct 15, 153(8), 455 - 8
A comparative study of tea-tree oil versus benzoylperoxide in the treatment of acne; Bassett IB et al.; Tea-tree oil (an essential oil of the Australian native tree Melaleuca alternifolia) has long been regarded as a useful topical antiseptic agent in Australia and has been shown to have a variety of antimicrobial activities; however, only anecdotal evidence exists for its efficacy in the treatment of various skin conditions . We have performed a single-blind, randomised clinical trial on 124 patients to evaluate the efficacy and skin tolerance of 5% tea-tree oil gel in the treatment of mild to moderate acne when compared with 5% benzoyl peroxide lotion . The results of this study showed that both 5% tea-tree oil and 5% benzoyl peroxide had a significant effect in ameliorating the patients' acne by reducing the number of inflamed and non-inflamed lesions (open and closed comedones), although the onset of action in the case of tea-tree oil was slower . Encouragingly, fewer side effects were experienced by patients treated with tea-tree oil.

J Chromatogr, 1990 Oct 12, 531, 509 - 48
High-performance liquid chromatography of antibiotics; Jehl F et al.; High-performance liquid chromatographic (HPLC) monitoring of antimicrobial agents has recently become more widely used, and represents an interesting alternative to other methods . The methodology is characterized by good specificity and accuracy, and it is applicable to almost all antibiotics . This review first describes the successive steps to investigate for the development of an HPLC method for a new antibiotic, and how to make use of it . Particular emphasis is put on the problems related to the standardization of sample preparation and to the development of mobile phases for use with different molecules belonging to the same class . The second part of the review describes one or more HPLC techniques for a representative antibiotic of each major class.

Dtsch Med Wochenschr, 1990 Oct 5, 115(40), 1499 - 506
{Intestinal spirochetosis in HIV infection: prevalence, isolation and morphology of spirochetes}; Kasbohrer A et al.; The prevalence of intestinal spirochaetosis was investigated in 39 HIV-positive homosexual males (mean age 39 {24-65} years) in different stages of HIV infection (3 with the lymphadenopathy syndrome, 8 with AIDS-related complex and 28 with AIDS) . Biopsies for cultural and histological demonstration of spirochaetes were obtained during routine ileoscopies . At the time of examination 35 of the 39 patients had intestinal symptoms . 27 patients had had no previous antimicrobial treatment . In 12 of the 27 previously untreated patients with intestinal symptoms spirochaetes were demonstrated, to different extent, from the terminal ileum to the rectum, while the treated group of eight and the control group of four were negative . There were no significant inflammatory changes histologically . Treatment with metronidazole in most cases improved symptoms . In their ultrastructure the microorganisms showed several complete convolutions, cone-shaped cell endings, cell length of 4-18 microns, cell diameter of 0.21-0.35 microns and five subterminal flagella . Morphological considerations favour the inclusion of these microorganisms in the genus Treponema rather than Brachyspira.

J Appl Bacteriol, 1990 Oct, 69(4), 593 - 8
Synergism within polyhexamethylene biguanide biocide formulations; Gilbert P et al.; Polyhexamethylene biguanides (PHMB) are mixtures of polymeric biguanides with an average polymer length (n) of 5, but containing high (n greater than 15, mol . wt 3300) and low molecular weight material (n = 2, mol . wt 400) . Studies involving discrete molecular weight fractions of PHMB have shown that antimicrobial activity of PHMB increases with increasing polymer length . Cell suspensions which had not been subjected to centrifugation and/or washing during their preparation were employed . Whilst activity was still observed to increase with n, the trend was much reduced as n exceeded six . Centrifugation and washing of cells markedly increased the activity of high but not low molecular weight materials and corresponded to losses upon centrifugation of envelope lipopolysaccharide (LPS) . Such envelope LPS represented high affinity binding sites on the surfaces of the cells . Combinations of various molecular weight fractions of PHMB were evaluated against filter-washed cells and revealed a profound synergy between extremes of polymer length.

J Appl Bacteriol, 1990 Oct, 69(4), 585 - 92
Barrier properties of the gram-negative cell envelope towards high molecular weight polyhexamethylene biguanides; Gilbert P et al.; The antimicrobial activities of four discrete molecular weight fractions of polyhexamethylene biguanides towards a number of Escherichia coli strains have been investigated . Whilst activity of the polymers was observed to increase in proportion to polymerization number, the dependence of activity upon molecular weight was five times greater towards sphaeroplasts than towards whole cells . This suggested that the cell envelope, whilst not conferring complete resistance to the agents, did provide a significant exclusion barrier . Comparison of the activities towards rough and deep-rough lipopolysaccharide strains showed growth inhibitory activity, but not bactericidal activity nor respiratory inhibition, to be enhanced in the rough strains . Uptake studies showed mixed H- and C-type adsorption with significantly greater numbers of high-affinity binding sites being associated with rough than deep-rough lipopolysaccharide . The binding affinity of polyhexamethylene biguanides towards cells was also enhanced in the rough strains . Binding affinity was, in all cases, significantly reduced in the presence of magnesium and suggested a mechanism of self-promoted uptake for these biocides, facilitated through core lipopolysaccharide.

J Appl Bacteriol, 1990 Oct, 69(4), 578 - 84
Chemical reactivity of some isothiazolone biocides; Collier PJ et al.; Chemical reactions between the isothiazolone biocides, N-methylisothiazol-3-one (MIT), benzisothiazol-3-one (BIT) and 5-chloro-N-methylisothiazol-3-one (CMIT) with cysteine have been investigated by u.v . and NMR spectroscopy . At physiological pH all three agents interacted oxidatively with thiols to form disulphides . Further interaction with thiols caused the release of cystine and formation of a reduced, ring-opened form of the biocide (mercaptoacrylamide) . In an analogous fashion to the initial reaction the mercaptoacrylamide reacted with another molecule of biocide to give biocide dimers . NMR spectral studies indicated that for CMIT the mercaptoacrylamide form is capable of tautomerization to a highly reactive thio-acyl chloride . Formation of mercaptoacrylamide was in all cases highly pH-dependent . Alcohol dehydrogenase was insensitive to all three agents but was highly sensitive to CMIT when co-administered with dithiothreitol . Capacity to form a thioacyl chloride from the mercaptoacrylamide is suggested to account for much of this enhanced activity . Stopped-flow spectroscopic studies showed rates of reaction with glutathione (GSH) to directly parallel antimicrobial activity . Additionally, CMIT was able to react directly with both ionization states of GSH (pH 7-10) whilst BIT and MIT appeared only to interact when the glutamyl-nitrogen of GSH was charged (pH 8.5).

Antimicrob Agents Chemother, 1990 Oct, 34(10), 2038 - 40
Antimicrobial susceptibilities of Erysipelothrix rhusiopathiae; Venditti M et al.; The in vitro susceptibilities of 10 isolates of Erysipelothrix rhusiopathiae to 16 antimicrobial agents were determined . Penicillin and imipenem were the most active agents, followed by piperacillin, cefotaxime, ciprofloxacin, pefloxacin, and clindamycin . Some resistance was observed with erythromycin, tetracycline, and chloramphenicol . Activity was poor or absent with vancomycin, teicoplanin, daptomycin, trimethoprim-sulfamethoxazole, gentamicin, and netilmicin.

Antimicrob Agents Chemother, 1990 Oct, 34(10), 2027 - 9
In vitro susceptibilities of Pseudomonas pseudomallei to 27 antimicrobial agents; Yamamoto T et al.; Clinical isolates of Pseudomonas pseudomallei isolated in Thailand from 1981 to 1989 were tested for their in vitro susceptibilities to 27 antimicrobial agents, including older and newer quinolones, broad-spectrum cephems, carbapenems, monobactams, penicillins, tetracyclines, chloramphenicol, rifamycin, sulfamethoxazole, trimethoprim, and fosfomycin . Tosufloxacin, meropenem, CS-533, and minocycline were active against P . pseudomallei at levels comparable to or even greater than those of antimicrobial agents tested in previous studies, such as ciprofloxacin, ceftazidime, imipenem, carumonam, and piperacillin . Drug-resistant P . pseudomallei was found in only 1% of the isolates . The drug-resistant P . pseudomallei isolates displayed a unique pattern of susceptibility to the above-listed drugs.

Antimicrob Agents Chemother, 1990 Oct, 34(10), 2019 - 23
Antimicrobial properties of N-carboxybutyl chitosan; Muzzarelli R et al.; N-Carboxybutyl chitosan, a modified chitin of crustacean origin, displayed inhibitory, bactericidal, and candidacidal activities when tested against 298 cultures of various pathogens . Examination by electron microscopy showed that microbial cells exposed to N-carboxybutyl chitosan underwent marked morphological alterations . The data are of importance in defining the suitability of N-carboxybutyl chitosan as a wound dressing.

Pharm Res, 1990 Oct, 7(10), 995 - 1002
In vitro skin permeation and bioassay of chlorhexidine phosphanilate, a new antimicrobial agent; Wang JC et al.; An in vitro technique was developed to study the permeation and antimicrobial activity of graded concentrations of a new antibacterial agent, chlorhexidine phosphanilate (CHP), in cream formulations using Franz diffusion cells . Formulations containing from 0.2 to 2% CHP were quantitatively applied to intact excised skin and to skin from which the stratum corneum and partial epidermis had been enzymatically removed . Receptor fluids from diffusion cells were sampled over time and assayed by HPLC methods for chlorhexidine and phosphanilic acid; 24- and 48-hr samples of the diffusate from studies with damaged skin were also bioassayed using clinical isolates of appropriate microbial species . Through intact skin almost no permeation of CHP was observed over 48 hr . The failure of CHP to penetrate intact human skin suggests that normal stratum corneum is the rate-limiting barrier to penetration by this antimicrobial agent . In damaged skin lacking stratum corneum barrier, the release of CHP from the formulation becomes the rate-determining step . Coincident with penetrating damaged skin, CHP dissociates, and the molar ratio of the chlorhexidine and phosphanilate moities in the diffusate changes to favor phosphanilic acid . The extent of changes in the permeation rates of both moieties of CHP was directly related to the CHP concentration in cream . Both CHP moieties were found to reach equilibrium in the dermis within 24 hr after application . It was also observed that CHP creams down to 0.2% concentration yielded diffusates with activity exceeding the minimum inhibitory concentration of all test microorganisms within 24 hr.

Nippon Juigaku Zasshi, 1990 Oct, 52(5), 907 - 14
Biological activity of obiopeptide-1, a synthetic peptide derived from the native immune-regulator obioactin; Suzuki N et al.; Tachyzoites of Toxoplasma gondii were killed in mouse macrophage and human somatic cell monolayers by a novel synthetic peptide (Obiopeptide-1) which is a Glycil-penta-Glutaminate (GpG) derivative of native Obioactin . In view of the worldwide prevalence of this protozoan disease and the lack of effective treatments, Obiopeptide-1 may be a new and unique antimicrobial active substance of non-antibiotic chemotherapeutic agents for intracellular parasites, T . gondii and associated nonspecific hypoimmune responses that occur in infected hosts.

J Am Osteopath Assoc, 1990 Oct, 90(10), 920 - 5
Update on infections in neutropenic hosts; Gulick PG; The incidence of neutropenia has increased owing to more aggressive treatment of cancer . The most frequent complication seen in neutropenic patients is infection . Over the past several years, there has been a change in the types of organism seen as major pathogens in neutropenia-induced infections . With the emergence of new antimicrobial agents and other immunomodulating agents, there has been much change in the therapy for these infections . The author provides an update on the causes of and the therapy for infections in neutropenic patients.

Burns, 1990 Oct, 16(5), 347 - 52
Treatment of dermal depth burn wounds with an antimicrobial agent-releasing silicone gel sheet; Sawada Y et al.; Silicone gel sheets containing 0.02 per cent Ofloxacin were used in the treatment of 24 patients with a total of 27 dermal depth burn wounds . The gel provided a continuing drug delivery system from the dressing to the wound . Clinically the silicone gel sheets did not adhere to the wound and could be removed easily without pain . No infection developed in any of the dermal depth burn wounds treated with the gel sheets . The silicone gel sheets were found to promote prompt epithelialization in 16 burn wounds of superficial dermal depth (mean 8.4 days) compared with ointment-impregnated gauze dressings (mean 14 days, P less than 0.01) . There was less pain and discharge by macroscopic observation of the absorbent materials from both dressings . In nine wounds of mixed superficial and deep dermal burn, the silicone gel also provided prompt epithelialization (mean 12 days) compared to the control wounds (mean 22 days, P less than 0.01).

Nippon Hifuka Gakkai Zasshi, 1990 Oct, 100(11), 1173 - 81
{Cutaneous infection by Mycobacterium fortuitum biovariant "third group"--a case report and bacteriological examination of the isolate}; Fujimoto W et al.; A 22-year-old woman with ten-year history of atopic dermatitis first noticed an erythematous ++, indurated, and fluctuant lesion on her back six month prior to visiting our hospital in February 1989 . The dusky red skin lesion gradually spread to the right side of her trunk and drained small amount of purulent or serosanguineous fluid . A skin biopsy specimen showed mixed pattern of nonspecific inflammatory infiltrate and granulomatous infiltrate in the dermis . A culture of the biopsy specimen showed a rapidly growing atypical acid-fast bacteria, which was identified as Mycobacterium fortuitum and classified as biovariant "third group" by positive growth on mannitol and inositol . Minimum inhibitory concentrations (MICs) of different antimicrobial agent using broth medium showed that the isolate was susceptible to the new quinolones such as ofloxacin and ciprofloxacin . The patient responded to treatment with doxycycline followed by with ofloxacin . Subspecies classification and antibiotic susceptibilities were discussed with special reference to treatment of rapidly growing mycobacteria.

Ann Pediatr (Paris), 1990 Oct, 37(8), 501 - 5
{Fatal cerebral and pulmonary aspergillosis in acute leukemia in a child}; Hue V et al.; Immediately after induction therapy for acute lymphoblastic leukemia, a 2 1/2-year-old child developed invasive pulmonary aspergillosis revealed by pneumothorax, an unusual manifestation . Despite treatment with amphotericin B, status epilepticus occurred; this manifestation was related to diffuse ischemic cerebral lesions probably caused by cerebral aspergillosis . Outcome was fatal . Early invasive pulmonary aspergillosis is responsible for non-specific pneumonia . Thoracic CT scan and fiberoptic bronchoscopy are informative investigations . At recovery of bone marrow aplasia, the occurrence of hemoptysis and the discovery of excavated lesions on roentgenograms are suggestive of the diagnosis . Cerebral aspergillosis should be routinely considered whenever neurologic symptoms develop in a patient with agranulocytosis, fever, and pneumonia . The prognosis of invasive aspergillosis depends above all on the promptness of treatment; amphotericin B should be given intravenously whenever broad spectrum antimicrobial therapy fails to induce apyrexia in a patient with agranulocytosis.

Otolaryngol Clin North Am, 1990 Oct, 23(5), 1003 - 18
Injuries of the external ear; Templer J et al.; Ear injuries occur in people of all ages but predominate in active people such as wrestlers, boxers, and bike riders . The types and extent of injury are a function of the force causing the injury . Shearing forces of moderate intensity cause hematoma formation, whereas greater force causes lacerations or even amputation . Sharp objects cause lacerations determined by the force, direction, and point of impact . The high ratio of surface area to mass makes the auricle vulnerable to extremes of temperature . People participating in high-risk activities should wear protective headgear . The goal of treatment is to restore the normal contours while preventing infection . Hematoma results in disfigurement by organization or chondritis . Evacuation and pressure dressings using sterile technique correct the condition . Second-degree burns are treated by regular cleansing and application of topical antimicrobials . Deeper burns require debridement, biologic dressings, or burying the cartilage subcutaneously for later reconstruction . Simple lacerations are closed under aseptic technique using either skin-to-skin sutures only or sutures of the skin combined with intercartilage sutures . Extensive and complex lacerations require meticulous care to match all fragments and prevent infection or loss of tissue . Bare cartilage must be covered with vascularized tissue . The treatment of total amputation is controversial . Some advocate reattachment as a composite graft using intravenous low molecular weight dextrans and heparin as adjuvants . Mladick dermabrades the amputated pinna, reattaches it with sutures, and then slips it into a pocket of elevated postauricular skin for 2 weeks . Others urge microvascular reanastomosis of the small nutrient vessels . Brent and Byrd separate the cartilage from its overlying skin and envelope it first with vascularized temporoparietal fascia and then a split-thickness skin graft . Chondritis is the most feared complication of injury or surgery of the pinna . It is an aggressive process, and prompt removal of pus and necrotic cartilage is required . Exteriorization and removal of all cartilage is effective but disfiguring . Removal of only affected cartilage and constant irrigation with antibiotic solutions is effective but requires prolonged hospitalization . Iontophoresis of antibiotics into the auricle may be effective and conserve tissue . Traumatic deformities are corrected with composite grafts from the opposite ear, costal cartilage, and local pedicled flaps.(ABSTRACT TRUNCATED AT 400 WORDS)

J Antimicrob Chemother, 1990 Oct, 26 Suppl B, 91 - 5
Monotherapy with pefloxacin in multidrug-resistant nosocomial gram-negative bacteraemia; Limson BM et al.; Twenty patients who developed nosocomial Gram-negative bacteraemias in the medical or surgical intensive care units were treated with pefloxacin . All organisms were susceptible to pefloxacin and had not responded to previous antimicrobial therapy . The bacteraemias were eradicated in 16 of the 20 patients, all of whom tolerated the therapy without adverse effects.

J Antimicrob Chemother, 1990 Oct, 26 Suppl B, 173 - 80
A randomized multicentre trial of pefloxacin plus metronidazole and gentamicin plus metronidazole in the treatment of severe intra-abdominal infections . Report from a Swedish Study Group; In vitro muscle cell proliferation and protein turnover as affected by serum from pigs fed antimicrobials; Dept . of Anim . Sci., University of Minnesota, St . Paul 55108The effect of antimicrobial supplementation of pigs on the capacity of their sera to influence proliferation and protein turnover in cultured muscle cells was evaluated . Mitogenic activity of sera increased when pigs were fed ASP250 (P less than .005) or carbadox (P less than .001), whereas the mitogenic activity of serum from pigs receiving the basal diet remained unchanged (P = .5) . Additionally, sera from ASP250-fed pigs significantly decreased (P less than .001) total cellular protein degradation compared with sera obtained from the same pigs prior to supplementation . Neither ASP250 nor carbadox stimulated proliferation of myogenic cells when added to the culture media . Inclusion of ASP250 in swine diets altered the composition of their sera in a way that stimulated muscle cell proliferation and reduced the rate of protein degradation in cultured myogenic cells . Likewise, the inclusion of carbadox in swine diets increased the ability of their sera to stimulate cultured muscle cell proliferation.

Ophthalmology, 1990 Oct, 97(10), 1281 - 7
Ocular syphilis; Tamesis RR et al.; The ability of syphilis to mimic different ocular disorders can lead to misdiagnosis and delay in appropriate antimicrobial therapy . The authors describe their experience over the past 5 years with the ocular manifestations of syphilis in 25 patients who comprised 2.45% of 1020 new patients . Uveitis was the most common ocular manifestation seen . All patients had positive results from FTA-ABS tests, whereas only 68% had reactive serum VDRLs . Two of five patients tested for human immunodeficiency virus (HIV) antibody were reactive . The authors recommend routine FTA-ABS and VDRL screening in patients with uveitis or unexplained ocular inflammation . They also recommend testing for HIV antibody in luetics and aggressive treatment with high-dose aqueous penicillin for syphilis.

J Clin Microbiol, 1990 Oct, 28(10), 2357 - 9
Microbiological characteristics of Weeksella virosa (formerly CDC group IIf) isolated from the human genitourinary tract; Reina J et al.; Weeksella virosa (formerly CDC group IIf) is a nonsaccharolytic, oxidase- and catalase-positive, gram-negative rod which is unable to grow on MacConkey agar . At 48 h of incubation on blood or chocolate agar, the colonies present a characteristic appearance: intensely mucoid, adherent, and cream colored as a result of the production of a nondiffusible yellow pigment . This microorganism has been isolated predominantly from the female genitourinary tract, which indicates the opportunity for sexual transmission . We present the microbiological study of three strains of W . virosa identified in a study of 707 female genital samples, representing an incidence of 0.42% . At the same time, we analyzed the principal biochemical tests used in the identification of this microorganism and the susceptibilities of the organism to the different antimicrobial agents assayed.

Postgrad Med, 1990 Oct, 88(5), 169 - 75, 178-84
Infectious diarrhea . Managing a misery that is still worldwide; Qadri SM; Infectious diarrhea is the largest single cause of morbidity and mortality in the world . Bacteria, viruses, and protozoan parasites are the most common causative agents . Treatment in most cases of bacterial and viral diseases consists of correcting fluid loss and electrolyte imbalance by oral or parenteral rehydration . Antimicrobial therapy is reserved for very ill patients only . With the exception of Cryptosporidium, for which no effective agent is yet available, all protozoan infections are treatable with metronidazole.

Obstet Gynecol, 1990 Oct, 76(4), 603 - 6
Cefazolin for hysterectomy prophylaxis; Hemsell DL et al.; Efficacy data for single-dose cefazolin prophylaxis at hysterectomy are meager, and there are none evaluating the impact of route of administration on efficacy . For these reasons, 772 women undergoing elective abdominal or vaginal hysterectomy for benign diseases were given 1 g cefazolin either intramuscularly or intravenously in a randomized clinical trial . Preoperative diagnoses and clinical, surgical, and outcome variables were similar by route of administration for each surgical approach . Risk factors for infection after abdominal hysterectomy included younger age, lower postoperative hemoglobin concentration, and pelvic hematoma; women who developed infection after vaginal hysterectomy were heavier than those who remained uninfected and were more likely to have a pelvic hematoma . The overall incidence of major operative site infection requiring parenteral antimicrobial therapy in evaluable women was 7.2%: 7.6% for 539 women undergoing abdominal hysterectomy and 6.3% for 207 women undergoing vaginal hysterectomy . Postoperative infection was unrelated to route of cefazolin administration.

J Med Chem, 1990 Oct, 33(10), 2845 - 9
Synthesis and antimicrobial and cytotoxic activities of pyrrole-containing analogues of trichostatin A; Massa S et al.; A number of aroylpyrroleacrylic acid derivatives were synthesized by standard procedures and evaluated for cytotoxicity in Vero cells and for capacity to inhibit the multiplication of viruses, bacteria, and fungi . While none of the test compounds showed any activity against bacteria and fungi, most of them inhibited the replication of some DNA viruses at concentrations allowing the exponential growth of uninfected cells . In particular three compounds (8, 9c, and 10h) showed an antiviral activity at doses that were from 4- to greater than 8-fold lower than the maximum nontoxic doses.

J Cell Biol, 1990 Oct, 111(4), 1363 - 71
Bactenecins, defense polypeptides of bovine neutrophils, are generated from precursor molecules stored in the large granules; Zanetti M et al.; Bactenecins are highly cationic polypeptides of bovine neutrophil granules and exert in vitro a potent antimicrobial activity . We have previously purified two bactenecins, designated in an abbreviated form Bac7 and Bac5 from their approximate molecular masses of 7 and 5 kD (Gennaro, R., B . Skerlavaj, and D . Romeo . 1989 . Infect . Immun . 57:3142-3146) . Here we have studied the biosynthesis, processing, and localization of precursors of Bac7 and Bac5 in bovine bone marrow cells of the myeloid lineage . In vitro translation directed by mRNA isolated from these cells has shown that the primary translation products are preprobactenecins of 23.5 and 21 kD, and are processed to polypeptides of 20 and 15.8 kD, respectively . The 20-kD polypeptide is the granule storage form of Bac7, or proBac7, as also demonstrated by Western blot analysis of lysates of peripheral neutrophils . Between 15 and 50 min from the beginning of its biosynthesis the 15.8-kD polypeptide is converted into the 15-kD granule storage form of Bac5, or proBac5 . As shown by immunogold EM, proBac7 and proBac5 are sorted and targeted to the matrix of the so called large granules, which are the predominant organelles in the cytoplasm of bovine neutrophils and are the exclusive store of the nonoxidative antimicrobial system of these cells . Solubilization of granules with Triton X-100 with concomitant unmasking of proteases leads to cleavage of the proforms to Bac7 and Bac5 . Experiments performed with protease inhibitors suggest that the proteolytic cleavage is catalyzed in detergent-solubilized neutrophils by neutral serine protease(s), very likely derived from the azurophil granules.

Sex Transm Dis, 1990 Oct-Dec, 17(4), 184 - 9
Accuracy of clinical diagnosis of genital ulcer disease; Dangor Y et al.; In Africa, establishment of an accurate clinical diagnosis in cases of genital ulcer disease is difficult owing to atypical presentation of ulcerations and mixed infections . This is compounded by the frequent lack of suitable laboratory facilities . In 240 cases of genital ulcer disease among mineworkers in Carletonville, South Africa, this study endeavored to correlate the clinical diagnosis with laboratory findings . Clinical accuracy and positive and negative predictive values were determined for each type of genital ulcer disease encountered . Overall, the accuracy of clinical diagnosis was 68% for single infections, 80% for chancroid, 55% for primary syphilis, 27% for lymphogranuloma venereum (LGV), and 22% for genital herpes . Adequate laboratory facilities are indispensible for the establishment of an accurate etiologic diagnosis of genital ulcer disease and thus the institution of appropriate antimicrobial therapy.

J Clin Periodontol, 1990 Oct, 17(9), 616 - 22
Randomized controlled trial of doxycycline in prevention of recurrent periodontitis in high-risk patients: antimicrobial activity and collagenase inhibition; McCulloch CA et al.; 82 patients with a recent history of periodontal abscesses and/or loss of gingival attachment (GAL) despite active periodontal therapy were enrolled in a double-blind, randomized, placebo-controlled trial . Clinical measurements and subgingival scaling were performed every 2 months . If any site exhibited greater than or equal to 2 mm loss of GAL or a periodontal abscess, patients were administered either 100 mg Doxycycline per day for 3 weeks or placebo . During 12 months of monitoring, 55 patients exhibited recurrent active disease and were then randomly assigned to either the Doxycycline or placebo groups . Clinical measurements of GAL and microbiological culture of subgingival bacteria were made at intervals between 1 week and 7 months after completion of the drug regime . Within 7 months, 15 out of 19 patients on placebo exhibited recurrent disease compared to 13 out of 29 patients on Doxycycline, a relative risk reduction of 43% (p less than 0.05) for Doxycycline compared to placebo . Minimal inhibitory concentrations of Doxycycline for subgingival plaque samples from active sites ranged between 25-100 micrograms/ml, which are several fold higher than reported crevicular fluid concentrations for this drug . However gingival crevicular fluid collagenase was inhibited in vitro at concentrations of 5-10 micrograms/ml Doxycycline . These data indicate that Doxycycline provides significant risk reduction of recurrent periodontitis in patients with active disease.

J Med Chem, 1990 Oct, 33(10), 2929 - 32
Synthesis of antimicrobial agents . 3 . Syntheses and antibacterial activities of 7-(4-hydroxypiperazin-1-yl)quinolones; Uno T et al.; A series of novel pyridone carboxylic acids having a 4-hydroxypiperazinyl group at the 7-position of norfloxacin and ciprofloxacin were prepared . The in vivo antibacterial efficacies of these compounds were superior to those of corresponding piperazinyl derivatives . From the results of the studies on the pharmacokinetic profile and toxicity, the 4-hydroxypiperazinyl derivatives were confirmed to be pharmacologically superior to corresponding piperazinyl derivatives . Thus, a 4-hydroxypiperazinyl group was revealed to be a beneficial substituent for potential use in future quinolone antibacterials.

J Reprod Med, 1990 Oct, 35(10), 955 - 8
C-reactive protein in assessing antimicrobial treatment of acute pelvic inflammatory disease; Teisala K et al.; Serial serum C-reactive protein (CRP) determinations were used in the evaluation of antimicrobial treatment of acute pelvic inflammatory disease (PID) as proven by laparoscopy and endometrial biopsy or microbiologic findings in the upper genital tract in 36 women . Sixteen patients were treated with ciprofloxacin and 20 with doxycycline plus metronidazole . The mean CRP levels did not differ significantly in patients with severe and moderate salpingitis in comparison with mild salpingitis on admission or during treatment, nor was there any significant difference between the mean CRP levels in patients with acute chlamydial/gonococcal and nonchlamydial/nongonococcal PID . The mean CRP levels decreased by the third day of treatment in all treatment groups, and the decrease by the sixth day of treatment was significant (P less than .05), reflecting the clinical response to therapy faster than did serial ESR determinations . After the documentation of acute PID, serial serum CRP determinations were a useful predictor of the short-term response to antimicrobial therapy.

Am J Med, 1990 Oct, 89(4), 483 - 90
Immunoproliferative small intestinal disease: portrait of a potentially preventable cancer from the Third World; Khojasteh A et al.; PURPOSE: To review the recent progress in the understanding of clinical and laboratory characterization as well as management of immunoproliferative small intestinal disease (IPSID) . DATA IDENTIFICATION: A literature search was conducted using Index Medicus, MEDLINE (1962 to 1989), and bibliographies of identified relevant articles . STUDY SELECTION: All international comprehensive reviews, reported epidemiologic or immunologic studies, and prospective clinical trials published or abstracted in English were selected . RESULTS OF DATA SYNTHESIS: A high incidence of lymphoma primarily in the gastro-intestinal tract in Third World countries has stimulated enormous epidemiologic and pathogenetic interests globally . IPSID, with a distinctive biologic marker (alpha heavy chain para-protein), affects the young underprivileged population of those countries . The initially benign-appearing antibiotic-responsive immunoproliferative lesions often evolve to fatal high-grade lymphomas . Roles of environmental and host factors in this evolutionary course are emerging . Recently demonstrated malignant potentials form the early onset of pathogenesis have given a new dimension to the traditional management strategy of IPSID . CONCLUSIONS: Epidemiologic, immunologic, and pathogenetic data that have emerged over the last 25-year study of IPSID have improved our understanding about the complexity of infection-immunity-cancer interrelationships, comparable to those that have arisen from the study of the acquired immunodeficiency syndrome . Early detection and institution of antimicrobial-based treatment regimens with judicious and consistent follow-up can save the lives of many young patients whose manpower is badly needed in Third World countries.

Rev Med Chir Soc Med Nat Iasi, 1990 Oct-Dec, 94(3-4), 631 - 4
{Practical treatments of suppurative skin mycoses and allergic skin mycoses due to Candida}; Munteanu M; In the inflammatory mycoses the author recommends an oral treatment consisting in griseofulvin, and, in case of severe inflammation, prednisone per os at the same time with a local treatment (painting with alcohol iodate 1%, followed by the application of a cream with cortisone associated with an antimicrobial antibiotic and pincer epilation) . This way the evaluation is 3-4 weeks shorter and the scars and alopecia are avoided . In the allergic manifestations due to Candida (urticaria, eczema, itching), after discussing their peculiarities the author recommends the desensitization with an extract of Candida cultivated right from patient's primitive focus . This type of desensitization is twice specific: specific anti-Candida and at the same time specific to patient's own strain, even in the case of saprophyte Candida . The very good results obtained after 2-3 months of treatment are presented.

Rev Med Chir Soc Med Nat Iasi, 1990 Oct-Dec, 94(3-4), 587 - 8
{The synthesis of aldoxime ester derivatives with biological activity}; Ungureanu M et al.; Continuing our investigations for obtaining etheric derivatives from the oximes of some carbonylic compounds, five carboxymethylic ethers of some aldoximes were synthetized . Their structure was confirmed by chemical and spectral analyses . The antimicrobial activity of the obtained products towards 6 microorganisms species was determined.

J Chemother, 1990 Oct, 2(5), 280 - 94
A review of the antimicrobial activity of the fluoroquinolones; Maple P et al.; The evolution of the fluoroquinolones is described, and structure-activity relationships outlined . The in-vitro antimicrobial activities of ciprofloxacin, enoxacin, norfloxacin, ofloxacin and pefloxacin against a wide range of organisms are critically reviewed . In-vitro factors influencing fluoroquinolone activity are discussed . Reports of the acquisition of resistance to the fluoroquinolones are evaluated . Finally, possible future directions for this group of antibiotics are discussed.

Rinsho Ketsueki, 1990 Oct, 31(10), 1664 - 9
{Comparison of ciprofloxacin with polymyxin B for infection prophylaxis in neutropenic patients with acute non-lymphocytic leukemia}; Moriuchi Y et al.; Twenty-four neutropenic patients receiving intensive chemotherapy for acute non-lymphocytic leukemia were studied in a randomized trial comparing ciprofloxacin with polymyxin B for prevention of infections . Both groups (12 patients each group) received amphotericin B for antifungal prophylaxis . 20 febrile episodes occurred in 22 courses of oral prophylactic ciprofloxacin and 22 occurred in 24 courses of oral prophylactic polymyxin B . Patients receiving ciprofloxacin had a mean time to the first infection-related febrile episode of 7.2 days, compared with 4.3 days for the polymyxin B group (p less than 0.01) . Patients receiving ciprofloxacin also had fewer days of fever (average 6.5 days versus 9.8 days for the polymyxin B group, p less than 0.02) . Duration of administration of parental antibiotics were also shorter in the ciprofloxacin group (p less than 0.001) . Although modifications of the empiric antibiotic regimen were required more frequent in patients receiving polymyxin B, this did not reach statistical significance . These results suggest that ciprofloxacin is a more efficacious oral antimicrobial agent than polymyxin B for the prevention of infections in neutropenic patients with acute non-lymphocytic leukemia.

Hosp Pract (Off Ed), 1990 Oct, 25 Suppl 4, 31 - 7
Spiral gradient endpoint: a new method of susceptibility testing; Hill GB; The key to SGE is an instrument that deposits the antimicrobial agent in predetermined, decreasing concentrations in a spiral pattern on an agar plate . The bacterial inoculum is streaked radially from the center of the plate across the spiral . The drug concentration at the point in the spiral where bacterial growth ends is its MIC.

Medicina (Firenze), 1990 Oct-Dec, 10(4), 373 - 85
{Infective endocarditis: a changing disease}; Venditti M et al.; Infective endocarditis is best characterized as a disease in evolution . The list of patients at risk, which formerly included almost exclusively patients with rheumatic heart disease, is being continuously modified and expanded . Nowadays, patients with prosthetic heart valves, users of illicit intravenous drugs, and patients with mitral valve prolapse rather than patients with rheumatic heart disease account for the majority of cases of infective endocarditis . Moreover, due to the widespread use of indwelling atrial catheters for parenteral nutrition as well as for intensive cytotoxic therapy, catheter-related right-sided endocarditis is emerging among nosocomial infections . With the advent of successful antimicrobial therapy, complications rather than endocardial infection pose the major therapeutic problems . In addition to progressive heart failure, myocardial abscesses, fungal endocarditis, relapsing infection, and major systemic emboli in the presence of large protuberant vegetations constitute indications for replacement of the valve . Despite progresses in diagnosis and therapy, infective endocarditis will most likely continue to challenge physicians even in the next future.

J Vet Diagn Invest, 1990 Oct, 2(4), 330 - 3
Minimal inhibitory concentrations of five antimicrobials against Treponema hyodysenteriae and Treponema innocens; Messier S et al.; The minimal inhibitory concentrations of carbadox, dimetridazole, lincomycin, ronidazole, and tiamulin against isolates of Treponema hyodysenteriae and Treponema innocens were determined by an agar-dilution method . The results obtained indicated that tiamulin was the most effective antimicrobial in vitro against T . hyodysenteriae, followed by carbadox . Dimetridazole, lincomycin, and ronidazole had poor efficacy in vitro against the T . hyodysenteriae isolates . Isolates of T . innocens were more sensitive to the various antimicrobials . Carbadox and tiamulin were the most effective in vitro, followed by ronidazole, dimetridazole, and lincomycin.

Farmaco, 1990 Oct, 45(10), 1101 - 9
Antimicrobial activity of some isothiosemicarbazones; Cocco MT et al.; The microbiological activity of a series of isothiosemicarbazones is reported . The experimental data relating to the microbiological screening show an interesting antibacterial activity associated to a good antifungal activity.

J Chemother, 1990 Oct, 2(5), 300 - 5
Influence of new quinolones on normal immune capabilities; Tawfik AF et al.; Ciprofloxacin, pefloxacin, norfloxacin, and ofloxacin were investigated for immunomodulatory activity on humoral and cell-mediated immune responses . Ciprofloxacin and pefloxacin altered the humoral immune responses of mice to sheep red blood cells . This effect was not exhibited by norfloxacin or ofloxacin . All four quinolones did not alter cell-mediated responses . When these antimicrobial agents were tested for their interaction with human polymorphonuclear phagocytic activity, all agents suppressed this activity . In addition, all except norfloxacin showed anti-inflammatory activity.

Aliment Pharmacol Ther, 1990 Oct, 4(5), 465 - 76
Pharmacological profile of duodenal alkaline secretion; Garner A et al.; Stimulation of mucosal alkaline secretion represents an opportunity for discovering novel drugs of potential benefit in maintenance therapy of duodenal ulcer disease . We screened over 200 agents representing the full spectrum of pharmacological categories in order to characterize stimulatory pathways and identify mechanistic leads . A variety of eicosanoids, phospho-diesterase inhibitors and adrenoreceptor agonists together with forskolin, 6-hydroxy-dopamine, 2-chloroadenosine, diazepam, testosterone, dipyridamole and dihydropyridazinone caused a reproducible increase in the metabolism-dependent component of alkaline secretion in bullfrog proximal duodenum . PGE2 (ED50 0.02 microgram/ml) was the most potent agent in vitro and was also the most effective stimulant of duodenal alkalinization in vivo in an anaesthetized cat preparation . Agents without effect on spontaneous alkaline secretion by amphibian duodenum included agonists and antagonists of histamine, 5-hydroxy-tryptamine, gamma-aminobutyric acid, dopamine, muscarinic and nicotinic receptors, inhibitors of amine uptake, monoamine oxidase and cholinesterase, plus various corticoids, diuretics, oestrogens, chemotherapeutic (anticancer) and antimicrobial agents . The major mechanism of stimulating alkaline secretion in the isolated duodenum is by increasing intracellular cyclic AMP levels . This may occur by either inhibiting metabolism of the nucleotide or by stimulating its formation . Additionally, many stimulants appear to act indirectly via liberation of endogenous prostaglandins as judged from the marked attenuation of responses in the presence of indomethacin to all agonists apart from exogenous PGE2, forskolin, ICI 63197 (PDE inhibitor), 2-chloroadenosine and diazepam . Whether purinergic agonists and benzodiazepines act directly on the enterocyte or by releasing other paracrine mediators is unknown.

Antimicrob Agents Chemother, 1990 Oct, 34(10), 1938 - 43
Mutants of Escherichia coli K-12 exhibiting reduced killing by both quinolone and beta-lactam antimicrobial agents; Wolfson JS et al.; Norfloxacin, ofloxacin, and other new quinolones, which are antagonists of the enzyme DNA gyrase, rapidly kill bacteria by largely unknown mechanisms . Earlier, we isolated, after mutagenesis, Escherichia coli DS1, which exhibited reduced killing by quinolones . We evaluated the killing of DS1 and several other strains by quinolones and beta-lactams . In time-killing studies with norfloxacin, DS1 was killed 1 to 2 log10 units compared to 4 to 5 log10 units for the wild-type parent strain KL16, thus revealing that DS1 is a high-persistence (hip) mutant . DS1 exhibited a similar high-persistence pattern for the beta-lactam ampicillin and reduced killing by drugs that differed in their affinities for penicillin-binding proteins, including cefoxitin, cefsulodin, imipenem, mecillinam, and piperacillin . Conjugation and P1 transduction studies identified a novel mutant locus (termed hipQ) in the 2-min region of the DS1 chromosome necessary for reduced killing by norfloxacin and ampicillin . E . coli KL500, which was isolated for reduced killing by norfloxacin without mutagenesis, exhibited reduced killing by ampicillin . E . coli HM23, a hipA (34 min) mutant that was isolated earlier for reduced killing by ampicillin, also exhibited high persistence to norfloxacin . DS1 differed from HM23, however, in the map location of its hip mutation, lack of cold sensitivity, and reduced killing by coumermycin . Results of these studies with strains DS1, KL500, and HM23 demonstrate overlap in the pathways of killing of E . coli by quinolones and beta-lactams and identify hipQ, a new mutant locus that is involved in a high-persistence pattern of reduced killing by norfloxacin and ampicillin.

Mol Cell Probes, 1990 Oct, 4(5), 375 - 83
Effects of growth phase and antibiotics on quantitative DNA/RNA hybridization; Adam T et al.; Synthetic probes complementary to ribosomal RNA are increasingly used in the detection of bacteria . Many applications, however, require the quantitation of bacteria . We therefore tested the influence of growth phase and representative antibiotics (ampicillin, chloramphenicol and gentamycin) on the outcome of DNA/RNA filter hybridization using radiolabelled probes and a multisample digital autoradiograph for quantitative monitoring . Hybridization efficiency seemed influenced by the binding capacity of the membrane, availability of target molecules and physiological growth control . For chloramphenicol the absolute hybridization signal remained constant over the experimental period . Only a slight decrease was found in experiments with gentamycin whereas viable counts dropped 10,000-fold . For ampicillin a decrease in viable counts was paralleled by diminishing signal strengths . Relative signal strengths (counts per viable cell) increased in all experiments with antibiotics . In conclusion; (i) RNA probes seem to detect bacteria even after onset of antimicrobial therapy; (ii) DNA/RNA filter hybridization appears not suitable for accurate quantitation of bacteria.

Arch Invest Med (Mex), 1990 Oct-Dec, 21(4), 389 - 92
Elimination of epimural microflora from guinea pig cecal epithelium by antimicrobial drugs; Mora-Galindo J et al.; The effect of antimicrobial drugs on epimural bacteria of guinea pig cecum was assessed by scanning electron microscopy . Metronidazole (500 hg/ml), neomycin (50 hg/ml) or both combined were given orally in drinking water ad libitum for five consecutive days, and representative fragments of cecum were processed for analysis . In untreated animals large areas of mucosa were lined by spiral-shaped bacteria were eliminated by treatment with neomycin, only remaining fusiform bacteria at openings of crypts . metronidazole was effective for eliminating all bacterial populations; the same effect was achieved with a combination of neomycin and metronidazole, rendering the cecum free of epimural bacteria, the health of guinea pig was unaffected by these treatments . The cecal epithelium of antimicrobial-treated animals can be used for experimental studies without interference of epimural bacteria.

N Engl J Med, 1990 Sep 20, 323(12), 776 - 82
Oral therapy for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome . A controlled trial of trimethoprim-sulfamethoxazole versus trimethoprim-dapsone; Medina I et al.; BACKGROUND . Antimicrobial drugs that can be taken orally are needed for the treatment of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS) . Preliminary data indicate that dapsone with trimethoprim may be an effective alternative to trimethoprim-sulfamethoxazole, which is frequently toxic . METHODS . In a double-blind trial, 60 patients with AIDS and mild-to-moderately-severe first episodes of P . carinii pneumonia (partial pressure of oxygen in arterial blood, greater than 60 mm Hg while breathing room air) were randomly assigned to 21 days of treatment with either trimethoprim-sulfamethoxazole (20 and 100 mg per kilogram of body weight per day, respectively) or trimethoprim-dapsone (20 mg per kilogram per day and 100 mg per day) . RESULTS . The orally administered treatment failed because of progressive pneumonitis in 3 of the 30 patients assigned to trimethoprim-sulfamethoxazole and in 2 of the 30 assigned to trimethoprim-dapsone (P greater than 0.3) . Major toxic effects required a switch to intravenous pentamidine for 17 patients (57 percent) in the trimethoprim-sulfamethoxazole group, as compared with 9 (30 percent) in the trimethoprim-dapsone group (P less than 0.025) . With trimethoprim-sulfamethoxazole, there were more instances of severe chemical hepatitis (six, as compared with one in the trimethoprim-dapsone group) and marked neutropenia (five vs . one) . Intolerable rash (three in each treatment group) and severe nausea and vomiting (two in each group) occurred with equal frequency with both drug combinations . Methemoglobinemia occurred in most of the patients treated with trimethoprim-dapsone, but it was asymptomatic and the level exceeded 20 percent in only one patient . Mild hyperkalemia (serum potassium level, 5.1 to 6.1 mmol per liter) also occurred in 53 percent of the patients treated with trimethoprim-dapsone . CONCLUSIONS . In patients with AIDS, oral therapy with trimethoprim-sulfamethoxazole and with trimethoprim-dapsone are equally effective for mild-to-moderate first episodes of P . carinii pneumonia, but with trimethoprim-dapsone there are fewer serious adverse reactions than with trimethoprim-sulfamethoxazole.

J Biol Chem, 1990 Sep 15, 265(26), 15365 - 7
Antimicrobial peptide, tachyplesin I, isolated from hemocytes of the horseshoe crab (Tachypleus tridentatus) . NMR determination of the beta-sheet structure; Kawano K et al.; The conformation of tachyplesin I, an antimicrobial cationic peptide of 17 residues found in the hemocyte debris of horseshoe crab, was investigated using two-dimensional NMR spectroscopy . The 1H NMR spectrum of tachyplesin I in aqueous solution could be completely assigned, and the secondary structure was substantiated by interpretation of the nuclear Overhauser effect, coupling constant, amide exchange rate, and temperature dependence of the amide chemical shift . Tachyplesin I takes on a fairly rigid conformation constrained by two disulfide bridges and adopts a conformation consisting of an anti-parallel beta-sheet (residues 3-8 and 11-16) connected by a beta-turn (residues 8-11) . In this planar conformation, five bulky hydrophobic side groups are localized in one side of the plane and six cationic side groups are distributed at the "tail" part of the molecule (residues 1-5 and 14-17) . This amphipathic structure of the molecule is presumed to be closely associated with the bactericidal activity.

Tijdschr Diergeneeskd, 1990 Sep 15, 115(18), 825 - 36
{Oxytetracycline and oral herd treatment: a literature review}; Schaftenaar W et al.; Pharmacotherapeutic, pharmacodynamic and pharmacokinetic aspects of oral mass medication with oxytetracycline (OTC) in pigs, calves and poultry are discussed in this review . Clinical studies with successful therapeutic results are scarce in literature; however, OTC is still frequently used for mass medication . Some practical advice to improve the bioavailability of OTC is given . This mainly concerns the reduction of the interaction between calcium ions and OTC . OTC may be useful for oral mass medication when applied as a prophylactic drug . Pharmacological studies are required in order to provide more knowledge about the efficacy of OTC-mass medication . Additional information can be acquired from the field by improving and extending the reciprocal co-operation between field veterinarians and diagnostic laboratories . This may lead to a more justified choice from the various possibilities of antimicrobial use in livestock.

J Biol Chem, 1990 Sep 15, 265(26), 15956 - 62
Isolation of two isoforms of a novel 15-kDa protein from rabbit polymorphonuclear leukocytes that modulate the antibacterial actions of other leukocyte proteins; Ooi CE et al.; We have recently reported the use of the highly selective and reversible binding of the potent bactericidal/permeability-increasing protein (BPI) to target Gram-negative bacteria (Escherichia coli) for its isolation from crude extracts of human polymorphonuclear leukocytes (PMN) . We now report the use of the same procedure for the purification from rabbit PMN of BPI and also of a novel 15-kDa species that consists of two nearly identical isoforms . These 15-kDa proteins have no demonstrable antibacterial activities by themselves . However, one isoform (p15A) potentiates strongly and the other (p15B) weakly the early antibacterial effects of both rabbit and human BPI . Both isoforms inhibit the late lethal action of BPI . Whereas the potentiating effect is specific for BPI the inhibitory effect is seen also with another antibacterial protein of PMN granules, azurocidin . Thus, we have identified in rabbit PMN a previously unrecognized 15-kDa protein species that may modulate during phagocytosis the antimicrobial effects of BPI (and other granule proteins).

N Engl J Med, 1990 Sep 13, 323(11), 705 - 12
Immunomodulatory and antimicrobial efficacy of intravenous immunoglobulin in bone marrow transplantation; Sullivan KM et al.; BACKGROUND . Graft-versus-host disease (GVHD) and infection are major complications of allogeneic bone marrow transplantation . Since intravenous immunoglobulin has shown benefit in several immunodeficiency and autoimmune disorders, we studied its antimicrobial and immunomodulatory role after marrow transplantation . METHODS . In a randomized trial of 382 patients, transplant recipients given immunoglobulin (500 mg per kilogram of body weight weekly to day 90, then monthly to day 360 after transplantation) were compared with controls not given immunoglobulin . By chance, the immunoglobulin group included more patients with advanced-stage neoplasms; otherwise, the study groups were balanced for prognostic factors . RESULTS . Control patients seronegative for cytomegalovirus who received seronegative blood products remained seronegative, but seronegative patients who received immunoglobulin and screened blood had a passive transfer of cytomegalovirus antibody (median titer, 1:64) . Among the 61 seronegative patients who could be evaluated, none contracted interstitial pneumonia; among the 308 seropositive patients evaluated, 22 percent of control patients and 13 percent of immunoglobulin recipients had this complication (P = 0.021) . Control patients had an increased risk of gram-negative septicemia (relative risk = 2.65, P = 0.0039) and local infection (relative risk = 1.36, P = 0.029) and received 51 more units of platelets than did immunoglobulin recipients . Neither survival nor the risk of relapse was altered by immunoglobulin . However, among patients greater than or equal to 20 years old, there was a reduction in the incidence of acute GVHD (51 percent in controls vs . 34 percent in immunoglobulin recipients; P = 0.0051) and a decrease in deaths due to transplant-related causes after transplantation of HLA-identical marrow (46 percent vs . 30 percent; P = 0.023) . CONCLUSIONS . Passive immunotherapy with intravenous immunoglobulin decreases the risk of acute GVHD, associated interstitial pneumonia, and infections after bone marrow transplantation.

J Intraven Nurs, 1990 Sep-Oct, 13(5), 279 - 84
Improved long-term maintenance of central venous catheters with a new dressing technique; Eisenberg PG et al.; Nursing procedures that may be important for maintaining in-dwelling central venous catheter sterility include the use of occlusive dressings, the frequency of dressing changes, the number and skill of nurses doing the dressing changes, the duration of catheterization, the use of antimicrobial ointment, and the extent to which sterile procedures are used during catheter placement . During a 9-month period, two different methods for applying central venous catheter dressings were compared . A new method designed to improve the stability of the dressing and to reduce tension on the catheter was found to be associated with longer maintenance of the dressings compared with a more traditional dressing; 14% fewer dressings were changed because of loss of occlusiveness . With this dressing technique and a strict protocol, including insertion and maintenance of central venous catheters by a nutritional support team, prolonged (greater than 7 days) maintenance of central venous catheters was found to be possible without an increase in the incidence of infection.

Am J Vet Res, 1990 Sep, 51(9), 1488 - 94
Effect of antimicrobial solution lavage on the palmar digital tendon sheath in horses; Baird AN et al.; Sixteen horses were allotted to 4 groups of 4 horses each to evaluate the effect of tendon sheath lavage with 4 solutions (balanced electrolyte solution, 0.1% povidone-iodine, 0.5% povidone-iodine, and 0.5% chlorhexidine) . The synovitis caused by 0.1% povidone-iodine lavage was not appreciably worse than that caused by balanced electrolyte solution lavage, but the 0.5% povidone-iodine and chlorhexidine lavages caused severe synovitis, and, therefore, should not be used for tendon sheath lavage.

Antimicrob Agents Chemother, 1990 Sep, 34(9), 1766 - 8
Therapy of pulmonary nocardiosis in immunocompromised mice; Gombert ME et al.; We compared the bactericidal efficacies of various antimicrobial agents and combinations thereof in experimentally induced Nocardia asteroides pneumonia in immunocompromised mice . Cortisone acetate treatment, which produced impaired cell-mediated immune function, was followed by nasal inoculation of 5 x 10(4) CFU of N . asteroides into each mouse . Therapy was begun 24 h after inoculation and continued for the next 96 h . Dosages of antimicrobial agents resulted in concentrations approximating levels in human serum . Animals from each of nine treatment groups were sacrificed every 24 h . The pulmonary tissue obtained was homogenized and quantitatively cultured . Results were calculated to indicate the number of CFU per gram of lung tissue . Amikacin and imipenem were the two most effective single agents studied . Sulfadiazine and ciprofloxacin were ineffective, and ceftriaxone reduced bacterial counts modestly . Combination therapy did not enhance the bactericidal activities of the agents tested . We conclude that amikacin and imipenem, as well as select broad-spectrum cephalosporins, represent therapy superior to the sulfonamides in this experimental model and may represent alternative treatment for patients who cannot tolerate sulfa agents (e.g., human immunodeficiency virus-infected patients) or who fail primary treatment.

Antimicrob Agents Chemother, 1990 Sep, 34(9), 1733 - 8
Comparative postantibacterial activities of pefloxacin, ciprofloxacin, and ofloxacin against intracellular multiplication of Legionella pneumophila serogroup 1; Rajagopalan-Levasseur P et al.; The inhibitory and postantibacterial activities of pefloxacin, ciprofloxacin, and ofloxacin against virulent Legionella pneumophila serogroup 1 were evaluated in cell-free and cellular models . In the absence of macrophages (with the tissue culture medium alone), bacterial numbers remained unchanged at 24 h in the presence of 0.1 microgram of pefloxacin, ciprofloxacin, or ofloxacin per ml and 1.0 microgram of pefloxacin per ml, whereas they were reduced in the presence of 1.0 microgram of ciprofloxacin or ofloxacin per ml . Experiments to evaluate the postantibacterial effects of these drugs were therefore performed with concentrations of 0.1 microgram/ml . In the cell-free model, brief exposure (1 h) of bacteria to each antimicrobial agent resulted in a transient decrease in numbers followed by logarithmic growth . In the cellular model, all three drugs (at 0.1 and 1.0 microgram/ml) inhibited the intracellular multiplication of L . pneumophila . The intracellular postantibacterial effects of 0.1 microgram of pefloxacin, ciprofloxacin, and ofloxacin per ml, which were left in contact with L . pneumophila-infected human macrophages for 24 h, were evaluated at various times after removal of the drugs . Pefloxacin was found to exhibit a significant inhibitory effect at 72 h, whereas following the removal of ciprofloxacin and ofloxacin, rapid bacterial multiplication occurred, leading to the destruction of the macrophage monolayer within 48 h . Thus, while pefloxacin, ciprofloxacin, and ofloxacin all inhibited the multiplication of L . pneumophila in human monocyte-derived macrophages, only pefloxacin exhibited a prolonged postantibacterial effect.

Arch Esp Urol, 1990 Sep, 43(7), 715 - 8
{Antimicrobial prophylaxis in urologic surgery}; Luzuriaga Graf J et al.; To evaluate the efficacy of preoperative antibiotic prophylaxis, we studied 130 patients who were submitted to prostate surgery . These patients were divided into 3 groups . Overall morbidity was lower for the patient group that had received antibiotic prophylaxis (Netilmicin, 3 doses) than for the group on placebo and the group on antibiotics postoperatively . The incidence of significant bacteriuria for the group on Netilmicin was less at 7 days (7.5%) and at 30 days (20.5%) than for the other groups: (22.55%) and (49.36%) at 7 and 30 days, respectively . The foregoing data indicate that preoperative antibiotic prophylaxis should be used for periods less than 24 h in all noninfected patients undergoing prostate surgery . The cost of antibiotic therapy, presence of opportunistic organisms and the duration of hospital stay are reduced by antimicrobial prophylaxis.

J Clin Anesth, 1990 Sep-Oct, 2(5), 306 - 11
Anesthetic considerations in patients with chronic granulomatous disease; Wall RT et al.; Chronic granulomatous disease (CGD) is a rare, genetically transmitted disorder characterized by recurrent, life-threatening infections with catalase-positive micro-organisms and excessive inflammatory reactions that lead to granuloma formation . Long-term prophylactic antimicrobial agents and aggressive surgical management are the mainstays of therapy . The authors provided anesthetics for 17 patients with CGD undergoing 55 surgical procedures . These patients presented to surgery with multiple organ system involvement and were at significant risk for complications in the perioperative period . Granulomatous lesions of the gastrointestinal (GI) tract may predispose such patients to regurgitation and aspiration.

Indian J Med Res, 1990 Sep, 91, 360 - 3
Incidence of Gardnerella vaginalis infection in pregnant & non-pregnant women with non-specific vaginitis; Fule RP et al.; The occurrence of G . vaginalis in patients with non-specific vaginitis (NSV) was studied . Of the 200 women with vaginitis screened, 84 were diagnosed to have non-specific vaginitis . G . vaginalis was isolated from 33 (39.28%) patients either alone or in combination with other organisms, while one of the healthy controls with no vaginal discharge yielded G . vaginalis on culture . The nature of vaginal discharge could not be correlated with the type of infection . Clue cells and amine test gave inconsistent results in the presence of G . vaginalis infection . A varying susceptibility pattern of G . vaginalis was observed against various antimicrobials, metronidazole (95%) and gentamicin (75%) showing highest sensitivity.

Clin Ther, 1990 Sep-Oct, 12(5), 440 - 6
A multicenter trial comparing the efficacy and safety of cefuroxime axetil and cefaclor in pneumonia of adults; Yangco BG et al.; The 185 hospitalized patients (aged 19 to 95 years) with pneumonia were randomly assigned to receive 500 mg of cefuroxime axetil orally (250 mg q12h), 1,000 mg of cefuroxime axetil orally (500 mg q12h), or 1,500 mg of cefaclor orally (500 mg q8h), daily, for a mean of nine days . Among the 151 evaluable patients, clinical cure was noted in 58% of the 500-mg cefuroxime axetil group, 94% of the 1,000-mg cefuroxime axetil group, and 88% of the cefaclor group, and clinical improvement in 32%, 4%, and 9% . Bacteriologic outcome was similar in the three groups . Adverse events were minor and comparable among the treatment groups . Cefuroxime axetil is a safe and effective oral antimicrobial for the treatment of pneumonia in adults.

Br J Hosp Med, 1990 Sep, 44(3), 209 - 11
Selective parenteral and enteral antisepsis regimen (SPEAR); Gould IM; With infection rates approaching 80% for patients staying in ICU for more than 5 days there is clearly a need for effective prophylaxis . SPEAR is a system of antimicrobial prophylaxis which extends the regimen of selective digestive tract decontamination to encompass systemic antimicrobial prophylaxis and includes oral non-absorbable antibacterial and antifungal agents with initial use of a broad-spectrum systemic antibacterial.

Ann Pediatr (Paris), 1990 Sep, 37(7), 475 - 9
{Value of Imocur in the prevention of recurrent infections in children under six years of age . Results of a multicenter, placebo-controlled trial}; Paupe J; Sixty-four children under six years of age with recurrent ear, nose and throat and/or lower respiratory tract infections (three episodes or more during the previous winter) were included in a double-blind, placebo-controlled study of the oral bacterial immunomodulator Imocur . Imocur provided better individual protection than the placebo throughout the three-month treatment period and the subsequent three-month follow-up period . Among the patients given Imocur, 34% remained free of infection and 37% required no antimicrobial drugs throughout the six-month study period, as compared with 3% and 10%, respectively, among the controls . The number of infectious episodes per patients during the six-month study period was 4.86 among controls versus 1.66 among patients given Imocur . Use of antimicrobial agents was reduced by half among patients treated with Imocur as compared with controls . Tolerance was outstanding, with no adverse effects among treated patients . These results show that Imocur is an effective immunomodulator for the treatment of recurrent ear, nose and throat and/or lower respiratory tract infections in children.

J Burn Care Rehabil, 1990 Sep-Oct, 11(5), 423 - 7
A survey of wound monitoring and topical antimicrobial therapy practices in the treatment of burn injury; Taddonio TE et al.; A survey was done to determine how burn wound microbial monitoring is performed and how topical antimicrobial agents are employed . The survey was sent to 90 burn-care facilities, which comprised most of the major burn centers in the United States . The survey contained questions concerning frequency and techniques of wound monitoring, personnel involved in monitoring, as well as questions about how decisions were made to initiate topical antimicrobial therapy, which agents were selected, and how they were administered . Sixty of 90 facilities (66%) responded to the survey . Although there were few areas of unanimous agreement, several trends did emerge . Most facilities monitored burn wounds for microbes (92%) . Wound monitoring was typically done at least twice weekly by either surface swab or quantitative biopsy . Nursing staff played a significant role in specimen collection in 69% of facilities and were solely responsible for obtaining biopsy specimens in 29% of facilities that used biopsies exclusively . All responding facilities used topical antimicrobial agents; silver sulfadiazine was the most popular (95%) . Only 33% of facilities surveyed had their own laboratory for microbial monitoring . Rapid techniques for early diagnosis of wound sepsis were used in 20% of units, and topical antimicrobial testing was used in 17% of facilities surveyed.

Rev Infect Dis, 1990 Sep-Oct, 12(5), 778 - 83
Comparison of species distribution and antimicrobial susceptibility of aerobic actinomycetes from clinical specimens; McNeil MM et al.; To compare the species distribution and antimicrobial susceptibility of aerobic actinomycetes, we evaluated 366 isolates referred to the Centers for Disease Control from October 1985 through February 1988 . We used conventional biochemical tests to identify the various species . Four species accounted for 191 (52%) of aerobic actinomycete isolates: Nocardia asteroides (98 isolates), Actinomadura madurae (42 isolates), Streptomyces griseus (28 isolates), and Nocardia brasiliensis (23 isolates) . Sputum and wounds were the most common sources . No isolate was resistant to amikacin, no N . brasiliensis isolate was resistant to sulfamethoxazole or trimethoprim-sulfamethoxazole, and no A . madurae isolate was resistant to ceftriaxone or imipenem . In summary, our findings show that unusual species of aerobic actinomycetes can cause infection, colonization, or both and that antimicrobial resistance varies markedly by species.

Rev Infect Dis, 1990 Sep-Oct, 12(5), 740 - 4
Brucella endocarditis: the role of combined medical and surgical treatment; Jacobs F et al.; Brucella endocarditis, although a rare complication of brucellosis, is the main cause of death related to this disease . This report describes a case of aortic endocarditis due to Brucella abortus in an elderly farmer with known aortic stenosis . Urgent valve replacement was performed because of progressive heart failure despite appropriate antimicrobial treatment . The infection was cured with trimethoprim-sulfamethoxazole and rifampin given for 3 months after surgery . A review of the literature reports on the 38 other cases of cured brucella endocarditis made clear the need for combined antimicrobial treatment and surgical valve replacement.

Infect Control Hosp Epidemiol, 1990 Sep, 11(9), 495 - 7
Strongyloides stercoralis; Zygmunt DJ; In many aspects, S stercoralis is a unique opportunistic pathogen . Via its autoinfections cycle, it is capable of producing both parasitic and bacterial infections at remote organ sites . These infections are often nosocomial . Diagnosis can be very difficult if appropriate microscopic evaluation is not done . Concomitant bacterial infections must be treated with appropriate antimicrobial agents; thiobendazole is the treatment of choice for the parasitic phase of these infections.

J Prof Nurs, 1990 Sep-Oct, 6(5), 300 - 9; discussion 310-2
Ambulatory care for patients with acute leukemia: an alternative to frequent hospitalization; Sullivan DH et al.; Over the past 5 years, 23 cancer patients diagnosed with adult acute leukemia have been able to receive their required therapies primarily on an ambulatory basis . This included chemotherapy, antimicrobials, and blood product infusions . The ambulatory primary nurse has been a vital facilitator in designing and implementing a care plan that includes drug administration, symptom management, and the complex coordination of community resources . The relationship that develops between the patient, family, and primary nurse is also a key factor in the effectiveness of such an ambulatory program.

Ir Med J, 1990 Sep, 83(3), 121 - 4
Septicaemia and the prevention of multiorgan failure--the intensive care perspective; Crowley K et al.; Septicaemia frequently presents without "classic" signs of infection--tachypnoea, hypotension and confusion are the commonest features . The mortality rate is 40 to 80% and in intensive care units, septicaemia accounts for 70% of all deaths . Despite the use of antimicrobial drugs to which the offending organism is sensitive, patients are still dying . Effects on distant organ systems are due to "Mediators" . "Microvascular Failure" resulting in tissue hypoxia is the unifying hypothesis of multiple organ failure in septicaemia . Mortality is correlated with the number of organ system failures . Supportive management is aimed at prevention of organ failure--manipulation of the circulation being the central key . Intravascular volume expansion, vasoactive drugs, mechanical ventilation and invasive monitoring are the means . Antimicrobial therapy must be guided by 'best guess' approach with multiple agents until isolation of the offending organism can recommend specific therapy . Aggressive surgical drainage or excision, is particularly applicable in abdominal sepsis . Several adjunctive therapies aimed at mediators of sepsis, are as yet experimental.

Eur J Clin Microbiol Infect Dis, 1990 Sep, 9(9), 654 - 8
Blood culture techniques for the diagnosis of melioidosis; Wuthiekanun V et al.; The effects of variations in laboratory technique on the speed and sensitivity of isolation of Pseudomonas pseudomallei from blood were evaluated prospectively . Pseudomonas pseudomallei was isolated from 154 of 546 cultures from 325 patients with suspected or confirmed melioidosis . Subcultures after 12 to 24 and 36 to 48 hours of incubation were positive in 52.3% and 80.8% respectively . The yields from 20 ml (blood to broth ratio 1:4) and 50 ml (blood to broth ratio 1:10) brain heart infusion broth bottles were equivalent in patients not receiving treatment for melioidosis . During therapy, the 50 ml bottles grew Pseudomonas pseudomallei significantly faster than the 20 ml bottles (p less than 0.01), and gave a higher overall yield for cultures processed in antimicrobial removal devices (p less than 0.05) . These devices themselves increased the speed of isolation of the organism from treated patients (p less than 0.01) . In most cases, all bottles collected from a patient before treatment were positive, and a single 20 ml bottle had an estimated relative sensitivity of 85.7% (95% confidence interval 77.1-94.3%) . Early subculture should be employed routinely for the laboratory diagnosis of septicaemic melioidosis . However, blood culture techniques do not need to be sophisticated . Culture of 5 ml blood in 20 ml broth is a simple and sensitive procedure suitable for regions where melioidosis is currently under-diagnosed.

Drugs, 1990 Sep, 40(3), 364 - 73
Current treatment recommendations for topical burn therapy; Monafo WW et al.; Infections in burn patients continue to be the primary source of morbidity and mortality . Topical antimicrobial therapy remains the single most important component of wound care in hospitalised burn patients . The goal of prophylactic topical antimicrobial therapy is to control microbial colonisation and prevent burn wound infection . In selected clinical circumstances topical agents may be used to treat incipient or early burn wound infections . At the present time silver sulfadiazine is the most frequently used topical prophylactic agent; it is relatively inexpensive, easy to apply, well tolerated by patients, and has good activity against most burn pathogens . In patients with large burns the addition of cerium nitrate to silver sulfadiazine may improve bacterial control . Mafenide acetate has superior eschar-penetrating characteristics, making it the agent of choice for early treatment of burn wound sepsis . However, the duration and area of mafenide application must be limited because of systemic toxicity associated with prolonged or extensive use . Other agents, such as nitrofurazone or chlorhexidine preparations, may be useful in isolated clinical situations . The undesirable side effects of silver nitrate solution limit its use by most clinicians at the present time.

J Protozool, 1990 Sep-Oct, 37(5), 436 - 41
Analysis of Pneumocystis carinii cyst wall . II . Sugar composition; De Stefano JA et al.; Pneumocystis carinii cysts are capable of resisting host defenses and antimicrobial drugs and are therefore thought to be responsible for relapses of P . carinii pneumonia in AIDS and other immunocompromised patients . The interaction of P . carinii with its host, and other P . carinii, might be mediated by molecules which form the outer surfaces of this organism . Carbohydrates are known to play many roles in cell-cell adhesion, and have been detected on the surface of P . carinii by lectin labeling experiments . In this study P . carinii cyst wall material was obtained from Zymolyase treatment . Alditol acetate derivatives of neutral and amino sugars or trimethylsilyl derivatives of methyl glycosides were prepared from the monosaccharides released from the sample by acid hydrolysis . Analyses were done by a combination of gas chromatography and mass spectrometry . Glucose was found to be the major sugar constituent . Mannose and galactose were present in equal ratios . A lesser amount of N-acetyl-D-glucosamine, and trace amounts of ribose and sialic acid were present in the cyst wall samples analyzed . These sugars may mediate P . carinii-host interaction and play an important protective role by creating a permeability barrier around the cyst.

J Protozool, 1990 Sep-Oct, 37(5), 428 - 35
Analysis of Pneumocystis carinii cyst wall . I . Evidence for an outer surface membrane; De Stefano JA et al.; It has long been thought that the cyst form of Pneumocystis carinii, which can resist host defenses and antimicrobial drugs, is responsible for relapses of P . carinii pneumonia . The thick wall of the cyst is immunogenic and rich in glucosyl/mannosyl and N-acetyl-D-glucosamine residues . In this study we have demonstrated the presence of a hitherto unreported outer membrane in the cyst wall of P . carinii . This membrane was detected by a combination of techniques, including transmission electron microscopy, freeze-fracture electron microscopy, and membrane labeling with fluorescent lipid analogs following treatment of P . carinii cysts from infected rats for 30 min with Zymolyase, a beta-1-3 glucanase . As in gram-negative bacteria and blue-green algae, this 2nd membrane may have an important role in osmoregulation and nutrient utilization; it may also mediate the interaction of P . carinii with its host and serve as a target for drug therapy.

Infect Dis Clin North Am, 1990 Sep, 4(3), 485 - 99
Antibiotic therapy for osteomyelitis; Gentry LO; Antibiotic therapy for osteomyelitis has dramatically changed within the past twenty years . The diagnostic criteria for osteomyelitis remain confusing to practicing physicians . Bone biopsy culture is now the standard for determining specific antimicrobial therapy . Many of the newest and most potent antimicrobials are now used to treat the increasingly broad bacterial spectrum of etiologies of osteomyelitis . There are tremendous economic incentives for outpatient and/or oral therapy . The third-generation cephalosporins and the new fluoroquinolones have replaced older, more toxic regimens, especially those containing aminoglycoside used to treat gram-negative osteomyelitis due to susceptible organisms.

Gut, 1990 Sep, 31(9), 973 - 6
Reduction of gastric ulcer recurrence after suppression of Helicobacter pylori by cefixime; Tatsuta M et al.; The effect on the recurrence of gastric ulcers after suppression of Helicobacter pylori by combined treatment with cimetidine and the antimicrobial drug cefixime was investigated . Twenty one of 43 patients with endoscopically proved gastric ulcer and H pylori infection were randomly assigned to receive cimetidine 800 mg daily for 12 weeks; the remaining 22 patients received cimetidine 800 mg daily for 12 weeks plus cefixime 100 mg daily for the last two weeks . After treatment, 88% of 17 patients on cimetidine only remained H pylori positive, whereas combined administration of cimetidine and cefixime had suppressed H pylori in 78% of 18 patients (p less than 0.05) . Seventeen patients in the former group whose ulcers healed but who remained H pylori positive and 18 patients in the latter group whose ulcers healed and who were no longer infected with H pylori continued to be followed after treatment . These patients underwent endoscopy to detect ulcer recurrence if symptomatic, or at 12 and 24 weeks if asymptomatic . At 12 weeks, recurrence was observed in seven of 15 (47%) patients in whom H pylori persisted, but in only one of 14 (7%) patients in whom H pylori had been suppressed (p less than 0.05) . At 24 weeks, however, recurrence rates were similar between the two groups . These findings indicate that H pylori infection may be closely related to early ulcer recurrence.

Gastroenterology, 1990 Sep, 99(3), 863 - 75
Bismuth therapy in gastrointestinal diseases; Gorbach SL; Bismuth therapy has shown efficacy against two major gastrointestinal disorders: peptic ulcer disease and diarrhea . In peptic ulcer disease it is as effective as the H2-receptor antagonists, costs considerably less, and offers a lower rate of relapse . When Helicobacter pylori is implicated, bismuth acts as an antimicrobial agent, suppressing the organism but not eliminating it . In recent studies, bismuth compounds have been used with conventional antibiotics, producing elimination of the organism, histological improvement, and amelioration of symptoms for periods longer than one year . Bismuth subsalicylate has shown modest efficacy in treating traveler's diarrhea and acute and chronic diarrhea in children, and it is effective prophylactically for traveler's diarrhea . An epidemic of neurological toxicity was reported in France in the 1970's with prolonged bismuth treatment, usually bismuth subgallate and subnitrate . Such toxicity has been rare with bismuth subsalicylate and colloidal bismuth subcitrate . However, recent studies have demonstrated intestinal absorption of bismuth (about 0.2% of the ingested dose) and sequestration of this heavy metal in multiple tissue sites, even occurring with conventional dosing over a 6-week period . These findings have inspired recommendations that treatment periods with any bismuth-containing compound should last no longer than 6-8 weeks, followed by 8-week bismuth-free intervals.

J Biol Buccale, 1990 Sep, 18(3), 215 - 26
Insulin-deficient diabetes impairs osteoblast and periodontal ligament fibroblast metabolism but does not affect ameloblasts and odontoblasts: response to tetracycline(s) administration; Sasaki T et al.; Insulin-deficient, adult, diabetic rats were administrated a tetracycline (either minocycline or a chemically-modified non-antimicrobial tetracycline: CMT) by oral gavage over a 3-week period . Untreated diabetic and non-diabetic rats served as controls . On day 21, all rats received an intravenous injection of 3H-proline, as a radioprecursor of procollagen in bone, dentine and periodontal ligament (PDL) or of amelogenin in enamel; perfusion fixation with an aldehyde mixture was carried out at 20 minutes and 4 hours after isotope injection . The parietal bones (calvaria), mandibules including molars, and lower incisors of these rats were dissected and processed for light microscopic autoradiography to study 3H-proline utilization by osteoblasts, PDL fibroblasts, odontoblasts and ameloblasts . In the control rats, at 20 minutes after 3H-proline injection, silver grains of labeled precursor were detected in the osteoblasts of the periosteal surfaces of the parietal bones . At the 4 hour time period, although some radioprecursor was still present in the osteoblasts, most had progressed to the osteoid matrix . In contrast, the flattened bone-lining cells in the untreated diabetics showed minimal uptake and secretion of labeled proline at both time periods . In both minocycline- and CMT-treated diabetic rats, the labeled proline was localized in the osteoblasts and the osteoid in a pattern reminiscent of that seen in the control rats at both time periods . Of interest, CMT administration appeared to increase the labeling of the osteoid matrix more than minocycline treatment . In non-diabetic control rats, the PDL fibroblasts exhibited a polarized elongated profile and incorporated and secreted radioprecursor similar to that described for the osteoblasts in these animals . The PDL fibroblasts in the untreated diabetics lost their regular arrangement and incorporated little if any 3H-proline; once again, tetracycline administration appeared to normalize, at least in part, the structure and 3H-proline incorporation by these connective tissue cells . In contrast, diabetes and tetracycline administration did not affect the incorporation and secretion of radioprecursor by odontoblasts and secretory ameloblasts during tooth development.

J Periodontal Res, 1990 Sep, 25(5), 316 - 9
Comparative effects of toothpaste brushing and toothpaste rinsing on salivary bacterial counts; Jenkins S et al.; The persistence of antimicrobial action of compounds and formulations in the mouth can be demonstrated by recording the magnitude and duration of the reduction of salivary bacterial counts following a single application . Such measures of substantivity appear to correlate with the plaque inhibitory properties of antimicrobial agents . For toothpastes, studies on the short-term inhibition of plaque formation use a number of delivery methods to measure the direct effect of the preparation divorced from toothbrushing . Such methods include paste slurries, paste in trays or cap splints . This study determined whether toothbrushing with a toothpaste produced the same effects on salivary bacterial counts compared to rinsing with a slurry . A group of 24 volunteers brushed or rinsed with a slurry of a commercial toothpaste . Each regimen was repeated twice on 4 separate days by all volunteers and salivary bacterial counts recorded at baseline and time periods to 7 hours . There were no significant differences between brushing or slurry rinsing on salivary bacterial counts and each method produced reproducible effects . This supports the use of the slurry method where the direct plaque inhibitory action of an antimicrobial toothpaste is to be assessed; and indicates that both methods equally make available and activate the relevant ingredients in formulations.

J Antibiot (Tokyo), 1990 Sep, 43(9), 1107 - 21
N15-alkyl and N15,N15-dialkyl derivatives of teicoplanin antibiotics; Malabarba A et al.; The synthesis and the biological properties of a series of N15-alkyl and N15,N15-dialkyl derivatives of teicoplanin A2, its pseudoaglycones and aglycone are described . The alkylation of the terminal amino group did not affect the ability of these teicoplanin derivatives to bind with Ac2-L-Lys-D-Ala-D-Ala, a synthetic model of the antibiotic's target peptide in bacterial cell walls, but influenced their in vitro and in vivo antimicrobial activities to a different extent, depending on the structure and length of the alkyl chains and the type and number of sugars present.

Pediatr Dent, 1990 Sep-Oct, 12(5), 292 - 7
The effects of dyadic combinations of endodontic medicaments on microbial growth inhibition; Seow WK; In recent years dyadic combinations of endodontic medicaments have been used increasingly in clinical pediatric dentistry with little regard to the possibility of pharmacological antagonism of the components . In this investigation, a microbial growth inhibition assay was used to determine changes in antimicrobial activity in dyadic mixtures of endodontic medicaments . The combinations assayed were Ledermix (corticosteroid-antibiotic) and Calyxl (calcium hydroxide), Ledermix and Kri (iodoform), Kri and Calyxl, and formocresol and eugenol . All these compounds have antibacterial activity when used individually . In the dyadic combinations assayed, results showed that adding calcium hydroxide to another antibiotic preparation has deleterious effects on growth inhibition, and combining any two antimicrobial medicaments produces no additive or synergistic effects . It is concluded that it may be clinically advantageous to use endodontic medicaments in the dyadic combinations shown in this investigation.

J Clin Microbiol, 1990 Sep, 28(9), 2139 - 41
Case report and seeded blood culture study of Brucella bacteremia; Zimmerman SJ et al.; Diagnosis of brucellosis requires prompt detection and identification of the coccobacillus for appropriate patient management, as the organism is associated with a potentially severe outcome . In a recent experience, an 18-year-old migrant farm worker presented at a local hospital with nonspecific symptoms . A significant Brucella titer of 2,560 was followed by the recovery of a gram-negative coccobacillus, subsequently identified as Brucella abortus, from subcultured 5-day-old BACTEC NR730 negative blood cultures . The organism proved to be susceptible to a variety of antimicrobial agents and resistant to nitrofurantoin . The patient was administered antimicrobial therapy for Brucella spp . consisting of tetracycline and streptomycin for 21 days . During the course of therapy the patient experienced defervescence and was discharged with the recommendation for periodic follow-up examinations . Seeded culture studies of this isolate with fresh human blood and target inocula of 5 and 500 CFU/ml indicated that the larger (500-CFU/ml) inoculum produced positive instrument detection within 2 days, whereas the smaller (5-CFU/ml) inoculum required 5.5 to 7.5 days for detection, depending on the medium used . These findings underscore the potential for Brucella bacteremia to escape instrument detection given a low bacterial inoculum.

J Infect Dis, 1990 Sep, 162(3), 723 - 6
Trimethoprim-sulfamethoxazole prophylaxis in the management of chronic granulomatous disease; Margolis DM et al.; Long-term oral antimicrobial prophylaxis is accepted practice in the management of patients with chronic granulomatous disease (CGD) . Reports of adverse outcome with trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis in other patient groups, and the recent occurrence of several severe fungal infections in patients followed at the National Institutes of Health (NIH), prompted a review of the NIH experience to examine the incidence of nonfungal and fungal infections in CGD patients with and without TMP-SMX prophylaxis . Prophylaxis decreased the incidence of nonfungal infections from 7.1 to 2.4 per 100 patient-months in patients with autosomal CGD (P less than .01) and from 15.8 to 6.9 infections per 100 patient-months (P = .06) in X-linked CGD patients . There was no significant change in the incidence of fungal infection in CGD patients on TMP-SMX (1.5-0.3 fungal infections/100 patient-months in autosomal CGD and 1.7-0.2 fungal infections/100 patient-months in X-linked CGD patients) . TMP-SMX prophylaxis is indicated for the management of patients with CGD and decreases the incidence of non-fungal infections without increasing the incidence of fungal infections.

Lijec Vjesn, 1990 Sep-Oct, 112(9-10), 319 - 22
{Ceftazidime in the therapy of gram-negative meningitis in childhood}; Bozinovic D et al.; Six cases of neonatal meningitis due to E . coli (3 cases), K . pneumoniae (1 case), P . aeruginosa (1 case) and S . marcescens (1 case), and eleven cases of suckling and little child meningitis caused by M . influenzae (10 cases) and N . meningitidis (1 case) were treated with ceftazidime . The susceptibility of agents was qualitatively tested according to the disk-diffusion method, and quantitatively according to biological dilution method on liquid broth . Ceftazidime concentrations in cerebrospinal fluid and sera were determined by the modified microbiological method using diffusion on agar . Efficacy of ceftazidime therapy was assessed by quickness of cerebrospinal fluid "sterilization", duration of antimicrobial therapy and outcome of the disease . In spite of very good agents susceptibility to ceftazidime determined by disk-diffusion method, notable differences were found in quantitatively determined susceptibility (minimal inhibitory and minimal bactericidal concentration) . Antibiotic penetrability was various in proportion with individual intensity of blood brain barrier break down . Bactericidal effect and prompt "sterilization" of cerebrospinal fluid within 48 hours after the beginning of ceftazidime therapy was achieved in those patients in whom ceftazidime cerebrospinal fluid concentration was 10 and several times higher than the minimal bactericidal concentration (all cases due to H . influenzae, N . meningitidis and E . coli) . In these cases the issue of the disease was also favourable and none of the patients died.(ABSTRACT TRUNCATED AT 250 WORDS)

Acta Otorrinolaringol Esp, 1990 Sep-Oct, 41(5), 347 - 50
{Changes in the flora of the oral cavity after oral topical antibiotics . Importance in antimicrobial prophylaxis in surgery of the neck and head}; Ramos Macias A et al.; A pilot study using 5 healthy adults was performed to assess the influence of topical antibiotics and antiseptics on oral flora . Samples of saliva were cultured before and after rinsing the mouth with several solutions: clindamycin, amoxyciclin + clavulanic, povidone-iodine and placebo . The results of this study suggest that, by reducing concentrations of oral flora, topical oral antibiotic prophylaxis is justified for patients having a high risk of developing a surgical infectious complications.

Eur Respir J, 1990 Sep, 3(8), 886 - 90
Azithromycin concentrations at the sites of pulmonary infection; Baldwin DR et al.; Azithromycin is a new macrolide antimicrobial . The distribution to the potential sites of pulmonary infection was assessed after the administration of a single 500 mg oral dose to 22 patients undergoing fibreoptic bronchoscopy . Concentrations of azithromycin in sputum, bronchial mucosa, eptihelial lining fluid (ELF) and alveolar macrophages (AM) were determined at intervals up to 96 h after dosing . The mean serum concentration was low at 12 h (0.13 micrograms.ml-1, SEM 0.05) but was still detectable at 96 h (0.01 micrograms.ml-1) . In contrast, peak sputum ELF, bronchial mucosal and AM levels were found at 48 h . Bronchial mucosal concentrations were significantly greater than ELF concentrations, which were in turn greater than sputum concentrations . Mean peak AM concentrations were sixfold greater than bronchial mucosal concentrations (23 micrograms.ml-1, SEM 5.1 and 3.89 micrograms.ml-1, SEM 1.2, respectively) . The high intracellular concentrations indicate that azithromycin is likely to be effective for sensitive intracellular pathogens and the favourable penetration into sputum, ELF and bronchial mucosa suggest that it should be useful in pneumonia and bronchial infections.

Pharm Weekbl Sci, 1990 Aug 24, 12(4), 121 - 7
Pharmacokinetics of antimicrobial agents in organ function impairment . A review; Janknegt R; The pharmacokinetics of antimicrobial drugs in various types of organ function impairment are reviewed . The influence of renal function impairment on antimicrobial agents is well-known, although less is known about the accumulation of metabolites during renal failure . Fewer data are available on liver function impairment and more information is needed on highly metabolized agents . Pharmacokinetic studies in severely ill patients are urgently needed to investigate the influence of disease states on pharmacokinetics and to study the possibility of oral administration to seriously ill patients.

Ugeskr Laeger, 1990 Aug 20, 152(34), 2404 - 7
{Breast milk substitutes based on cow milk}; Kofoed PE; "Adapted" or "humanized" breast-milk substitutes based on cows' milk are manufactured according to directives from a publication issued by the Ministry of Agriculture . The accepted recommendations for the daily intake (RDA) of nutrients is adjusted to the neonates' relatively low tolerance and provides a certain margin of safety in case of illness and slight inaccuracies in preparation . The recommendations are, however, often based on animal experiments, studies of pathological conditions etc . because the needs of the neonate are not known . There is a fundamental difference between RDA for chemical energy and various nutrients as the energy requirement is stated on the basis of average values while the requirements for specific nutrients are gives as upper and lower limiting values . In addition to nutrients, a long series of hormones, enzymes and antimicrobial factors are transferred to the infant via breast-milk . The nutritional significance of these is entirely or partially unknown . It is thus impossible to give the bottle-fed infant a diet which is quantitatively and qualitatively identical with that of a breastfed baby . Nevertheless, experience has shown that bottle-feeding usually proceeds satisfactorily . Galactosaemia and certain forms of medication in the mother constitute absolute contraindications to breast-feeding while phenylketonuria, certain maternal infections are relative contraindications to breast-feeding . Mothers should be prepared for breast-feeding already during pregnancy but in the cases where the mother cannot, should not or does not wish to breast-feed, it is important to counteract any feelings of guilt, neglect or incompetence and, on the other hand, give her thorough training in artificial feeding of the infant.

Cas Lek Cesk, 1990 Aug 17, 129(33), 1025 - 8
{Nitric oxide--a new and nontraditional transmitter}; Sevcik J et al.; NO is obviously identical with the relaxation factor produced by the vascular endothelium (EDRF) and is also the substance responsible for some other biological activities . It is formed in the organism from L-arginine by the action of the enzyme NO synthetase . The main mechanism of action is the activation of the enzyme guanyl cyclase and the result is an increase of the intracellular level of cyclic guanyl monophosphate . Depending on the type of effector cell, either vasodilatation occurs and adhesion is inhibited and the blood platelets coagulate or the cytotoxicity of macrophages increases . With the development of new, more effective inhibitors of NO synthetase there is also the possibility to study the physiological importance of NO in more detail . These new discoveries provide a more profound biochemical and pharmacological basis and perhaps also new indications or preventive possibilities of the known treatment of vascular spasms by nitroderivatives; moreover, there is the possibility to seek new ways in the anti-tumourous and antimicrobial treatment and elsewhere.

Blood, 1990 Aug 15, 76(4), 825 - 34
The ontogeny of a 57-Kd cationic antimicrobial protein of human polymorphonuclear leukocytes: localization to a novel granule population; Pereira HA et al.; The ontogeny of a 57-Kd cationic antimicrobial protein (CAP57) that has substantial similarities to bactericidal permeability increasing protein (BPI) has been determined immunocytochemically . CAP57 was detected in the granules of mature peripheral blood neutrophils . However, it was absent from other cells of the peripheral blood: eosinophils, red blood cells (RBCs), and mononuclear cells . In human bone marrow, CAP57 was confined to the neutrophilic series . The earliest stage of development of the myeloid cells at which CAP57 was demonstrated was the promyelocyte . Double immunofluorescent labeling showed that CAP57 was detected in cells positive for myeloperoxidase . The absence of lactoferrin in certain cells (promyelocytes) containing CAP57 indicated that CAP57 was synthesized and packaged in a population of granules prior to the development of granules that contain lactoferrin . CAP57 could not be demonstrated in HL60 cells either by enzyme-linked immunosorbent assay (ELISA) or by immunocytochemistry . However, the presence of another granule-associated cationic antimicrobial protein of molecular weight 37 Kd (CAP37) was readily detected in undifferentiated HL60 cells . Amino acid sequence analysis showed that CAP57 and BPI were identical . Further indication of the identity between CAP57 and BPI was that monoclonal anti-CAP57 antibodies cross reacted with BPI . Sucrose density-gradient centrifugations showed CAP57 was confined to a granule population that exhibited a buoyant density intermediate of the previously described light and heavy azurophil granules . Further resolution of the individual azurophil granule populations by Percoll density-gradient centrifugation revealed that CAP57 was most concentrated in the density range of 1.093 to 1.100 g/cc . These results strongly suggest the unique finding that CAP57 may be associated with a heretofore unreported granule type.

N Engl J Med, 1990 Aug 2, 323(5), 285 - 9
The carriage of Escherichia coli resistant to antimicrobial agents by healthy children in Boston, in Caracas, Venezuela, and in Qin Pu, China; Lester SC et al.; BACKGROUND AND METHODS . The healthy members of a community represent its largest reservoir of bacteria resistant to antimicrobial agents . We compared the resistance to eight agents of Escherichia coli in stool samples from untreated, healthy children in cities on three continents . RESULTS . When screened by a selective method that detected 1 resistant colony in 10,000 colonies, nearly half the children in Boston (18 of 39) had no resistant colonies--a finding consistent with the findings of other surveys performed in developed countries . However, all but 1 of 41 children screened in Caracas, Venezuela, and all but 2 of 53 in Qin Pu, China, carried resistant strains . Only 1 child in Boston but 25 in Caracas and 34 in Qin Pu carried strains resistant to trimethoprim . None of the children in Boston or Caracas but 17 in Qin Pu carried strains resistant to gentamicin . Among 10 colonies selected randomly from each stool sample, the average frequency of resistance in Caracas was 3.6 times greater than in Boston, and that in Qin Pu was 5.3 times greater . There was resistance to five or more antimicrobial agents in 20 percent of the Qin Pu strains and in 6 percent of the Caracas strains but in none of the Boston strains . CONCLUSIONS . In addition to clinical isolates, as reported previously, the bacteria that colonize health children in the community may be resistant far more often in some regions than in others . A low rate of carriage of antimicrobial resistance in the community should become a public health goal.

Anticancer Drug Des, 1990 Aug, 5(3), 243 - 8
Structural studies on bio-active compounds . Part XIV . Molecular modelling of the interactions between pentamidine and DNA; Sansom CE et al.; Molecular mechanics modelling was carried out on the antimicrobial aromatic diamidine, pentamidine, bound to the minor groove of several AT-rich DNA octamers . The pentamidine molecule was found to span four base pairs, with its highly charged amidinium groups forming hydrogen bonds to the O2 of thymine or the N3 of adenine, but not to the backbone phosphate groups . The mean binding energy of the pentamidine-DNA complexes was -52 kcal/mol, of the same order as that of berenil-DNA complexes . There was no significant energy difference between those models which contained GC base pairs and those which did not . The presence of bound pentamidine resulted in some distortion of helix geometry involving helix opening towards the minor groove in most cases and a decrease in the number of residues per turn.

Am Rev Respir Dis, 1990 Aug, 142(2), 430 - 3
Sex differences in the susceptibility of mice to infection induced by Mycobacterium intracellulare; Yamamoto Y et al.; Sex differences in the susceptibility of Balb-c mice to Mycobacterium intracellulare infection were studied . When mice were given M . intracellulare intravenously, macroscopic lesions were considerably more extensive in the lungs, liver, and kidneys of male mice than in female mice . A significantly more marked growth of organisms occurred in these visceral organs of the male mice during the course of infection for as long as 16 wk after the challenge . This difference can be partly explained by the finding that the antimicrobial activity of host peritoneal macrophages is more potent in the female mice.

Arch Pharm (Weinheim), 1990 Aug, 323(8), 471 - 4
Synthesis of novel naphtho{2,1-b}-1,4,5-oxa- or thiadiazepines as potential antimicrobial and anticancer agents; Khalil MA et al.; Two novel series of quinone derivatives have been synthesized . Thus, condensation of 2-ethoxycarbonylmethylthio-; 3-ethoxycarbonylmethylthio-2-methyl- and 3-ethoxycarbonylmethoxy-2-methyl derivatives of 1,4-naphthoquinone with substituted phenylhydrazines afforded the corresponding hydrazones, while cyclization of the same quinones with the same substituted hydrazines in glacial acetic acid gave the corresponding naphtho{2,1-b}-1,4,5-oxa- or thiadiazepine derivatives . The antimicrobial and anticancer activities of the synthesized compounds were studied.

Int J Clin Pharmacol Ther Toxicol, 1990 Aug, 28(8), 339 - 43
Changing pattern of antimicrobial utilization in an Indian teaching hospital; Pradhan SC et al.; A study was conducted at Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India, on the pattern of antimicrobial utilization in hospitalized patients . A retrospective study was conducted during a one-month period between January 18 to February 17, 1987 . The data were analyzed according to modified Kunin's criteria . The results were compared with a similar study conducted a decade ago . The study revealed a marked increase in the use of antimicrobial agents (from 19.9% to 56.1%) . A more appropriate use of antimicrobial agents was observed (from 66.8% to 79.5%) . A significant increase in their appropriate use for therapeutic purpose (50% to 88.2%), but not for prophylaxis (79.05% to 71.18%) was seen . The study revealed a marked increase in the use of antimicrobial agents during the last decade resulting in the emergence of nosocomial infections of resistant strains of organisms.

Semin Perinatol, 1990 Aug, 14(4 Suppl 1), 2 - 9
Antimicrobial defenses in the neonate; Quie PG; Serious life-threatening neonatal infections with microbial species that are infrequently associated with infections in adults are related to the immature immune system of human newborn infants . The usually sterile intrauterine environment of the fetus is associated with a primed but inactive immune system at the time of birth . Sudden introduction into a complex microbial world stimulates the inflammatory system and an effective host defense rapidly develops . Defense mechanisms include innate phagocytic and complement systems, and specific adaptive immunity including antimicrobial antibodies . Fortunately, neonates have protective antibodies against many microbes at birth provided by their mothers via placental transfer of IgG . Specific antimicrobial antibody production by the newborn infant is delayed . Neutrophil numbers in the circulation are high in the normal neonate, but the bone marrow pool of cells is limited . Chemotactic responsiveness of circulating phagocytic cells is decreased in comparison with adult cells, although phagocytic and microbicidal activity of neonatal neutrophils and monocytes are normal . The newborn infant's lymphocyte system is relatively mature, and neonatal mononuclear cells have normal antigen-presenting and secretory function . T lymphocytes are present in normal numbers and although response of these cells to antigens is somewhat slower than in adult cells, a near normal response suggests intrauterine stimulation by maternally derived immunoregulators . B lymphocytes are also present in newborn human infants . However, maturation of B lymphocytes into antibody-producing plasma cells occurs gradually during the first weeks of life.(ABSTRACT TRUNCATED AT 250 WORDS)

J Chemother, 1990 Aug, 2(4), 244 - 6
Acute prostatitis: which antibiotic to use first; Becopoulos T et al.; Six antimicrobial agents were administered to 48 patients (divided in 6 groups) who underwent prostatectomy . Half of the patients received the antibiotic in a single dose one hour before the operation and the rest in divided doses 24 hours before the operation . The concentration levels in serum and in prostatic tissue were measured for each of the antibiotics and for each mode of administration . The obtained ratios of prostatic tissue to serum concentrations and the relative antimicrobial activity to local pathogens of each agent indicate that the agent of choice for prostatic disease is netilmicin followed by aztreonam, cefuroxime and the ticarcillin-clavulanic acid combination.

J Chemother, 1990 Aug, 2(4), 218 - 37
Impact of antimicrobial agents on human intestinal microflora; Nord CE et al.; The most common and significant cause of disturbances in the normal intestinal microflora is the administration of antimicrobial agents . The microflora can be influenced by antimicrobial agents because of incomplete absorption of any orally administered antimicrobial agent, secretion of an antimicrobial agent in the bile, or secretion from the intestinal mucosa . In most cases, the influence is not beneficial to the patient because suppression of the indigenous microorganisms often permits potential pathogens to overgrow and cause septic conditions, stomatitis, diarrhea, or colitis . Antimicrobial agents that influence the normal microflora also promote the emergence of antimicrobial-resistant strains . During the last fifteen years, the impact of different antimicrobial agents on the human microflora has been studied by several investigators . In this article published data on the impact of beta-lactam antibiotics, macrolides, tetracyclines, nitroimidazoles, clindamycin and quinolones on the human intestinal microflora are reviewed.

J Biochem (Tokyo), 1990 Aug, 108(2), 261 - 6
Tachyplesins isolated from hemocytes of Southeast Asian horseshoe crabs (Carcinoscorpius rotundicauda and Tachypleus gigas): identification of a new tachyplesin, tachyplesin III, and a processing intermediate of its precursor; Muta T et al.; Tachyplesins and their analogs are antimicrobial peptides composed of 17 or 18 amino acid residues present abundantly in acid extracts of hemocyte debris of horseshoe crabs . We purified here tachyplesin isopeptides from hemocytes of two species of Southeast Asian horseshoe crabs, Carcinoscorpius rotundicauda and Tachypleus gigas, and determined their amino acid sequences . The major tachyplesin isolated from both species was identified, respectively, as tachyplesin I, which had previously been found in hemocytes of the Japanese horseshoe crab (Tachypleus tridentatus) . The yield from both species was very high (more than 70 mg per 100 g wet weight of hemocytes), i.e., comparable with that from T . tridentatus . In addition to tachyplesin I, a new tachyplesin isopeptide, named tachyplesin III, was also isolated from T . gigas hemocytes, in which an arginine replaced the 15th lysine of tachyplesin I . The carboxyl-terminal residue of the isolated tachyplesins I and III was confirmed, respectively, to be an arginine alpha-amide by chemical analysis . Furthermore, a tachyplesin peptide derivative with a carboxyl-terminal extension of glycine-lysine was newly found in the hemocytes of C . rotundicauda . It appeared to be an intermediate derived from a tachyplesin precursor during processing to the mature form.

FEMS Microbiol Lett, 1990 Aug, 58(3), 269 - 73
Antimicrobial effect of human milk on Bordetella pertussis; Redhead K et al.; It has been demonstrated that human milk, unlike bovine milk, can reduce the viability of Bordetella pertussis . This antibacterial activity was not due to the presence of antibiotics or antibodies in the human milk . Reducing the level of available iron or increasing the concentration of lysozyme in bovine milk did not induce anti-B . pertussis activity . Analysis of total fatty acids revealed that human milk contained significantly more linoleic acid than bovine milk . However, the addition of linoleic acid to bovine milk did not inhibit the growth of B . pertussis.

Antimicrob Agents Chemother, 1990 Aug, 34(8), 1498 - 500
In vitro cultivation of Cryptosporidium parvum and screening for anticryptosporidial drugs; McDonald V et al.; Sporozoites of Cryptosporidium parvum which were excysted in vitro from oocysts isolated from calves or patients with acquired immune deficiency syndrome underwent development in monolayers of the mouse fibroblast cell line L929 . Asexual multiplication occurred, with the maximum numbers of parasites usually being observed between 24 and 48 h after infection . Gametocytes were also found, but their numbers were relatively small compared with those of the asexual stages . A study was made of the effect on parasite development of 20 antimicrobial agents, most of which were anticoccidial or antimalarial agents . The majority of the drugs had a limited inhibitory effect on parasite development, but usually only at high concentrations . The two most active drugs were monensin and halofuginone, which reduced parasite multiplication by more than 90% at high concentrations . In the case of monensin, however, inhibition of parasite development at higher concentrations was due, at least in part, to a toxic effect of the drug on the host cells.

Antimicrob Agents Chemother, 1990 Aug, 34(8), 1467 - 72
In vivo assessment of antimicrobial agents against Toxoplasma gondii by quantification of parasites in the blood, lungs, and brain of infected mice; Piketty C et al.; The in vivo effects of antimicrobial agents against Toxoplasma gondii were evaluated in mice that were infected intraperitoneally with 10(4) tachyzoites of the RH strain by determination of survival rates and study of the kinetics of growth of T . gondii in infected mice . At various intervals after infection, subcultures of serial dilutions of blood, lung, and brain homogenates were performed in fibroblast tissue cultures for determination of parasitic loads . Pyrimethamine (18.5 mg/kg per day), sulfadiazine (375 mg/kg per day), and clindamycin (300 mg/kg per day) were administered for 10 days from day 1 or day 4 after infection . Untreated control mice died within 9 days and showed early and predominant lung involvement . All mice treated with sulfadiazine administered from day 1 survived and were apparently healthy; parasitic loads decreased early after treatment, but a relapse was observed 5 days after the cessation of therapy . When pyrimethamine was administered from day 1, 7 of 11 mice died within 25 days; by determination of parasitic loads, the effect of pyrimethamine was only demonstrable from day 6, and a relapse was constantly observed after the cessation of therapy . When pyrimethamine and sulfadiazine were administered in combination, 100% of mice survived; when therapy was started at day 1, parasites remained undetectable; in mice treated from day 4, parasites were eradicated by day 8 but infection relapsed 8 days after the cessation of therapy . All mice treated with clindamycin from day 1 or day 4 died within 10 days, but parasitemia was always undetectable . These results indicate that study of the kinetics of parasitic loads in blood and organs may provide additional information on the effect of antimicrobial agents against T . gondii in regard to the evolution of the infection and may represent a reliable basis for the determination of therapeutic regimens in humans.

Neurol Clin, 1990 Aug, 8(3), 605 - 17
Bacterial meningitis: an update; Shelton MM et al.; Antibiotics and improvements in supportive care have greatly reduced the mortality from bacterial meningitis . Nevertheless, the incidence of neurodevelopmental sequelae remains unacceptably high . Ampicillin and chloramphenicol remain the standard for antimicrobial therapy against which other agents must be compared . A number of adjunct therapies are being investigated for their possible effectiveness in reducing hearing loss and other neurologic effects of this disease . There continues to be a need for carefully performed follow-up studies to assess any possible benefit of these agents . A significant percentage of children surviving an episode of bacterial meningitis have obvious or subtle neurodevelopmental deficits . The role of the pediatric neurologist should not end with management of acute problems such as seizures but should be expanded to aid in close developmental monitoring of these high-risk children.

J Antibiot (Tokyo), 1990 Aug, 43(8), 956 - 60
Himastatin, a new antitumor antibiotic from Streptomyces hygroscopicus . I . Taxonomy of producing organism, fermentation and biological activity; Lam KS et al.; Strain C39108-P210-51 (ATCC 53653), an actinomycete isolated from a soil sample collected in India, was found to produce a new antitumor antibiotic, designated himastatin . Taxonomic studies on its morphological, cultural and physiological characteristics identified this producing strain as Streptomyces hygroscopicus C39108-P210-51 . Himastatin shows antimicrobial activity against Gram-positive bacteria but it is inactive against Gram-negative bacteria . Himastatin prolongs the life span of mice inoculated with P388 leukemia and B16 melanoma cells.

J Clin Periodontol, 1990 Aug, 17(7 ( Pt 2)), 479 - 93
Antibiotics in periodontal therapy: advantages and disadvantages; Slots J et al.; Antibiotic treatment of periodontitis aims at eradicating or controlling specific pathogens . Prime candidates for antibiotic therapy are patients with recently diagnosed active periodontitis or a history of recurrent disease who fail to stabilize following mechanical/surgical therapy . Since a variety of microbes with differing antimicrobial susceptibility profiles may cause periodontitis, selection of antimicrobial agents should be based on proper microbial diagnosis and sensitivity testing, as well as consideration of the patient's medical status . The risk of treating chemotherapeutically solely on the basis of clinical features, radiographic findings or a limited microbiological analysis, is failure to control the pathogens or overgrowth of new pathogens . A review of published papers reveals that appropriate systemic antibiotic therapy may enhance healing in patients with recent or high risk of periodontal breakdown . Systemic antibiotic therapy seems more predictable than topical administration in eradicating periodontal pathogens from deep periodontal pockets . Several promising antimicrobial agents for periodontitis treatment need testing in placebo-controlled, double-blind, randomized clinical trials.

Epidemiol Infect, 1990 Aug, 105(1), 11 - 20
Prevalence of verocytotoxigenic Escherichia coli in ground beef, pork, and chicken in southwestern Ontario; Read SC et al.; Samples of ground beef (225), pork (235) and chicken (200) were randomly selected from meat processing plants in the southwestern Ontario area . Supernatants of broth cultures of the samples were tested for verocytotoxins using a Vero cell assay . Neutralization of cytotoxic activity using antisera specific for three types of verocytotoxin (Verotoxin 1, Verotoxin 2 and Shiga-like toxin II) was performed on positive samples . Isolation of verocytotoxigenic Escherichia coli (VTEC) was attempted from positive samples . VTEC were confirmed as E . coli biochemically, tested for drug resistance, and serotyped . Based on neutralization studies, the prevalence of VTEC in beef and pork was at least 36.4% and 10.6%, respectively . This is much higher than has been reported from a survey of retail meats in which a method designed to detect only E . coli O 157.H7 was used . Isolations of VTEC were made from 10.4% of the beef samples and 3.8% of the pork samples . No VTEC were recovered from the chicken samples . The majority of VTEC isolates were susceptible to commonly used antimicrobial agents . A number of the serotypes of the VTEC isolates recovered have been associated with human disease; however, no VTEC of serotype O 157.H7 were isolated.

Arch Intern Med, 1990 Aug, 150(8), 1589 - 97
Antipyresis and fever; Styrt B et al.; While understanding of the mechanisms of fever has progressed in recent years, much uncertainty remains as to whether fever in itself (as distinct from its cause) is beneficial or harmful, and what circumstances warrant antipyretic therapy . This review was designed to identify studies providing information on the effects of fever and of pharmacologic and physical therapy . Fever or analogous behavioral thermal upregulation apparently has positive effects on defense against infection in some animal models . Retrospective studies in humans suggest that failure to mount a febrile response is associated with poor outcome in certain infections but do not establish a causal relationship . Induction of fever apparently had therapeutic value in infections such as syphilis before specific antimicrobials were developed . Fever may have deleterious effects in the context of borderline cardiovascular or neurologic function or pregnancy, but data in most instances cannot separate effects of fever per se from that of underlying disease . Antipyretic drugs are effective in diminishing fever, but they have significant side effects and may suppress signs of ongoing infection . Physical cooling is important when physiologic thermoregulatory mechanisms are overwhelmed, but may sometimes increase discomfort and metabolic stress in fever . Antipyretic therapy should not be instituted routinely for every febrile episode but should be based on evaluation of relative risks in the individual case and reassessed if anticipated benefits are not achieved.

Postgrad Med, 1990 Aug, 88(2), 64 - 8, 71-3, 77-81
The new antimicrobial agents . When they're the best choice and when they're not; Rey AM et al.; The number of antibiotics available to the clinician for treatment of infectious diseases continues to increase . However, choosing an agent just because it is new is not always cost-effective and may encourage the development of bacterial resistance . The site of infection, pharmacokinetic data, minimum inhibitory concentration, and cost must all be considered in selecting the optimal antimicrobial agent for a particular clinical situation.

Geriatrics, 1990 Aug, 45(8), 63 - 4, 69-71, 74-5
Meningitis as it presents in the elderly: diagnosis and care; Roos KL; The clinical presentation of bacterial meningitis in the elderly is often more subtle than in younger patients . Delay in diagnosis and treatment contributes significantly to morbidity and mortality . The presence of fever and a change in mental status in an elderly patient should raise suspicion for the presence of meningitis and prompt examination of the cerebrospinal fluid . Knowledge of the bacterial pathogens causing meningitis in this age group and administration of the recommended antimicrobial agents can greatly reduce morbidity and neurologic sequelae . This review updates the primary care physician in the diagnosis and management of this serious infection.

Gastroenterology, 1990 Aug, 99(2), 386 - 92
Secretory immunity in celiac disease: cellular expression of immunoglobulin A subclass and joining chain; Kett K et al.; Two-color immunofluorescence staining in situ demonstrated increased proportions of immunoglobulin A2 subclass-producing cells in jejunal mucosa from adult patients with untreated (47%, P less than 0.01) or treated (37%, P less than 0.05) celiac disease compared with controls (28%) . Costaining was also performed for joining chain, which is a key factor in the epithelial transport of secretory antibodies; its expression by immunoglobulin A2 cells was only marginally reduced in untreated patients (96%) compared with treated patients and controls (98%) . Also, immunoglobulin A1 cells showed similar joining chain positivity (89%) in all three groups . Considering the expanded total jejunal immunoglobulin A-cell population and the subclass-associated joining chain expression, it could be calculated that the potential of immunoglobulin A2 cells for contribution to secretory immunity was increased 3.9 times in untreated (P less than 0.01) and 1.8 times in treated (P less than 0.05) patients and that of immunoglobulin A1 cells was increased 1.7 times in untreated (P less than 0.05) but remained unaltered in treated patients . The estimated relative contributions of locally produced immunoglobulin A2 to secretory immunoglobulin A would thus be 51% and 37% in the two patient categories, respectively, compared with 31% in the controls . These data suggested enhanced secretory immunity in celiac disease and might reflect a protective, possibly antimicrobial, immune response . It could not be excluded, however, that increased generation of secretory immunoglobulin A at the same time contributes to the gluten-induced pathogenesis of celiac disease.

Chem Pharm Bull (Tokyo), 1990 Aug, 38(8), 2296 - 8
Biological activities of racemomycin-B, beta-lysine rich streptothricin antibiotic, the main component of Streptomyces lavendulae OP-2; Inamori Y et al.; Racemomycin-B (RM-B), the main component of Streptomyces lavendulae OP-2 which is the basis of 50% of the antibiotics produced, is a streptothricin antibiotic which contains three beta-lysine moieties in the molecule . RM-B had antimicrobial activity against plant-pathogenic microorganisms and growth-inhibitory activity against the root of Brassica rapa L . at the concentration of 50 ppm . It strongly inhibited the growth of Pseudomonas syringae pv . tabaci IFO-3508 (minimum inhibitory concentration (MIC): 0.4 microgram/ml), and also showed antifungal activity against six kinds of Fusarium oxysporum species (MIC: 0.1-2.0 micrograms/ml) . The antimicrobial activity of RM-B was much stronger than those of RM-A and -C which contain, respectively, one and two beta-lysine moieties in their molecules . The above activities of RM-A, -C and -B were thus in the order of -B greater than -C greater than -A: namely, the biological activity of racemomycin compounds tended to be stronger with increase in the number of beta-lysine moieties in the molecule.

Anat Rec, 1990 Aug, 227(4), 427 - 36
Tetracycline administration normalizes the structure and acid phosphatase activity of osteoclasts in streptozotocin-induced diabetic rats; Kaneko H et al.; Diabetes induces osteopenia, which is characterized by a deficiency of osteoid and decreased activity of osteoblasts . We recently found that tetracyclines prevent the loss of osteoid and bone matrix and the degeneration of osteoblasts in diabetic rats by a mechanism independent of their antimicrobial efficacy . However, bone remodeling requires the activity of osteoclasts as well as osteoblasts . To determine the in vivo effects of tetracycline on osteoclasts in long bones, either a tetracycline (minocycline, TC) or its chemically modified non-antibiotic analogue (CMT), 4-de-dimethylaminotetracycline, was administrated daily to streptozotocin-induced diabetic rats by oral intubation . After 21 days, the rats were perfusion-fixed with a mixture of formaldehyde and glutaraldehyde, and the humeri were dissected and processed for ultracytochemical demonstration of acid trimetaphosphatase (ACPase) activity . In untreated non-diabetic (control) rats, the osteoclasts at the zone of provisional ossification exhibited abundant mitochondria and cisterns of rough endoplasmic reticulum (RER) throughout the cytoplasm, prominent stacks of Golgi membranes, and lysosomes in the perinuclear cytoplasm, and numerous various pale vacuoles in the cytoplasmic area adjacent to well-developed ruffled border . Intense ACPase activity was observed in the Golgi saccules, lysosomes, pale vacuoles, and the extracellular canals of ruffled border . The reaction products were also noted along the resorbing bone surfaces associated with the osteoclast ruffled border . The osteoclasts in the untreated diabetic rats showed a cytoplasmic organization similar to that of the non-diabetic control rats, but showed little or no ruffled border which was replaced by a broad clear zone in some of these cells . However, most of the osteoclasts on bone matrix in the diabetics were devoid of both a ruffled border and a clear zone . ACPase activity was detected in the osteoclast cytoplasm of diabetic rat, as in the controls, but to a much lesser extent along the broad clear zone facing the resorbing bone surfaces . The osteoclasts in TC-treated diabetic rats possessed both a clear zone and a small ruffled border . However, in some cases, they lacked both structures reminiscent of the untreated diabetic cells . The osteoclasts of CMT-treated diabetic rats exhibited structural and enzymatic features essentially identical to those of the non-diabetic control rats . These results suggest that the diabetes-induced osteopenia results, at least in part, from degeneration of osteoclasts (as well as atrophic osteoblasts) and that tetracyclines may be effective in preventing these abnormalities by a mechanism not dependent on the drugs' antimicrobial properties.

Enferm Infecc Microbiol Clin, 1990 Aug-Sep, 8(7), 441 - 2
{Pyomyositis in AIDS}; Montejo M et al.; We describe two cases of pyomyositis in two patients with acquired immunodeficiency syndrome . Neither of the two cases had previous history of predisposing factors and both patients began with fever and pain at the site of the lesions . Aspiration by punction was required in addition to the antimicrobial therapy.

Enferm Infecc Microbiol Clin, 1990 Aug-Sep, 8(7), 438 - 40
{Microbiological diagnosis of patients undergoing ambulatory peritoneal dialysis}; Gaztelurrutia L et al.; A prospective study was performed to evaluate two culture methods for the diagnosis of bacterial peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD): a total bag volume method, and culture of 50 ml with prior saline wash . Peritonitis was present in 45 patients (47.4%) . The wash method was more sensitive (80%) than bag culture method (62.2%), specially in patients with antimicrobial drugs therapy (p < 0.05) . Therefore, specificity was greater for the bag procedure (78% vs . 62%).

Rev Port Estomatol Cir Maxilofac, 1990 Aug-Oct, 31(3), 151 - 7
{Rational use of antimicrobial agents in oral medicine}; Mano Azul A; This article reviews the state of art of scientific knowledge on oral infections microbiology, with the purpose of bringing a contribute to a better selection of chemotherapeutic agents . It is also presented a description of the main groups of antibiotics, antifungals and antivirals, as well as their indications, dosages and routes of administrations.

Bull Tokyo Dent Coll, 1990 Aug, 31(3), 205 - 10
SDS-polyacrylamide gel electrophoretic patterns of human parotid saliva treated with polyvinylpyrrolidone-iodine in vitro; Shibuya M et al.; In the intraoral application of polyvinylpyrrolidone-iodine (PVP-I) as an antimicrobial agent, a color fading phenomenon is observed that might be caused by the binding of iodine with saliva . We have investigated the binding of iodine with saliva as iodine binding factor (IBF) . The presence and characteristics of the IBF were investigated in parotid saliva stimulated by sour lemon drops, unstimulated parotid saliva, and whole saliva . A high level of the binding ability with iodine was observed in stimulated parotid saliva with the treatment of PVP-I compared with the unstimulated, but there were no significant differences in the amounts of total proteins between the stimulated and unstimulated . Electrophoretic patterns of saliva treated with PVP-I and untreated were examined to detect the IBF . The protein band of SDS-polyacrylamide gel electrophoresis near M.W . 60,000 of stimulated parotid saliva disappeared after treatment of PVP-I . This evidence indicates that the color fading phenomenon of PVP-I is associated with a polypeptide level in saliva.

J Immunol, 1990 Aug 1, 145(3), 940 - 4
Macrophage deactivating factor and transforming growth factors-beta 1 -beta 2 and -beta 3 inhibit induction of macrophage nitrogen oxide synthesis by IFN-gamma; Ding A et al.; Macrophage deactivating factor (MDF) and three members of the transforming growth factor-beta family (TGF-beta 1, -beta 2, and -beta 3) blocked the ability of IFN-gamma to induce release of reactive nitrogen intermediates from mouse peritoneal macrophages . Raising the concentration of IFN-gamma did not diminish the potency of the inhibitors (50% inhibition by approximately 7 nM MDF, 2 pM TGF-beta 1, 4 pM TGF-beta 2, and 8 pM TGF-beta 3) . These inhibitors partially blocked induction of nitrite release in macrophages activated with the combination of IFN-gamma plus TNF-alpha, but were incapable of inhibiting when macrophages were activated by the combination of IFN-gamma plus LPS . MDF and TGF-beta 1, -beta 2, and -beta 3 inhibited IFN-gamma-induced nitrite release only if present during the induction phase; once IFN-gamma-nitrite release had commenced, addition of the same cytokines was no longer inhibitory . Maximum inhibition of synthesis over a 48-h period required that the inhibitors be present during the first 3 h of induction . Thus, cytokines can suppress as well as induce macrophage synthesis of reactive nitrogen intermediates, products with cytotoxic, antimicrobial, and vasodilatory properties.

J Immunol, 1990 Aug 1, 145(3), 831 - 9
IL-2 . A cofactor for induction of activated macrophage resistance to infection; Belosevic M et al.; Macrophages cultured with IL-2 and IFN-gamma before exposure to microorganisms developed the ability to resist infection with the obligate intracellular parasite, Leishmania major . The induction of this macrophage effector response was maximal by 6 to 8 h after lymphokine addition, and was independent of lymphokine treatment sequence . Activation of macrophages for resistance to infection was the result of the direct action of IL-2 and IFN-gamma on macrophages: the effector reaction was demonstrated in both resident peritoneal macrophages depleted of T cells and bone marrow-derived cells, a homogeneous macrophage population . Radiolabeled murine rIFN-gamma, human rIL-2, and mAb to the IL-2R (7D4), each bound to murine bone marrow-derived macrophages in a specific and saturable manner, which suggested that unstimulated macrophages have receptors for both lymphokines . Treatment of macrophages with IFN-gamma increased the specific binding of IL-2; treatment of cells with IL-2, however, did not up-regulate the IFN-gamma-R . Addition of protein or RNA synthesis inhibitors (cycloheximide, emetine, actinomycin D) during exposure to rIL-2 and rIFN-gamma totally abrogated the ability of macrophages to express this effector reaction; inhibitors of protein kinase C, PG, or calcium redistribution had no effect . Soluble polyclonal anti-TNF-alpha antibodies in culture fluids after activation of macrophages with IL-2 and IFN-gamma totally abrogated the expression of resistance to infection . The T cell growth hormone IL-2 acts as cofactor with IFN-gamma for induction of a macrophage antimicrobial activity, and TNF-alpha may be the effector molecule for resistance to infection regulated by these two lymphokines.

Ann Surg, 1990 Aug, 212(2), 209 - 12
Addition of parenteral cefoxitin to regimen of oral antibiotics for elective colorectal operations . A randomized prospective study; Schoetz DJ Jr et al.; The efficacy of cefoxitin, a perioperative parenteral antibiotic, combined with mechanical bowel preparation and oral antibiotics to prevent wound infections and other septic complications in patients undergoing elective colorectal operations, was examined in a prospective randomized study . All 197 patients who completed the study received mechanical bowel preparation and oral neomycin/erythromycin base . In addition a perioperative parenteral antibiotic was given in three divided doses to 101 patients . The other 96 patients received no parenteral antibiotics . The overall incidence of intra-abdominal septic complications was 7.3% (7 of 96) in the control group (no cefoxitin) and 5% (5 of 101) in the treatment group (cefoxitin) . This difference was not statistically significant . The incidence of abdominal wound infection was 14.6% in the control group and 5% in the treatment group, a statistically significant difference (p = 0.02) . The addition of perioperative parenteral cefoxitin greatly reduced the incidence of wound infections in patients undergoing elective colorectal operations who had been prepared with mechanical bowel cleansing and oral antimicrobial agents.

Parodontol, 1990 Aug, 1(3), 203 - 22
{Immunological aspects of periodontal diseases . Prospects for diagnosis and therapy}; Flemmig TF; Achievements in bacteriology and immunology have significantly contributed to the understanding about the etiology and pathogenesis of periodontal diseases . Studies have demonstrated that interactions between bacteria and the immune system play a central role in the etiology of periodontal disease . In the immune system four components can be distinguished according to their function in the periodontium . These include a) the secretory system; b) the polymorphonuclear leukocytes, antibody and complement system; c) lymphocytes and monocytes; d) the immunoregulatory system . Polymorphonuclear leukocytes are of utmost importance for the maintenance of periodontal health . In neutrophil defects severe periodontal diseases are frequently found . Prepubertal periodontitis, juvenile periodontitis and rapidly progressing periodontitis are examples for the periodontal manifestation of neutrophil defects . Therapy of periodontal disease that is related to immune defects requires a modified treatment plan . Efforts are being made to extend the diagnosis, prevention and therapy of periodontal diseases . Presently, biochemical, immunological and microbiological methods are being evaluated for their clinical applicability . Preliminary results indicate that, in the future, biochemical markers in the gingival crevicular fluid may be used for the diagnosis of active sites . Therapy may be enhanced by the administration of non-steroidal anti-inflammatory drugs and specific antimicrobials . However, before these methods can be applied in clinical periodontics, further long-term studies are needed.

Quintessence Int, 1990 Aug, 21(8), 647 - 8
Use of the acid-etch technique to maintain antimicrobial-containing acrylic resin strips in situ; Latcham NL; A technique that utilizes acid-etched composite resin to maintain antimicrobial-containing acrylic resin strips in situ is described . The advantage of this technique is that placement of a periodontal pack is unnecessary, so control of supragingival plaque is not hindered at the site of the local antimicrobial delivery . The technique described may improve the effectiveness and the clinical acceptability of local antimicrobials in the treatment of periodontal disease.

J Antibiot (Tokyo), 1990 Aug, 43(8), 938 - 47
New analogues of rosaramicin isolated from a Micromonospora strain . I . Taxonomy, fermentation, isolation and physico-chemical and biological properties; Funaishi K et al.; Antibiotics 6108 A1, B, C and D, a new series of analogues of rosaramicin, were found together with rosaramicin, juvenimicin A4 and M-4365 A1 from the cultured broth of strain BA06108 which was assigned to be a new species of Micromonospora . 6108 A1 and C showed inhibitory activity against Gram-positive and some Gram-negative bacteria as potent as rosaramicin and exhibited low acute toxicity in mice . However, 6108 B showed less potent antimicrobial activity and 6108 D showed higher toxicity than those two antibiotics.

Clin Prev Dent, 1990 Aug-Sep, 12(3), 8 - 11
Mechanical devices versus antimicrobial rinses in plaque and gingivitis reduction; Finkelstein P et al.; The effectiveness of mechanical oral cleaning and oral antimicrobial rinses was compared for gingivitis and bacterial plaque control in 158 subjects . Teeth were brushed ad lib throughout; four of the five groups used either an interdental cleaner, dental floss, an essential oil mouthwash or a cetypyridinium mouthwash . Gingival bleeding (EIBI), visual inflammation (VGI), and tooth plaque coverage were evaluated at zero, six and 12 weeks of product use . After six weeks, bleeding reduction was 42% greater for the interdental cleaner and 21% greater for the dental floss than for the control . All groups showed a further decrease after 12 weeks, but only the 49% reduction of the interdental cleaner was significantly greater than the control . The rinses showed no more reduction in bleeding sites than the control throughout the study . VGI scores were no different from the control for any of the groups . However, the EIBI proved much more sensitive than the visual method finding three times as many inflamed sites . Plaque was reduced by both antimicrobial rinses 27% more than the control over 12 weeks; the interdental cleaner and dental floss groups showed no significant incremental plaque reductions . The results suggest antimicrobial rinses reduce plaque on visible tooth surfaces, but do not penetrate sufficiently between teeth to affect interdental plaque and thus interdental inflammation . However, by disturbing interdental plaque, both dental floss and the interdental cleaner have little effect on visible tooth surface plaque accumulation, yet produce a significant reduction in gingival inflammation.

J Hosp Infect, 1990 Aug, 16(2), 161 - 6
Surgical hand disinfection: effect of sequential use of two chlorhexidine preparations; Rotter ML et al.; The antimicrobial efficacy of three 'two-phase' surgical hand disinfection procedures was compared, in a volunteer study, to 60% n-propanol, applied for 5 min, which is the reference hand-disinfection procedure used in Austria and West Germany (FRG) . The procedures involved sequential use of unmedicated soap or a disinfectant-detergent containing 4% chlorhexidine gluconate (CHX; 'Hibiscrub') followed by a handrub preparation containing 70% w/w isopropanol plus 0.5% CHX ('Hibisol') . The immediate and sustained effects (3 h) of washing with unmedicated soap (3 min) followed by rubbing on 'Hibisol' (4 min) were significantly smaller (log10 reductions of 1.72 and 1.12) than with each of the other procedures . Use of 'Hibiscrub' (3 min) and 'Hibisol' (4 min) produced log10 reductions of 2.50 and 1.71, equalling those of the reference procedure with n-propanol (2.49 and 1.78) . When 'Hibisol' was used for 5 min rather than 4 min, a considerable, though not significant, increase in effect was achieved (log10 reductions of 2.90 and 2.07) . Replacement of unmedicated soap by 'Hibiscrub' could significantly improve the effectiveness of the hand disinfection procedure commonly used by surgeons in German-speaking countries; namely to wash hands first with soap and then disinfect them with an alcoholic preparation . It may also be of additional advantage as this adds another 'layer' of CHX when 'Hibisol' rather than alcohol alone is used.

Antibiot Khimioter, 1990 Aug, 35(8), 20 - 2
{Antimicrobial and hemolytic activities of gradex}; Petrykina ZM et al.; Gradex is a polymer preparation resulting from formation of covalent bonds between the molecules of gramicidin S, a polypeptide antibiotic, and dextran, a polymeric carrier . Antimicrobial and hemolytic activities of gradex were studied . It was shown that the antimicrobial activity of gradex was due to the presence of gramicidin S in its composition . The activity level was lower than that of gramicidin S . It was also found that the gradex reduced form in concentrations up to 300 micrograms/ml had practically no hemolytic effect against human erythrocytes . The reduced form of gradex is promising for development of an artificial ++anti-brucellosis vaccine.

Zhongguo Yi Xue Ke Xue Yuan Xue Bao, 1990 Aug, 12(4), 274 - 80
{Preparation of a monoclonal antibody (HI30)-mitomycin C conjugate utilizing dextran T-40 and its specific cytotoxicity against human leukemia cell line CEM}; Zhu Z; The anticancer drug mitomycin C (MMC) was conjugated with an affinity-purified murine monoclonal antibody (HI30) to a human T lymphocyte surface differentiation antigen with dextran T-40 as the intermediate carrier . The conjugate (HI30:MMC molar ratio, 1:7) retained full antibody binding activity as determined by an indirect immunofluorescence assay . E . Coli HB101 growth inhibition test showed that the antimicrobial activity {MMC equivalent (microgram/ml)} of the conjugate was about 29.2% as potent as free MMC . In a cytotoxicity test, the conjugate was about 3-10 times more cytotoxic against the antibody-reactive human T lymphocyte leukemia CEM cells than was free MMC or the mixture of HI30 and MMC {IC50 of the MMC equivalent (microgram/ml) was 0.4147, 2.212, 2.171, respectively} and was less cytotoxic against the antibody-nonreactive L1210 cells (IC50 were 1.311, 0.8683, 0.7308, respectively) . The selective cytotoxicity was also confirmed by competitive inhibition with free antibody, showing a dependence on antibody binding of the target cell surface antigen . There was no detectable free MMC released from HI30-Dex-MMC conjugate stored at 4 degrees C for over one month as measured by chromatography on a Sephadex G-25 column.

JAMA, 1990 Jul 18, 264(3), 373 - 6
Outbreak of Mycobacterium chelonae infection associated with use of jet injectors; Wenger JD et al.; Between January 1 and May 15, 1988, foot infections due to Mycobacterium chelonae subspecies abscessus were diagnosed in eight persons who had undergone invasive procedures at a podiatry office . A cohort study was performed to evaluate risk factors for disease . Persons who underwent procedures before 10:30 AM were more likely to have developed infection than those with procedures after that time (relative risk, 5.6) . In addition, procedures involving any of the second through fourth toes were more likely to have resulted in infection than procedures involving only the first and/or fifth toes (relative risk, 4.4) . Persons with 0, 1, or 2 risk factors had attack rates of 5%, 14%, and 60%, respectively . Mycobacterium chelonae subspecies abscessus organisms of the same antimicrobial resistance pattern as the patients' strains were cultured from distilled water in a reusable, nonsterilized container . A jet injector used to administer lidocaine was held between procedures in a mixture of the distilled water and a disinfectant as recommended by the manufacturer . Inoculation of patients with mycobacteria by the jet injector may have only occurred early in the day due to slow killing of the bacteria by the disinfectant . The outbreak emphasizes the pathogenicity of this water-associated organism and the need for high-level disinfection of jet injectors.

Biochim Biophys Acta, 1990 Jul 9, 1026(1), 105 - 12
Phase separation in phospholipid bilayers induced by biologically active polycations; Ikeda T et al.; The interaction of various polyionenes with phospholipid bilayer membranes was explored by means of differential scanning calorimetry (DSC) with special reference to their antimicrobial activities . A strong interaction was observed between the polyionenes and acidic phospholipids, whereas zwitterionic phospholipid bilayers were not affected significantly by the polycations . Addition of the polyionenes was found to result in phase separation in mixed bilayer membranes composed of acidic and zwitterionic phospholipids . The ability to induce phase separation strongly depended on the structure of the polyionenes . Polyionenes with rigid spacers were found to be most effective to induce phase separation and to be most active in antimicrobial activity . Polyionenes with rigid and flexible spacers in the alternate fashion exhibited less activities which were similar to those of all flexible spacers . Furthermore, their mode of interaction with bilayers was again similar to those of all flexible spacers . Our results indicate that the rigid spacers are favorable for strong interaction with membranes which are assumed to be the target sites of the polycationic biocides, leading to the higher activity . Other factors affecting both the antimicrobial activity and the mode of interaction with membranes were molecular weight and hydrophobicity . With increasing molecular weight, both the activity and ability to induce phase separation increased . Introduction of hydrophilic groups into the spacers resulted in loss of activity and ability to induce phase separation . The antimicrobial activity and the mode of interaction with membranes were correlated and interpreted on the basis of conformational concept of the polyionenes in solution.

FEBS Lett, 1990 Jul 2, 267(1), 135 - 8
Phosphorylation of magainin-2 by protein kinase C and inhibition of protein kinase C isozymes by a synthetic analogue of magainin-2-amide; Nakabayashi H et al.; Magainins are a family of antimicrobial peptides present in the skin extracts of Xenopus laevis . Both magainin-1 and -2 do not have any significant effect on the activity of protein kinase C (PKC) . Magainin-2 was found to be readily phosphorylated by PKC to 0.5 mol 32P/mol of peptide . Neither magainin-1, which has a sequence of S8AGK and not S8AKK as in the case of magainin-2, nor the magainin-2 analogue with substitution of Ala for Ser8 was phosphorylated by the kinase, suggesting that Ser8 is the phosphorylation site of magainin-2 . One synthetic analogue of magainin, designated magainin B, which has a greater tendency for alpha-helix formation in non-aqueous environment than the parent peptide resulting from substitution of Ser8, Gly13, and Gly18 with Ala in magainin-2-amide, is a potent inhibitor of PKC . This peptide inhibits all three PKC isozymes with IC50 less than 20 microM . Magainin B also inhibits the binding of {3H}phorbol 12,13-dibutyrate to the kinase . These results suggest that magainin-2 may be modified by PKC through phosphorylation and that certain synthetic analogues of magainins may be used as inhibitors of PKC.

J Burn Care Rehabil, 1990 Jul-Aug, 11(4), 301 - 4
Wet disc testing of mafenide hydrochloride, chlorhexidine gluconate, and triple antibiotic solution against bacteria isolated from burn wounds; Holder IA; Various antimicrobial solutions for topical use on burn wounds tested, in vitro with a newly described wet disc assay, for their activity against bacterial isolates from patients with burns . The antimicrobial activity of triple antibiotic solution was shown to reside in the neomycin component . The activity of 2.5% mafenide hydrochloride solution was equal to that of 4% mafenide HCl and could be used clinically with significant savings and perhaps, fewer side effects . Chlorhexidine gluconate had broad antimicrobial activity in an 0.05% solution in water; however, dissolving the active ingredient in saline nullified its activity significantly . The wet disc assay appears to be a useful means by which to assess the efficacy of solutions for topical use.

J Pharm Sci, 1990 Jul, 79(7), 603 - 5
Quantitative structure-antimicrobial activity relationship in 5 beta-cholanyl-24-benzylamine derivatives; Fini A et al.; Some representative physicochemical properties of benzylamido and amino derivatives of common bile acids have been determined and correlated with their antimicrobial activity against gram-positive bacterial strains . Steroid hydroxyls do not affect the basicity of amino derivatives; they promote solubility in a parallel way to unconjugated bile acids and mainly control hydrophobicity of this class of compounds as measured by log P values . Activity was correlated to hydrophobicity; that is, the nature of the side chain modulated activity, affected basicity, and facilitated changes in partition ability . Benzylamino derivatives proved to be even more active than the corresponding amides when ionization is taken into account . Trihydroxy derivatives possess the lowest log P values and were practically inactive . Decreased activity was also observed in those cases where, due to the orientation of the hydroxy group in the 6 or 7 position, the back beta face of the molecule had a reduced hydrophobic surface area . Antimicrobial activity, in terms of -log MIC (minimal inhibitory concentration), was found to correlate linearly with log P values of uncharged species . This linear relationship is discussed with respect to the structure of the steroid moiety and the ability of these molecules to cross cellular membranes.

J Antibiot (Tokyo), 1990 Jul, 43(7), 796 - 808
Quinaldopeptin, a novel antibiotic of the quinomycin family; Toda S et al.; Quinaldopeptin, a new type of quinomycin antibiotic, was isolated from the culture of Streptoverticillium album strain Q132-6 . The antibiotic exhibited strong in vitro antimicrobial and cytotoxic activity and significantly prolonged the survival time of mice inoculated with a murine tumor . Quinaldopeptin is a symmetric cyclic peptide linked only by peptide bonds and differs from known antibiotics of the quinomycin family by the lack of ester linkage.

Antimicrob Agents Chemother, 1990 Jul, 34(7), 1399 - 401
In vitro synergy of clindamycin and aminoglycosides against Chlamydia trachomatis; Pearlman MD et al.; The importance of Chlamydia trachomatis as an etiologic agent in the development of pelvic inflammatory disease (PID) is well documented . Although there are numerous antimicrobial agents that are effective against C . trachomatis, one of the most frequent combinations that is used to treat PID is clindamycin and gentamicin . The efficacy of clindamycin as the sole treatment for chlamydial infections has been questioned . In fact, the Centers for Disease Control (Atlanta, Ga.) has recommended the use of doxycycline following clindamycin and gentamicin treatment of PID confirmed or suspected to be caused by C . trachomatis . This study was designed to determine whether there is any synergistic in vitro activity between clindamycin and gentamicin or tobramycin on inhibition of C . trachomatis replication . In this experiment, the MIC of clindamycin decreased two- to threefold when an aminoglycoside was added . This occurred even though aminoglycosides by themselves had essentially no effect against C . trachomatis . The mechanism of this interaction is uncertain.

Antimicrob Agents Chemother, 1990 Jul, 34(7), 1390 - 2
Comparison of in vitro antimicrobial susceptibilities of Mycobacterium avium-M . intracellulare strains from patients with acquired immunodeficiency syndrome (AIDS), patients without AIDS, and animal sources; Byrne SK et al.; Difloxacin, A-56620, cefazolin, cefotaxime, ceftizoxime, cephapirin, SK&F 88070, and spectinomycin were used to compare the in vitro susceptibilities of Mycobacterium avium-M . intracellular isolates from patients with acquired immunodeficiency syndrome (AIDS), patients without AIDS, and diseased animals . Against the isolates from humans without AIDS, the quinolone compounds difloxacin and A-56620 were found to be the most effective, each inhibiting 50% of strains at a concentration of 2 micrograms/ml . The remaining antimicrobial agents had MICs for 50% of strains tested of at least 32 micrograms/ml . Statistically significant differences were observed in the antibiogram patterns among the M . avium-M . intracellulare strains from each of the three sources.

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