Antimicrobial

Clin Infect Dis, 1995 Feb, 20(2), 443 - 4
Rapid development of resistance to clarithromycin following monotherapy for disseminated Mycobacterium chelonae infection in a heart transplant patient; Tebas P et al.; Mycobacterium chelonae (formerly known as M . chelonae subspecies chelonae) is a rapidly growing mycobacterium that can cause disseminated infections, especially in immunocompromised hosts . The bacterium is typically resistant to antimicrobial agents; less than 20% of M . chelonae isolates are susceptible to trimethoprim-sulfamethoxazole, doxycycline, erythromycin, or ciprofloxacin . Findings in a recent study suggested that clarithromycin may be the drug of choice for the treatment of cutaneous (disseminated) disease due to M . chelonae . We describe a 60-year-old heart transplant patient with disseminated M . chelonae infection for whom monotherapy with clarithromycin failed because of the rapid development of resistance to the drug.

Clin Infect Dis, 1995 Feb, 20(2), 363 - 71
Outcome for hospitalized patients with fever and neutropenia who are infected with the human immunodeficiency virus; Hambleton J et al.; We conducted a retrospective cohort study to evaluate the occurrence of bacteremia and associated mortality among hospitalized patients who were seropositive for the human immunodeficiency virus (HIV) and who developed fever and neutropenia following antineoplastic chemotherapy or for other reasons . Review of medical records revealed 224 episodes in 142 patients . Of these episodes, 57% occurred following antineoplastic chemotherapy, and 43% occurred under other circumstances . Members of the chemotherapy group had significantly less-advanced HIV disease, a lower mean absolute-neutrophil-count nadir, and a shorter duration of hospitalization . There was no difference between the two groups in the frequency of bacteremia or mortality due to all causes when they were compared by multivariate analysis . Statistically significant univariate and multivariate predictors of bacteremia included sepsis syndrome and concurrent infection . Predictors of mortality included sepsis syndrome, concurrent infection, bacteremia, and antimicrobial therapy . This study suggests that the cause of neutropenia in HIV-seropositive patients is not a predictor of the outcome of fever and neutropenic episodes . Instead, clinical presentation and concomitant illnesses have a greater impact on outcome for a patient.

Clin Pharmacokinet, 1995 Feb, 28(2), 143 - 60
The importance of pharmacokinetic/pharmacodynamic surrogate markers to outcome . Focus on antibacterial agents; Hyatt JM et al.; Pharmacokinetic/pharmacodynamic surrogate relationships have been used to describe the antibacterial activity of various classes of antimicrobial agents . Studies that have evaluated these relationships were reviewed to determine which of these surrogate markers were further dependent on antimicrobial class . The fluoroquinolone and aminoglycoside agents exhibit concentration-dependent killing . Studies have demonstrated that peak serum concentration: minimum inhibitory concentration (MIC) and area under the serum concentration-time curve (AUC): MIC ratios are important predictors of outcome for these antimicrobial agents . Area under the inhibitory concentration-time curve (AUIC24) {i.e . AUC24/MIC} is a useful parameter for describing efficacy for these agents, while an adequate peak concentration: MIC ratio seems necessary to prevent selection of resistant organisms . For beta-lactam antibiotics, the duration of time that the serum concentration exceeds the MIC (T > MIC) was the significant pharmacokinetic/pharmacodynamic surrogate in cases where the bacterial inoculum was low, or where very sensitive organisms were tested . However, in studies using more resistant organisms or larger inoculum sizes there is some concentration-dependence to the observed effect . Studies using reasonable dosage intervals have demonstrated covariance between T > MIC and AUC/MIC ratio for beta-lactam antibiotics . Since glycopeptide antibiotics display relatively slow but concentration-independent killing, and are cell wall active agents similar to beta-lactams, it has been presumed that T > MIC is the important pharmacokinetic surrogate related to efficacy for these agents . Some studies have shown that a concentration multiple of the MIC may be necessary for successful outcome with vancomycin . AUIC24 may prove to be an important pharmacokinetic surrogate if both time and concentration are indeed important parameters . To select an appropriate antimicrobial agent, the clinician must consider many patient-specific as well as organism-specific factors . Utilisation of known pharmacokinetic/pharmacodynamic surrogate relationships should help to optimise treatment outcome.

Intern Med, 1995 Feb, 34(2), 96 - 9
Severe hyponatremia and hyperkalemia induced by trimethoprim-sulfamethoxazole in patients with Pneumocystis carinii pneumonia; Noto H et al.; An antimicrobial agent trimethoprim-sulfamethoxazole (Tmp-Smx) does not usually cause electrolyte disturbances at regular doses, and few cases of Tmp-Smx-induced electrolyte imbalance have been reported in the English-language literature to date . Recently, however, we treated two patients with Pneumocystis carinii pneumonia who developed severe hyponatremia and hyperkalemia on administration of high-dose Tmp-Smx . These electrolyte disturbances were attributable to the direct effect of Tmp-Smx on the renal distal tubules, were reversible, and corrected by infusion of a sodium-enriched and potassium-free liquid . Therefore, it is suggested that even after electrolyte disturbances have occurred, high-dose Tmp-Smx therapy may be continued for severe infectious diseases under appropriate electrolyte correction.

Antimicrob Agents Chemother, 1995 Feb, 39(2), 445 - 52
Piperacillin-tazobactam plus amikacin versus ceftazidime plus amikacin as empiric therapy for fever in granulocytopenic patients with cancer . The International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer; Cometta A et al.; Gram-positive bacteria have become the predominant infecting organisms in granulocytopenic cancer patients . Empiric antibiotic regimens used in febrile neutropenic patients often include an extended-spectrum cephalosporin, but the response to therapy in gram-positive coccal bacteremia has been unsatisfactory . Thus, new antibiotics with better activity against gram-positive bacteria should be tested . The objective of this prospective randomized controlled study was to evaluate and compare the efficacy and tolerance of piperacillintazobactam plus amikacin with that of ceftazidime plus amikacin, the standard regimen of the International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer, in the empiric treatment of febrile granulocytopenic cancer patients . A total of 858 episodes were eligible for this study, and 706 episodes were assessable for efficacy . The antibiotic treatment was successful in 210 (61%) of 342 episodes in the piperacillin-tazobactam-amikacin group compared with 196 (54%) of 364 episodes treated with ceftazidime plus amikacin (P = 0.05) . The time to defervescence was significantly shorter (P = 0.01) and the time to failure was significantly longer (P = 0.02) in the piperacillin-tazobactam-amikacin group . A significant difference in response to bacteremic infections between the two patient groups was found: piperacillin-tazobactam plus amikacin was successful in 40 of 80 episodes (50%), and ceftazidime plus amikacin was successful in 35 of 101 episodes (35%) (P = 0.05) . A multivariate analysis showed that the probability of failure was significantly greater with ceftazidime plus amikacin than with piperacillin-tazobactam plus amikacin (P = 0.02) . This trial suggests that piperacillin-tazobactam plus amikacin is more effective than ceftazidime plus amikacin for the empiric treatment of fever and bacteremia in granulocytopenic cancer patients . Although cutaneous reaction was more frequently associated with piperacillin-tazobactam plus amikacin than with ceftazidime-amikacin, this unwanted effect was relatively mild and its incidence was comparable to that of other penicillin compounds.

Antimicrob Agents Chemother, 1995 Feb, 39(2), 301 - 7
Antimicrobial activities of amphiphilic peptides covalently bonded to a water-insoluble resin; Haynie SL et al.; A series of polymer-bound antimicrobial peptides was prepared, and the peptides were tested for their antimicrobial activities . The immobilized peptides were prepared by a strategy that used solid-phase peptide synthesis that linked the carboxy-terminal amino acid with an ethylenediamine-modified polyamide resin (PepsynK) . The acid-stable, permanent amide bond between the support and the nascent peptide renders the peptide resistant to cleavage from the support during the final acid-catalyzed deprotection step in the synthesis . Select immobilized peptides containing amino acid sequences that ranged from the naturally occurring magainin to simpler synthetic sequences with idealized secondary structures were excellent antimicrobial agents against several organisms . The immobilized peptides typically reduced the number of viable cells by > or = 5 log units . We show that the reduction in cell numbers cannot be explained by the action of a soluble component . We observed no leached or hydrolyzed peptide from the resin, nor did we observe any antimicrobial activity in soluble extracts from the immobilized peptide . The immobilized peptides were washed and reused for repeated microbial contact and killing . These results suggest that the surface actions by magainins and structurally related antimicrobial peptides are sufficient for their lethal activities.

Ther Drug Monit, 1995 Feb, 17(1), 101 - 3
Time course of appearance of ofloxacin in human scalp hair after oral administration; Uematsu T et al.; The time course of appearance of antimicrobial ofloxacin (OFLX) in human scalp hair was monitored in three healthy male volunteers after the oral administration of 100 mg OFLX three times daily for 2 consecutive days . Hair samples were collected from each subject by plucking several strands of frontal hair every day from 1 till 16 days after administration . A single hair was dissolved in 1 M NaOH to extract OFLX by chloroform, and the drug was measured by high-performance liquid chromatography and fluorescence detection . OFLX started to appear in the hair 1 to 3 days after administration and reached the maximal level approximately 4 to 9 days, remaining at almost the same level thereafter . This finding suggests the slow transfer of OFLX from hair follicle cells to hair matrix may be due to the slow dissociation of OFLX from bound melanin.

Postgrad Med J, 1995 Feb, 71(832), 71 - 8
Immunotherapy in the management of sepsis; Fagan EA et al.; The pathophysiological effects of severe sepsis, septic shock and related syndromes result from tissues damaged by the uncontrolled production of the mediators of inflammation . Early deaths are related primarily to the acute effects of the systemic inflammatory response . Later deaths are related more closely to the consequences of multiple organ dysfunction . Monoclonal antibodies and other immunotherapies have been developed against bacterial products, cytokines and other mediators involved in this systemic inflammatory response . Immunotherapies may improve outcome in the critically ill with sepsis if used early and as part of the therapeutic regimen of antimicrobial agents and intensive care support.

Tuber Lung Dis, 1995 Feb, 76(1), 51 - 8
Therapeutic effect of KRM-1648 with various antimicrobials against Mycobacterium avium complex infection in mice; Saito H et al.; A new benzoxazinorifamycin, KRM-1648 (KRM), was studied for its therapeutic efficacy in combination with other antimicrobials against Mycobacterium avium complex infections in mice . When M . intracellulare-infected (intravenously) mice were given KRM, clarithromycin (CAM), sparfloxacin (SPFX), or ethambutol (EB) each alone or in combination, by gavage, once daily 6 times per week (streptomycin {SM} was given subcutaneously twice per week) from day 1, KRM + CAM exhibited combined efficacy in terms of reducing the incidence of gross lung lesions and the bacterial loads in the lungs and spleens . The addition of either EB or EB + SPFX to KRM + CAM increased the efficacy . Moreover, the multi-drug regimen of KRM + CAM + EB + SPFX or ofloxacin {OFLX}) was more efficacious than rifampicin (RMP) + CAM + EB + SPFX (or OFLX) . In M . avium infection, KRM + clofazimine was the most efficacious among two-drug combinations tested followed by KRM + SM . KRM + CAM was considerably less effective against M . avium than against M . intracellulare infection . KRM + EB and KRM+OFLX failed to show such a combined effect.

J Antibiot (Tokyo), 1995 Feb, 48(2), 158 - 61
New metabolites with nematicidal and antimicrobial activities from the ascomycete Lachnum papyraceum (Karst.) Karst . VII . Structure determination of brominated lachnumon and mycorrhizin A derivatives; Stadler M et al.; The structure determination of lachnumon B1 (16) and lachnumon B2 (17), brominated derivatives of lachnumon (1), as well as mycorrhizin B1 (18) and mycorrhizin B2 (19), brominated derivatives of mycorrhizin A (3), is described . The compounds, which exhibit similar antimicrobial and nematicidal activity as their chlorinated analogues, were isolated from extracts of cultures of the ascomycete Lachnum papyraceum to which CaBr2 had been added . The structures were elucidated by spectroscopic methods.

J Antibiot (Tokyo), 1995 Feb, 48(2), 154 - 7
New metabolites with nematicidal and antimicrobial activities from the ascomycete Lachnum papyraceum (Karst.) Karst . VI . Structure determination of non-halogenated metabolites structurally related to mycorrhizin A; Stadler M et al.; The structure determination of four new biologically active non-halogenated metabolites isolated from submerged cultures of the ascomycete Lachnum papyraceum is described . The compounds are structurally related to the antibiotic mycorrhizin A: (l'Z)-Dechloromycorrhizin A (12), a stereoisomer of dechloromycorrhizin A (5) previously isolated from the same fungus, as well as papyracon A (13), papyracon B (14) and papyracon C (15) containing an exocyclic double bond . The amounts of the latter three increased significantly when CaBr2 was added to the culture medium . The structures were determined by spectroscopic methods.

J Antibiot (Tokyo), 1995 Feb, 48(2), 149 - 53
Metabolites with nematicidal and antimicrobial activities from the ascomycete Lachnum papyraceum (Karst.) Karst . V . Production, isolation and biological activities of bromine-containing mycorrhizin and lachnumon derivatives and four additional new bioactive metabolites; Stadler M et al.; Eight novel bioactive metabolites were isolated from submerged cultures of the ascomycete Lachnum papyraceum (Karst.) Karst, when CaBr2 was added to the cultures after the onset of secondary metabolism . Four of these metabolites (16 to 19) are bromo analogues of mycorrhizin A and lachnumon, while (l'Z)-dechloromycorrhizin A (12) and the papyracons A (13), B (14), and C (15) are non-halogenated compounds structurally related to the mycorrhizins . All compounds exhibited antimicrobial, cytotoxic, nematicidal and phytotoxic activities . The brominated mycorrhizins and lachnumons were found to be slightly less active than the chlorine-containing compounds . All mycorrhizin derivatives were mutagenic in the Ames test, suggesting DNA-alkylating properties.

Arch Dis Child, 1995 Feb, 72(2), 165 - 6
Non-tuberculous mycobacterial lymphadenopathy; Clark JE et al.; The surgical and antimicrobial treatment of non-tuberculous mycobacterial lymphadenopathy in 17 children was reviewed . Node excision was curative, but most nodes were still incised leaving discharging lesions . Standard antituberculous treatment was unhelpful, but a new macrolide/quinolone combination appeared to be effective in three cases.

Kekkaku, 1995 Feb, 70(2), 97 - 101
{In vitro antimycobacterial activity of a new quinolone, T-3761}; Tomioka H et al.; We evaluated the in vitro antimicrobial activity of T-3761 and ofloxacin against representative pathogenic mycobacteria by the agar dilution method, using 7H11 agar medium . T-3761 showed appreciable antimicrobial activity against Mycobacterium tuberculosis (MIC90: 3.13 micrograms/ml), M . kansasii (MIC90: 6.25 micrograms/ml) and M . fortuitum (MIC90: 3.13 micrograms/ml), whereas the agent was not active against M . marinum (MIC90: 25 micrograms/ml), M . scrofulaceum (MIC90: 50 micrograms/ml), M . avium (MIC90: > 100 micrograms/ml), M . intracellulare (MIC90: > 100 micrograms/ml), M . chelonae subsp . abscessus (MIC90: > 100 micrograms/ml) and M . chelonae subsp . chelonae (MIC90: 50 micrograms/ml) . The in vitro antimicrobial activity of T-3761 against M . fortuitum was a little more potent than that of ofloxacin, whereas the activity of T-3761 against the other mycobacteria was slightly inferior to that of ofloxacin . The antimycobacterial activity of T-3761 against M . tuberculosis H37Rv (MIC in vitro: T-3761 = 3.13 micrograms/ml, OFLX = 0.78 micrograms/ml) phagocytosed in murine peritoneal macrophages was less active than that of ofloxacin, when the macrophages were cultured in RPMI-1640 medium containing 1 microgram/ml or 10 micrograms/ml of these agents for up to 5 days . The activity of 10 micrograms/ml of T-3761 was equivalent to that of 1 microgram/ml of ofloxacin.

J Appl Bacteriol, 1995 Feb, 78(2), 134 - 41
Methylchloroisothiazolone-induced growth inhibition and lethality in Escherichia coli; Chapman JS et al.; Exposure of log phase Escherichia coli cells to inhibitory levels of 5-chloro-2-methyl-isothiazolin-3-one (MCI) results in rapid bacteriostasis and a delayed onset of bactericidal activity . Inhibition of respiration occurs within the same time frame as bacteriostasis, and is followed by a decline in intracellular ATP levels . In vitro and in vivo experiments suggest that growth inhibition is the result of selective inhibition of particular targets, with succinate dehydrogenase being identified as a possible target . Such selectivity was not anticipated from this highly reactive molecule . MCI-induced lethality is positively correlated with a loss of reduced protein sulphydryls (r2 = 0.79) . A greater than equimolar loss of reduced protein sulphydryls, compared with the number of MCI molecules added, and a reduction in killing by MCI after induction of the OxyR regulon suggest that free radical generation may have a role in the antibacterial activity of MCI . We present an examination of the in vivo effects of MCI exposure on bacterial cells, and evidence that the isothiazolones exhibit selectivity in their cellular targets and antimicrobial effects.

Endod Dent Traumatol, 1995 Feb, 11(1), 6 - 9
Observation of bacteria and fungi in infected root canals and dentinal tubules by SEM; Sen BH et al.; The aim of this study was to observe the root canal flora and possible penetration of microorganisms into dentinal tubules in teeth with necrotic pulps . Ten infected maxillary and mandibular molars with periapical lesions were extracted and fixed in 2.5% phosphate-buffered glutaraldehyde solution for nine days . After separation from the crowns, longitudinal grooves were cut in the roots, and they were split into two halves . The specimens were prepared for SEM . The root canals and the dentinal tubules of the fractured dentin were scanned systematically from the cervical to the apical area of the root . Cocci and rods were seen in 6 specimens . Penetration of bacteria into the dentinal tubules ranged from 10 to 150 microns . In 4 specimens, the root canals were heavily invaded by yeasts . The antimicrobial effect of routinely used endodontic disinfectants also on yeasts may be considered in persistent root canal infections.

Immunol Lett, 1995 Feb, 45(1-2), 117 - 21
Functional alterations of human blood monocytes after exposure to various nickel compounds in vitro: an effect on the production of hydrogen peroxide; Zeromski J et al.; It is generally known that nickel, a metal with distinct carcinogenic properties, can significantly alter the functioning of host defense mechanisms and impair various components of the immune system . In the present study the influence of 3 nickel salts on the production of hydrogen peroxide (H2O2) by human monocytes was examined in in vitro culture . Highly purified, resting and PMA-stimulated normal human monocytes were cultured with subtoxic concentrations of nickel subsulfide nickel sulfate, nickel acetate and manganese chloride . A portion of the cells was cultured with nickel-manganese salt mixture . Following culture cells were tested in an in vitro functional assay for H2O2 production . It has been shown that all nickel salts, used in micromole concentrations, suppressed H2O2 formation both in resting and PMA-stimulated monocytes, while it was not the case when manganese chloride was used for cell cultures . The strongest suppressive effect was manifested by nickel sulfate . The cells subjected to nickel-manganese mixture displayed H2O2 production similar to that of control ones . These results show that nickel salts in micromole concentrations exert a suppressive effect on oxygen-dependent antimicrobial system of human monocytes and manganese prevents this effect.

Eur J Oral Sci, 1995 Feb, 103(1), 8 - 10
Calprotectin levels in oral fluids: the importance of collection site; Cuida M et al.; Calprotectin is a major protein of granulocytes and monocytes with antimicrobial properties, and is released during activation or cell death . In the present study the levels of calprotectin in various oral fluids were analyzed in 12 healthy adults using different collection devices . Parotid saliva, stimulated whole saliva and "mucosal transudate" were collected and analyzed by enzyme-linked immunosorbent assay (ELISA) . The results showed mean concentrations of 3.2, 22.0 and 40.9 mg/l in the respective oral fluids, illustrating great variation of calprotectin levels between different oral fluids . The results are in accordance with the composition of these saliva samples; the lowest calprotectin level was obtained in parotid saliva, which contains the purest secretion . These findings illustrate the importance of careful sampling procedures . The levels of salivary calprotectin are markedly influenced by the site of collection.

Boll Chim Farm, 1995 Feb, 134(2), 80 - 4
Novel diarylsulphide derivatives as potential cytotoxic agents; el-Subbagh HI et al.; A series of diarylsulphides bearing amino, acetamido, sulphonamido, benzamido or arylideneamino synthons have been synthesized and evaluated for their antimicrobial and cytotoxic activities . Some of the tested compounds proved to possess a remarkable activity . The detailed synthesis, spectroscopic and biological data are reported.

Boll Chim Farm, 1995 Feb, 134(2), 77 - 9
Synthesis and antimicrobial activity of some new carbazoles, indazoles, quinolines, quinazolines and naphthalenes from 3-methyl-5-phenyl-6-benzylidene-2-cyclohexene-1-one; El-Ablak FZ et al.; Reaction of the title compound (1) with phenylhydrazine using the Fisher indole synthesis, resulted in the formation of the carbazole derivative (2) . Condensation of (1) benzaldehyde afforded the 6-benzylidene derivative (3) . Treatment of compound (3) with some hydrazines and hydrazides resulted in the formation of the indazoles (4) . Michael addition of some active methylene components with (3) gave quinolines (5) and naphthalenes (7) . The reaction of (3) with urea and thiourea gave the uraciles (6) . The newly synthesized compounds were screened for antibacterial activity.

Rev Med Chil, 1995 Feb, 123(2), 185 - 91
{Comparison of 2 treatment schemes to eradicate Helicobacter pylori}; Hoffenberg P et al.; INTRODUCTION: Anti secretory drugs, antimicrobials and bismuth salts are used with variable success to eradicate Helicobacter pylori . AIM: To assess the effectiveness and rates of reinfection of two therapeutic modalities H pylori infection in adult patients with duodenal ulcer or non ulcer dyspepsia . METHODS: During upper gastrointestinal endoscopy, 5 antral and 2 fundic biopsies were obtained and sent for microbiological and anatomopathological study . Patients infected with Helicobacter pylori were randomly assigned to receive during two weeks omeprazole 20 mg od plus amoxicillin 500 mg tid (group A) or bismuth subsalicylate 260 mg bid, metronidazole 250 mg tid and amoxicillin 500 mg tid (group B) . A new endoscopy with antral and fundic biopsies was performed to all patients four weeks after discontinuing treatment and six months later to those in whom H pylori was eradicated . RESULTS: Eighty patients (40 in each treatment group) completed the treatment and follow up . H pylori was eradicated in 22 patients of group A (55%) and 28 of group B (70%) . Minor adverse effects were reported by 5 patients in group A (12%) and 11 in group B (27.5%) . Six months later, reinfection was documented in 12 patients of group A and 8 of group B (54% and 30% of those with successful treatment respectively) . Ten of twenty five patients with duodenal ulcer had reinfections, but there was only one ulcer relapse . CONCLUSIONS: These two treatment modalities have similar results.

Int J Immunopharmacol, 1995 Feb, 17(2), 91 - 102
Adjuvants, endocrines and conserved epitopes; factors to consider when designing "therapeutic vaccines"; Rook GA et al.; Research into immunity to complex intracellular parasites has recently placed emphasis on the identification of peptide sequences recognised by T-cells, often with the dual objectives of finding species-specific protective epitopes, and of understanding selection of Th1 versus Th2 response patterns . In this review it is suggested that although such work is interesting, it will not achieve these objectives, which must, however, be addressed before we can design the new generation of therapeutic vaccines which may eventually replace antimicrobial drugs in the treatment of infection . First, we suggest that the balance of Th1 to Th2 lymphocyte activity is not determined by epitopes, but rather by adjuvant effects of microbial components which we have barely begun to define, and local endocrine effects mediated by conversion of prohormones into active metabolites by enzymes in lymph node macrophages . Cytokines play a role as mediators within these pathways . In chronic disease states there is a tendency for T-cell function to shift towards Th2 . We describe immunopathological consequences of this tendency, including a putative role for agalactosyl IgG, and review evidence for involvement of changes in the endocrine system, brought about not only by the cytokine-hypothalamus-pituitary-adrenal axis, but also by direct actions on peripheral endocrine organs of excess levels of cytokines such as TNF alpha, TGF beta and IL-6 . We summarise evidence that the epitopes that are targets for protective cell-mediated responses to complex organisms are usually not species specific . In tuberculosis, cellular responses to species-specific components appear to be associated with immunopathology rather than protection . Finally, we discuss how application of these principles has led to remarkable results in the immunotherapy of tuberculosis, including multidrug-resistant disease.

Alcohol Clin Exp Res, 1995 Feb, 19(1), 11 - 6
Effects of ethanol on cellular immunity to facultative intracellular bacteria; Jerrells TR et al.; Alcohol abuse has been associated with an increase in infectious diseases caused by pathogenic and opportunistic microorganisms . Study results obtained from this laboratory and other laboratories have shown that consumption of large amounts of ethanol is associated with numerous changes in the immune system . The purpose of this article is to report findings obtained from this laboratory, as well as review those obtained from other laboratories, from experiments designed to evaluate the effects of ethanol on various components of antimicrobial host-defense mechanisms . The effects of ethanol on various aspects of immunity obtained with the use of in vivo and in vitro model systems are reviewed as they pertain to antimicrobial defenses . All current data would support the suggestion that ethanol affects both the development of an antigen-specific immune response and the effector mechanisms of the cellular immune response . Findings obtained from animal models show that ethanol prevents the formation of granulomas in infected tissues, perhaps by inhibiting the response of macrophages to T-cell cytokines . Data obtained from this laboratory also support the suggestion that the inability of the immune system to control the intracellular growth of microorganisms results in an exaggerated inflammatory response that is responsible for at least a part of the tissue damage.

Pharm World Sci, 1995 Jan 27, 17(1), 1 - 11
Liposomes as delivery systems in the prevention and treatment of infectious diseases; Bergers JJ et al.; Research on the potential application of liposomes in the prevention and treatment of infectious diseases has focussed on improvement of the therapeutic index of antimicrobial drugs and immunomodulators and on stimulation of the immune response to otherwise weak antigens in vaccines composed of purified micro-organism subunits . In this review current approaches in this field are outlined . The improved therapeutic index of antimicrobial drugs after encapsulation in liposomes is a result of enhanced drug delivery to infected tissue or infected cells and/or a reduction of drug toxicity of potentially toxic antibiotics . Liposomal encapsulation of immunomodulators that activate macrophages aims at reducing the toxicity of these agents and targeting them to the cells of the mononuclear phagocyte system in order to increase the nonspecific resistance of the host against infections . Studies on the immunogenicity of liposomal antigens have demonstrated that liposomes can potentiate the humoral and cell mediated immunity to a variety of antigens.

Schweiz Rundsch Med Prax, 1995 Jan 24, 84(4), 98 - 105
{sensitivity of bacteria to chemotherapeutic agents (Zurich, 1993)}; Wust J et al.; This paper describes the incidence of Gram-negative and Gram-positive bacteria susceptible to antibacterial agents . The data are based on all susceptibility tests performed at the Department of Medical Microbiology of the University of Zurich . The evaluation of the results from 1987 to 1993 shows that susceptibilities against the antimicrobial agents tested have not changed markedly in this period with few exceptions . The tables may be of help to the physician in his decision for a 'calculated chemotherapy' of bacterial infections.

J Biol Chem, 1995 Jan 20, 270(3), 1048 - 56
The role of amphipathicity in the folding, self-association and biological activity of multiple subunit small proteins; Perez-Paya E et al.; The effect that altering amphipathicity has on the folding process and self association of melittin, a small model protein, has been investigated using single amino acid substitutions of lysine 7, a residue distant from the contact residues involved in the hydrophobic core of tetrameric melittin . While substitutions of such a residue were not expected to interfere with the packing process, the largest alterations in the potential overall amphipathicity of melittin were found to prevent the folding into an alpha-helical conformation to occur and, in turn, to prevent the self association . Amphipathic alpha-helices were found to be a key determining feature in the early folding process of the self association of peptides and protein segments . Those substitutions, which prevented the inducible amphipathic folding ability, were also found to result in a loss in hemolytic and antimicrobial activity . These results, combined with studies of the binding to artificial liposomes and to polysialic acids, indicate that the losses in activity were due to an initial inability to be induced into an amphipathic alpha-helix and to self associate . Ultimately, melittin's self association is proposed to be required to penetrate the carbohydrate barrier present in biological membranes.

JAMA, 1995 Jan 18, 273(3), 214 - 9
Trends in antimicrobial drug prescribing among office-based physicians in the United States; McCaig LF et al.; OBJECTIVE--To assess changes in oral antimicrobial drug prescribing by office-based physicians from 1980 through 1992, with emphasis on the treatment of otitis media and sinusitis and on the possible impact of demographic variables on such use . DESIGN--The National Ambulatory Medical Care Survey is a sample survey of office-based physicians in the United States conducted by the National Center for Health Statistics, Centers for Disease Control and Prevention . SETTING--Physicians' offices . PATIENTS OR OTHER PARTICIPANTS--Physicians sampled for the 1980, 1985, 1989, and 1992 National Ambulatory Medical Care Surveys, which included groups of 2959, 5032, 2540, and 3000 physicians, respectively . Sample physicians responding in 1980, 1985, 1989, and 1992 reported data for 46,081, 71,594, 38,384, and 34,606 sample office visits, respectively, including information on antimicrobial drug prescribing . MAIN OUTCOME MEASURE--Trends in the antimicrobial drug prescription rates . RESULTS--From 1980 through 1992, increasing prescribing measured by the annual drug prescription rate per 1000 population, was found for the more expensive, broad-spectrum antimicrobial drugs, such as the cephalosporins; decreasing rates were observed for less expensive antimicrobial drugs with a narrower spectrum, such as the penicillins . No trend was found for trimethoprim-sulfamethoxazole, the erythromycins, or the tetracyclines . During the decade, an increasing trend in the visit rate to office-based physicians for otitis media was observed, while the visit rate for sinusitis among adults was found to be higher in 1992 than in each of the other study years . CONCLUSIONS--The increased use of broader-spectrum and more expensive antimicrobial drugs have implications for all patients because of the impact on health care costs and the potential for the emergence of antimicrobial resistance . The data suggest that the incidence of otitis media and sinusitis is increasing.

Med J Aust, 1995 Jan 16, 162(2), 95 - 7
Upper gastrointestinal tract; Crotty B et al.; Drug therapy for upper gastrointestinal disease in the elderly must be moderated by the likelihood of increased sensitivity to the side effects of drugs . For example, in the frail elderly with helicobacter-associated duodenal ulcers, maintenance therapy with an H2-receptor antagonist or omeprazole may be preferable to attempting to eradicate Helicobacter pylori with the current antimicrobial regimens.

J Am Vet Med Assoc, 1995 Jan 15, 206(2), 206 - 9
Comparison of clinical signs, diagnostic findings, organisms isolated, and clinical outcome in dogs with bacterial pneumonia: 93 cases (1986-1991); Jameson PH et al.; Medical records were reviewed for 93 dogs with bacterial pneumonia from which transtracheal aspiration samples were obtained for culturing of Mycoplasma spp and aerobic bacteria . On the basis of culture results, there were 65 Mycoplasma-positive dogs, including 7 dogs for which only Mycoplasma spp were isolated, and 28 Mycoplasma-negative dogs . Most dogs were > 5 years old, and differences in breed or gender distribution among the 3 groups of dogs were not detected . Hematologic and serum biochemical analysis results did not differ significantly between Mycoplasma-positive and Mycoplasma-negative dogs . Fifty-three of 93 (57%) dogs had a concurrent medical problem that may have predisposed them to developing bacterial pneumonia as a sequelae to aspiration or immunosuppression . Mycoplasma-positive dogs were significantly (P < 0.005) more likely to have > 1 species of bacteria isolated from their transtracheal aspiration samples . Clinical outcome was favorable when antimicrobials were selected on the basis of antimicrobial susceptibility results for the other bacterial isolates and not on results of the antimicrobial activity against Mycoplasma spp . It could not be determined whether Mycoplasma spp were primary pathogens or only opportunists.

J Am Vet Med Assoc, 1995 Jan 15, 206(2), 203 - 5
Contamination and infection of fractures resulting from gunshot trauma in dogs: 20 cases (1987-1992); Doherty MA et al.; Medical records of 20 dogs with gunshot fractures were reviewed to determine the prevalence of preoperative contamination and postoperative osteomyelitis . Fractures were repaired primarily by application of a bone plate (n = 16) or external fixator (n = 2) in buttress fashion or application of interfragmentary screws and pins (n = 2) . In 17 dogs, an autogenous bone graft was also used . Results of bacteriologic culture of swab specimens obtained intraoperatively for 15 of the 16 dogs that received antimicrobials preoperatively and for all 4 dogs that did not receive antimicrobials preoperatively were negative . Three dogs developed osteomyelitis at 6, 8, and 10 weeks following surgery; for all 3, results of bacteriologic culture of specimens obtained intraoperatively had been negative . Fracture healing was uncomplicated in the remaining dogs (mean follow-up time, 23 months; range, 2 to 58 months) . Despite the potential for contamination associated with gunshot trauma, results indicated a low prevalence of preoperative fracture contamination and postoperative osteomyelitis . These results imply either a low contamination rate or treatable contamination of the perifracture area.

Contemp Intern Med, 1995 Feb, 7(2), 47 - 54, 57-60
Current recommendations for community-acquired pneumonia; Esposito AL; The question of which antimicrobial agents to use is compounded by the imprecision of presenting signs and symptoms and the limitations of diagnostic tests . The use of empiric therapy is explored along with suggested management if treatment fails.

JAMA, 1995 Jan 4, 273(1), 41 - 5
Randomized comparative trial and cost analysis of 3-day antimicrobial regimens for treatment of acute cystitis in women; Hooton TM et al.; OBJECTIVE--To determine the efficacy, safety, and costs associated with four different 3-day regimens for the treatment of acute uncomplicated cystitis in women . DESIGN--A prospective randomized trial with a cost analysis . STUDY POPULATION--Women with acute cystitis attending a student health center . INTERVENTIONS--Treatment with 3-day oral regimens of trimethoprim-sulfamethoxazole, 160 mg/800 mg twice daily, macrocrystalline nitrofurantoin, 100 mg four times daily, cefadroxil, 500 mg twice daily, or amoxicillin, 500 mg three times daily . RESULTS--Six weeks after treatment, 32 (82%) of 39 women treated with trimethoprim-sulfamethoxazole were cured compared with 22 (61%) of 36 treated with nitrofurantoin (P = .04 vs trimethoprim-sulfamethoxazole), 21 (66%) of 32 treated with cefadroxil (P = .11 vs trimethoprim-sulfamethoxazole), and 28 (67%) of 42 treated with amoxicillin (P = .11 vs trimethoprim-sulfamethoxazole) . Persistence of significant bacteriuria was less common with trimethoprim-sulfamethoxazole (3%) and cefadroxil (0%) compared with nitrofurantoin (16%; P = .05 vs trimethoprim-sulfamethoxazole) and amoxicillin (14%; P = .11 vs trimethoprim-sulfamethoxazole) . Persistence of bacteriuria was associated with amoxicillin-resistant strains in the amoxicillin group but nitrofurantoin-susceptible strains in the nitrofurantoin group . Trimethoprim-sulfamethoxazole was more successful in eradicating Escherichia coli from rectal cultures soon after therapy and from urethral and vaginal cultures at all follow-up visits compared with the other treatment regimens . Adverse effects were reported by 16 (35%) of 46 patients receiving trimethoprim-sulfamethoxazole, 18 (43%) of 42 receiving nitrofurantoin, 12 (30%) of 40 receiving cefadroxil, and 13 (25%) of 52 receiving amoxicillin . The mean costs per patient were less with trimethoprim-sulfamethoxazole ($114) and amoxicillin ($131) compared with nitrofurantoin ($155) and cefadroxil ($155) . CONCLUSIONS--A 3-day regimen of trimethoprim-sulfamethoxazole is more effective and less expensive than 3-day regimens of nitrofurantoin, cefadroxil, or amoxicillin for treatment of uncomplicated cystitis in women . The increased efficacy of trimethoprim-sulfamethoxazole is likely related to its antimicrobial effects against E coli in the rectum, urethra, and vagina.

Asepsis, 1995 3RD-4TH QUART, 17(2), 14 - 20
Forum: trauma and infection: considerations for patient and health care professional; Ziglar MK et al.; Trauma and infection are leading causes of morbidity, mortality and health care expenditures despite remarkable advances in treatment over the past two decades . Numerous research studies report that in those trauma patients who survive the initial injury, infections account for over one-third of the deaths . While the immediate resuscitation of trauma patients is based on the principles of management for restoring airway, breathing, and circulation, long-term survival requires prevention of infection . Additionally, infection of the health care professional has long been known as a possible complication of caring for acutely ill and injured patients . This article reviews the risk of infection, the pathogenesis of infection, prevention, antimicrobial therapy and infection control for health care professionals.

J Calif Dent Assoc, 1995 Jan, 23(1), 57 - 9
Necrotizing ulcerative periodontitis in an HIV patient; Gowdey G et al.; This case report emphasizes: aggressive HIV-related periodontal lesions can be managed by general practitioners using standard scaling and root planing procedures in combination with proper antibiotic and antimicrobial pharmaceuticals; these lesions can be managed over long periods of time with adequate home care and professional recall; motivation from both the dental team and the patient can translate into a very rewarding result which can improve the quality of life for persons who experience the extreme consequences of HIV-associated dental disease.

Eur J Cardiothorac Surg, 1995, 9(9), 528 - 30
Homograft replacement of fungal endocarditic pulmonary valve; Tolan M et al.; Right-sided infective endocarditis is uncommon but is increasingly seen as a reflection of the prevalence of drug abuse, chronic intravenous catheters and associated congenital malformations . Isolated pulmonary valve endocarditis has rarely been reported and there has been only one previous report of isolated pulmonary valve fungal endocarditis . This resolved with antimicrobials . We describe a case of isolated mycotic pulmonary valve endocarditis resistant to existing anti-fungal chemotherapy, which necessitated pulmonary valve resection and replacement with a homograft.

J Clin Gastroenterol, 1995, 21 Suppl 1, S169 - 73
Helicobacter pylori detected deep in gastric glands: an ultrastructural quantitative study; Taniguchi Y et al.; To determine the presence of Helicobacter pylori deep in the gastric glands and in the parietal cell canaliculi, biopsied specimens from 15 patients were observed by electron microscopy . In the specimens, 818 H . pylori and 1,846 parietal cells were detected . Most of the H . pylori (93.9%, 768/818) were present on the mucosal surface . However, a few organisms (50/818, 6.1%) were detected deep in the mucosa . The mean number of H . pylori per specimen was 2.13 (32/818, 3.9%) and 1.20 (18/818, 2.2%), deep in the gland and in the parietal cell canaliculi, respectively . All appeared morphologically intact . Although the combination of culture and histology from biopsy tissues is usually used for isolation of H . pylori in most laboratories, such organisms are considered difficult to detect with conventional methods and to dislodge with antimicrobial therapy . Therefore, H . pylori present deep in the mucosa are suggested to be one of the factors in recrudescence after eradication therapy . In addition, H . pylori in the parietal cell canaliculi may affect parietal cell function or alter gastric physiology.

Acta Neurochir (Wien), 1995, 137(1-2), 78 - 84
Intracranial mycotic infections in neurosurgical practice; Jamjoom AB et al.; Intracranial mycotic infections requiring neurosurgical intervention are being diagnosed more frequently . This study is a review of 17 cases of intracranial mycotic infections that were treated in a neurosurgical unit in Saudi Arabia over an 8-year period . A primary focus of infection was identified in 41% of patients while 18% of patients had a predisposing factor . Forty-seven percent of patients presented with a brain abscess (solitary 29%, multiple 18%) while 35% had a granuloma . 18% meningitis and ventriculitis and 12% hydrocephalus . The Aspergillus species and Ramichloridium machenziei were the commonest pathogens . Following the appropriate surgical and antimicrobial treatment, the mortality rate was 41% and there was evidence of residual disease at follow-up in 18% . The reason for a fatal outcome was failure to consider a fungal aetiology and to obtain a tissue diagnosis early-because of late referral (2 cases), as well as failure to respond to antimycotic therapy (4 cases) and rupture of the internal carotid artery due to Aspergillus arteritis (one case) . It is concluded that an early tissue diagnosis is crucial in the management of intracranial mycotic infection so that the appropriate surgical and antimycotic treatment can be started early.

Curr Top Med Mycol, 1995, 6, 47 - 71
Treatment of eumycetoma and actinomycetoma; Welsh O et al.; Mycetoma is a chronic disease caused by aerobic actinomycetes and eumycetes which mainly affects the lower extremities . It predominates among farm workers in tropical, subtropical and adjacent zones . Clinically it is characterized by a firm swelling with abscesses and fistulae discharging pus that contains granules or grains of the causal agent . Their color, size, consistency and histopathology contribute to their identification . Cultures and metabolic studies determine the disease's etiology . Eumycete and actinomycete antigens can be used serologically to diagnose and predict prognosis of the disease . Many different antimicrobials and antifungal drugs have been used with varying degrees of success . Trimethoprim-sulfamethoxazole alone or together with diamino-diphenyl-sulfone is the treatment of choice for actinomycetoma . Amikacin is used for severe cases, unresponsive to previous treatment, and for those in danger of dissemination to adjacent organs . Surgery is seldom used for actinomycetoma . In eumycetoma a combination of medical treatment and surgery is advised . Small eumycetomas are easily surgically removed . Ketoconazole at a dosage of 400 mg/day is the medical treatment of choice for eumycetoma caused by M . mycetomatis . The therapeutic response to itraconazole varies . Fluconazole has been unsuccessful in the treatment of eumycetoma but amphotericin B has shown good to poor therapeutic response.

Intervirology, 1995, 38(3-4), 206 - 13
Nitric oxide inhibits Epstein-Barr virus DNA replication and activation of latent EBV; Kawanishi M; Nitric oxide (NO), a mediator of biological functions, has antimicrobial activity against a variety of pathogens including viruses . Effects of NO donors on EBV replication in two EBV lytic systems, Raji cells infected with P3HR-1 virus and P3HR-1 cells activated with TPA plus n-butyrate, were studied . S-nitroso-N-acetylpenicillamine (SNAP), which generates NO when placed in an aqueous solution, and 3-morpholinosydnonimine (SIN-1), which liberates NO and O2-, resulting in the formation of peroxynitrite, were used as NO donors . Immunoprecipitation analysis showed that in superinfected Raji cells, SNAP inhibited EBV late protein synthesis but not EBV early protein expression . Analysis of the structure of EBV DNA termini demonstrated that SNAP suppressed the amplification of EBV DNA in superinfected Raji cells at a dose which did not affect synthesis of EBV early proteins required for EBV DNA replication . In TPA plus n-butyrate-treated P3HR-1 cells, SNAP inhibited synthesis of both early and late proteins of EBV . Northern blot analysis of RNA expressed in TPA plus n-butyrate-treated P3HR-1 cells demonstrated that expression of EBV immediate-early mRNAs coded from BZLF1 and BRLF1 genes was inhibited by SNAP . SIN-1 showed no or little effect on EBV replication in both cell systems . Cell viability and cellular protein synthesis were not affected by either NO donor under the conditions used . These findings suggest that NO prevents EBV replication by inhibiting EBV DNA amplification during the lytic phase of the life cycle as well as by blocking activation of the latent EBV genome . The mechanism for inhibiting of EBV replication by NO was discussed in relation to the role of NO in EBV latency in vivo.

Med Tr Prom Ekol, 1995, (10), 35 - 7
{Antimicrobial means for individual protection used by medical personnel in emergency situations}; Selov AV et al.; For protection of medical staff from infections during emergencies, the authors recommend individual antimicrobial means--medical gowns and special suits protecting skin against extremely dangerous causal agents, surgical masks and individual means with autonomous air supply for lower intake of bacteria.

Microbios, 1995, 84(339), 79 - 85
Presence of sterile hyphae in moulds: relationship with inhibitory activity; Calvo MA et al.; The relationship involving the presence of sterile hyphae in moulds and their inhibitory activity on 34 micro-organisms was investigated . From the results it was evident that antimicrobial activity varied when morphological changes were observed in the cultures.

J Enzyme Inhib, 1995, 9(4), 263 - 75
Belactins A and B, new serine carboxypeptidase inhibitors produced by Actinomycete . I . Taxonomy, production, isolation and biological activities; Murakami S et al.; Belactins A and B, new inhibitors of serine carboxypeptidase were discovered in the fermentation broth of Saccharopolyspora sp . MK19-42F6 . They were purified by ethyl acetate extraction, silica gel chromatography, Sephadex LH20 chromatography, Capcellpak C18 SG120 reversed phase HPLC and centrifugal partition chromatography (CPC) following their inhibitory activity against carboxypeptidase Y (CP-Y) . The inhibition constants (Ki) of belactins A and B against CP-Y are 0.14 and 0.27 microM respectively . Belactins A and B have highly specific inhibitory activities for CP-Y among various peptidases, have no antimicrobial activities at 100 micrograms/ml and have low toxicities.

J Clin Dent, 1995, 6 Spec No, 84 - 8
Effect of a stabilized stannous fluoride dentifrice on plaque acid (toxin) production; White DJ et al.; A Plaque Glycolysis and Regrowth Method (PGRM) has been used to examine the effects of single brushing with a new stabilized stannous fluoride dentifrice on plaque acid production . Plaque samples collected 45 minutes after subject toothbrushing were compared with samples collected prior to toothbrushing for glycolytic activity (pH reduction in incubation media), and the composition and proportion of acids produced during metabolism (capillary electrophoresis) . Subjects brushed with both active SnF2 and placebo dentifrices in a cross-over design . Acetic and lactic acid were found to be produced during PGRM metabolism . SnF2 dentifrice was observed to significantly inhibit plaque glycolysis, reducing the pH drop associated with acid production . and specifically inhibiting both lactic acid and acetic acid production . Control dentifrice had a modest inhibitory effect on acid production, primarily inhibiting acetic acid production . SnF2 dentifrice inhibited lactic acid production more effectively than control dentifrice, and this effect appeared to be related to SnF2 specificity in metabolic inhibition, as opposed to the components of control dentifrice, namely ionic fluoride and surfactant . These experimental results support the in vivo antimicrobial activity of SnF2 formulated in a new stabilized matrix (currently marketed as Crest Gum Care), and demonstrate the utility of the PGRM method in elucidating specific mechanisms of action for antimicrobial agents.

J Clin Dent, 1995, 6 Spec No, 80 - 3
Antimicrobial effects of a stabilized stannous fluoride dentifrice in reducing plaque acid production--a single-brushing PGRM study; Liang N et al.; A Plaque Glycolysis and Regrowth Method (PGRM) has been used to evaluate the in vivo antimicrobial activity of a new stabilized stannous fluoride dentifrice in comparison to a control dentifrice (Regular Crest, containing NaF) and a second commercial dentifrice containing SnF2 . In the method, plaque collected from subjects prior to toothbrushing served as control for subsequent plaque samples collected following toothbrushing with assigned formulations . Inhibition of plaque metabolic activity was determined by the comparative acidogenicity of normalized plaque samples as contrasted with control plaques incubated similarly . Results from a sixteen-person cross-over study demonstrated that the improved stabilized stannous fluoride dentifrice significantly reduced plaque metabolism of sucrose in comparison to both placebo and commercial SnF2 dentifrice formulations following a single toothbrushing with 2.5 grams of dentifrice for over 90 minutes following treatment . These results support the strong antimicrobial activity of the stabilized stannous fluoride dentifrice, currently marketed as Crest Gum Care, in inhibiting plaque metabolism/acid production following in vivo toothbrushing.

J Clin Dent, 1995, 6 Spec No, 71 - 9
Effects of nine weeks' use of a new stabilized stannous fluoride dentifrice on intrinsic plaque virulence expressed as acidogenicity and regrowth: a modified PGRM study; Kasturi R et al.; A new stabilized stannous fluoride dentifrice, currently marketed as Crest Gum Care has been examined for its effects on intrinsic plaque metabolic and regrowth activity and effects on plaque resistance to SnF2 throughout nine weeks of toothbrushing . Subjects brushed their teeth 1 X, 2 X or 3 X/day with stabilized stannous fluoride dentifrice or placebo dentifrice for nine weeks, presenting in the morning on weeks 3, 6-9 for plaque sampling . Following nine weeks, subjects were crossed-over and repeated the experiment on their alternative assigned product (active SnF2/placebo) . Sampled dental plaques were evaluated for standardized glycolysis and regrowth activity using the "Plaque Glycolysis and Regrowth Method" (PGRM) . Following the second nine-week treatment period, subjects concluding either placebo or SnF2 toothbrushing participated in a single-treatment PGRM experiment using stabilized stannous fluoride dentifrice . Toothbrushing with stabilized stannous fluoride dentifrice in this experiment produced significant and sustained reductions in both plaque glycolytic and regrowth activity as compared to placebo treated plaques . In the concluding single-brushing PGRM experiment, SnF2 dentifrice was shown to produce equal inhibitory actions in plaque from subjects completing stannous fluoride or placebo treatments . This result confirmed that nine weeks toothbrushing with stabilized stannous fluoride dentifrice produced no development or resistance of plaque to SnF2 inhibition . These results support the strong in vivo antimicrobial actions of the stabilized stannous fluoride dentifrice, Crest Gum Care.

J Clin Dent, 1995, 6 Spec No, 59 - 70
A new Plaque Glycolysis and Regrowth Method (PGRM) for the in vivo determination of antimicrobial dentifrice/rinse efficacy towards the inhibition of plaque growth and metabolism--method development, validation and initial activity screens; White DJ et al.; A new method, the Plaque Glycolysis and Regrowth Method (PGRM), is described for the evaluation of antimicrobial effects on plaque metabolism in vivo . The method relies on the experimental observation that in vivo sampled dental plaques, collected from different quadrants of the dentition, produce equivalent rates of metabolic activity and regrowth when similarly dispersed and normalized into incubation media . In applications of the technique to antimicrobial evaluations, overnight fasted dental plaque is collected from a non-treated quadrant of the dentition along the gingival margin . Topical formulations are used in vivo . Following this, dental plaques are collected from other dentition quadrants at extended times, allowing for the back diffusion, clearance and natural intraoral deactivation of antimicrobials within the oral cavity . In vivo treated and non-treated plaque samples are subsequently tested for metabolic and regrowth activity under controlled and standardized conditions in vitro following normalization for biomass . The technique thus combines the necessary biological factors important to the legitimate evaluation of antimicrobial effects in vivo, while benefiting from the improved precision and control provided by in vitro assessment of plaque activity . In this paper evidence is presented validating the PGRM method, and initial activity screens of commercial antimicrobial mouthrinses and toothpastes, including a new stabilized stannous fluoride dentifrice, are described.

Drug Metabol Drug Interact, 1995, 12(2), 161 - 9
Synthesis of 3-methyl-4-{(2,4-dihydro-4-substituted-3H-1,2,4-triazole-3-thione-5-yl) phenylhydrazono}-5-isoxazolone and evaluation of their antimicrobial activities; Komurcu SG et al.; 3-Methyl-4-{(2,4-dihydro-4-substituted-3H-1,2,4-triazole-3-thione-5-yl) phenylhydrazono}-5-isoxazolone derivatives have been synthesised . The structure of these compounds was determined using spectral data and elemental analyses . These compounds were tested for antimicrobial activity.

Drug Metabol Drug Interact, 1995, 12(2), 145 - 50
Synthesis and antimicrobial activity of some new 1-{4-(4-fluorobenzoylamino)-benzoyl}-4-substituted thiosemicarbazides; Durgun BB et al.; 1-Aroyl-4-substituted thiosemicarbazides were obtained by the addition of 4-(4-fluorobenzoylamino)benzoylhydrazine to methyl, ethyl, propyl, allyl, cyclohexyl, phenyl and phenethyl isothiocyanates . The structures of the synthesized compounds were confirmed using UV, IR, 1H-NMR (for compounds 4c, 4g) and mass (for compounds 4b, 4c, 4g) spectral methods together with elemental analyses . None of the synthesized compounds has been reported previously.

Scand J Infect Dis, 1995, 27(5), 499 - 502
Analysis of restriction fragment length polymorphism and ribotyping of multiresistant Stenotrophomonas maltophilia isolated from persisting lung infection in a cystic fibrosis patient; Wust J et al.; A cystic fibrosis patient was infected by Stenotrophomonas maltophilia over at least 15 months . The bacteria became increasingly resistant to antimicrobial agents . Determination of restriction fragment length polymorphism and ribotyping showed that resistance was due to changes in that S . maltophilia rather than to infection by another strain.

World Health Organ Tech Rep Ser, 1995, 855, 1 - 59
Evaluation of certain veterinary drug residues in food . Forty-third report of the Joint FAO/WHO Expert Committee on Food Additives; Clinical perspectives of granulocyte transfusions: efficacy to date; Department of Pathology and Pediatrics, University of Iowa College of Medicine, Iowa City 52242-1182, USAThe literature pertaining to the use of granulocyte transfusions as treatment for progressive bacterial, yeast, and fungal infections in severely neutropenic patients is reviewed . Efficacy in treating bacterial infections that are unresponsive to antimicrobial therapy is well established--especially if bone marrow failure does not recover rapidly and neutropenia is persistent . The role of therapeutic granulocyte transfusions for yeast and fungal infections has potential merit, but current data are incomplete and findings are inconsistent . The possibility of greater success has been raised by use of recombinant granulocyte colony stimulating factor to greatly increase the yield of neutrophils collected from normal donors.

Scand J Gastroenterol Suppl, 1995, 210, 82 - 4
Sucralfate affects the susceptibility of Helicobacter pylori to antimicrobial agents; Slomiany BL et al.; BACKGROUND: Infection with Helicobacter pylori is regarded as a primary factor in the pathogenesis of gastric disease, and successful therapies now include a combination of antiulcer drugs with antimicrobial agents . In this study, we investigated the effect of sucralfate and omeprazole on the vitro anti-H . pylori activity of metronidazole, erythromycin, tetracycline, and amoxycillin . METHODS: Aliquots of H . pylori culture were transferred to the wells containing different concentrations of antibiotics either alone or in the presence of various doses of sucralfate and omeprazole and incubated for 3 days for MIC evaluation . RESULTS: The assays in the absence of sucralfate and omeprazole gave MIC value 0.10 mg/l for erythromycin, 0.12 mg/l for amoxycillin, 0.15 mg/l for tetracycline, and 14 mg/l for metronidazole . Inclusion of sucralfate evoked a 28% enhancement in the MIC of metronidazole, 2.5-fold in tetracycline, 8-fold in erythromycin, and 2-fold in amoxycillin . In the presence of omeprazole, the MIC of erythromycin improved 4-fold, tetracycline 1.6-fold, and amoxycillin, 2-fold . CONCLUSIONS: The results demonstrate that sucralfate enhances the anti-H . pylori activity of antibiotics and that this effect is comparable to that of omeprazole.

Annu Rev Microbiol, 1995, 49, 277 - 304
Peptides as weapons against microorganisms in the chemical defense system of vertebrates; Nicolas P et al.; The innate immunity of vertebrates to microbial invasion is arbitrated by a network of host-defense mechanisms involving both the long-lasting highly specific responses of the cell-mediated immune system and a nonspecific chemical defense system based on a series of broad-spectrum antimicrobial peptides that are analogous to those found in insects . Vertebrate antibiotic peptides secreted by nonlymphoid cells of the mucosal surfaces of the respiratory and gastrointestinal tracts as well as by the granular glands of the skin reportedly cause the lysis of numerous pathogenic microorganisms, including viruses, gram-positive and gram-negative bacteria, protozoa, yeasts, and fungi, as well as of cancer cells . Antimicrobial peptides isolated from vertebrates have three characteristic properties: They are relatively small (20-46 amino acid residues), basic (lysine- or arginine-rich), and amphipathic . Although these peptides differ widely in length and amino acid sequences, they may be grouped in four broad families based on characteristic structural features . Although the precise mechanism of action of these peptides remains to be defined, their microbicidal effect very likely results from their capacity to form channels or pores within the microbial membrane in order to permeate the cell and impair its ability to carry out anabolic processes . This secondary, chemical immune system provides vertebrates with a repertoire of small peptides that are promptly synthesized upon induction, easily stored in large amounts, and readily available for antimicrobial warfare.

Pathobiology, 1995, 63(2), 93 - 9
Interferon-gamma-induced downregulation of CD4 inhibits the entry of human immunodeficiency virus type-1 in primary monocytes; Dhawan S et al.; We have previously shown that the treatment of monocytes with interferon-gamma (IFN-gamma) prior to exposure with human immunodeficiency virus type-1 (HIV) results in complete inhibition of HIV infection of monocytes . In the present report, we have extended this study to obtain information on the mechanism(s) underlying IFN-gamma-induced inhibition of HIV infection of monocytes . To examine the effect of IFN-gamma on HIV entry, the first event in the infectious cycle of the virus, we amplified HIV-gag sequences in the genomic DNA and RNA of IFN-gamma treated monocytes, and found no evidence for the presence of either proviral DNA or HIV RNA sequences . These results were consistent with the absence of intracellular HIV particles either in the latent or actively replicating state as determined by flow-cytometric analysis of these cells . Furthermore, no HIV-induced cytopathic effects, such as multinucleated giant cell formation or cell death, were observed in IFN-gamma-treated monocytes after their exposure to HIV . Stimulation of IFN-gamma-treated monocytes 6 days postinfection with tumor necrosis factor-alpha (TNF-alpha), which is known to augment HIV replication in the infected cells, did not result in the induction of the HIV indicating the absence of latent HIV infection in IFN-gamma-treated monocytes . Treatment of monocytes with IFN-gamma, TNF-alpha, or with a combination of the two agents which is known to induce antimicrobial free radical nitric oxide (NO2- in the murine system did not induce NO2- production human monocytes suggesting the antiviral activity of IFN-gamma to be independent of NO2(-)-mediated killing of HIV or HIV-infected monocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Drugs, 1995, 49 Suppl 2, 159 - 63
Fluoroquinolone toxicities . An update; Lietman PS; The main types of adverse effects associated with quinolones are uncommon and reversible and vary in frequency among different agents . Phototoxicity appears more frequent with lomefloxacin than with some other quinolones . Three mechanisms have been proposed to explain the neurotoxic effects, including rare proconvulsant activity, associated with quinolone therapy . Arthropathy remains a dilemma for paediatricians deciding whether to use quinolones in growing children . Importantly, the experience with temafloxacin, which has now been withdrawn from the market, emphasises the need for thorough postmarketing surveillance . Nonetheless, it should be remembered that the fluoroquinolones as a group are effective and very well tolerated antimicrobial drugs.

Oncol Res, 1995, 7(5), 213 - 25
Difloxacin reverses multidrug resistance in HL-60/AR cells that overexpress the multidrug resistance-related protein (MRP) gene; Gollapudi S et al.; In this study, we have examined the in vitro chemosensitizing activity of difloxacin, a quinolone antimicrobial agent, in the multidrug-resistant human myeloid leukemia HL-60/AR cell line . HL-60/AR cells were found to overexpress multidrug resistance-associated protein (MRP) mRNA as compared to HL-60 cells . Difloxacin, in a concentration-dependent manner, increased the sensitivity of HL-60/AR cells to daunorubicin, adriamycin, and vincristine, and partially corrected the altered drug transport . In addition, difloxacin corrected subcellular distribution of adriamycin by inducing redistribution of the drug from the perinuclear region to the nucleus in HL-60/AR cells . The chemosensitizing effect of difloxacin was observed at clinically achievable concentrations . We conclude that difloxacin is an effective chemosensitizer of MRP-associated multidrug-resistant tumor cells and is a potential candidate for clinical use to reverse multidrug resistance.

J Clin Lab Anal, 1995, 9(5), 308 - 19
Myelin- and microbe-specific antibodies in Guillain-Barré syndrome; Terryberry J et al.; We surveyed the frequency of reported infections and target autoantigens in 56 Guillain Barre syndrome (GBS) patients by detecting antibodies to myelin and microbes . Sulfatide (43%), cardiolipin (48%), GD1a (15%), SGPG (11%), and GM3 (11%) antibodies were the most frequently detected heterogenous autoantibodies . A wide spectrum of antimicrobial IgG and IgM antibodies were also detected; mumps-specific IgG (66%), adenovirus-specific IgG (52%), varicella-zoster virus-specific IgG (46%), and S . pneumoniae serotype 7-specific IgG (45%) were the most prevalent . Our results indicate that polyclonal expansion of physiologic and pathologic antibodies and/or molecular mimicry likely occurs following infection and is related to other autoimmune factors in the etiology of GBS . Although no single definitive myelin-specific autoantibody was identified, our results suggest a unique pattern of reactivity against autoantigens.

Prog Clin Biol Res, 1995, 392, 567 - 79
Monophosphoryl lipid A as a prophylactic for sepsis and septic shock; Gustafson GL et al.; The ability of monophosphoryl lipid A (MLA) to provide prophylactic protection against septic shock was evaluated in a mouse model of induced endotoxin hypersensitivity . Treatments of hypersensitized animals with low doses of MLA attenuated endotoxin lethality and endotoxin-mediated liver damage . These effects were related to the ability of MLA to suppress accumulation of TNF-alpha and IFN-gamma in the bloodstream of animals . MLA treatments had only a modest effect in suppressing the accumulation of nitrate in the bloodstream . This implied that MLA did not suppress induction of macrophage and hepatocyte nitric oxide synthetases that contribute to antimicrobial defense and protect against endotoxin-mediated liver damage . The MLA treatments did not appear to compromise inflammatory defenses against local infection since locally recruited leukocytes remained responsive to endotoxin after hypersensitivity had been attenuated . In agreement with these findings, other studies have shown that the induction of endotoxin tolerance by MLA parallels the induction of resistance of animals to lethal challenges with either Gram negative or Gram positive bacteria . As predicted from preclinical studies, human trials of the clinical form of MLA (MPL-immunostimulant) have confirmed that MLA could attenuate systemic responses to endotoxin in normal volunteers, including the attenuation of blood cytokine accumulation and attenuation of symptomatic responses.

Med Tr Prom Ekol, 1995, (8), 33 - 5
{Use of products made of antimicrobial materials in the prevention of foot mycoses}; Sedov AV et al.; Field trials were conducted to evaluate effectiveness of mycoses prophylaxis gained by use of antimicrobial insoles and foot-binding with fungicide agents . The trials involved 100 novice soldiers . Bacteriology and bacterioscopy studies diagnosed 47 soldiers as having subclinical mycosis of feet . Using antimicrobial insoles and foot-binding caused considerably lower occurrence of pathogenic fungi in the skin samples; using antimicrobial insoles with regular foot-binding resulted in no changes of the skin microflora . The authors recommend wide application of antimicrobial stuff with fungicide agents for prophylaxis of feet mycosis.

Infect Control Hosp Epidemiol, 1995 Jan, 16(1), 7 - 11
Multidrug-resistant Mycobacterium tuberculosis in an HIV dental clinic; Cleveland JL et al.; OBJECTIVE: To investigate possible transmission of multidrug-resistant tuberculosis (MDR-TB) in a dental setting . DESIGN: A retrospective, descriptive study of dental workers (DWs), patients, and practice characteristics . PATIENTS: Two dental workers (DW1 and DW2) with acquired immunodeficiency syndrome and MDR-TB . SETTING: A hospital-based (Hospital X) human immunodeficiency virus (HIV) dental clinic in New York City . METHODS: To identify dental patients with tuberculosis (TB), patients treated in the dental clinic at Hospital X during 1990 were cross-matched with those listed in the New York City Department of Health Tuberculosis Registry . Mycobacterium tuberculosis isolates from both DWs and from dental patients with TB were tested for antimicrobial susceptibility and typed by restriction fragment length polymorphism (RFLP) analysis . Infection control practices were reviewed . RESULTS: M tuberculosis isolates infecting DW1 and DW2 were resistant to isoniazid and rifampin and had identical RFLP patterns . DW1 and DW2 worked in close proximity to each other in a small HIV dental clinic in Hospital X during 1990 . Of 472 patients treated in the dental clinic in 1990, 41 (8.7%) had culture-proven M tuberculosis infection . Of these 41, 5 had isolates with resistance patterns similar to both DWs; however, for four available isolates, the RFLP patterns were different from the patterns of the DWs . Sixteen of the 41 patients received dental treatment while potentially infectious . Dental patients were not routinely questioned about TB by dental staff, nor were all dental staff screened routinely for TB . No supplemental environmental measures for TB were employed in the dental clinic in 1990 . CONCLUSIONS: Our investigation suggests that MDR-TB transmission may have occurred between two DWs in an HIV dental clinic . Opportunities for transmission of TB among dental staff and patients were identified . TB surveillance programs for DWs and appropriate infection control strategies, including worker education, are needed to monitor and minimize exposure to TB in dental settings providing care to patients at risk for TB.

Biopolymers, 1995, 37(2), 105 - 22
Structure-activity studies on magainins and other host defense peptides; Maloy WL et al.; Host defense peptides are widely distributed in nature, being found in species from bacteria to humans . The structures of these peptides from insects, horseshoe crabs, frogs, and mammals are known to have the common features of a net cationic charge due to the presence of multiple Arg and Lys residues and in most cases the ability to form amphipathic structures . These properties are important for the mechanism of action that is thought to be a nonreceptor-mediated interaction with the anionic phospholipids of the target cell followed by incorporation into the membrane and disruption of the membrane structure . Host defense peptides have been shown to have broad spectrum antimicrobial activity, able to kill most strains of bacteria as well as some fungi, protozoa, and in addition, many types of tumor cells . Specificity for pathogenic cells over host cells is thought to be due to the composition of the cell membranes, with an increased proportion of anionic phospholipids making the pathogen more susceptible and the presence of cholesterol making the host membranes more resistant . Structure-activity relationship studies have been performed on insect cecropins and apidaecins, horseshoe crab tachyplesins and polyphemusins, and the frog magainins, CPFs (caerulein precursor fragments) and PGLa . In general, changes that increased the basicity and stabilized the amphipathic structure have increased the antimicrobial activity; however, as the peptides become more hydrophobic the degree of specificity decreases . One magainin-2 analogue, MSI-78, has been developed by Magainin Pharmaceuticals as a topical antiinfective and is presently in clinical trials for the treatment of infected diabetic foot ulcers.

Enferm Infecc Microbiol Clin, 1995 Jan, 13(1), 23 - 32
{Comparative study of the prevalence of hospital infections at a Valencia county hospital}; Morales Suarez-Varela MM et al.; BACKGROUND: Nosocomial infections presently imply a 10-day average prolongation of hospital stay per infection, with an important increase in mortality and costs . A comparison is made between the prevalence of nosocomial infections, microorganisms isolated and antimicrobial agents used in the Arnau de Vilanova Hospital (Valencia, Spain), and those corresponding to other hospitals of similar characteristics in the triple-province Valencia Community . METHODS: Cross-sectional epidemiological study, reflecting the prevalence of hospital infections globally and in each of services . RESULTS: The global prevalence of hospital infections was 6.08% . Services with greatest prevalence are Intensive Care, Internal Medicine and Surgery . Respiratory tract and postoperative wound infections were the most frequent presentations . CONCLUSIONS: Global prevalence was slightly less than in the Valencian Community for 1992 (8.28%), with a predominance of gram-negative over gram-positive germs, in contrast with the results reported globally for the Valencia an hospitals.

J Periodontol, 1995 Jan, 66(1), 69 - 74
Antimicrobial susceptibility of periodontopathic bacteria associated with failing implants; Sbordone L et al.; The aim of this study was to examine the subgingival microflora associated with failing implants, and to determine their susceptibility to commonly used antibiotics in periodontal therapy and dental practice . Thirteen partially edentulous patients with 19 failing implants were selected . Clinical examination included probing depth, attachment level, gingival index, plaque index, and radiographic analyses . Two subgingival plaque samples were taken from each failing implant and analyzed for microbial composition . Fusobacterium nucleatum, Porphyromonas gingivalis, and Prevotella intermedia were the prevalent cultivable microflora . Antimicrobial susceptibility of isolates was determined by the agar dilution technique . Antibacterial activity of penicillin G, amoxicillin, amoxicillin-clavulanate, and the combination amoxicillin-metronidazole was significantly higher than with other antibiotics tested . These data indicated that the commonly-used antibiotics were highly effective against bacteria isolated around failing implants, which would suggest the use of these antibiotics to control peri-implant infections.

J Periodontol, 1995 Jan, 66(1), 47 - 51
The effect of a single application of subgingival antimicrobial or mechanical therapy on the clinical parameters of juvenile periodontitis; Unsal E et al.; Twenty-six (26) patients, 18 female and 7 male, aged 16 to 25 years (mean age 19.03 +/- 2.2 years) previously diagnosed as suffering from localized juvenile periodontitis were randomly assigned to one of the following treatment groups: 9 patients acted as controls; 8 received subgingival chlorexidine gel; and 9 had subgingival tetracycline paste application . All treatment modalities resulted in a pronounced improvement in PI, GI, and GI-S by 12 weeks (P < 0.001) . The mean probing depths also decreased, but there were no significant differences found between the three groups . However, when the interproximal sites of the 3 groups were examined separately from the buccal and lingual sites, it was found that there was a significant (P < 0.05) difference between the probing depths, with the control group showing the greatest reduction of 2.58 mm and the chlorhexidine group showing the least reduction of 1.37 mm . It was concluded that a single application of topical subgingival tetracycline did not result in any short-term improvement over that achieved by standard non-surgical therapy in the clinical parameters of these localized juvenile periodontitis patients.

Klin Padiatr, 1995 Jan-Feb, 207(1), 19 - 23
{Neurological complications in infectious endocarditis}; Groll A et al.; Despite considerable progress in both diagnostic studies and therapeutic management serious complications of infectious endocarditis have become rather more common . Next to intracardiac complications arterial embolization to the central nervous system is the second most common life-threatening event, which might lead to infarction, hemorrhage, mycotic aneurysm and/or metastatic infection with a wide spectrum of neurological symptoms and an overall very poor prognosis . The most effective prevention of neurological complications is the early diagnosis of infectious endocarditis with isolation of the infecting agent and adequate antimicrobial chemotherapy in combination with well-timed cardiosurgical measures . Computed tomography and cerebral angiography is mandatory in any patient with neurological symptoms to check the need for a neurosurgical intervention as well as in patients assigned for anticoagulation for cardiac reasons.

J Appl Bacteriol, 1995 Jan, 78(1), 39 - 46
The antimicrobial activity of hexapeptides derived from synthetic combinatorial libraries; Blondelle SE et al.; A series of peptides identified through the use of synthetic hexapeptide combinatorial libraries (represented by the formula Ac-RRWWCO-NH2) were examined for their antimicrobial activity against five different micro-organisms . Their toxicity was also evaluated in an in vitro haemolytic assay . The peptides showed activity against the five micro-organisms, although higher activities were found against Gram-positive bacteria . Both growth inhibition and cell viability assays were carried out to demonstrate the bactericidal activities of these peptides against two of the micro-organisms tested . The dimeric cystine forms of these peptides were shown to have biological activities identical to the monomeric forms.

Bull Group Int Rech Sci Stomatol Odontol, 1995 Jan-Feb, 38(1-2), 45 - 50
Comparative study of heat release of various cement base materials during their setting; Panagiotouni E et al.; An ideal cement base material in order to protect the pulpal tissue from several external irritations (microbial, mechanical, thermal, galvanic and osmotic irritations) must present the following requirements: to attach or bond to the residual dentin, to be biocompatible, to present suitable physicomechanical, antimicrobial and optical properties, to be color stable, easy to use and rapid to set . Thermal phenomena developed during the mixing and setting are a factor influencing the biocompatibility properties of these materials . Cement base materials are used under various types of filling materials (amalgams, composite resins, gold and porcelain inlays) and are placed in contact with the dentin that contains exposed dentinal tubules . The purpose of this study was to investigate the possible exothermic reaction of these materials and to measure the developing temperatures for a time period from their mixing up to the completion of their setting . We studied the following types of cement base materials: a) Zinc oxide eugenol cement, b) Zinc phosphate cement, c) Zinc polycarboxylate cement and d) Glass ionomer cement both light- and self-cured . From the obtained results we observed that ZOE cements developed the lowest temperatures ranging from 32.8 degrees C to 37 degrees C, while Zinc phosphate cements developed the highest temperatures ranging from 44.4 degrees C to 52 degrees C . The other two types of materials Zinc polycarboxylate and Glass ionomer cements developed biocompatible temperatures ranging from 38 degrees C to 40.8 degrees C, which usually do not cause deteriorations and harms to the pulp . We concluded that the ZOE cements presented the best thermal behaviour followed by Zinc polycarboxylate and Glass ionomer cements . Hence, these materials can be safely used without causing any pulpal response.

Aust Fam Physician, 1995 Jan, 24(1), 49 - 53, 56
Antibiotics for common respiratory infections; Christiansen K; One of the most common reasons for prescribing antibiotics is an infection in the respiratory tract . There are a large number of antimicrobial agents available, some of long standing and others relatively new to the market . The rationale for the choice of agent, including emerging resistances, spectrum of activity, antibiotic pharmacokinetics, adverse reactions and cost, is discussed for the various sites of infection.

Ann Hematol, 1995 Jan, 70(1), 59 - 60
Microangiopathic hemolytic anemia and severe thrombocytopenia in Brucella infection; Di Mario A et al.; A case of Brucella septicemia presenting at the onset as a severe microangiopathic hemolytic anemia with coexisting dramatic hemorrhagic syndrome (severe epistaxis, gross hematuria, and skin purpura) is reported . A hemogram showed severe thrombocytopenia, anemia, and leukopenia . Bone marrow morphology showed the typical features associated with Brucella infection: numerous histiocytes with signs of activation, multiple granulomata, giant cells, and hemophagocytosis . After appropriate antimicrobial therapy, the clinical and hematological status of the patient improved, and he is alive and well 1 year later with disappearance of all hematological abnormalities.

J Allergy Clin Immunol, 1995 Jan, 95(1 Pt 1), 52 - 9
Extrathoracic and intrathoracic airway responsiveness in sinusitis; Bucca C et al.; BACKGROUND: Asthma associated with sinusitis is supposed to be sustained by bronchoconstrictive reflexes originating in extrathoracic airway (EA) receptors . OBJECTIVE: The study was designed to evaluate the relationship between EA responsiveness and bronchial responsiveness in sinusitis . METHODS: We performed histamine inhalation challenge in 106 patients with chronic sinusitis, during disease exacerbation and after treatment with antimicrobials and nasal flunisolide (100 micrograms daily) for 2 weeks . Forced expiratory volume in 1 second (FEV1) and maximal mid-inspiratory flow (MIF50) were the respective indexes of bronchial and EA narrowing; the histamine concentrations causing a 20% fall in FEV1 (PC20) and 25% drop in MIF50 (PC25MIF50) were used as thresholds of bronchial and EA responsiveness . Thresholds of 8 mg/ml or less were assumed to indicate bronchial hyperresponsiveness (B-HR) or EA hyperresponsiveness (EA-HR) . RESULTS: During sinusitis exacerbation 76 patients had EA-HR, which in 46 was associated with B-HR . The values of PC20 were closely related with those of PC25MIF50 (p < 0.001) . EA-HR and B-HR were strongly associated with pharyngitis . After treatment, mean PC25MIF50 and PC20 were significantly increased (p < 0.001) . The improvement of PC25MIF50 was closely related to that of PC20 (p < 0.001) and to the decrease in neutrophils in nasal lavage (p < 0.05) . EA-HR reversed in 58 patients and improved in 10; B-HR reversed in 29 and improved in 12 . CONCLUSIONS: Our findings suggest that in sinusitis, B-HR may be sustained by constrictive reflexes originating in pharyngeal receptors, made hypersensitive by seeding of the inflammatory process.

Med Clin North Am, 1995 Jan, 79(1), 53 - 77
Infectious emergencies in patients with diabetes mellitus; Smitherman KO et al.; Although it remains controversial as to whether diabetics have an overall increased incidence of infection as compared to nondiabetics, several potentially life-threatening infections do appear to be uniquely associated with diabetes . These infections generally occur in older diabetics with less than optimal glucose control . For each entity, selected symptoms and signs may suggest the diagnosis but confirmation of via tissue biopsy with culture and histopathology or radiography is usually necessary . Management typically require both antimicrobial treatment and surgery.

Cancer Chemother Pharmacol, 1995, 35(3), 188 - 90
Vinblastine and erythromycin: an unrecognized serious drug interaction; Tobe SW et al.; Vinblastine and erythromycin are among the most commonly used chemotherapeutic and antimicrobial agents, respectively . No interaction between the two has ever been reported . Towards the end of a phase I study of vinblastine plus oral cyclosporin (to reverse multidrug resistance), three patients also received erythromycin to raise their cyclosporin levels . All developed severe toxicity consistent with a much higher vinblastine dose than was actually given . This apparent potentiation of vinblastine toxicity has not been previously described.

Drugs Exp Clin Res, 1995, 21(1), 17 - 22
Imipenem and immune response: in vitro and in vivo studies; Pasqui AL et al.; Imipenem is a new beta-lactam antibiotic endowed with very high antimicrobial activity; it is used in severe infections which often occur in those conditions characterized by impairment of the immune system . The aim of this study was to evaluate the effect of imipenem on some immune functions, both in vitro and in vivo . The authors studied the effect in vitro of three different drug concentrations (15, 30 and 60 mg/l) on polymorphonuclear leucocyte (PMN) phagocytosis and superoxide anion production, as well as on lymphomonocyte proliferative response and cytokine production . Preincubation of PMN with the highest dosages (30 and 60 mg/l) was found to increase phagocytosis evaluated via both cytofluorimeter and chemiluminescence, while no effect was detected on superoxide anion production or on lymphomonocyte tests . In the in vivo study, the authors administered imipenem/cilastatin (1500 mg/day) to 15 elderly and diabetic patients, in whom both PMN functions (phagocytosis and superoxide anion production) and lymphocyte tests (CD3, CD4, CD8, CD19, IL2 and sIL2R serum levels) were studied before and on the 3rd and 7th days of treatment . The drug assimilation did not modify the lymphocyte parameters, whereas it increased PMN superoxide anion production and phagocytosis which were depressed in basal conditions . In the former case, such increase was slight and insignificant, whereas in the latter it was significant.

Scand J Infect Dis, 1995, 27(1), 39 - 43
Endotoxin, interleukin-6 and phospholipase-A2 as markers of sepsis in patients with hematological malignancies; Rintala E et al.; The concentrations of endotoxin, interleukin-6 (IL-6) and group II phospholipase-A2 (PLA2-II) were measured in serum or plasma during cytotoxic chemotherapy, fever of unknown origin and sepsis in 56 patients with hematological malignancies and during sepsis and viral infections in 22 non-hematological patients . High concentrations of IL-6, PLA2-II and endotoxin were detected in sepsis, the levels being similarly elevated in hematological and non-hematological patients . The levels of IL-6 and PLA2-II correlated closely with that of C-reactive protein (CRP) . The levels of PLA2-II and IL-6 declined earlier than the level of CRP during the course of antimicrobial treatment . The levels of IL-6 also rose earlier than the level of CRP . The ability of IL-6 and PLA2-II and endotoxin to discriminate between sepsis and other causes of fever was comparable to that of CRP . IL-6 and PLA2-II are, together with CRP, valuable tools for the detection of sepsis in patients with hematological malignancies who undergo cytotoxic medication . Endotoxin is not suitable for routine laboratory diagnosis of sepsis.

Scand J Infect Dis, 1995, 27(1), 23 - 7
Human nocardiosis in northern Italy from 1982 to 1992 . Northern Italy Collaborative Group on Nocardiosis; Farina C et al.; We conducted a retrospective survey of nocardiosis in 9 city hospitals in northern Italy from 1982 to 1992 . The medical records of 30 patients with documented nocardiosis were reviewed . Microbiological data included morphology, biochemical characteristics, serology and in vitro susceptibility testing . The 29 isolates (1 case was diagnosed on the basis of serological results) were Nocardia asteroides (n = 25) and Nocardia farcinica (n = 4) . Predisposing factors including immunosuppression for organ transplant rejection prophylaxis, lung disease (silicotuberculosis and pulmonary fibrosis), solid tumours and hematological malignancies, and AIDS . Three patients had no identified risk factors . 20 cases of pulmonary nocardiosis were observed . Sites of infection in patients without previous pulmonary involvement were: brain abscesses, soft tissues, pericardium, blood, and cerebrospinal fluid . Most strains tested were susceptible to amikacin and imipenem . Resistance to several antimicrobial agents was found, particularly erythromycin, fosfomycin, pefloxacin, sulphonamides and trimethoprim . Antimicrobial chemotherapy included sulphonamides, amikacin, ceftriaxone, imipenem and minocycline . 21 patients survived, although 2 relapsed transiently . Nocardiosis appears to be more common than generally realised by physicians in northern Italy . The local species distribution and disease spectrum are similar to those described elsewhere . Nocardiosis should be part of the differential diagnosis in patients with pulmonary infiltrates or brain abscess, particularly those with predisposing factors.

Virchows Arch, 1995, 426(3), 301 - 5
Reaction of human lungs to aspirated animal fat (ghee): a clinicopathological study; Annobil SH et al.; We report the clinical findings and pathological lung changes in four children following a cultural practice of forced feeding with animal fat (ghee) during infancy . The clinical presentation was of acute or chronic chest infection which failed to respond to antimicrobial therapy . The radiographic features ranged from extensive bronchopneumonia to collapse/consolidation and bronchiectasis . The light microscopy findings included diffuse mononuclear interstitial pneumonia, intraalveolar desquamation of pneumocytes, lipid granuloma formation, lung atelectasis and bronchiectasis . In the two children with longstanding reactions, the striking feature was the minimal lipid engulfment by the macrophages, the continuation of the mononuclear interstitial pneumonia, bronchiectasis and minimal lung fibrosis . In these two older children, the lung lymphatics were probably the main channels for drainage of the aspirated ghee.

J Biomater Sci Polym Ed, 1995, 6(9), 833 - 44
Degradation behaviour of ionic stepwise polyaddition polymers of medical interest; Ferruti P et al.; The aim of this presentation is to review some of our recent work mostly on poly(amidoamine)s (PAAs) and some other families of polymers structurally related to PAAs of medical interest . PAAs are obtained by stepwise polyaddition of primary monoamines, or bis secondary amines, to bisacrylamides . There are several other ter-amino polymers structurally related to PAAs, such poly(amido phosphine)s (PAPs), poly(ester-amine)s (PEAs), poly(ketone-amine)s (PKAs), poly(amidothioeteramine)s (PATAs) poly(esterthioether amine)s (PTEAs), and poly(sulphone thioetheramine)s (PSTAs) . Most of the PAAs exhibit heparin complexing ability . PAAs are also being considered as soluble carriers for delivering anti-cancer drugs . Some of these polymers have been studied as antimicrobial agents . PAAs with different structures degrade at different rates under physiological conditions . The degradation rate is also strongly influenced by pH . The quaternarized PATAs and PTEAs are reasonably stable over a period of some days, but ultimately degrade to oligomeric products, while the quaternized PAAs do rapidly degrade.

J Antimicrob Chemother, 1995 Jan, 35(1), 31 - 52
Assessment of therapeutic potential by means of a probability model of antimicrobial action; Schalkowsky S et al.; The probability model of antimicrobial action is based on the definition of bactericidal activity as the probability, q, that any cell in the population will be killed during a division interval . Bacteriostatic activity is defined as a change in the division intervals (generation times) of the cells . A simplified, homogeneous model is used which assumes that, at a constant concentration of the drug, all cells have the same kill probability and the same generation times . Birth-death analysis techniques require that the combined bacteriostatic and bactericidal effects of the drug (they are not mutually exclusive) are accounted for . Moreover, to suitably reflect the combined effect, the rate of change of the viable population, i.e . the slope of a kill curve (activity), needs to be expressed not in terms of exposure time, but in units of drug-free generations (DFGs), obtained by dividing exposure time by a measured DFG time interval (growth rate) . A Discrete MIC (DMIC) is defined as the zero slope kill curve, coinciding with the horizontal axis and dividing population change into a restrained (subinhibitory) growth region, below the DMIC, and population reduction above it . At the DMIC, the probability of a cell being killed is 0.5, resulting in no change from the initial inoculum concentration, since half the cells are killed but the remaining cells double . The DMIC is found to be a measure of bactericidal activity only, even though bacteriostatic activity may also be present . An antibiotic-organism activity profile includes measurement of the DMIC, rate of change of activity at the DMIC and normalized activity at a number of clinically relevant drug concentrations . An overall, quantitative efficacy value over a dosing interval can be obtained from the activity profile and expressed as the number of DFGs which are needed to achieve a 99.9% reduction of the viable population at the site of infection . These reference efficacy values can be used to derive interpretive standards (break-points) based upon a quantitative relationship between laboratory measurements and population reduction at the site of infection . Model-derived measures of efficacy also provide a basis for assessing drug combination activity, including quantitative criteria of synergy and antagonism.

J Antimicrob Chemother, 1995 Jan, 35(1), 149 - 54
Heat stability of the antimicrobial activity of sixty-two antibacterial agents; Traub WH et al.; Sixty-two antimicrobial agents, including several combinations, were examined for stability at 56 degrees C for 30 min and 121 degrees C for 15 min, respectively . A microtiter broth dilution MIC test and an agar disk diffusion test served to test each chemo-agent for residual antimicrobial activity . Eleven drugs were partially heat-labile (MICs raised four- to eight-fold after autoclaving) and 26 drugs were heat-labile (MICs raised > or = 16-fold following autoclaving); the remainder proved heat-stable (MICs raised < or = two-fold after autoclaving) . Surprisingly, the beta-lactams, azlocillin, aztreonam, mezlocillin, and oxacillin, were remarkably heat-stable.

J Ind Microbiol, 1995 Jan, 14(1), 41 - 5
Fungal colonization of air filters for use in heating, ventilating, and air conditioning (HVAC) systems; Simmons RB et al.; New and used cellulosic air filters for HVAC systems including those treated with antimicrobials were suspended in vessels with a range of relative humidities (55-99%) and containing non-sterile potting soil which stimulates fungal growth . Most filters yielded fungi prior to suspension in the chambers but only two of 14 nontreated filters demonstrated fungal colonization following use in HVAC systems . Filters treated with antimicrobials, particularly a phosphated amine complex, demonstrated markedly less fungal colonization than nontreated filters . In comparison with nontreated cellulosic filters, fungal colonization of antimicrobial-treated cellulosic filters was selective and delayed.

Lett Appl Microbiol, 1995 Jan, 20(1), 14 - 8
Antifungal effects of Allium sativum (garlic) extract against the Aspergillus species involved in otomycosis; Pai ST et al.; Otomycosis due to saprophytic keratolytic fungi represents a small percentage of clinical external otitis . Although there are certain antibacterial and antifungal agents available, they usually are very caustic, potentially ototoxic and cannot be used if the ear drum is perforated . Garlic is utilized as a folk medicine in many countries for its antimicrobial and other beneficial properties . In response to a lack of otic preparations, the authors studied the efficacy of garlic extracts against the fungi belonging to the genus Aspergillus which are the most common cause of this infection . Aqueous garlic extract (AGE) and concentrated garlic oil (CGO) along with various commercial garlic supplements and pharmaceutical prescriptions were used in an in-vitro study . AGE and especially CGO were found to have antifungal activity . These agents showed similar or better inhibitory effects than the pharmaceutical preparations and demonstrated similar minimum inhibitory concentrations.

Ann Pharm Fr, 1995, 53(2), 86 - 9
{Limiting tests of benzyle halides or heavy alkyles in tensioactive and antimicrobial quaternary ammonium salts}; Willemot J; As working material at the final stage of the synthesis of tensioactive and antimicrobial quaternary ammoniums salts, the alcoyles halides residuums have been let aside . The author developed limiting tests about these impurities particularly on the benzododecinium bromide . Four alternative methods are thus proposed.

Am J Surg Pathol, 1995, 19 Suppl 1, S37 - 43
Helicobacter pylori and gastric carcinogenesis; Correa P; Recent epidemiologic evidence indicates that Helicobacter pylori infection increases the risk for gastric carcinoma . Infection with H . pylori leads to chronic gastritis, which usually persists for life unless treated with antimicrobial drugs . Because the great majority of gastritis patients never develop neoplasias, research concerning those who do may provide clues about carcinogenesis . In affluent populations, H . pylori infection leads to nonatrophic gastritis, predominantly involving diffusely the antrum (diffuse antral gastritis), the basic lesion seen in patients with duodenal ulcer, which has not been associated with increased risk for gastric carcinomas . In populations with high gastric cancer risk, H . pylori infection is associated with multifocal atrophic gastritis, which frequently advances to intestinal metaplasia, occasionally to dysplasia, and rarely to carcinoma . H . pylori infection increases the rate of proliferation of the gastric epithelial cells and decreases the gastric secretion of ascorbic acid, processes that may modulate the process of carcinogenesis . Infection with H . pylori is characterized by infiltration of lymphocytes, polymorphonuclear leukocytes, and macrophages in the gastric mucosa . There is considerable interest in investigating oxygen radicals originating in white blood cells and the possibility that they induce mutations with carcinogenic potential in the gastric epithelium.

Pharmacotherapy, 1995 Jan-Feb, 15(1 Pt 2), 9S - 14S
Bacterial resistance mechanisms to beta-lactam antibiotics: assessment of management strategies; Dudley M; Several mechanisms render antimicrobials inactive; one of these, beta-lactamase hydrolysis of beta-lactam antimicrobials, is a common and serious problem resulting in loss of antimicrobial activity . Resistance in gram-negative organisms may be caused by chromosomally or plasmid-mediated beta-lactamases . Chromosomally mediated resistance may result from exposure to inducer compounds (induction) or by selection of stably derepressed mutants . Plasmids are extrachromosomal elements of DNA that can transfer resistance between bacteria . Common plasmid-encoded beta-lactamases are the TEM- and SHV-type enzymes, which include the newer extended-spectrum beta-lactamases . Infections caused by resistant bacteria frequently result in longer hospital stays, higher mortality, and increased cost of treatment . When bacteria develop resistance during antimicrobial therapy, therapeutic failure ensues in approximately 50% of patients . Clinical studies demonstrate that resistance mediated by beta-lactamases is a critical issue . Strategies for overcoming it include use of beta-lactam-beta-lactamase inhibitor combinations, development of new antimicrobial compounds, and use of regimens that optimize in vivo exposure to drug.

Pharmacotherapy, 1995 Jan-Feb, 15(1 Pt 2), 22S - 26S
Rationale and experience in treating suspected hospital-based mixed infections; Billeter M; Ochsner Foundation Hospital of the Ochsner Medical Institutions (OMI), a 532-bed tertiary care facility in New Orleans, uses a formulary review process common to many institutions . Considered in the selection of antimicrobial therapy are efficacy, safety, and cost . At OMI, ticarcillin-clavulanate plus gentamicin are the standard broad-spectrum antimicrobial agents for initial treatment of suspected mixed infections . The pharmacy department provides an aminoglycoside-monitoring program and convenient dosing guidelines . The regimen has resulted in good therapeutic outcomes and few adverse effects . Bacterial resistance has not been detected . Future plans include a large-scale concurrent review of patient outcomes, resistance patterns, and rates of fungal overgrowth associated with these agents.

Minerva Med, 1995 Jan-Feb, 86(1-2), 21 - 32
{Antimicrobial and sporicidal efficacy of various disinfectant solutions}; Gismondo MR et al.; The often indiscriminate use of antimicrobial agents has led to increased bacterial resistance over the past years . This phenomenon is above all evident in nosocomial environments but also at a community level . It is therefore important that, in addition to the rational use of antibiotics, an accurate prophylaxis is performed which includes the correct use of disinfectants . This study examines the antimicrobial activity of various commercially available disinfectant solutions consisting of one or more active ingredients . An analysis of the results reveals that products consisting of an association of individual components (quaternary ammonium chloride with o-phenylphenol and/or isopropyl alcohol; chlorhexidine with benzalkonium chloride or with diazolidinylurea and isopropanol) demonstrate a greater efficacy in terms of microbicidal concentration and contact times.

Kansenshogaku Zasshi, 1995 Jan, 69(1), 45 - 53
{Long-term monitoring of female acute uncomplicated cystitis cases after lomefloxacin single-dose therapy}; Hirose T et al.; Female acute uncomplicated cystitis responds relatively well to antimicrobial chemotherapy, but this is also a disease which shows a high frequency of recurrence . However, there have been no published reports regarding long-term monitoring of the course of this disease after therapy has been administered . Accordingly, using primarily a questionnaire, the authors carried out long-term monitoring (for a mean of 242 days) of the natural course of cases of female acute uncomplicated cystitis after single-dose therapy with lomefloxacin (LFLX), a new quinolone antimicrobial agent . The subjects of this study were female patients diagnosed as having acute uncomplicated cystitis with pain upon urination, pyuria (> or = 10 WBCs/hpf) and bacteriuria (> or = 10(4) cfu/ml) . LFLX was orally administered as a single dose of 100 mg or 300 mg, and the therapeutic efficacy was evaluated on the 3rd and 7th days thereafter . In principle, the evaluation of cure was performed on the 7th day after LFLX administration, and monitoring was conducted to detect early recurrence during the next 7 days (i.e., through the 14th day after treatment) . Then the subjects were monitored for late recurrence during a mean follow-up period of 242 days by means of a questionnaire . Confirmation of recurrence was carried out to the greatest extent possible . It was possible to carry out long-term monitoring of the natural course of 101 cases of female acute uncomplicated cystitis in which the clinical efficacy on the 3rd day after LFLX treatment had been evaluated as good or excellent.(ABSTRACT TRUNCATED AT 250 WORDS)

Kansenshogaku Zasshi, 1995 Jan, 69(1), 1 - 6
{Epidemiological study for comparative biological profiles on MRSA strains isolated in 1992 vs . 1993}; Ishikawa K et al.; The trend of epidemiological study against MRSA strains which were isolated in 1992 and in 1993 was investigated . Number of stains tested yearly consisted of 30 isolates that were considered to play pathogenic roles for inpatients in clinical departments at our institute . In comparing with biological studies on MRSA strains and the epidemiological surveillance of the background of the isolation, the data summarizes as followings; 1) No . of MRSA strains which were producible for TSST increased from 24/30, 80% up to 30/30, 100% . 2) No . of enterotoxin type harbouring biotype of B/C increased 0/30, 0% up to 12/30, 40% . 3) No . of type of plasmid DNA profile increased in varying from 3 types (A, B, C) to 8 types (A-H) . 4) The in vitro activity of antimicrobials, as such MINO, GM, IPM, CMZ was less potent than that of the prior year, and even for VCM, ABK, the activity proved less potent in 1-2 tubes in MIC90 . 5) No . significant hospital acquired infection was detected between the inpatients, with MRSA infection and isolates from plasmid DNA profiles . 6) Since the ratio of the coincidence of plasmid DNA profiles of MRSA was only in 4 patients out of 27, 14.9 &, nosocomial infections with MRSA brought to patients have not only been considered by medical, paramedical staff, but that the infection may be caused by broad contamination at the institute.

J Ethnopharmacol, 1995 Jan, 45(1), 71 - 4
Comparative antimicrobial study of the resinous exudates of some Chilean Haplopappus (Asteraceae); Urzua A et al.; The antimicrobiol properties and preliminary chemical information of the resinous exudates from twigs and leaves of nine Haplopappus species from Chile: H . diplopappus; H . anthylloides; H . schumannii; H . cuneifolius; H . velutinus; H . uncinatus; H . multifolius, H . illinitus and H . foliosus are presented . The results show that those species of genus Haplopappus share similar antimicrobial activities although they differ dramatically in the chemical composition.

Am J Nephrol, 1995, 15(2), 152 - 6
Penectomy in diabetic patients undergoing maintenance dialysis; Bali I et al.; Penectomy was performed to sustain life in 2 patients with insulin-dependent and non-insulin-dependent diabetes mellitus, respectively, who were undergoing maintenance hemodialysis . Both patients previously had manifested a series of serious macro- and microvascular diabetic complications . The histopathologic findings in both cases included gangrenous necrosis of penile tissue, while case 2 also evinced calcification of penile arteries . Penectomy has been reported as the result of penile malignancy, anticoagulant toxicity, self-inflicted injury, and criminal assault . Other reports document penectomies attributed to perineal infection (Fournier's syndrome) in diabetic patients with uremia . In five previously reported cases of penectomy in diabetic patients undergoing dialysis, systemwide arteriopathy was present in all . There is an association between uremia in diabetics and predisposition to an ischemic-infectious lesion of the penis that fails to respond to antimicrobial therapy.

Urol Nefrol (Mosk), 1995 Jan-Feb, (1), 16 - 8
{The phagocytic test in the assessment of antimicrobial protection in inflammatory urologic diseases}; Kuznetsov VF et al.; As shown in in vitro original modelling of red cell action on phagocytic process in the whole blood of patients with urological inflammation, these patients have increased count of neutrophils involved in phagocytosis, but low specific absorption of these neutrophils due to red cells . In chronic renal insufficiency characterized by a low phagocytic activity of neutrophils only stimulating potential of red cells can be noted.

Mikrobiol Z, 1995 Jan-Feb, 57(1), 102 - 10
{Ionizing radiations and the antimicrobial resistance of the body in warm-blooded animals}; Rudenko AV et al.; Various aspects of ionizing radiation action on microorganisms and course of endo- and exogenous infections are considered . The immune response is discussed from the standpoint of its significance in development of infectious-inflammatory processes under conditions of radiation of a microorganism and higher radiation background . Quantitative and functional changes in the immune system of the organism subjected to radiation are discussed in detail and peculiarities of these changes under low doses of radiation are shown . The analysis of the data obtained has confirmed a decrease of the natural resistance of organism to various infectious agents of endo- and exogenous origin under the effect of ionizing radiation; the main reason of that is disturbance of the immunity system, particularly at the cellular level.

Clin Infect Dis, 1995 Jan, 20(1), 73 - 6
Isolation of nontuberculous, non-avium mycobacteria from patients infected with human immunodeficiency virus; Raszka WV Jr et al.; Mycobacterium avium serovars account for 97% of typeable M . avium complex (MAC) organisms causing infection in patients with AIDS . We reviewed 216 consecutive cultures that yielded nontuberculous mycobacteria (NTM) from 212 patients . Only the first isolate of each species of NTM recovered from each patient was analyzed in the study . Among the 92 patients infected with the human immunodeficiency virus, 96 NTM organisms were identified; M . avium was recovered from 50 (77%) of the 65 NTM-positive cultures of blood or bone marrow, while Mycobacterium intracellular and other non-avium NTM accounted for 18% and 5% of the isolates, respectively . Little difference in the susceptibility of isolates to antibiotics was noted between HIV-positive and HIV-negative patients or between M . avium and M . intracellulare . These data demonstrate that HIV-positive patients develop disseminated disease with NTM other than M . avium more frequently than has been previously reported and that these patients do not appear to be infected with NTM that are more resistant to antimicrobial agents than are NTM isolated from HIV-negative patients.

Clin Infect Dis, 1995 Jan, 20(1), 47 - 51
Successful treatment of New World cutaneous leishmaniasis with a combination of topical paromomycin/methylbenzethonium chloride and injectable meglumine antimonate; Soto J et al.; Colombian patients with New World cutaneous leishmaniasis were treated with a combination of a topical formulation (15% paromomycin sulfate/5% methylbenzethonium chloride, twice a day) and parenteral meglumine antimonate (20 mg of antimony {Sb}/kg.d}) . Cohort 1 received topical therapy for 10 days and Sb for 7 days; 18 (90%) of the 20 patients were cured (follow-up, 12 months) . Other clinical data suggested that neither the topical formulation alone nor the 7-day regimen of Sb alone would have cured many patients . In a subsequent cohort, which received topical therapy for 10 days and Sb for 3 days, the cure rate was 42% (eight of 19 patients) . In Colombian cohorts (historical controls) treated with Sb alone for 10-15 days, the cure rate was 31%-36% . Side effects in cohort 1 patients consisted of local reactions to the topical formulation: burning and pruritis in 25% of patients and vesicle formation in 15% of patients . This is the first report that a regimen partially composed of topical antimicrobial agents can be highly effective for treatment of New World cutaneous leishmaniasis.

Eur J Surg, 1995 Jan, 161(1), 23 - 7
Biochemical analysis of peritoneal fluid in patients with and without bacterial infection; Simmen HP et al.; OBJECTIVE: To find out if the concentrations of biochemical variables in peritoneal fluid differed in the presence or absence of infection . DESIGN: Prospective study . SETTING: University hospital, Switzerland . SUBJECTS: 80 patients undergoing abdominal operations, 23 of whom were operated on for an intra-abdominal infection . 57 Patients with no sign of infection served as controls . MAIN OUTCOME MEASURES: Concentrations of 24 biochemical variables measured in specimens of peritoneal fluid obtained during the operation . RESULTS: Major differences between specimens taken from infected and uninfected patients including: glucose 5.4 compared with 0.8 mmol/l, lactate 7.9 and 17.2 mmol/l, aspartate aminotransferase 83 and 520 U/l, phosphate 1.1 and 3.7 mmol/l, potassium 4.5 and 10.1 mmol/l, lactate dehydrogenase 2021 and 7998 U/l, and gamma-glutamyl transferase 57 and 169 U/l . CONCLUSION: Intra-abdominal infection significantly alters the composition of peritoneal fluid . The assessment of milieu factors at the site of infection may help in the design of more predictive in vitro tests to guide antimicrobial treatment of intra-abdominal infections . In addition, the knowledge of discriminatory variables in peritoneal fluid may be useful in the diagnosis of intra-abdominal infection.

J Burn Care Rehabil, 1995 Jan-Feb, 16(1), 86 - 90; discussion 85
Regional and institutional variation in burn care; Fakhry SM et al.; In reviewing the literature on burn therapy and observing clinical burn care, we noted differences among institutions and individual experts in several areas . To study variation in burn care, we surveyed the 140 burn centers listed by the American Burn Association to determine how burn care is currently administered in the United States and Canada . Responses were obtained from 83 hospitals (60%) . The survey addressed resuscitation, operative and nonoperative wound care, medications, antimicrobial agents, and pain control . The major influence on care appeared to be the experience of the director (considered "very influential" in 85%) compared with the literature ("very influential" in 12%) and habit/what works for us ("very influential" in 48%) . The Parkland formula was used "always" or "often" by 78%, and the Brooke formula "never" by 81% of respondents . Lactated Ringer's solution was the most popular initial fluid, and most (78%) respondents changed fluids after 24 hours . However, the fluids used in the second 24 hours varied equally among several choices . The use of colloids also varied without a set pattern . Furosemide (Lasix) and nonsteroidal antiinflammatory drugs were used "rarely" or "never" by 67% of centers in the acute stage . H2 blockers were used for gastritis prophylaxis "always" or "often" in 60% (vs 53% for antacids and 20% for sucralfate {Carafate}) . Tube feedings were started on day 1 after burn injury "always" by less than 30% of centers . Total parenteral nutrition was not commonly used . Most centers use of silver sulfadiazine on the body and hands, but facial topical antimicrobial therapy varied.(ABSTRACT TRUNCATED AT 250 WORDS)

Trends Microbiol, 1995 Jan, 3(1), 27 - 31
Determinants of cell entry and intracellular survival of Mycobacterium tuberculosis; Riley LW; The ability of Mycobacterium tuberculosis to sustain a chronic infection and cause disease in a subset of those infected depends on its products--virulence factors--that enable the organism to enter and survive indefinitely inside mononuclear phagocytic cells by subverting cellular antimicrobial mechanisms . Characterizing these factors is essential to understanding the pathogenesis of M . tuberculosis.

Eye, 1995, 9 ( Pt 1), 110 - 5
Toxicity of antibiotics and antifungals on cultured human corneal cells: effect of mixing, exposure and concentration; Berry M et al.; Toxic effects of topical drugs may be masked by manifestations of the disease they cure . The toxicity of drug mixtures has not been thoroughly studied . We therefore investigated cytopathic effects on primary cultures of human corneal cells of six topical antimicrobials singly and in combinations of any two, to determine the combined toxicity ranking and the interaction between duration of exposure and concentration . Preconfluent cultures were exposed to fixed dilutions of single drugs, or to equal-dilution mixtures of two drugs, for 7 and 14 days . Diminishing concentrations of single drugs were applied sequentially to cultures for 14 days . The number of metabolically competent cells was assessed by measuring hexosaminidase and total protein . Toxic effects depended on substance, concentration and exposure . The scale of toxicity determined for single drugs after 7 days of exposure was: gentamicin > econazole > or = methicillin > or = clotrimazole > or = miconazole > or = chloramphenicol . After 14 days this order changed: in particular chloramphenicol showed a highly increased toxicity . The order of diminishing effects was: gentamicin > chloramphenicol > or = methicillin > miconazole > econazole > clotrimazole . A clear reduction in cytopathic effects was observed when drug concentration was decreased progressively only in cultures treated with gentamicin or methicillin . All drug combinations were more toxic than their components at equal dilution . Combinations containing chloramphenicol ranked most toxic overall, those containing econazole least . A tapering off combination regime did not improve cell survival . These in vitro toxicity data complement clinical studies and suggest ways in which topical drugs can be chosen to minimise toxic effects to corneal surface.

J Clin Periodontol, 1995 Jan, 22(1), 22 - 35
Tetracyclines in the management of periodontal diseases . A review; Seymour RA et al.; Periodontal diseases essentially comprise a group of oral infections whose primary aetiological factor is dental plaque . Removal of the cause (and its effects) is the primary aim of both non-surgical and surgical treatment regimens, although the infective nature of the diseases has led to the widespread use of antimicrobials as an adjunct to mechanical debridement . The tetracyclines are primarily bacteriostatic agents that are effective against many Gram-negative species including putative periodontopathogens such as Actinobacillus actinomycetemcomitans (A.a.) . The proven efficacy of this group of drugs in the management of periodontal diseases may be related not only to their antibacterial actions, but to a number of additional properties that have been recently identified . These include collagenase inhibition, anti-inflammatory actions, inhibition of bone resorption and their ability to promote the attachment of fibroblasts to root surfaces . Consequently, tetracyclines have also been used as an adjunct to bone grafting in periodontal defects, and as agents for 'conditioning' root surfaces to enhance the regeneration of periodontal tissues . When tetracyclines are taken orally, consideration must be given both to the potential unwanted effects and to interactions with other drugs that are taken concurrently . Such problems are minimised however, when the drugs are incorporated into controlled, slow-release formulations which are currently being researched and marketed for intra-oral use.

Farmaco, 1995 Jan, 50(1), 73 - 6
New thioxopyrimidines . Synthesis and evaluation for antimicrobial activity; Cocco MT et al.; A convenient and simple synthesis of some new thioxopyrimidines was developed starting from 3-amino-3-(dialkylamino)propenethioamide derivatives . The prepared compounds were assayed in vitro for antimicrobial activity and found practically inactive.

Farmaco, 1995 Jan, 50(1), 69 - 72
Synthesis of some 4H-pyrido{1,2-a}pyrimidin-4-ones investigated as antimicrobial agents; Ferrarini PL et al.; Synthesis of some 4H-pyrido{1,2-a}pyrimidin-4-ones and assay of their antibacterial and antifungal activity are reported . Compounds 3a-e,g were prepared by reaction of substituted 2-chloromethyl-4H-pyrido{1,2-a}pyrimidin-4-ones 2a-c with suitable amines . These compounds and the previously obtained analogues 5a-o and 6a,b have been tested for their antimicrobial activity . All tested compounds were devoid of antimicrobial activity.

Vet Surg, 1995 Jan-Feb, 24(1), 32 - 5
A one-stage marsupialization procedure for management of infected umbilical vein remnants in calves and foals; Edwards RB 3rd et al.; Five Holstein calves and two foals with omphalophlebitis were treated by surgical marsupialization of the umbilical vein remnant because complete resection of the infected tract was not possible . The infected umbilical stalk was resected, and the umbilical vein remnant was marsupialized in a one-stage procedure by suturing it into the abdominal wall lateral to the abdominal incision . Antimicrobial drugs were administered, and the marsupialized tract was irrigated until closure by second intention healing . Cellulitis associated with the marsupialization site occurred in two calves but resolved with antimicrobial therapy . Owners reported that, 9 to 60 months after surgery, there were no complications associated with the procedure.

J Clin Microbiol, 1995 Jan, 33(1), 188 - 92
Primary identification of Microbacterium spp . encountered in clinical specimens as CDC coryneform group A-4 and A-5 bacteria; Funke G et al.; Over nearly two decades, 13 yellow- or orange-pigmented, fermentative gram-positive rods belonging to the genus Microbacterium were encountered in clinical specimens . All 13 strains, 10 of which came from blood cultures, were initially identified as CDC coryneform group A-4 and A-5 bacteria according to the scheme of Hollis and Weaver for the identification of gram-positive rods . The clinical isolates were compared with the type strains of the six species constituting the genus Microbacterium as well as with three Microbacterium strains isolated from hospital environments . By biochemical methods only 5 of 13 clinical isolates could be identified to species level . Peptidoglycan analysis proved to be a valuable tool for differentiation between Microbacterium spp . and related genera, whereas cellular fatty acid analysis did not allow species identification within the genus Microbacterium . The 22 Microbacterium strains studied were, in general, susceptible to antimicrobial agents used in the treatment of infections caused by gram-positive rods . This report is the first one concerning the isolation of Microbacterium strains from clinical specimens . The sources as well as the mode of transmission remain to be established.

Antimicrob Agents Chemother, 1995 Jan, 39(1), 50 - 5
Long-chain alkanoylcholines, a new category of soft antimicrobial agents that are enzymatically degradable; Ahlstrom B et al.; A new category of amphiphilic hydrolyzable quaternary ammonium compounds with rapid and high levels of antimicrobial activity was studied . The compounds, alkanoylcholines with hydrocarbon chains of 10 to 14 carbon atoms, are hydrolyzed by butyrylcholine esterase, which is present in human serum and mucosal membranes . The hydrolysis products are common components of human metabolism . Alkanoylcholines were tested and found to be active against gram-negative and gram-positive bacteria as well as yeasts . The microbicidal activities of the alkanoylcholines were comparable to the activities of the stable quaternary ammonium compounds of corresponding chain length and increased with an increasing number of carbon atoms . The compounds were also found to be hydrolyzed by enzymes present in certain microorganisms . The degradation was achieved after reaching the microbicidal effect.

Am J Vet Res, 1995 Jan, 56(1), 70 - 7
Potential for oxytetracycline administration by three routes to cause milk residues in lactating cows, as detected by radioimmunoassay (Charm II) and high-performance liquid chromatography test methods; Anderson KL et al.; Milk antimicrobial residues are a serious concern for the dairy industry . Residues of the tetracycline family of antimicrobials have been reported in market milk by investigators, using radioimmunoassay and microbial receptor technology (hereafter referred to as the Charm II test) . In response to these reports, an investigation was conducted to determine the potential of 3 extra-label routes of oxytetracycline (OTC) administration to cause milk residues above the Food and Drug Administration safe value of 30 parts per billion (ppb) . Lactating Holstein cows were administered OTC once by use of 1 of 3 routes: IV at 16.5 mg/kg of body weight (n = 6); IM at 11 mg/kg (n = 6); and intrauterine (IU) at 2 g in 500 ml of saline solution/cow (n = 6) . Duplicate milk samples were collected at the milking prior to drug administration and for the next 13 milkings at 12-hour intervals . Concentrations of OTC in milk samples were analyzed by use of the Charm II tes for tetracyclines (limit of OTC detection, approx 5 ppb) and were compared with concentrations determined by use of a high-performance liquid chromatography (HPLC) method (lower limit of OTC quantitation, approx 2 ppb) . The potential for milk OTC residues above the Food and Drug Administration safe value of 30 ppb after treatment was considerably greater for the IV and IM routes, compared with the IU route.(ABSTRACT TRUNCATED AT 250 WORDS)

Rev Belge Med Dent, 1995, 50(1), 34 - 45
{Dental care and prevention of infectious endocarditis}; Peetermans WE et al.; Infective endocarditis causes substantial morbidity and mortality despite adequate antimicrobial, medical and surgical treatment . The rationale for antibiotic prophylaxis against endocarditis is derived from the etiology and pathogenesis of the disease . Endocarditis usually follows bacteremia with certain endocarditis-prone bacteria in a patient with a predisposing heart condition . Protection by antibiotic prophylaxis is estimated to reach only 50% for a lot of reasons (transient bacteremia without dental or surgical intervention, predisposing heart disease not diagnosed previously, etc) . Most authorities in the field of infective endocarditis strongly advocate the use of antibiotic prophylaxis for patients at risk . Clear guidelines are published by various highly qualified scientific committees . Recent schemes allow orally administered antibiotic prophylaxis because of a better doctor and patient compliance.

J Clin Gastroenterol, 1995, 20 Suppl 1, S32 - 7
Antibacterial properties of lansoprazole alone and in combination with antimicrobial agents against Helicobacter pylori; Nakao M; The activities of various types of anti-ulcer agents against Helicobacter pylori (Hp) strains were determined using an agar dilution method . Among the compounds tested, proton pump inhibitors were found to exhibit significant activity against this organism . The activity of lansoprazole was four times more potent than that of omeprazole and bismuth subsalicylate, with MICs ranging from 1.56 to 25 micrograms/ml . Exposure of Hp to lansoprazole led to extensive loss of viability and suppression of virulence factors such as motility, adhesiveness to epithelial cells, and urease activity . Lansoprazole produced aberrant bacterial morphology characterized by elongation and constriction of the cells and collapse of cell surface structures . The combination of lansoprazole with antimicrobial agents such as penicillins, cephalosporins, macrolides, tetracyclines, aminoglycosides, quinolones, and metronidazole produced an additive or synergistic growth inhibition of Hp.

J Clin Gastroenterol, 1995, 20 Suppl 1, S24 - 7
Adjuvant therapy for Helicobacter pylori eradication: role of lansoprazole shown in vitro; Megraud F; The recognition of Helicobacter pylori (H . pylori) as a major cause of gastroduodenal diseases has led to the use of antibiotics to treat these diseases . However, antibiotics used alone are not very effective, and adjuvant therapy is required . The most potent adjuvant therapy consists of increasing the stomach pH with proton pump inhibitors (PPIs) . In addition to this action on stomach pH, PPIs, and especially lansoprazole, have been found to have antimicrobial activity against H . pylori . At high concentrations, they are even bactericidal . Furthermore, they can inhibit H . pylori urease activity . These properties, as well as their antisecretory activity, provide the grounds for their use in eradication of H . pylori.

Med Tr Prom Ekol, 1995, (5), 42 - 4
{The use of individual protective devices for decreasing the microbial contamination of the inhaled air}; Sedov AV et al.; The work was aimed to justify application of gas masks and respirators with autonomous air source fo lower bacterial contamination of inhaled air . The studies also covered possible catch of bacteria by cotton and filters FPP-15-1.5, those composed of antimicrobial materials, containing furagin or copper ions . As the studies proved, for lower bacterial contaminations of inhaled air one can apply autonomous air source apparatus with filters made of Petrianov tissue, antimicrobial tissue (containing furagin or copper ions), as they reduce fungal content of the air . Such filters are self-disinfecting, but do not influence total contamination of the air.

Nat Toxins, 1995, 3(3), 166 - 73
Studies on structure-activity relationship of seiridins, phytotoxins, produced by three species of Seiridium; Sparapano L et al.; The phytotoxins seiridin (SEI) and iso-seiridin (ISE), two delta alpha,beta-butenolides produced in vitro by Seiridium cardinale, S . cupressi, and S . unicorne, as well as their derivatives obtained by chemical modification of each toxin, were analyzed for their bioactivity . The effects each compound on host and non-host plants and their antimicrobial activity on bacteria were investigated . The toxicity of both seiridins (SEIs) decreased in the derivatives with modifications of the gamma-lactone ring or with acetylation of the hydroxy group of the aliphatic side chain at C-4 . Shoot tissues of Cupressus macrocarpa artificially infected by S . cardinale leached electrolytes more than those of C . sempervirens and C . arizonica . Electrolyte loss from shoot tissues of cypress plants treated with each derivative also decreased for most of them . Seed germination was not affected by SEI and ISE derivatives . Inhibition of root growth of three herbaceous test plants was studied . SEI and 3,4-dihydro SEI were active to germlings of lettuce . No ISE derivative affected root growth of lettuce and oat germlings . Reduction was observed on roots of radish germlings treated with acetyl ISE or 3,4-dihydro ISE . No derivative of SEI or ISE elicited hormone-like activity as SEI did . Antibacterial activity shown by SEI and ISE at 150 microM accounted for both hydrogenated derivatives of SEI . The integrity of the delta alpha,beta-unsaturated-gamma-lactone ring and the location of the hydroxy group in the heptyl side chain are features of importance in biological activity of the two butenolides.

Crit Rev Biotechnol, 1995, 15(2), 139 - 77
Solvent selection for whole cell biotransformations in organic media; Salter GJ et al.; Although they were used historically as antimicrobial agents, there is a modern requirement to devise organic solvent systems for exploitation in the biotransformation by intact cells of substrates that are poorly soluble in water . Water-immiscible solvents are normally less cytotoxic than are water-miscible ones . While a unitary mechanism is excluded, damage to the membrane remains the likeliest major mechanism of cytotoxicity, and may be conveniently assessed using an electronic biomass probe . Studies designed to account for the mechanisms of action of general anesthetics and of uncouplers parallel those designed to account for the cytotoxicity of organic solvents . Although there are hundreds of potential physical descriptors of solvent properties, many are broadly similar to each other, such that the intrinsic dimensionality of solvent space is relatively small (< 10) . This opens up the possibility of providing a rational biophysical basis for the optimization of the solvents used for biotransformations . The widely used descriptor of solvent behavior, log P (the octanol:water partition coefficient), is a composite of more fundamental molecular descriptors; this explains why there are rarely good correlations between cytotoxicity and log P when a wide variety of solvents is studied . Although the intrinsic dimensionality of solvent space is relatively small, pure solvents still populate it rather sparsely . Thus, mixtures of solvents can and do provide the opportunity of obtaining a solvent optimal for a biotransformation of interest.

Curr Top Microbiol Immunol, 1995, 196, 19 - 36
S-nitrosothiols and the bioregulatory actions of nitrogen oxides through reactions with thiol groups; Stamler JS; The reactivity of selected RS-NOs has led to the misconception that these compounds are uniformly unstable under physiological conditions . Moreover, current evidence supports the notion that biological responses elicited by RS-NOs may result from either liberation of nitric oxide or from NO group transfer chemistry involving either NO+ or NO- . Some evidence suggests that such reactions may be enzymatically controlled . The data supporting the potential biological relevance of RS-NOs include: (1) evidence that these compounds form under physiological conditions; (2) their identification in insects, lower mammals, and several human biological systems; and (3) findings that RS-NOs possess a wide range of biological activities, including antimicrobial effects, vasodilation, platelet inhibition, bronchodilation and inhibition of intestinal motility, while being relatively resistant to reactions with O2 and O2- associated with NO . toxicity . It is further noteworthy that biological activity of RS-NO is often not related to the propensity to liberate NO., and these adducts are generally more potent and selective in their action than NO . itself (Stamler et al . 1989; Cooke et al . 1990; Rockett et al . 1991; Jansen et al . 1991; Lipton et al . 1993) . The data presented here support the idea that RS-NO may be involved in stabilizing nitric oxide-like bioactivity, in transporting and targeting the NO group to specific (thioregulatory) effector sites, in mitigating the cytotoxic effects of nitric oxide that result from reaction with oxygen species, and may serve to regulate protein function in a posttranslational modification akin, perhaps, to phosphorylation . The recently demonstrated NO group transfer reactions to plasma membrane proteins containing reactive sulfhydryls (Lipton et al . 1993; Stamler 1994) also raises the possibility of signal transduction initiated through more traditional "agonist-receptor" mediated pathways.

Microbios, 1995, 82(332), 171 - 2
Antimicrobial activity of essences from labiates; Larrondo JV et al.; Bacteria, filamentous fungi and yeasts were subjected to the action of Lavandula officinalis, Melissa officinalis and Rosmarinus officinalis essences in a steam phase, using a microatmospheric technique . Due to the methodology employed, L . officinalis essence was more active in filamentous fungi than the other essential oils studied . All three essences possessed a similar degree of activity against the micro-organisms tested, though a relatively higher activity was seen in the case of M . officinalis.

Retina, 1995, 15(2), 154 - 9
Vitreous cavity penetration of ceftazidime after intravenous administration; Aguilar HE et al.; PURPOSE: Penetration of ceftazidime, a third generation cephalosporin, into the vitreous cavity after intravenous administration was investigated . METHODS: Because antimicrobial penetration varies with surgical status of the eye and with inflammation, studies were conducted in phakic, aphakic, and aphakic, vitrectomized eyes in both normal and inflamed conditions . Ceftazidime 50 mg/kg was administered every 8 hours and vitreous cavity concentrations were tested at intervals from 2 to 72 hours after the initial dose . RESULTS: No penetration was found into control phakic and aphakic eyes, but drug concentrations were detected in inflamed eyes at 24 hours . Vitreous concentrations of ceftazidime in aphakic, vitrectomized eyes reached levels well above the minimal inhibitory concentration (MIC) for Pseudomonas organisms within 2 hours of intravenous administration in control eyes (8.5 micrograms/ml) and inflamed eyes (35.4 micrograms/ml) . Inflammation and removal of the lens and vitreous significantly enhanced ceftazidime penetration at all time periods tested . CONCLUSION: Ceftazidime penetrates into the vitreous cavity of inflamed eyes after intravenous administration and achieves concentrations above the MIC for Pseudomonas organisms . Penetration is greatest in aphakic, vitrectomized eyes.

J Gastroenterol Hepatol, 1995 Jan-Feb, 10(1), 66 - 9
Mucosal pharmacokinetics and pilot study of short course of parenteral imipenem in the eradication of Helicobacter pylori; Sung JJ et al.; Eradication of Helicobacter pylori infection is known to reduce the incidence of duodenal ulcer recurrence . The most commonly used regimen for H . pylori infection is triple antimicrobial therapy for 1-2 weeks . This treatment is associated with frequent side effects and hence unsatisfactory compliance . As in vitro data showed that H . pylori is sensitive to imipenem, the pharmacokinetics of this drug in the gastric milieu, and the clinical efficacy of imipenem with omeprazole in eradicating H . pylori infection were studied . Imipenem/cilastatin levels in serum, gastric secretion and gastric mucosa were assayed in four patients after intravenous injection of a bolus dose of 500 mg . The serum and gastric secretion levels of imipenem achieved were more than 10 times the minimum inhibitory concentration of the drug for H . pylori . Gastric mucosal levels of imipenem vary considerably with time, which probably indicates rapid elimination of the drug into the gastric lumen . In the second part of this study, imipenem/cilastatin was given intravenously for the first 2 days after diagnosis of H . pylori infection in patients with endoscopically confirmed duodenal ulcers . The patients were also treated with 4 weeks of omeprazole . Clearance of H . pylori was initially achieved at the end of 2 days in 20 out of 22 (91%) patients . However, when the biopsies were repeated at 8 weeks, recurrence of H . pylori infection was evident in 19 cases (86.3%) indicating a failure of eradication . It was concluded that imipenem/cilastatin in combination with omeprazole failed to eradicate H . pylori infection.

Wien Med Wochenschr, 1995, 145(7-8), 170 - 3
{Lymphocyte proliferation test in cutaneous manifestations of Lyme borreliosis}; Breier F et al.; The humoral immunoreactivity in Lyme borreliosis is a well characterized parameter for establishing the diagnosis of a Borrelia burgdorferi (Bb) infection . Since patients with seronegative Lyme borreliosis have been described, lymphocyte proliferation tests may be used for detecting patients who only develop a cellular immunoreactivity against Bb organisms . We performed a the lymphocyte proliferation assays in order to determine the cellular immunoreactivity to these spirochetes in given patients with histologically confirmed diagnosis of erythema migrans (EM), acrodermatitis chronica atrophicans (ACA), and for control purposes patients with Lyme disease non associated dermatoses (NLDH) and healthy volunteers (G) . Stimulation index was defined as 3H thymidine-uptake in peripheral mononuclear cells, calculated as quotient dpm (stimulated cells)/dpm (unstimulated cells) (dpm = disintegrations per minute) . Stimulation indices > 10 were considered positive . We detected elevated cellular immunoreactivity of peripheral mononuclear cells in 33% EM-patients (3/9) and in 23% (3/13) ACA patients tested . Patients tested before and after antibiotic therapy showed a significant decrease of stimulation index after antimicrobial treatment (p < 0.05) . Patients the EM, who are mostly seronegative at the onset of cutaneous eruption exhibit in a third of patients an elevated cellular immune response to Bb . Therefore lymphocyte proliferation assays can be recommended as an additional test system in case of lack of serological response . The significant decrease of stimulation index after antimicrobial therapy indicates for downregulation of the cellular immune response to these spirochetes investigated, and counts for the specificity of this test system.

Patol Fiziol Eksp Ter, 1995 Jan-Mar, (1), 23 - 5
{Sensitivity to non-radiation effects in animals examined in the phase of increased radioresistance developed after sublethal irradiation}; Butomo NV et al.; The sensitivity to some non-radiation agents in mice which displayed an increased radioresistance 12 days following sublethal radiation was investigated . The animals demonstrated no enhanced cross-resistance to acute hypoxia, injections of KCN, strychnine, sarcolysine, hexenal . Resistance to typhoid fever endotoxin as well as the indices of nonspecific antimicrobial host defense (NBT-test, segregative activity of RES, white blood cell counts, antibody production ability) were reduced as compared with those of intact mice . The serum corticosterone level was normal.

AIDS Care, 1995, 7(3), 321 - 36
In-patient care for symptomatic, HIV-infected persons: a longitudinal study of hospitalizations, in-patient drug use, and related costs; Dijkgraaf MG et al.; Patterns in the costs of hospital in-patient care and in-patient drug treatment of 121 symptomatic, HIV-infected patients are described for a university hospital between 1987 and 1991 . Trend analyses have been performed on quarterly and yearly data using parametric and non-parametric statistical techniques . During the 5-year study period the demand for hospital beds almost quadrupled despite a constant number of admissions per person-year and a 40% decrease in the average length of stay . The demand for beds was highest in the autumn and winter months . The impact of female and/or heterosexual subgroups on the yearly utilization of resources increased and reasons for hospitalization became more diverse; there were fewer hospitalizations for Pneumocystis carinii pneumonia infection . Antimicrobial drug treatment accounted for the increased drug treatment costs . The implications for AIDS-treating specialists, hospital managers, and scenario analysts are discussed.

Z Naturforsch {C}, 1995 Jan-Feb, 50(1-2), 1 - 9
Kuehneromycins A and B, two new biological active compounds from a Tasmanian Kuehneromyces sp . (Strophariaceae, Basidiomycetes); Erkel G et al.; In a search for new inhibitors of RNA-directed DNA-polymerases kuehneromycin A (1) was isolated from fermentations of a Tasmanian Kuehneromyces species . Its structure was elucidated by spectroscopic methods . Kuehneromycin A (1) is a non-competitive inhibitor of avian myeloblastosis virus (Ki 200 microM) and moloney murine leukemia virus (Ki 40 microM) reverse transcriptases . The second compound, kuehneromycin B (2) is a strong inhibitor of platelet aggregation stimulated with different inducers . In addition, both compounds exhibit cytotoxic and antimicrobial activities.

Immunology, 1995 Jan, 84(1), 135 - 41
Rat, mouse and human neutrophils stimulated by a variety of activating agents produce much less nitrite than rodent macrophages; Padgett EL et al.; The role of reactive nitrogen intermediates (RNI) in the antimicrobial activities of neutrophils from various mammalian species is unclear . However, it has been reported that rodent neutrophils possess the inducible form of nitric oxide synthase and that inflammatory neutrophils from rats produce potentially antimicrobial levels of RNI . In the present study, neutrophils from humans, rats and mice were evaluated for production of nitrite, a stable end-product of RNI . Human neutrophil preparations (> 95% neutrophils) isolated from peripheral blood were stimulated for 2-24 hr with agents known to trigger the Ca(2+)-dependent constitutive nitric oxide synthase, or to stimulate synthesis of the inducible nitric oxide synthase . Superoxide dismutase was added to some cultures to decrease the levels of superoxide, a compound reported to react with RNI and yield products other than nitrite . Even though the cells were viable and responsive to stimuli, they did not produce nitrite concentrations indicative of antimicrobial potential . Preparations of inflammatory (casein-elicited) mouse neutrophils also failed to produce high concentrations of nitrite . Inflammatory rat neutrophils (2.5 x 10(6)/ml) produced nitrite concentrations of approximately 40 microM in 24-hr cultures, but plots of nitrite production versus cell number for neutrophil and macrophage preparations indicated that contaminating macrophages could account for all the nitrite production in the neutrophil preparations . Thus, neutrophils from rats, mice and humans seem comparable in their inability to produce high levels of nitrite in response to a variety of stimuli . This suggests that in most circumstances the constitutive nitric oxide synthase known to be present in these cells is limited to the production of low levels of nitric oxide for intercellular signalling . In addition, this raises questions about the presence or functional status of inducible nitric oxide synthase in rodent neutrophils.

Aliment Pharmacol Ther, 1995, 9 Suppl 1, 39 - 42
No Helicobacter pylori, no Helicobacter pylori-associated peptic ulcer disease; Tytgat GN; Virtually all duodenal ulcers (DUs) and the vast majority of gastric ulcers (GUs) are the consequence of Helicobacter pylori-associated inflammation . In DUs, the inflammation is maximal in the antrum and is associated with gastric metaplasia in the bulb . Gastrin homeostasis is disturbed by H . pylori gastritis and there is robust acid secretion . Successful eradication of the infection cures the ulcer diathesis . Amalgamated figures for ulcer relapse per year in H . pylori-positive DUs are > 60% compared with 2.6% for H . pylori-negative DU patients . The corresponding figures for GU are > 50% for H . pylori-positive and 2.0% for H . pylori-negative individuals . This striking difference in relapse rate persists, as the re-infection rate in the developed world is < 1% per year . Recurrent bleeding in bleeding-prone DUs is essentially abolished after cure of the infection . Proton pump inhibitors (PPIs) are increasingly used in eradication regimens . PPIs have intrinsic antimicrobial activity . MICs for lansoprazole (LAN) are lower than for omeprazole (OME) . Two weeks of triple therapy (bismuth, tetracycline, imidazole) has, on average, a superior eradication efficacy (> or = 90%) compared with dual therapy (PPI, amoxycillin or clarithromycin) (> or = 80%) . When a combination of PPI and two antibiotics has been used, results comparable to triple therapy have been reported . However, the side-effects profile and patient acceptability of PPI plus one or two antibiotic regimens are better than for traditional triple therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Aliment Pharmacol Ther, 1995, 9 Suppl 1, 31 - 7
Unanswered questions about Helicobacter pylori; Walsh JH; There is general agreement that Helicobacter pylori eradication is indicated in all infected patients with duodenal ulcer disease and is probably indicated in all infected patients with gastric ulcer disease . However, translation of treatment recommendations into practice leads to some difficult clinical decisions . Three of the more perplexing questions are whether or not all patients with dyspepsia and H . pylori should be treated, whether or not a definitive diagnosis of ulcer should be established by an invasive method, and whether H . pylori eradication is sufficient to prevent recurrence of bleeding ulcers, especially in patient groups that have a high frequency of nonsteroidal anti-inflammatory drug (NSAID) use . Another common problem is the question of whether or not to establish the success of an eradication regimen in an individual patient and the choice of method to obtain this information . There is also an obvious need to develop better antimicrobial regimens aimed specifically at Helicobacter pylori . At the basic level, almost nothing is known about the mechanisms by which H . pylori produces peptic ulcer in 10-20% of infected patients while producing gastritis in all infected subjects . There is good evidence that host factors, including intrinsic rate of acid secretion, family history and smoking are independent additive risk factors for ulcer . Ingestion of NSAIDs appears to be an independent and separate risk factor . There is evidence that strains of H . pylori that lack certain genetic markers may have a reduced likelihood of causing ulcers, but the 'ulcer' marker is present in the majority of infected subjects without ulcer.(ABSTRACT TRUNCATED AT 250 WORDS)

Rev Hosp Clin Fac Med Sao Paulo, 1995 Jan-Feb, 50(1), 52 - 4
{Infections of central venous catheters}; Faintuch J et al.; The central venous catheter is considered the lifeline of patients requiring long-term parenteral nutrition, and its infectious complications accordingly represent a frequent cause for hospitalization and morbidity . Modern catheters made of Silastic increase the duration and efficiency of venous access, but their substitution is also more complex and expensive . In a small series of patients undergoing home parenteral nutrition due to short bowel syndrome, and carrying . Silastic catheters, infection of the cannula was treated by administration of systemic as well as local antimicrobial agents . The septic process was resolved without the need of removing the catheters, and with excellent tolerance to the medications . It is concluded that in-situ sterilization of long-term catheters should be attempted in selected cases.

Life Sci, 1995, 57(21), 1973 - 80
Pentamidine does not interfere with nitrite formation in activated RAW 264.7 macrophages but inhibits constitutive brain nitric oxide synthase; Baer HP et al.; Pentamidine effects on the interferon-gamma- or interferon-gamma plus bacterial lipopolysaccharide-induction of nitric oxide synthase in the macrophage cell line RAW 264.7, determined by measuring nitrite release into culture supernatants, were investigated . At concentrations above 10 microM, pentamidine caused visible toxic effects including cell lysis which also was assessed by measuring lactic dehydrogenase release . A progressive inhibitory effect of pentamidine could not be clearly dissociated from these toxic and lytic effects which were extensive at 100 microM . At 1 microM pentamidine, the dose response dependence of nitrite formation on interferon-gamma was not affected . Tumor necrosis factor-alpha caused some enhancement of interferon-gamma-induced nitrite release only at high doses of 100 and 10,000 unit/ml . Pentamidine had no effect on isolated inducible nitric oxide synthase from RAW 264.7 cells but inhibited the constitutive enzyme from pork cerebellum non-competitively . The lack of any stimulatory effect of pentamidine on nitrite production in RAW 264.7 cells suggests that NOS induction and NO production by macrophages is not the mechanism of the antimicrobial effects of this drug.

Ann Intern Med, 1994 Dec 15, 121(12), 905 - 11
Clarithromycin therapy for bacteremic Mycobacterium avium complex disease . A randomized, double-blind, dose-ranging study in patients with AIDS . AIDS Clinical Trials Group Protocol 157 Study Team; Chaisson RE et al.; OBJECTIVE: To determine the antimicrobial activity and tolerability of clarithromycin for treating bacteremic Mycobacterium avium complex disease in patients with the acquired immunodeficiency syndrome (AIDS) . DESIGN: A randomized, double-blind, dose-ranging study . SETTING: Outpatient clinics . PATIENTS: 154 patients with human immunodeficiency virus (HIV) infection and blood cultures positive for M . avium complex who had symptomatic disease . INTERVENTIONS: Random assignment to clarithromycin at dosages of 500 mg, 1000 mg, or 2000 mg twice daily for 12 weeks . MAIN OUTCOME MEASURE: Median number of colony-forming units of M . avium complex per milliliter of blood . RESULTS: Clarithromycin decreased mycobacterial CFUs from 2.7 to 2.8 log 10/mL of blood at baseline to less than 0 log 10/mL during follow-up (P < 0.0001) . After 2 weeks, patients receiving 500 mg twice daily were less likely to be culture negative than were patients receiving 1000 or 2000 mg twice daily (11% compared with 33% or 29%; P = 0.08) . At 6 weeks, the median number of CFUs of M . avium complex/mL of blood was 0 or 1 for all three groups . Clarithromycin-resistant isolates of M . avium complex developed in 46% of patients at a median of 16 weeks . Median survival was longer in patients assigned to 500 mg twice daily (median, 249 days) than in patients assigned to 1000 mg or 2000 mg . Death in the first 12 weeks was lowest in the 500-mg group (P = 0.007) . CONCLUSIONS: Clarithromycin therapy acutely decreased M . avium complex bacteremia in patients with HIV infection by more than 99% . Clarithromycin, 500 mg twice daily, was well tolerated and associated with better survival . Emergence of clarithromycin-resistant organisms was an important problem.

Am J Ophthalmol, 1994 Dec 15, 118(6), 701 - 6
Povidone-iodine for ophthalmia neonatorum prophylaxis; Isenberg SJ et al.; PURPOSE: The agents currently used to prevent ophthalmia neonatorum are less than optimal, with reports indicating evidence of bacterial resistance, ineffectiveness, and toxicity . Povidone-iodine ophthalmic solution, which has been shown to be effective in the preoperative preparation of the eye, generates no resistance, is an effective antimicrobial agent, and has low toxicity . We evaluated the effectiveness and safety of povidone-iodine for ophthalmia neonatorum prophylaxis . METHODS: A bacterial culture was taken from the conjunctiva of each eye of 100 infants within 30 minutes of birth . A drop of 2.5% povidone-iodine solution was then placed on one eye, while the other eye received either one drop of silver nitrate 1% ophthalmic solution or 0.5% erythromycin ointment . Conjunctival bacterial cultures were again taken two to four hours after birth . At each culture and at 24 hours after birth, the eyes were examined for toxic changes . To measure the effectiveness of the medications, the number of bacterial colony-forming units and species from each culture was compared . RESULTS: All three agents significantly reduced the number of colony-forming units, but povidone-iodine caused the most significant decrease . The number of species was reduced significantly by povidone-iodine (P = .00051) and silver nitrate (P = .007), with povidone-iodine yielding the most significant decrease . Erythromycin did not significantly reduce the number of species . Silver nitrate demonstrated more ocular toxicity at the 24-hour determination point than did either of the other two medications (P < .001) . CONCLUSIONS: Povidone-iodine 2.5% ophthalmic solution is an effective antibacterial agent on the conjunctiva of newborns and causes less toxicity than silver nitrate.

FEBS Lett, 1994 Dec 12, 356(1), 33 - 8
Characterization of the promoters of the guinea pig neutrophil cationic peptide-1 and -2 genes; Nagaoka I et al.; Guinea pig neutrophils contain the antimicrobial cationic peptides GNCP-1 and GNCP-2 in the granules . To understand the regulation of the gene expression, the promoters for the GNCP-1 and GNCP-2 genes were characterized . Sequencing analysis of the genomic clones showed that the nucleotide sequences of the 5'-upstream regions (1.7 kb) from exon 1 were homologous (90-93%) between the GNCP-1 and GNCP-2 genes . However, transient transfection assays using luciferase reporter gene constructs revealed that the promoter activity of GNCP-1 was 2-fold greater than that of GNCP-2 . Furthermore, DNase I footprint analysis demonstrated that three regions (I, II and III) were protected on the GNCP-1 promoter, whereas only two protected regions (II and III) were identified on the GNCP-2 promoter . Together these observations indicate that GNCP-1 and GNCP-2 are encoded by homologous genes, but the expression of the GNCP-1 and GNCP-2 genes is likely to be different at the level of transcription.

Clin Intensive Care, 1995, 6(2), 52 - 6
Pilot clinical trial of an anti-TNF alpha monoclonal antibody for the treatment of septic shock; Boillot A et al.; OBJECTIVE: To determine the safety and pharmacokinetics of an anti-tumour necrosis factor (TNF alpha) monoclonal antibody in the treatment of septic shock, and to evaluate the biological evolution of cytokine response . DESIGN: Open-label, prospective, pilot trial with escalating doses of a murine monoclonal antibody (B-C7) directed against TNF alpha . SETTING: University medical centre intensive care unit . PATIENTS: Nine patients with septic shock, who received standard supportive care and antimicrobial therapy in addition to the anti-TNF alpha antibody . INTERVENTIONS: Patients were treated intravenously with one of three escalating doses of B-C7 monoclonal antibody (MoAb): 0.4 mg/kg, 0.8 mg/kg, 1 mg/kg . RESULTS: MoAb was well tolerated despite the development of human anti-mouse antibodies (HAMA) for each patient; B-C7 plasma levels were dose-dependent . At study entry, TNF alpha and IL-6 levels were detected in six and seven patients respectively; IL-1 levels were low and interferon-gamma was undetectable . CONCLUSIONS: No side effects were noted during treatment regardless of the dose used; however, further studies are needed to determine the clinical efficacy of this agent in septic shock.

Scand J Immunol, 1994 Dec, 40(6), 675 - 80
Effects of human calprotectin (L1) on in vitro immunoglobulin synthesis; Brun JG et al.; Calprotectin (L1) is a major cytoplasmic protein of neutrophilic granulocytes and monocytes/macrophages which is released from leucocytes during activation or cell death . Apart from in vitro antimicrobial and antiproliferative activity little is known about the biological function of the protein . Since previous investigations have shown that calprotectin plasma levels are elevated in various inflammatory rheumatic diseases, we wanted to investigate if calprotectin has an effect on immune cell functions . Peripheral blood mononuclear cells, either unstimulated or polyclonally stimulated with mitogen, were incubated with calprotectin and effects were assessed by enumeration of immunoglobulin secreting cells (ELISPOT) . The results indicate that incubation with high concentrations of calprotectin (> 64 micrograms/ml) inhibit the production of the three classes of immunoglobulins investigated (IgG, IgM and IgA), both for mitogen stimulated and unstimulated lymphocytes . Except for the highest concentration of calprotectin (500 micrograms/ml), it seems plausible that the observed inhibitory effect of calprotectin on Ig production is not a result of a direct toxic effect of calprotection on B lymphocytes . Altogether, these effects of high calprotectin levels might be of importance in the immunoregulation of inflammatory conditions.

J Pharmacol Exp Ther, 1994 Dec, 271(3), 1544 - 9
Effects of fluoroquinolones on cultured articular chondrocytes flow cytometric analysis of free radical production; Thuong-Guyot M et al.; Using flow cytometry, we previously established in an ex vivo model that fluoroquinolones induce a stimulation of the oxidative metabolism in immature chondrocytes . To assess these findings in an in vitro model, primary cultures of immature articular chondrocytes were incubated with four quinolone solutions: ofloxacin, ciprofloxacin, nalidixic acid at 10 micrograms/ml for 24 hr and pefloxacin at 1, 10 and 100 micrograms/ml for various periods of time (2, 4, 6, 12, 24 and 48 hr) . Three fluorochromes were used: DCFH-DA, reflecting cellular production of H2O2, rhodamine 123 (Rh123) and 10-N-nonyl-acridine orange (NAO), which are specific for mitochondrial activity and mass, respectively . In immature chondrocyte cultures treated with pefloxacin, ofloxacin and nalidixic acid at 10 micrograms/ml for 24 hr, levels of cellular fluorescent dichlorofluorescein DCF (oxidized form of DCFH-DA) were significantly higher than in control cells . No significant increase could be registered with ciprofloxacin . In the same experimental conditions, incorporation of Rh123 and NAO was not significantly modified . Pefloxacin (10 micrograms/ml, 24 hr) did not induce any significant increase of DCFH-DA processing either in mature chondrocytes or in alveolar macrophages removed from immature rabbits . Quinolones induce in vitro an early stimulation of the oxidative metabolism in immature but not in mature chondrocytes, a phenomenon that could explain juvenile onset of quinolone arthropathy . This in vitro model could be proposed as an easy and reproducible method for screening potential arthrotoxicity of antimicrobial agents, capable of stimulating the formation of H2O2.

J Leukoc Biol, 1994 Dec, 56(6), 807 - 11
Identification of a proline-arginine-rich antibacterial peptide from neutrophils that is analogous to PR-39, an antibacterial peptide from the small intestine; Shi J et al.; Neutrophil nonoxidative defense mechanisms include several low molecular weight antimicrobial peptides . We have isolated a proline-arginine-rich antibacterial peptide from porcine neutrophils . This cationic, low molecular weight peptide has a very high degree of identity (97%) to a bactericidal peptide, PR-39, that has been found in the porcine small intestine . Isolation of the same antimicrobial peptide from both neutrophils and cells of the small intestine in the same species is unique and suggests an important role for this protein in innate immune defenses.

J Infect Dis, 1994 Dec, 170(6), 1613 - 6
Experimental evidence for Moraxella-induced penicillin neutralization in pneumococcal pneumonia; Hol C et al.; Resistance of microorganisms to antimicrobial agents is an increasing problem in the treatment of infectious diseases . In mixed infections, an interesting development can arise when one organism protects another from being killed by an antibiotic . Unfortunately, in the case of respiratory tract infections, experimental evidence of this development is poor . In this study, mice intranasally infected with a lethal number of pneumococci and treated with a curative dose of penicillin or amoxicillin died from pneumococcal pneumonia when they were coinoculated with beta-lactamase-producing Moraxella catarrhalis . beta-lactamase-negative M . catarrhalis did not show a similar indirect pathogenic effect . Treatment with a combination of amoxicillin and the beta-lactamase inhibitor clavulanic acid was not affected by beta-lactamase-producing M . catarrhalis . These findings help explain antibiotic failure in respiratory tract infections, even though the causative microorganism is sensitive to the antibiotic in vitro.

J Infect Dis, 1994 Dec, 170(6), 1606 - 9
Characteristics of antibiotic-resistant Escherichia coli O157:H7 in Washington State, 1984-1991; Kim HH et al.; The resistance of Escherichia coli O157:H7 to amoxicillin/clavulanic acid, ampicillin, ceftazidime, ceftriaxone, cefuroxime, cephalothin, chloramphenicol, ciprofloxacin, gentamicin, streptomycin, sulfisoxazole, tetracycline, ticarcillin, tobramycin, and trimethoprim-sulfamethoxazole was examined, and resistant strains were characterized . All 56 isolates collected between 1984 and 1987 were susceptible to all antibiotics tested; 13 (7.4%) of 176 strains isolated between 1989 and 1991 were resistant to streptomycin, sulfisoxazole, and tetracycline . lambda-restriction fragment length polymorphism analysis suggested that the 13 resistant strains belonged to nine different clones . The emerging resistance of E . coli O157:H7 to antibiotics could portend an increased prevalence of this pathogen in food animals that receive antibiotics . Antimicrobial resistance of E . coli O157:H7 could be useful as a rapid epidemiologic marker and as a way to select this pathogen from suspected vehicles of transmission, but this resistance could also complicate therapeutic trials with sulfa-containing antibiotics.

Dis Colon Rectum, 1994 Dec, 37(12), 1325 - 7
Seminal vesicle fistula following abdominoperineal resection for recurrent adenocarcinoma of the rectum . Report of a case; Kollmorgen TA et al.; PURPOSE: Fistula formation between the seminal vesicles and a pelvic abscess after abdominal perineal resection for recurrent rectal cancer is reported in a 32-year-old male previously treated with low anterior resection, chemotherapy, and radiation . METHODS: The case history was reviewed for clinical presentation, radiologic studies, and laboratory data . RESULTS: Successful management of this previously unreported complication included percutaneous abscess drainage, antimicrobial therapy, and oral administration of Proscar (Merck, Sharpe & Dohme, Rathway, NJ) . CONCLUSION: Multiple factors predisposed this patient's development of a seminal vesicle fistula . These include extensive scarring from previous surgery, pelvic radiation, and an immunologically depressed status . The efficacy of Proscar in the successful management of this case remains unknown.

J Clin Oncol, 1994 Dec, 12(12), 2667 - 76
Dose-ranging study of recombinant human granulocyte-macrophage colony-stimulating factor in small-cell lung carcinoma; Hamm J et al.; PURPOSE: This randomized, multicenter, dose-finding study was undertaken to determine the dose of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) that can safely reduce neutropenia after cyclophosphamide, doxorubicin, and etoposide (CAVP-16) chemotherapy in patients with small-cell lung cancer (SCLC) . Secondary clinical end points included incidence of infection, intravenous (IV) antimicrobial use, and chemotherapy delivered . PATIENTS AND METHODS: A total of 290 newly diagnosed SCLC patients were to receive six cycles of standard CAVP-16 chemotherapy on days 1 to 3 of every 21 days alone or with rhGM-CSF at 5, 10, or 20 micrograms/kg, administered subcutaneously (SC) on days 4 to 13 of each cycle . RESULTS: In cycle 1, median absolute neutrophil count (ANC) nadirs were twofold to threefold higher in patients who received rhGM-CSF, although all values were less than 500/microliters, and recovery from neutropenia was faster at all rhGM-CSF dosages versus observation (P < or = .01) . In cycle 2, 56% of all patients given rhGM-CSF received full chemotherapy dosages (87.5% to 112.5% of projected dose) versus 36% of observation patients . During days 5 to 21 of cycle 1, fewer patients who received 10 micrograms/kg of rhGM-CSF required antibiotics compared with observation patients (11% v 29%, P < or = .01) . Adverse events that occurred more frequently in rhGM-CSF-treated patients included injection-site reaction, edema, asthenia, paresthesia, diarrhea, myalgia, musculoskeletal pain, Pruritus, and rash (P < or = .10) . Fever occurred more frequently in the 10- and 20-micrograms/kg rhGM-CSF groups than in the observation groups . The incidence in the 5-microgram/kg group was comparable to that in observation patients . Patients who received rhGM-CSF had a higher incidence of thrombocytopenia . CONCLUSION: rhGM-CSF at 5 to 10 micrograms/kg reduces chemotherapy-associated neutropenia and should be the dose range used in future studies.

Arch Otolaryngol Head Neck Surg, 1994 Dec, 120(12), 1317 - 20
Microbiology and management of chronic maxillary sinusitis; Brook I et al.; OBJECTIVE: Assessment of the microbiology and management of patients who suffered from chronic maxillary sinusitis was studied retrospectively . DESIGN: Retrospective analysis of microbiology and antimicrobial therapy of 68 patients who underwent the Caldwell-Luc procedure for chronic sinusitis had not received antimicrobials before surgery and whose cultures showed bacterial growth . SETTING: This study was performed at the Naval Hospital in Bethesda, Md . INTERVENTION: Amoxicillin-clavulanic acid was given to 18 patients, amoxicillin or ampicillin to 25, cefaclor to 17, and erythromycin to eight . RESULTS: A total of 183 isolates (123 anaerobic and 60 aerobic) were recovered . Anaerobic organisms only were recovered from 35 (51%), specimens, and aerobic or facultative bacteria only in 12 (18%), and mixed aerobic and anaerobic flora in 21 (31%) . Thirty-four aerobic and anaerobic beta-lactamase-producing bacteria were isolated from 28 patients . The 18 patients who received amoxicillin-clavulanic acid had the most rapid and complete response to therapy, none required a change in therapy, and surgical drainage was required in one case . Of 25 patients who received amoxicillin or ampicillin, eight required a change of therapy due to clinical failure (32%), including three who also had surgical drainage . Of 17 that received cefaclor, five had an antibiotic change (29%), one with surgical drainage . Of the eight who were treated with erythromycin, three needed antibiotic change (38%), two with surgical drainage . Resistant organisms were recovered from most of the patients that required therapeutic change . CONCLUSIONS: These findings indicate the major role of aerobic and anaerobic beta-lactamase-producing bacteria organisms in the polymicrobial etiology of chronic maxillary sinusitis and illustrate the superiority of therapy effective against these bacteria.

Infect Immun, 1994 Dec, 62(12), 5505 - 10
Moderate stress protects female mice against bacterial infection of the bladder by eliciting uroepithelial shedding; Dalal E et al.; We have previously shown (M . Aronson, O . Medalia, D . Amichay, and O . Nativ, Infect . Immun . 56:1615-1617, 1988) that shedding of viable uroepithelial cells (elicited by invading microorganisms) constitutes an antimicrobial defense mechanism . The present study deals with two different stress-involving procedures, in which increased uroepithelial shedding rendered female mice resistant to vesical infection . Moderate stress was induced in female mice by exposing the animals either to constant illumination for 96 h or to 37 degrees C heat for 24 h . In both cases, the rate of infection was considerably reduced as a result of increased epithelial shedding (P < 0.0001) . Stress was manifested by both reduced thymic weight and increased blood corticosterone levels . Shedding was also elicited by intraperitoneal injection of norepinephrine together with hydrocortisone or by intravesical injection of corticosterone . Constant illumination as well as heat enormously facilitated the migration of polymorphonuclear cells into the bladder following the action of chemotactic stimuli . Male mice subjected to identical stress-generating conditions did not display considerable epithelial shedding or increased migration of polymorphonuclear cells, and they were not protected from intravesical infection.

Infect Immun, 1994 Dec, 62(12), 5397 - 403
Killing of Giardia lamblia by cryptdins and cationic neutrophil peptides; Aley SB et al.; Antimicrobial polypeptides such as the defensins kill a wide range of organisms, including bacteria, fungi, viruses, and tumor cells . Because of the recent finding that intestinal defensins, also known as cryptdins, are synthesized by the Paneth cells of the small intestinal crypts and released into the lumen, we asked whether defensins and other small cationic antimicrobial peptides could kill the trophozoites of Giardia lamblia, which colonize the small intestine . Four mouse cryptdins, two neutrophil defensins (HNP-1 {human} and NP-2 {rabbit}), and the unique tryptophan-rich bovine neutrophil polypeptide indolicidin each had some antigiardial activity against trophozoites in vitro . Cryptdins 2 and 3, indolicidin, and NP-2 each reduced viability by more than 3 log units in 2 h, and killing by all peptides was dose and time dependent . Exposure of trophozoites to peptides frequently resulted in cell aggregation and dramatic changes in morphology . The mechanism of binding and lysis appeared to involve charge interactions, since 150 mM NaCl as well as millimolar levels of Ca2+ and Mg2+ inhibited killing by most of the peptides . Our studies show that G . lamblia is sensitive to defensins and indolicidin and suggest that these small polypeptides could play a role in nonimmune host defenses.

J Ethnopharmacol, 1994 Dec, 44(3), 137 - 42
Evaluation of some pharmacological activities of Eugenia uniflora L; Schapoval EE et al.; In view of the extensive use of Eugenia uniflora in folk medicine, different extracts of dried and fresh leaves of the plant were assayed to test its possible pharmacological activities . The infusion of fresh leaves had a highly significant anti-inflammatory effect when administered p.o . to rats 1 h before subplantar injection of carrageenin . The infusion increased the pentobarbital sleeping time and also had an effect on intestinal transit, and had no acute toxic effect . No analgesic or antimicrobial activities were observed with any of the extracts used.

Clin Invest Med, 1994 Dec, 17(6), 531 - 9
Reduction of vitamin K2 concentrations in human liver associated with the use of broad spectrum antimicrobials; Conly J et al.; It is unclear whether menaquinones produced by the intestinal microflora play any role in human nutrition . Reports of coagulopathy due to vitamin K deficiency occurring in patients receiving broad spectrum antibiotics indirectly suggest that vitamin K2 produced by the gut microflora may be utilized by the host . We analyzed the vitamin K1 (phylloquinone) and vitamin K2 (menaquinone) content in a convenience sample of 22 human post-mortem liver samples, including 9 individuals who had been receiving broad spectrum antimicrobials prior to death and 13 individuals who had been victims of sudden, unexpected deaths . There were no significant differences in the mean (+/- SEM) phylloquinone content between the 2 groups {21.9 (+/- 15.5) vs . 16.0 (+/- 9.3) pmol/g wet weight (excluding those who had received supplemental vitamin K1)} but there was a significant difference (p < 0.05) in the total menaquinone (MK) content, 70.0 (+/- 23.3) vs . 423.1 (+/- 141) pmol/g between the 2 groups . These findings suggest an association between receipt of broad spectrum antibiotics and a reduction in hepatic menaquinone concentration, lending support to the hypothesis that a reduction in the gut microflora responsible for their production leads to reduced hepatic stores of this form of the vitamin.

Farmaco, 1994 Dec, 49(12), 823 - 7
New heterocyclic derivatives of benzimidazole with germicidal activity--XII--Synthesis of N1-glycosyl-2-furyl benzimidazoles; Pedini M et al.; Over the last decade, several derivatives of benzimidazole have been synthesized; some of them turned out to have a good antimicrobial activity; however, all of them were not soluble in water . Therefore the N1-heterosides of four derivatives of 2-(2'-furyl) benzimidazole, chosen from those with the highest biological activity have been now synthesized . These compounds were expected to have some new properties, including a good water-solubility and a higher or at least similar biological activity; furthermore, taking into account some previously published data on similar molecules, an antileukemic activity was expected . However, no one of these hypothesis was confirmed experimentally.

Ear Nose Throat J, 1994 Dec, 73(12), 900, 903, 907 - 13
Cephalosporin antibiotics; Otto RA et al.; The last three decades have seen the emergence of a cornucopia of antimicrobials in the cephalosporin class . This becomes even more apparent when one realizes that over 60 pages of the 1993 AHFS drug information text is dedicated to the cephalosporin class . Due to similarities in nomenclature and the proliferation of available agents, the clinician is constantly challenged by this confusing array of antimicrobials . The intent of this manuscript will be to distill the volumes of information available on cephalosporins into a more manageable format and close with a summary of the most clinically important cephalosporin antimicrobials.

Int J Clin Pharmacol Ther, 1994 Dec, 32(12), 675 - 82
Adverse drug reactions resulting in hospital admission; Huic M et al.; A 14-month (1992/3) prospective study was performed in two departments of the University Hospital Centre (UHC) in Zagreb . The aim of the study was to assess the rate of drug-related hospitalizations, drugs that caused adverse drug reactions (ADRs), and all factors which could have been of importance for their appearance . One hundred and thirty (2.5%) of 5,227 patients were admitted to hospital because of ADRs . The most frequently ADR-related drugs were nonsteroidal anti-inflammatory drugs and analgesics (64.6%) . They were followed by cardiovascular agents (20.8%) and antimicrobials (3.8%) . Acetylsalicylic acid (aspirin) caused 38.5% of hospital admissions, other nonsteroidal anti-inflammatory drugs (NSAIDs) 23.1% and medigoxin 15.4% of hospitalizations . The most frequent ADRs were upper gastro-intestinal tract bleeding (64.6%), cardiac rhythm disturbances (13.9%), blood cell disorders (4.6%) and hypoglycemia (2.3%) . Regarding the patients' age, 52.3% of patients was younger and 47.7% older than 65 . Sixty-one point five percent of patients was taking more than one drug, older patients (48 patients--77.4%) have been taking a significantly higher number of drugs than the younger (32 patients--47.1%) (p < 0.0001) ones . Drug interactions caused 23.8% of ADRs . Only 11 (8.5%) of patients suspected themselves that the drug might have caused the ADR . Improvement was observed in the majority of patients (65.4%), 25.4% recovered completely, 4 (3.0%) died in the hospital because of ADRs . 3.0% of patients as well died of their underlying diseases, 2.3% were transferred to other departments for their underlying diseases, and one patient left the hospital on his free will.

Analyst, 1994 Dec, 119(12), 2737 - 41
Investigation of Charm Test II receptor assays for the detection of antimicrobial residues in suspect meat samples; Korsrud GO et al.; Charm Test II receptor assays for beta-lactams, sulfonamides, (dihydro)streptomycin and erythromycin were applied to 257 bovine muscle and kidney samples, and 215 porcine muscle and kidney samples collected from animals suspected to contain antimicrobial residues . The assays were run in conjunction with Agriculture and Agri-food Canada's routine diagnostic confirmation analyses for suspect samples collected at federally inspected packing plants . All samples were subjected to the Charm Test II receptor assays and thin layer chromatography-bioautography (TLC-BA) . Selected samples were quantitatively analysed using a liquid chromatographic method for penicillin G and a thin layer chromatography-fluorescence densitometry (TLC-FD) method for sulfonamides . The Charm Test II assays for beta-lactams, (dihydro)streptomycin and erythromycin were an acceptable alternative to the TLC-BA screen for laboratory confirmation of the presence of these compounds, with enhanced sensitivity for (dihydro)streptomycin and erythromycin . In addition, the Charm Test II provided a sensitive screen for sulfonamides as confirmed by the standard TLC-FD procedure . The analysis time, laboratory space and analyst time required to complete the Charm Test II assays is less than that for TLC-BA . Operating costs are similar for both analyses, but the Charm Test II does require capital expenditure for a scintillation counter.

Analyst, 1994 Dec, 119(12), 2543 - 8
Immunochemical detection of antibiotics and sulfonamides; Martlbauer E et al.; To control the maximum residue limits (MRLs) for residues of veterinary drugs in food of animal origin, according to EU regulations, a broad spectrum of sensitive analytical methods is required . One effective approach is the development of immunoassays, particularly for screening purposes . Strategies for the production of specific polyclonal and monoclonal antibodies against beta-lactams, tetracyclines, streptomycin, chloramphenicol, sulfonamides and trimethoprim, are outlined, as well as methods for the synthesis of the respective enzyme-labelled antigens . The sensitivity and the specificity of the antibodies were characterized, and the immunochemical test systems were designed as quantitative routine tests (microtitre plate format) and as rapid qualitative tests (membrane-based assay formats) . The detection limits of the assays were found to be well below the regulatory limits . The range of recovery, for the analysis of artificially contaminated samples, was between 68 and 104% . In principle, the enzyme immunoassays for antimicrobial drugs showed the advantage of sensitivity and speed together with the simplicity of manipulations involved in the procedure . However, because of the results of the specificity studies, as well as the possibility of false positive results owing to unspecific inhibition of the assay, confirmation of immunoassay results is still required for all legal and statutory purposes.

Analyst, 1994 Dec, 119(12), 2521 - 8
Veterinary drugs: disposition, biotransformation and risk evaluation; Fink-Gremmels J et al.; Veterinary drugs may only be produced, distributed and administered after being licensed . This implies that, prior to marketing, a critical evaluation of the pharmaceutical quality, the clinical efficacy and the over-all pharmacological and toxicological properties of the active substances will be performed by national and/or supranational authorities . However, despite a sophisticated legal (harmonized) framework, a number of factors involved in residue formation and safety assessment remain unpredictable or dependant on the current 'state of the art' in the understanding of molecular pharmacology and toxicology . For example, drug disposition and residue formation in the target animal species may be influenced by a broad variety of physiological parameters including age, sex and diet, as well as by pathological conditions especially the acute phase response to infection . These factors affect both drug disposition and metabolite formation . Furthermore, current thinking in toxicological risk assessment is influenced by recent developments in molecular toxicology and thus by an increased but still incomplete understanding of the interaction of a toxic compound with the living organism . General recognized principles in the evaluation of potential toxicants are applied in the recommendation of withdrawal times and the establishment of maximum residue limits (MRL values) . Apart from toxicological-based assessment, increasing awareness is directed to other than toxicological responses, especially the potential risk of effects of antimicrobial residues on human gastrointestinal microflora . Thus, the methodology of risk assessment is discussed in the context of the recently established legal framework within the European Union.

J Clin Pharm Ther, 1994 Dec, 19(6), 391 - 6
Stability of caffeine oral formulations for neonatal use; Barnes AR et al.; The stability of an oral formulation of 10 mg/ml caffeine citrate (equivalent to 5.03 mg/ml caffeine free base), which was preserved with potassium sorbate, was assessed at a range of temperatures . There was no appreciable change in pH or caffeine content over 1 year, even at storage temperatures of 32 degrees C and 45 degrees C . A batch-to-batch difference in the stability of potassium sorbate was detected, with losses over 1 year of 2% and 11% for two batches at 25 degrees C and 10% and 30%, respectively, at 45 degrees C . The formulation complied with the Antimicrobial Preservative Efficacy test of the British Pharmacopoeia throughout a period of storage at 25 degrees C for 1 year . There was no detectable benefit to preservative efficacy by adding 20% w/v sorbitol as an osmotic agent . The formula with no sorbitol may be preferable due to the potential for sorbitol to cause gastrointestinal upset . A shelf-life of 1 year at room temperature is feasible . The additional precaution of limiting the in-use storage life to 1 month after opening is recommended to ensure acceptable microbiological quality.

Rinsho Byori, 1994 Dec, 42(12), 1215 - 26
{Why should we measure MIC?}; Tajima Y; In actual infectious diseases, bacterial invasion and the effect of antibiotics show "dynamic" behavior, being continuously influenced by various factors . Therefore, "some" knowledge and experience are essential to treat a patient and to make an appropriate decision through only limited information . On the other hand, many patients today still die of infection at the terminal state of illness . Therefore, the importance of "clinical microbiology" has not faded away at all, and will increase much more in the future . However, medical students are not well taught "drug-dynamics" and "how to perform empiric therapy" in the under-graduate curriculum . Thus, such knowledge must be obtained by "self-effort"; i.e., why MIC should be measured, how to make use of MIC for treatment, what the most important information upon treatment of infection is, what moiety is not reflected by MIC, how to judge from which point of MICs, and so on . Furthermore, education or guidance in such fields are not always provided even in the post-graduate training course . To solve these difficulties, we originated a new computer system supporting antimicrobial chemotherapy, which has actually been working well in our hospital from May of 1994 . This system is intended to convey maximally the "meaning" of the test results, instead of just reporting only "prosaic" results . In this system, detailed information on various kinds of bacteria and antibiotics is immediately available on every computer monitor . Furthermore, the data base on the average concentration of various antibiotics expected to be reached in each organ by every dose method is already in the system . When MIC actually measured is larger or smaller than such a value, a signal of "untreatable" or "treatable" will appear on the monitor . This is an epoch-making system in Japan, and will help the physicians to provide effective therapy.

J Prosthodont, 1994 Dec, 3(4), 219 - 27
Gypsum compatibility of antimicrobial alginates after spray disinfection; King BB et al.; PURPOSE: This investigation examined the gypsum compatibility of two antimicrobial alginates after spray disinfection . Subjective compatibility evaluations were compared with objective quantitative profilometer readings of gypsum cast surface roughness . MATERIALS AND METHODS: COE Hydrophilic Gel Alginate, Jeltrate Plus, Antimicrobial Alginate, and their nonantimicrobial counterparts, Coe Alginate and Jeltrate Plus, were used in this study . After spray disinfection with water (control), Alcide LD, Biocide, OMC II, and 0.5% NaOCI, impressions of the American National Standards Institute/American Dental Association (ANSI/ADA) specification no . 18 detail reproduction die and impressions made simultaneously of a smooth glass die were cast in Microstone, Silky-Rock, and Die-Keen . Five specimens were made for each alginate/disinfectant/gypsum combination for a total of 300 samples each for both the subjective and objective analyses . For the subjective analysis of gypsum compatibility, the specimens made from the ANSI/ADA specification no . 18 test die were evaluated by using a 1-to-4 visual rating system at magnification x12 . For the objective analysis, the arithmetic average surface roughness of each specimen made from the smooth glass die was recorded three times with a 200-mg skidless stylus instruments . RESULTS: The results of the ANSI/ADA specification no . 18 testing for gypsum compatibility showed that 11 of 60 possible combinations did not pass the test . All impressions made with nonantimicrobial COE Alginate passed the test regardless of the disinfectant/gypsum combination . The results of the three-factor analysis of variance for the subjective and objective analyses showed significant interactions between alginates, disinfectants, and stones at the P < .05 level . To further delineate these differences, unpaired t tests (P < .05) within brands for each disinfectant/gypsum combination were performed . CONCLUSIONS: The addition of 1% chlorhexidine diacetate to COE Hydrophilic Gel Alginate has decreased its compatibility with the dental stones and disinfectants tested when compared with its nonantimicrobial counterpart . In terms of gypsum compatibility, the nonantimicrobial COE Alginate was compatible with all disinfectant and gypsum combinations tested . The addition of 1.70% didecyldimethyl ammonium chloride to Jeltrate Plus Antimicrobial Alginate has increased its compatibility with all the dental stones tested . A strong positive correlation (r = 0.7398) was found between visual gypsum compatibility evaluation scores and surface roughness of gypsum casts.

J Paediatr Child Health, 1994 Dec, 30(6), 470 - 5
Antimicrobial factors and microbial contaminants in human milk: recent studies; May JT; An overview of recent studies of antimicrobial factors and microbial contaminants found in human milk is presented . The incidence of gastrointestinal and respiratory infections in infants receiving human milk continues to be lower than in those not breast-fed due to the presence of specific antibody and possibly anti-adhesion factors in the milk . Whether the many other antimicrobial factors, which have been shown to be active in vitro or in animal model systems, have any influence on infant infections is still not clear . Microbial contaminants in human milk are rare, as are associated infant infections from the milk . However, some contaminants such as cytomegalovirus are commonly transferred to infants from the milk of seropositive mothers, fortunately without any adverse effects in the infants . Human T-lymphotropic virus type 1 is transferred via human milk in endemic areas, human milk being the main source of mother-to-infant transmission . While some reports suggest human immunodeficiency virus type 1 transfer may occur through human milk, this is not the predominant mode of transmission to infants.

Arzneimittelforschung, 1994 Dec, 44(12A), 1441 - 7
General pharmacology of pidotimod and testing for drug interactions; Manzardo S et al.; Pidotimod ((R)-3-{(S)-(5-oxo-2-pyrrolidinyl) carbonyl}-thiazolidine-4-carboxylic acid, PGT/1A, CAS 121808-62-6) is a new biological response modifier . General pharmacology and interactions with some drugs were tested . The drug, at doses of 200 mg/kg i.p . and 400 mg/kg p.o., did not affect the normal behaviour, did not modify the responses to stimulation of autonomic nervous system or central nervous system . Pidotimod did not display any cardiovascular or respiratory effect up to 125 mg/kg i.v . in 3 animal species . The drug did not show antimicrobial or antifungal activities nor interact with some of the most common therapeutics (antibiotics, tolbutamide, pentobarbital, antihypertensives, chlorothiazide, warfarin, non-steroidal antiinflammatory agents) . On the basis of these results pidotimod shows a safe profile; moreover it does not interact with many therapeutic agents.

Arzneimittelforschung, 1994 Dec, 44(12A), 1425 - 30
Effects of pidotimod on macrophage functions in methylprednisolone-treated mice; Taramelli D et al.; CD-1 mice were treated with methylprednisolone (mPDN) 2-5 mg/kg s.c., for 11 or 6 days, in order to achieve an immunosuppressed state . For the same length of time a group of mice also received pidotimod ((R)-3-{(S)-(5-oxo-2-pyrrolidinyl) carbonyl}-thiazolidine-4-carboxylic acid . PGT/1A, CAS 121808-62-6) i.p . at 100 or 10 mg/kg . At the end of treatment, peritoneal macrophages (MO) were recovered, purified by adherence to plastic and activated in vitro with different stimuli . After 24 h of incubation, the supernatants were collected and assayed for the presence of tumor necrosis factor-alpha (TNF-alpha) and nitrite (NO2-), which is the stable derivative of nitric oxide (NO) in acqueous solution . It is well known that TNF-alpha and NO represent two out of many molecules secreted by activated MO which are essential for killing microorganisms and for natural response to infections . It was observed that MO from mPDN-treated mice were unable to produce sufficient levels of both TNF-alpha and NO when stimulated in vitro with lipopolysaccharide, IFN-gamma or conidia from an opportunistic fungus, Aspergillus fumigatus, confirming that corticosteroids are able to inhibit the antimicrobial activity of MO . However, MO from mice received mPDN plus pidotimod fully recovered the capacity to produce TNF-alpha and NO in response to the same stimuli . Optimal dose of pidotimod was 100 mg/kg . In addition, pidotimod was also able to reconstitute the cellularity of the peritoneum and of the spleens of mice immunodepressed by mPDN.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharm Acta Helv, 1994 Dec, 69(3), 159 - 62
Cytotoxicity tests of antibacterial agents on human fibroblasts cultures; Rivalland P et al.; The authors tried to determine and compare the cytotoxicity of several primary substances used in cosmetic or pharmaceutic industry as antimicrobial agents, on single-layer cultures of human fibroblasts . The cytotoxic effect of Germall 115*, Kathon CG* and Pentonium* was pointed out using the colorimetric method with MTT (3-{4-5-dimethyl thiazol 2-yl}-2,5 diphenyl tetrazolium bromide) . For each one of these substances, we tested different concentrations with variable contact times . These trials allowed us to classify these products by increasing toxicity as follows: Kathon CG* and Pentonium* . In our experimental conditions, Germall 115* was not cytotoxic.

J Antibiot (Tokyo), 1994 Dec, 47(12), 1456 - 65
Directed biosynthesis of 5"-fluoropactamycin in Streptomyces pactum; Adams ES et al.; A new pactamycin analogue, 5"-fluoropactamycin, was prepared by directed biosynthesis . Supplementation of the fermentation medium of Streptomyces pactum, var . pactum with 3-amino-5-fluorobenzoic acid, an analogue of 3-aminobenzoic acid, an advanced precursor in pactamycin biosynthesis, resulted in co-production of pactamycin and the new pactamycin analogue . A similar feeding experiment with 3-amino-5-methylbenzoic acid did not result in formation of the corresponding methylated pactamycin analogue, but only in inhibition of pactamycin production . Comparison of antimicrobial and cytotoxic activities of pactamycin and 5"-fluoropactamycin showed no significant differences.

Immun Infekt, 1994 Dec, 22(6), 200 - 3
{Microbiological diagnosis of sepsis}; Ullmann U; The detection of microorganisms responsible for septicemia from blood and their susceptibility testing against antimicrobial agents is the main requirement to treat this life threatening infection . The sample of specimens, their transport and the handling of blood cultures in the microbiological laboratory are really important, e.g . the number of blood cultures needed, the proper interval between these cultures, the volume of blood cultures and the use of sterile techniques . Recommendations are given for this important management . Conventional methods for blood cultures as well as new automatically working techniques are described.

J Dent Res, 1994 Dec, 73(12), 1811 - 7
Physiological regulation of the secretion of histatins and statherins in human parotid saliva; Jensen JL et al.; The small salivary phosphoproteins, histatins and statherins, have important functions in the oral cavity in terms of antimicrobial actions and regulation of calcium phosphate homeostasis . Neither the effects of various physiological stimuli on their secretion nor the nature of the efferent receptor involved in the stimulus-secretion coupling has been determined previously . These aspects are important for improved understanding of the secretory control of salivary proteins and may have implications regarding the effects of specific medications on salivary constituents and oral health . The effects of graded mechanical (chewing on short and long silicone tubings) and gustatory stimulation (0.5, 1.5, and 5.0% citric acid) on the secretion of histatins and statherins were studied in the presence and absence of adrenolytic agents (n = 10) . In this model, secretory rates of both proteins increased with increases in flow rate, with 5.0% citric acid representing a particularly potent stimulus . Histatin and statherin secretory rates were significantly reduced by the beta 1-adrenolytic agent (histatins to 58 to 72% and statherins to 11 to 29% of that in corresponding control experiments), but not by the alpha 1-adrenolytic agent . Since the beta 1-adrenergic receptors played an important role in the stimulus-secretion coupling of these proteins, protective salivary functions in the oral cavity may be compromised during beta 1-adrenolytic treatment.

Appl Environ Microbiol, 1994 Dec, 60(12), 4553 - 8
Ability of laboratory methods to predict in-use efficacy of antimicrobial preservatives in an experimental cosmetic; Farrington JK et al.; The abilities of nine antimicrobial systems to preserve an experimental water-based cosmetic formulation were evaluated by six microbiological challenge tests: the U.S . Pharmacopeia test; the British Pharmacopeia test; the Cosmetic, Toiletry, and Fragrance Association test; the rapid screen test; the sequential challenge test; and the post-use test . The antimicrobial systems contained various combinations and amounts of two parabens and a quaternary compound in order to provide a broad range of preservation . The results obtained were compared with the abilities of the formulations to support maintenance and growth of microorganisms in microfloras obtained from human axilla areas and finger skin during an 8-week simulated in-use test . Without statistical analysis all of the tests predicted the results obtained with well-preserved or poorly preserved formulations . The rapid screen test was the best test for predicting differences at intermediate levels of preservation . Statistically, all of the tests were equivalent predictors of preservation efficacy in the in-use test (P = 0.05) . At the P = 0.10 level, only the U.S . Pharmacopeia, British Pharmacopeia, rapid screen, Cosmetic, Toiletry, and Fragrance Association tests were significantly predictive . The results of prediction by a test, based on the preservative levels used, agreed well with the in-use test results (P = 0.01) . A total of 20% of the formulations that contained excessive microbial levels contained human axilla microorganisms . The levels of preservation in failed products were similar to the levels of preservation in unused controls.

Am J Trop Med Hyg, 1994 Dec, 51(6), 870 - 4
Etiology of acute diarrhea among United States Embassy personnel and dependents in Cairo, Egypt; Haberberger RL Jr et al.; The purpose of this study was to identify the enteropathogens causing acute diarrheal disease in Americans living in the North Africa/Middle East region during a 34-month period from February 12, 1985 to December 30, 1987 to guide preventive and therapeutic measures . Stool specimens were examined and an epidemiologic questionnaire was administered to patients with acute diarrhea at the Outpatient Health Unit of the United States Embassy in Cairo, Egypt . The subjects consisted of 126 American employees and dependents of the U . S . Embassy in Cairo, Egypt with diarrhea of less than two-weeks duration . Subjects received routine medical care administered by the U.S . Embassy Medical staff . A possible etiologic agent was detected in 41% of the subjects . Enteroadherent Escherichia coli was the most commonly isolated enteropathogen . A high degree of antimicrobial resistance was noted among the bacterial isolates, but all were susceptible to the quinolone antibiotics . Episodes of acute diarrhea occurring among American expatriates in Cairo, Egypt were primarily of bacterial etiology, but only a small portion were caused by the bacterial pathogens routinely identified in a standard clinical bacteriology laboratory . Most of the diarrheal episodes were due to noninvasive enteroadherent E . coli that may cause prolonged disease requiring antimicrobial therapy.

Planta Med, 1994 Dec, 60(6), 550 - 2
Nematicidal activities of two phytoalexins from Taverniera abyssinica; Stadler M et al.; The traditional analgesic and antipyretic Ethiopian drug "Dingetegna" is made of dried root material of Taverniera abyssinica A . Rich (Leguminosae) . In a screening for nematicidal natural products, "Dingetegna" extracts showed strong nematicidal activities towards C . elegans . In the following, medicarpin and 4-hydroxymedicarpin were isolated as nematicidal constituents from the extracts . In a microwell plate assay for nematicidal activity, both compounds exhibited an LD50 of 25 micrograms/ml towards C . elegans . Beside these nematicidal effects, weak cytotoxic and antimicrobial activities were observed . In addition, both compounds inhibited oxygen consumption of axenically grown C . elegans, L 1210 cells, and filamentous fungi . Respiration in sensitive bacteria was not affected . In L 1210 cells, the incorporation of precursors into macromolecules was affected in the presence of glucose, indicating that inhibition of respiration is not the only target site of the compounds.

Planta Med, 1994 Dec, 60(6), 532 - 7
Biological activities of selected marine natural products; Konig GM et al.; Sixty-nine natural products derived from Phaeophyta (brown algae), Rhodophyta (red algae), Porifera (sponges), Cnidaria (soft corals), and Mollusca (nudibranchs) were investigated for their cytotoxic, antimalarial, and antimicrobial effects . Fifty-six were found to mediate a positive response in one or more of these test systems.

Singapore Med J, 1994 Dec, 35(6), 626 - 30
Update of systemic antimicrobials: emphasis on oral agents; Allen DM et al.; There has been a proliferation of antimicrobial agents in the market and we can expect many more new agents to be available for use in the hospital and community later . In the outpatient setting, the number of oral antimicrobial agents are varied, providing greater flexibility in managing community acquired infections . Unfortunately, the extensive use of antimicrobial agents has contributed to the development of resistance of some bacteria to multiple antimicrobials . This paper will review the basis of activity of antimicrobial agents commonly used in the outpatient clinic . The spectrum of antibacterial activity of these agents is discussed in relation to the common organisms encountered in general practice . Guidelines for the control of the development of bacterial antimicrobial resistance are also given.

Eur J Gastroenterol Hepatol, 1994 Dec, 6 Suppl 1, S121 - 4
Effects of anti-ulcer agents on antibiotic activity against Helicobacter pylori; Sunairi M et al.; OBJECTIVE: To investigate the mechanism of action of a series of potential combination therapies for use against Helicobacter pylori . DESIGN: The effects of certain anti-ulcer agents on the antimicrobial activity of antibiotics effective against H . pylori were determined in vitro . METHODS: H . pylori was cultured on Skirrow's agar . Amoxycillin, clarithromycin, erythromycin and tetracycline were used . The anti-ulcer agents studied comprised aluminum chloride, sofalcone {2'-carboxymethyl 4,4'-bis(3-methyl-2-butenyloxy)chalcone} and zinc chloride . Urease activity was measured by the urease-indophenol method . The minimum inhibitory concentration was determined by a plating method, with H . pylori streaked on plates containing various concentrations of the antibiotics plus sublethal doses of the anti-ulcer agents . RESULTS: This in vitro study showed that sofalcone had a direct antibacterial effect and, in addition, inhibited the adhesive property of H . pylori . It did not inhibit the antimicrobial activity of the antibiotics amoxycillin, clarithromycin, erythromycin or tetracycline against H . pylori . The metal ions had inhibitory effects on the antimicrobial activity of amoxycillin, erythromycin and tetracycline, but not on that of clarithromycin . CONCLUSION: This study suggests that sofalcone is a suitable candidate for combination therapy.

J Antimicrob Chemother, 1994 Dec, 34(6), 875 - 83
In-vitro and in-vivo activity of a new quinolone AM-1155 against Mycoplasma pneumoniae; Ishida K et al.; We investigated the in-vitro and in-vivo activity of a new quinolone AM-1155 against Mycoplasma pneumoniae, and compared it with ofloxacin, ciprofloxacin, lomefloxacin, tosufloxacin, erythromycin and minocycline . AM-1155 was the most potent agent in vitro of the quinolones tested . Its pre-treatment minimal inhibitory concentrations for 90% of the 41 strains (MIC90) was 0.06 mg/L . In contrast, pre-treatment MIC90 values for ofloxacin, ciprofloxacin, lomefloxacin, tosufloxacin, erythromycin, and minocycline were 1, 1, 2, 0.5, 0.0156, and 0.5 mg/L, respectively . Post-treatments MIC90s, which may reflect mycoplasmacidal potency, of AM-1155, ofloxacin, ciprofloxacin, lomefloxacin, tosufloxacin, erythromycin and minocycline were 0.125, 1, 2, 4, 0.5, 0.125 and 4 mg/L, respectively . In-vitro activities of antimicrobial agents were assessed in an experimental pulmonary infection model in Syrian golden hamsters . AM-1155 was the most effective agent among five antimicrobial agents (AM-1155, ofloxacin, tosufloxacin, erythromycin, minocycline) tested in terms of reduction in viable M . pneumoniae cells and in reducing macroscopic lung lesions . These results suggest that AM-1155 will be a useful antimicrobial agent for the treatment of M . pneumoniae infections.

J Am Vet Med Assoc, 1994 Dec 1, 205(11), 1577 - 80
Epiglottitis in horses: 20 cases (1988-1993); Hawkins JF et al.; Epiglottitis was diagnosed and treated in 20 horses (13 Thoroughbreds and 7 Standardbreds) over a 5-year period . Eighteen horses were used for racing, and 2 Standardbreds were broodmares . Primary clinical signs were exercise intolerance, respiratory noise, and coughing . The most common endoscopic diagnosis made by referring veterinarians was epiglottic entrapment (11 horses) . In 19 horses, endoscopic evaluation at admission revealed mucosal ulceration and thickening of the lingual surface of the epiglottis . Other endoscopic findings included dorsal displacement of the soft palate (14 horses), and dorsal deviation of the epiglottic axis (11 horses) . Only 1 horse had epiglottic entrapment . Treatment consisting of stall confinement for 7 to 14 days, topical administration of a solution of furacin, dimethyl sulfoxide, glycerin, and prednisolone, and systemic administration of nonsteroidal anti-inflammatory drugs and corticosteroids was effective in controlling epiglottic edema and inflammation . Antimicrobials were administered to 6 horses . Racing performance of the 18 racehorses was evaluated by examination of racing records . One horse was still convalescing at the time of the study, and 1 horse had been euthanatized 1 week after treatment for epiglottitis because of colic . The remaining 16 horses all started at least 1 race (mean time between initial examination and start of first race, 74 days; range, 8 to 265 days) . Thirteen horses started at least 4 races following treatment for epiglottitis; racing performance after treatment was the same in 8 and decreased in 5 . Long-term sequelae of epiglottitis included epiglottic deformity (5 horses), intermittent or persistent dorsal displacement of the soft palate (4 horses), and epiglottic entrapment (1 horse).

J Am Vet Med Assoc, 1994 Dec 1, 205(11), 1569 - 73
Ventricular tachycardia and myocardial dysfunction in a horse; Traub-Dargatz JL et al.; Ventricular tachycardia develops less frequently than supraventricular dysrhythmias and generally is more indicative of cardiac disease . The horse in this report had clinical signs of lethargy and hypophagia and was determined to have sustained ventricular tachycardia . Echocardiography was a valuable diagnostic tool and revealed an echodense area in the left ventricle that had subnormal ventricular performance . A primary heart problem of an inflammatory nature was suspected . The horse responded favorably to treatment with lidocaine, antimicrobials, and aspirin, as well as stall rest . The horse was used successfully as a sire and hunter-jumper after treatment, but subsequently died 2.2 years later of massive hemoperitoneum . Necropsy revealed an extensive area in the left ventricle that appeared thin and fibrotic.

Rozhl Chir, 1994 Dec, 73(8), 392 - 3
{Peroperative prophylaxis with peroral Tarivid (Hoechst) in laparoscopic cholecystectomy}; Stembera S; The author gives an account on the healing of surgical wounds in a group of 111 patients operated on account of cholelithiasis . The patients were given ofloxacin by the oral route during the peroperative stage as ultra-short antimicrobial prophylaxis . The possibility to administer the drug by the oral route in the peroperative period is a new finding.

Mil Med, 1994 Dec, 159(12), 732 - 5
Regulation of beta-lactamase induction in gram-negative bacteria: a key to understanding the resistance puzzle; Niemeyer DM; Infections caused by drug-resistant microorganisms have posed a medical challenge since the advent of antimicrobial therapy . With the emergence of resistant strains, new antibiotics were available and introduced with great success until this decade . The appearance of multiresistant microorganisms pose a real and immediate public health concern . Are we entering into the post-antibiotic era? Will we return to pre-antimicrobial-era conditions, with morbidity and mortality resulting from untreatable infectious complications? The race to stay ahead of multiresistance involves not only continued drug development and selective use but elucidation of bacterial regulation of resistance . One way to ensure continued success of antimicrobial therapy is the identification of new bacterial targets--genes and their products involved in regulating or mediating resistance . Discussion will focus on one well-defined resistance mechanism in Gram-negative bacteria, the chromosomally located amp operon, responsible for one mechanism of beta-lactam resistance.

Mol Microbiol, 1994 Dec, 14(5), 895 - 904
Amoebapores, a family of membranolytic peptides from cytoplasmic granules of Entamoeba histolytica: isolation, primary structure, and pore formation in bacterial cytoplasmic membranes; Leippe M et al.; Three peptides with pore-forming activity were isolated from the cytoplasmic granules of pathogenic Entamoeba histolytica by acidic extraction, gel filtration and reversed-phase high-performance liquid chromatography . Partial amino acid sequence analysis of the three active peptides revealed that the most abundant of them was amoebapore and the other two were isoforms thereof . Cloning and sequencing of genomic DNA resolved the amino acid sequence of the two newly recognized peptides . The three peptides designated amoebapores A, B and C were found to have the same molecular size but to differ markedly in their primary structure, although all six cysteine residues are conserved . Despite sequence divergence, structural implications predict for the three peptides a similar amphipathic alpha-helical conformation stabilized by disulphide bonds . All three isoforms exhibit pore-forming activity toward lipid vesicles, but they differ in their kinetics . They also are capable of perturbing the integrity of bacterial cytoplasmic membranes and thereby kill Gram-positive bacteria . The amoebapores represent a distinct family of membrane-active peptides that may function intracellularly as antimicrobial agents but may also confer cytolytic activity on the parasite.

J Nat Prod, 1994 Dec, 57(12), 1711 - 6
Biological effects of prenylated hydroquinones: structure-activity relationship studies in antimicrobial, brine shrimp, and fish lethality assays; De Rosa S et al.; Twenty-three hydroquinone and quinone derivatives were assayed for antimicrobial effects and brine shrimp and fish lethalities, to establish relevant structure-activity relationships (SAR) . Linear 2-prenyl-1,4-hydroquinones used for bioassay were obtained either by isolation from the sponge Ircinia spinosula or by synthesis . Corresponding quinones, as well as hydroquinones possessing saturated side-chains composed of one to eight isopentane units, were also synthesized and biologically evaluated . Terpenoid 1,4-benzoquinones displayed moderate antimicrobial activity against three microorganisms, SAR studies indicate the optimum length of the side-chain is in the range of five to fifteen carbon atoms.

Vet Clin North Am Equine Pract, 1994 Dec, 10(3), 527 - 34
Antimicrobial therapy of adult horses with emergency conditions; Brumbaugh GW; In emergency conditions, antimicrobial treatment is subordinate to truly life-supporting measures . Antimicrobial treatment should be formulated rationally for each patient and should not simply be a matter of following a recipe . This article presents principles for guiding rational therapeutic decision-making and examples of conditions in which those principles can be applied.

Mol Mar Biol Biotechnol, 1994 Dec, 3(6), 327 - 33
In vitro activity of the antimicrobial peptide magainin 1 against Bonamia ostreae, the intrahemocytic parasite of the flat oyster Ostrea edulis; Morvan A et al.; Magainins are peptide antibiotics with broad antibacterial and antiparasitic activities, originally extracted from the skin of Xenopus laevis . We investigated the effects of magainin 1 against Bonamia ostreae, the intrahemocytic parasite of the flat oyster Ostrea edulis . Viability of purified protozoa was assessed microscopically by the uptake of the vital dyes acridine orange and ethidium bromide . Following exposure to magainin 1, Bonamia viability was reduced in a dose-dependent manner . Within the peptide concentration of 500 micrograms/ml, the parasite viability was reduced by 94% . Electron microscopy showed membrane damage and release of cytoplasmic organelles in the injured Bonamia . The study of magainin 1 activity against Ostrea edulis hemocytes did not show any morphological change in the host cells, and the peptide did not impair the capabilities of hemocytes to produce chemiluminescence when stimulated to phagocytize zymosan particles . The possibility to genetically transform molluscs to generate disease-resistant organisms is currently under investigation . Antimicrobial peptides such as magainins may provide effective gene sequences to be manipulated.

Biomaterials, 1994 Dec, 15(15), 1235 - 41
Recent results on functional polymers and macromonomers of interest as biomaterials or for biomaterial modification; Ferruti P et al.; Different families of functionalized polymers with potential as biomaterials, or for biomaterial modification, have been investigated . In particular, degradation studies have been performed on poly(amidoamines), a family of polymers obtained by polyaddition of amines to bisacrylamides, and endowed with heparin-complexing ability . Some new poly(amidoamines) with more resistance towards hydrolytic degradation than traditional ones have been discovered . Other ter-amino polymers deriving from the polyaddition of ter-amino functionalized bis-thiols to bis-acrylic esters, or other activated unsaturated compounds, have been studied . Their quaternarization products have been proven, in a parallel work, to act as powerful antimicrobial agents . By performing in situ the polyaddition reaction, semi-interpenetrated networks based on silicone rubber and the same polymers have been prepared . Finally, end-functionalized amphiphilic oligomers have been prepared by radical polymerization techniques, and their use for enzyme modification considered.

Rhinology, 1994 Dec, 32(4), 161 - 5
Endoscopic versus Caldwell-Luc approach in chronic maxillary sinusitis: comparison of symptoms at one-year follow-up; Penttila MA et al.; The aim of this prospective randomized study was to compare functional endoscopic sinus surgery (FESS) with the standard Caldwell-Luc (C-L) procedure in relieving the symptoms of chronic maxillary sinusitis . One hundred and fifty consecutive adult patients were operated after the failure of treatment with antimicrobials and repeated antral irrigations: 143 patients were available for the follow-up examination, at a median of 12 months after the operation . The patients' global evaluation showed marked improvement in 50.7% of the C-L group and in 76.7% of the FESS group . Overall subjective symptoms deteriorated in 5.5% of C-L operated patients, but not at all in the FESS group . Patients' compliance, asked post-operatively, was 80.2% in C-L patients and 93.0% in FESS patients.

J Chemother, 1994 Dec, 6(6), 404 - 7
Effect of temperature on antimicrobial susceptibilities of Pseudomonas species isolated from drinking water; Papapetropoulou M et al.; The susceptibility of 20 strains of Pseudomonas species isolated from drinking waters (4 P . aeruginosa, 7 P . fluorescens, 5 P . stutzeri, 1 P . maltophilia, 1 P . cepacia, 1 P . putida and 1 P . pickettii) to a variety of antibiotics (gentamicin, amikacin, azlocillin, cefotaxime, chloramphenicol and polymyxin B) were determined by Stoke's method at 20 degrees C, 30 degrees C, 37 degrees C and 42 degrees C . Minimum inhibitory concentrations (MIC) were determined for aminoglycosides on Mueller-Hinton agar at the above temperatures . There was a significant difference in susceptibility between 20 degrees C or 30 degrees C (most resistant), 37 degrees C (more susceptible) and 42 degrees C (most susceptible) to gentamicin and to a lesser degree to amikacin for P . maltophilia, P . cepacia and most strains of P . fluorescens . The P . aeruginosa, P . stutzeri, P . putida and P . pickettii strains showed no difference in susceptibility at 20 degrees C, 30 degrees C, 37 degrees C and 42 degrees C . The need for standardized conditions with special regard to temperature when antibiotic susceptibility tests are performed for P . maltophilia, P . cepacia and P . fluorescens strains is stressed.

Chem Pharm Bull (Tokyo), 1994 Dec, 42(12), 2472 - 4
Correlation between zeta-potential of a cell in a new cationic disinfectant solution and minimum inhibitory concentration of the disinfectant; Makino M et al.; In the previous paper, we described the synthesis of new quaternary ammonium slats with antimicrobial activity: N-alkyl-N-2-hydroxyethyl-N,N-dimethylammonium butyl phosphate (4) and N-alkyl-N-(2-hydroxy-3-phenoxy)-propyl-N,N-dimethylammonium butyl phosphate (5) . In this study, we examined the relationship between the MIC (minimum inhibitory concentration) of these new cationic disinfectants, 4 (six compounds) and 5 (three compounds), and the xi-potential against Escherichia coli in solutions of these compounds . The MIC values of these disinfectants against E . coli were highly correlated with the concentration that induced electric charge inversion (xi-potential=0) of E . coli from negative to positive.

Antimicrob Agents Chemother, 1994 Dec, 38(12), 2775 - 9
Nitric oxide donor-mediated killing of bioluminescent Escherichia coli; Virta M et al.; The antimicrobial activities of two nitric oxide-releasing compounds against Escherichia coli were investigated by using recombinant E . coli cloned with a luciferase gene from Pyrophorus plagiophthalamus . Since luciferase uses intracellular ATP to generate visible light which can be measured from living cells in real time, we wanted to compare the extent to which cell viability parallels light emission . Results from luminescence measurements and CFU counts were in good agreement, and the decrease in light emission was shown to provide a rapid and more sensitive indication of cytotoxicity.

Antimicrob Agents Chemother, 1994 Dec, 38(12), 2738 - 42
Effects of clarithromycin and rifabutin alone and in combination on intracellular and extracellular replication of Mycobacterium avium; Mor N et al.; The combined effect of clarithromycin and rifabutin against Mycobacterium avium multiplying either within human monocyte-derived macrophages or extracellularly in a liquid medium was additive: both MICs and MBCs were twofold lower for the combination than they were for each drug alone . Prolonged exposure for 4 weeks of M . avium-infected macrophages to combined concentrations that were only twofold greater than the MICs resulted in a 100-fold decrease in the number of viable bacteria, while in the drug-free controls a 100-fold or greater increase in comparison with the initial viable counts took place . Comparison of this effect with the results of the prolonged exposure to each drug alone suggested that under these experimental conditions rifabutin enhanced the antimicrobial activity of clarithromycin against intracellular bacteria . At the same time, inhibition of intracellular growth by a 2-h pulsed exposure of the infected macrophages to the combination of the two drugs was not different from the effect induced by clarithromycin alone . In conclusion, clarithromycin played the major role in the antimicrobial activity of the tested combination, while rifabutin may have enhanced this effect during a prolonged exposure of the intracellular bacteria to these two agents.

Med J Malaysia, 1994 Dec, 49(4), 317 - 26
Antimicrobial resistance in 6 Malaysian general hospitals; Cheong YM et al.; Knowledge of local antimicrobial resistance patterns of bacteria is a valuable guide to empirical antimicrobial therapy . This paper reports the resistance patterns of more than 36,000 bacteria isolated between August 1991 and July 1992 in six Malaysian hospitals and discusses the implications of the results . A customized menu driven software programme was developed to analyse the results . Generally, resistance to the commonly used antibiotics like ampicillin, cloxacillin, cephalosporins, gentamicin, cotrimoxazole and tetracycline was high . Some differences in resistance rate amongst the six hospitals were also noted . Continuous surveillance of antimicrobial resistance in hospitals is encouraged for the effective control of the emergence of antimicrobial resistance.

Ital J Gastroenterol, 1994 Dec, 26(9), 449 - 58
Chronic gastritis, intestinal metaplasia, dysplasia and Helicobacter pylori in gastric cancer: putting the pieces together; Dobrilla G et al.; Chronic gastritis may favour the development of gastric cancer more as a condition than as precancerous lesion . Since, in most cases, it is pathologically correlated with Helicobacter pylori infection, it is reasonable to postulate at least an indirect role for this organism in the pathogenesis of gastric cancer . H . pylori, however, is only one of the risk factors involved, in that additional factors (excess salt, cigarette smoking, deficiency of foodstuffs with an antioxidizing effect) may facilitate the malignant transformation of chronic atrophic gastritis into intestinal-type gastric cancer . Gastric carcinogenesis therefore presents itself as a multifactorial, multistage process, furthered by the occurrence of precancerous lesions which are usually interrelated (type-III intestinal metaplasia, severe dysplasia) and by functional alterations such as achlorhydria, which, though it is not enough in itself to cause gastric cancer, promotes abnormal intragastric bacterial development, a condition which may be followed by abnormal intragastric formation of cancerogenous nitroso compounds . The existence of a close correlation between both gastric cancer and H . pylori infection and low socio-economic and hygienic status of the population lends further strength to the hypothesis that an "H . pylori factor" is involved in gastric carcinogenesis . Consequently, to reduce the risk of gastric cancer, various strategies have been devised to prevent H . pylori infection (improvement in socio-environmental conditions, anti-H . pylori vaccine) and/or to eradicate the organism (by means of therapeutic regimens including antimicrobial agents, which, however, can be implemented only in patients who have not developed diffuse atrophy and/or dysplasia, in whom H . pylori may no longer be detectable) . Definitive proof of the real extent of the relationship between H . pylori and gastric cancer and of the efficacy of therapeutic and preventive measures can be provided only by controlled trials in populations with a high prevalence of chronic non-atrophic gastritis which are difficult to organize.

Immunol Lett, 1994 Dec, 43(1-2), 87 - 94
Nitric oxide: cytokine-regulation of nitric oxide in host resistance to intracellular pathogens; Green SJ et al.; To discover how nitric oxide (NO) synthesis is controlled in different tissues as cells within these tissues combat intracellular pathogens, we examined three distinctively different experimental murine models designed for studying parasite-host interactions: macrophage killing of Leishmania major; nonspecific protection against tularemia (Francisella tularensis) by Mycobacterium bovis (BCG); and specific vaccine-induced protection against hepatic malaria with Plasmodium berghei . Each model parasite and host system provides information on the source and role of NO during infection and the factors that induce or inhibit its production . The in vitro assay for macrophage antimicrobial activity against L . major identified cytokines involved in regulating NO-mediated killing of this intracellular protozoan . L . major induced the production of two competing cytokines in infected macrophages: (1) the parasite activated the gene for tumor necrosis factor (TNF), and production of TNF protein was enhanced by the presence of interferon-gamma (IFN-gamma) . TNF then acted as a autocrine signal to amplify IFN-gamma-induced production of NO; and (2) the parasite upregulated production of transforming growth factor-beta (TGF-beta), which blocked IFN-gamma-induced production of NO . Whether parasite-induced TNF (parasite destruction) or TGF-beta (parasite survival) prevailed depended upon the presence and quantity of IFN-gamma at the time of infection . The relationship between NO production in vivo and host resistance to infection was demonstrated with M . bovis (BCG).(ABSTRACT TRUNCATED AT 250 WORDS)

Biochem Biophys Res Commun, 1994 Nov 30, 205(1), 948 - 54
Antimicrobial peptides from the skin of a Korean frog, Rana rugosa; Park JM et al.; Six antimicrobial peptides, named gaegurins, were isolated from the skin of a Korean frog, Rana rugosa, and their amino acid sequences were determined by automated Edman degradation . All peptides contain two invariant cysteine residues, one at their C-terminus and the second at the seventh position from the C-terminus . The heptapeptides containing these two cysteine residues, which we designate 'Rana boxes', are conserved in the antimicrobial peptides derived from other Rana species . Each peptide manifested a broad spectrum of antimicrobial activity against Gram positive and Gram negative bacteria, fungi and protozoa with slightly different specific activities . All gaegurins manifest very little or no hemolytic activity . These properties provide the potential for application of these peptides to effective therapeutic agents for control of pathogenic microorganisms.

Tidsskr Nor Laegeforen, 1994 Nov 30, 114(29), 3463 - 5
{Preoperative hand disinfection}; Kristiansen BE et al.; At Telemark Central Hospital we decided to change the procedure for preoperative disinfection of the hands in order to improve antimicrobial efficacy and to minimize skin problems for the personnel . Previously, preoperative disinfection of hands was performed by scrubbing the hand with a detergent containing chlorohexidine (Hibiscrub) which often caused dryness, fissures and dermatitis . In the recent years it has been amply shown that alcoholic solutions have a very good and immediate antibacterial effect on the skin flora, while chlorohexidine has a prolonged effect . In this paper we describe our new procedures for preoperative disinfection of hands and the necessary planning and preparation we undertook to obtain acceptance for these procedures among the personnel.

Schweiz Rundsch Med Prax, 1994 Nov 22, 83(47), 1324 - 31
{Therapy of infectious endocarditis}; Blatter M et al.; The response of infective endocarditis to antimicrobial therapy is slow because host defence mechanisms in heart valves are absent, high bacterial densities occur in vegetations and the infecting agents have a low metabolic activity . In this situation, only an optimal antibiotic treatment can be effective; therefore early identification of the microorganism by means of blood cultures and the use of bactericidal antibiotics with proven efficacy in clinical trials are essential . The antibiotics should be administered intravenously, because constant and high serum levels are important . The choice of the empirical therapy is based on the patient's history, on clinical signs and symptoms as well as on some additional examinations in order to define the most probable organisms involved . As soon as the infecting agent is identified, the treatment should be optimized . A daily clinical examination of the patient and frequent laboratory controls are needed . In case of poor clinical response to the antimicrobial therapy, the search for complications is frequently more appropriate than changing the antibiotics . The duration of therapy depends on the infecting agent, the evolution and the antibiotic regimen that has been chosen . After treatment, blood cultures should be taken at four and eight weeks, since most relapses appear within this period.

Med J Aust, 1994 Nov 21, 161(10), 615 - 8
Control of infections in child care; Ferson MJ; The control of infections in child-care centres involves vaccination of children and staff, attention to hygiene (particularly to handwashing), exclusion of children (and employees) while infectious and/or grouping of infectious children, separation of toilet-trained children from those in nappies, and judicious use of antimicrobial agents and vaccination during outbreaks . By reporting cases of infectious diseases in patients with child-care contact to public health authorities, doctors can assist in controlling such diseases in child care.

Proc Natl Acad Sci U S A, 1994 Nov 8, 91(23), 11138 - 42
"Libraries from libraries": chemical transformation of combinatorial libraries to extend the range and repertoire of chemical diversity; Ostresh JM et al.; The generation of diverse chemical libraries using a "libraries from libraries" concept is described . The central features of the approaches presented are the use of well-established solid-phase synthesis methods for the generation of combinatorial libraries, combined with the chemical transformation of such libraries while they remain attached to the solid support . The chemical libraries that are generated by this process have very different physical, chemical, and biological properties compared to the libraries from which they were derived . A wide range of chemical transformations are possible for peptide-based or other libraries, and an almost unlimited range of useful chemical diversities can be envisioned . In the example presented, the amide functionalities in an existing combinatorial library made up of peptides were permethylated while the library remained attached to the solid-phase support used in its synthesis . After removal of the permethylated mixtures from their solid support, this library, now lacking the typical -CONH- amide bonds of peptides, can be tested in solution with virtually all existing assay systems to identify individual compounds having specific biological activities of interest . An illustration of the use of such libraries is presented, in which the described permethylated library was used to identify individual permethylated compounds having potent antimicrobial activity against Gram-positive bacteria.

Proc Natl Acad Sci U S A, 1994 Nov 8, 91(23), 11035 - 9
Syndecans, cell surface heparan sulfate proteoglycans, are induced by a proline-rich antimicrobial peptide from wounds; Gallo RL et al.; Cell surface heparan sulfate proteoglycans, such as the syndecans, are required for cellular responses to heparin-binding growth factors and extracellular matrix components . Expression of syndecan-1 and -4 is induced in mesenchymal cells during wound repair in the mouse, consistent with a role for syndecans in regulating cell proliferation and migration in response to these effectors . Here we show that wound fluid contains inductive activity that mimics the in vivo induction in time of appearance, specificity for mesenchymal cells, and selectivity for syndecan-1 and -4 . We have purified and synthesized a 4.8-kDa proline-rich protein from wound fluid that reproduces this induction of syndecan-1 and -4 in cultured cells . This peptide, identical to the antibacterial peptide PR-39, is released into the wound by the cellular infiltrate and induces syndecan expression at the same peptide concentrations that lyse bacteria . These results indicate that wounds contain a multifunctional protein that induces mammalian cells to express cell surface heparan sulfate proteoglycans as part of the wound repair process and that kills bacteria as part of a nonimmune defense mechanism.

Br J Nurs, 1994 Nov 24-Dec 7, 3(21), 1129 - 34
Drug therapy and peptic ulceration; Kelly J; Peptic ulceration can be treated by various types of drugs including antacids, protectors, antimicrobials and acid-secretion reducers . Nurses have a role to play in administering medicines, educating patients and, in future, prescribing drugs.

J Antibiot (Tokyo), 1994 Nov, 47(11), 1295 - 304
Rapid screening of the antimicrobial activity of extracts and natural products; Chand S et al.; A spectrophotometric method has been developed for the rapid measurement of the antimicrobial activity of natural products, including crude extracts or pure materials . The assay depends on the measurement of non-specific esterase activity using fluorescein diacetate (FDA) hydrolysis in broth cultures of microbes after they have been treated with test compounds . The assay is accurate, reproducible and economical in both time and materials . The speed and economy of the method make it suitable for the rapid screening of many samples and the bioassay directed purification of antimicrobial substances . The assay can also be used with a wide variety of micro-organisms since most micro-organisms are FDA positive . Applications are described in the fields of marine natural products chemistry and essential oils research.

J Antibiot (Tokyo), 1994 Nov, 47(11), 1284 - 9
New nematicidal and antimicrobial compounds from the basidiomycete Cheimonophyllum candidissimum (Berk & Curt.) sing . I . Producing organism, fermentation, isolation, and biological activities; Stadler M et al.; Six new bisabolane type sesquiterpenoids, cheimonophyllons A (1), B (2), C (3), D (4), E (5), and cheimonophyllal (6) were isolated from the culture fluid of the basidiomycete, Cheimonophyllum candidissimum . The compounds exhibited nematicidal, weak antifungal and antibacterial as well as cytotoxic activities . The main product, cheimonophyllon A (1) (C15H22O4), was also active in the Ames mutagenicity test.

J Antibiot (Tokyo), 1994 Nov, 47(11), 1280 - 3
Aldecalmycin, a new antimicrobial antibiotic from Streptomyces . III . Determination of absolute configuration; Sawa R et al.; The planar structure of aldecalmycin (1) had been determined in the previous paper, together with the conformations of the substituted trans decalin ring having one double bond and the sugar: beta-glucopyranoside type . The absolute configuration of 1 was a following problem to be solved . X-Ray crystallographic analysis of crystalline 4'-6'-O-benzylidenedihydroaldecalmycin (4) revealed the relative configuration . On the other hand, the stereoisomerism of the sugar was determined to be D by the optical rotation value of tetra-O-acetyl-alpha-methylglucopyranoside derived from 1 . These results established the absolute configuration of 1.

J Antibiot (Tokyo), 1994 Nov, 47(11), 1273 - 9
Aldecalmycin, a new antimicrobial antibiotic from Streptomyces . II . Structure elucidation by NMR studies; Sawa R et al.; A new antibiotic, aldecalmycin (1) was isolated from the culture broth of Streptomyces sp . MJ147-72F6 . The 1H and 13C NMR spectra of 1 were complicated due to the presence of a beta-ketoaldehyde moiety . Therefore, 1 was converted into an ethylene ketal derivative (2) and into a dihydroaldecalmycin (3) . These derivatives gave assignable NMR spectra . The planar structure was elucidated by using 1H-1H COSY, 2D-HOHAHA, 1H-13C COSY and HMBC spectra of 2 . The conformation of the decalin ring was elucidated by using ID-HOHAHA, NOE difference and NOESY spectra of 3 . The geometry of double bond in the side chain was determined by NOE difference and NOESY spectra of 3.

J Dent Res, 1994 Nov, 73(11), 1748 - 55
Chemostat flow cell system: an in vitro model for the evaluation of antiplaque agents; Herles S et al.; We developed an experimental in vitro model of dental plaque to assess the potential efficacy of antiplaque agents . The model used a chemostat, which provided a continuous source of 5 species of oral bacteria grown in an artificial "saliva-like" medium . This mixture was pumped through six flow cells, each containing two types of surfaces on which plaque formed and was subsequently measured . Formation of bacterial plaque on hydroxyapatite surfaces was assessed by measurement of the DNA and protein content of the plaque film . The amount of bacterial plaque formed on germanium surfaces was measured by attenuated total reflectance (ATR/FT-IR) spectroscopy . Plaque viability was also assessed by a fluorescent staining technique . The quantity of plaque formed on both types of surfaces gradually increased with the duration of flow (from 24 to 72 h) through the cells during a 72-hour experimental period . The flow cells were then pulsed with experimental treatment solutions for 30 s, twice daily . Parallel to results of human clinical studies, the model was capable of discriminating among water, a placebo mouthrinse, and an active antimicrobial mouthrinse formulation containing 0.03% triclosan . It therefore offers a valuable alternative to animal model testing and allows for more rapid evaluations under well-controlled experimental conditions.

Am J Med, 1994 Nov, 97(5), 459 - 67
Interferon-gamma and host antimicrobial defense: current and future clinical applications; Murray HW; In the 1980s, substantive experimental data and emerging clinical results suggested that interferon-gamma (IFN-gamma), a T-cell-derived lymphokine with broad macrophage-activating effects, had considerable potential in the treatment of nonviral infections as a host defense-enhancing antimicrobial agent . During the past 6 years, the breadth of the experimental activity with IFN-gamma against nonviral pathogens has been expanded still further, and pilot studies and formal clinical trials using IFN-gamma have been undertaken in the treatment of patients both at risk for and with active infections . Thus far, IFN-gamma has been approved for use as prophylaxis in patients with chronic granulomatous disease . However, IFN-gamma also appears effective as adjunctive therapy for at least one disseminated intracellular infection (visceral leishmaniasis), and in conjunction with conventional therapy, may benefit patients with certain forms of cutaneous leishmaniasis, disseminated Mycobacterium avium complex infection, and lepromatous leprosy . Despite a rationale for its use, IFN-gamma has not yet been tested in tuberculosis or fungal or common bacterial infections nor sufficiently examined in the prevention and/or treatment of the opportunistic infections related to acquired immunodeficiency syndrome . IFN-gamma remains a promising host defense-enhancing cytokine with still unexplored clinical potential.

AJR Am J Roentgenol, 1994 Nov, 163(5), 1031 - 5
Ventilator-associated pneumonia: clinical considerations; Kollef MH et al.; Nosocomial (i.e., originating or taking place in a hospital) pneumonia is the leading cause of death from acquired nosocomial infections . The estimated prevalence of nosocomial pneumonia in intensive care units ranges from 10% to 65%, with fatality rates of 13-55% . Ventilator-associated pneumonia (VAP) specifically refers to nosocomial pneumonia in a mechanically ventilated patient that was neither present nor already developing at the time of intubation (i.e., clinical evidence of VAP occurring > 48 hr after intubation) . During the past decade, some studies have suggested that VAP can be an important determinant of out-come for critically ill patients requiring mechanical ventilation . Recent investigations have provided new insights into the pathogenesis of VAP, and improved techniques have been developed for its diagnosis . Most important, emerging clinical data now suggest that new management strategies for VAP, including more specific indications for antimicrobial use, may significantly improve patients' outcomes.

Toxicol Appl Pharmacol, 1994 Nov, 129(1), 146 - 54
The correlation of serum luteinizing hormone levels with the induction of Leydig cell tumors in rats by oxolinic acid; Yamada T et al.; Studies were performed to examine the mechanism by which testicular Leydig cell tumors are induced in rats by administration of the antimicrobial agent oxolinic acid (1-ethyl-1,4-dihydro-6,7-methylenedioxy-4-oxo-3-quinolinecarboxylic acid) . In these studies, the effects of oxolinic acid on serum levels of luteinizing hormone (LH), testosterone, and prolactin and the binding of testosterone to prostatic androgen receptors were examined . In a long-term hormonal study, male Wistar rats were fed a diet containing oxolinic acid at 0, 100, 1000, or 3000 ppm for 104 weeks . A statistically significant increase in serum LH levels was observed at 1000 and 3000 ppm, but no dose of oxolinic acid had a significant effect on serum testosterone levels . Serum LH levels were no longer elevated above control levels within 2 weeks of cessation of the administration of oxolinic acid . Oxolinic acid was found to have no effect on the rate of clearance of exogenous LH from the circulation . Serum prolactin levels were decreased by the administration of oxolinic acid . The increase in serum LH induced by oxolinic acid was completely blocked by the intraperitoneal injection of the dopamine antagonist haloperidol (2 mg/kg) . In addition, no significant affinity of oxolinic acid for androgen receptors was found in an in vitro study . These findings suggest that: (1) oxolinic acid induces Leydig cell tumors in rats by chronically stimulating the release of LH from the pituitary, (2) the mechanism of stimulating the release of LH involves facilitation of the dopaminergic systems in the hypothalamus-pituitary axis, and (3) oxolinic acid has no effect on androgen-mediated feedback inhibition.

Chest, 1994 Nov, 106(5), 1438 - 42
Usefulness of miniature flexible fiberoptic bronchoscopy in children; Nussbaum E; A miniature flexible fiberoptic bronchoscope (FFB) (Olympus BF-N20) (2.2 mm diameter) was applied to 53 children (20 female subjects) ranging in age from 3 months to 15 years (mean, 4.19 years) . Most common indications for bronchoscopy included stridor or weak cry and persistent wheezing or cough unresponsive to inhaled bronchodilators, chest physiotherapy, steroids, and antimicrobial agents . There were no complications . In 38 children (71.6 percent) it was diagnostically useful, particularly for the investigations of upper airway obstruction (66 percent) . In 22 children (41.5 percent) it provided guidance for surgical interventions . The instrument was particularly useful during its application in infants with severe upper airway obstruction who otherwise would require open rigid-tube bronchoscopy in the operating room . It was of limited value when excessive bronchial secretions obstructed the view of the working field for which a bronchoscope with a built-in suction channel was needed . It is concluded that this miniature FFB is a useful diagnostic tool in infants and children particularly for obstructed upper airways but has limited applications in children with peripheral airway disease . The 2.2-mm bronchoscope may have its greatest advantage in preterm neonates and intubated infants, where the small glottic or endotracheal tube size renders the 3.5-mm bronchoscope useless.

Crit Care Med, 1994 Nov, 22(11), 1720 - 8
Platelet-activating factor receptor antagonist BN 52021 in the treatment of severe sepsis: a randomized, double-blind, placebo-controlled, multicenter clinical trial . BN 52021 Sepsis Study Group; Dhainaut JF et al.; OBJECTIVE: To evaluate the safety and efficacy of a natural platelet-activating factor receptor antagonist, BN 52021 (Ginkgolide B), in the treatment of patients with sepsis syndrome . DESIGN: Prospective, randomized, placebo-controlled, double-blind, phase III, multicenter clinical trial . SETTING: Twenty-one academic medical center intensive care units in France . PATIENTS: Two hundred sixty-two patients with sepsis syndrome who received standard supportive care and antimicrobial therapy, in addition to the administration of platelet-activating factor receptor antagonist or placebo . INTERVENTIONS: Patients received either a 120-mg dose of platelet-activating factor receptor antagonist intravenously every 12 hrs over a 4-day period or placebo . MAIN OUTCOME MEASUREMENTS: All patients were evaluated for 28-day, all-cause mortality . RESULTS: The 28-day mortality rate was 51% for the placebo group and 42% for the platelet-activating factor receptor antagonist group (p = .17) . However, the efficacy of platelet-activating factor receptor antagonist was significantly greater in patients with Gram-negative sepsis (test for interaction, p = .03) . In a separate analysis of patients with and without Gram-negative sepsis, the 28-day mortality rate was 57% for the patients receiving placebo (30 deaths of 53 patients) and 33% for patients receiving platelet-activating factor receptor antagonist (22 deaths of 67 patients; p = .01) . Platelet-activating factor receptor antagonist also significantly (p = .01) reduced the mortality rate among patients with Gram-negative sepsis who were in shock at entry into the study (mortality rate was 65% for placebo vs . 37% for platelet-activating factor receptor antagonist) and among patients > 60 yrs of age (mortality rate was 74% for placebo vs . 31% for platelet-activating factor receptor antagonist) . A Cox proportional-hazards model identified five independent prognostic factors: a) adequacy of antibiotic therapy; b) severity of illness; c) renal failure; d) hematologic failure; and e) hepatic failure at study entry . When the Gram-negative sepsis population was stratified by age and these five prognostic factors were controlled for, the relative risk of death of the platelet-activating factor receptor antagonist group was 0.61 (0.34 to 1.08, 95% confidence interval; p = .09) . This risk corresponds with an adjusted reduction in mortality rate of 39% for patients receiving platelet-activating factor receptor antagonist . No differences in mortality rates were found between the placebo and the platelet-activating factor receptor antagonist groups in the absence of Gram-negative sepsis . There were no differences in adverse events between the placebo and the treated groups . CONCLUSION: The studied platelet-activating factor receptor antagonist (BN 52021) seems to be a safe and promising treatment for patients with severe Gram-negative sepsis.

Clin Pharmacol Ther, 1994 Nov, 56(5), 587 - 91
Photoreactions with a fluoroquinolone antimicrobial: evening versus morning dosing; Lowe NJ et al.; Quinolone antimicrobials absorb ultraviolet radiation and, with appropriate drug concentrations, may cause photoreactions . Photoreactions have been reported for several quinolones, including lomefloxacin, a difluorinated quinolone antimicrobial . This study was designed to determine whether the interval between administration of lomefloxacin and exposure to ultraviolet A (UVA) light would affect skin responses . The minimal erythema dose (MED) and severity of local reactions were the main parameters of evaluation . Exposure to UVA radiation 2 hours after morning dosing caused an increase in skin sensitivity as assessed by changes in MED (p < 0.05) . No changes were observed with exposure 16 hours after evening dosing (p = 1.00) . Edema and blisters at the radiation sites were observed in only the morning dosing group . A significant negative correlation was observed between lomefloxacin plasma concentrations and change MEDs (r = -0.72; p < 0.05) . An evening dosing strategy may minimize the risk of phototoxic effects.

Am J Respir Crit Care Med, 1994 Nov, 150(5 Pt 1), 1456 - 9
Persistence of Pneumocystis carinii in patients with AIDS receiving chemoprophylaxis; Epstein LJ et al.; Pneumocystis carinii organisms have been shown to persist throughout therapy in the majority of patients with Pneumocystis carinii pneumonia (PCP) . This study evaluated the relationship between persistence of organisms and recurrence of disease, and the effect of chemoprophylaxis on bronchoalveolar lavage specimens . Seven patients receiving PCP chemoprophylaxis underwent serial bronchoalveolar lavage (BAL) examinations at 1, 4, and 7 mo after recovery from a first episode of PCP . Specimens were examined for persistent organisms with Gomori's methenamine silver stain and immunofluorescent antibody staining . There were no persistent organisms 1 mo after completion of antimicrobial treatment in six of the seven patients . The one patient with persistent organisms demonstrated clearance of organisms by 4 mo and had no recurrence of PCP . One patient had a recurrence of PCP at 4 mo, after a negative 1-mo BAL . We conclude that a positive BAL result by silver stain or immunofluorescent antibody staining more than a month after ending treatment may indicate clinical recurrence of PCP and not just persistence of nonpathologic cysts . These findings suggest that recurrences of PCP are more likely due to new infection than to relapse of prior disease.

Am J Respir Crit Care Med, 1994 Nov, 150(5 Pt 1), 1332 - 40
Colonization in patients receiving and not receiving topical antimicrobial prophylaxis; Bonten MJ et al.; The influence of topical antimicrobial prophylaxis (TAP) on colonization of oropharynx and trachea was studied in patients receiving and not receiving prophylaxis . Twenty-two patients in Intensive Care Unit (ICU) I (Group 1) received TAP (tobramycin, colistin, and amphotericine B in oropharynx and stomach) . Simultaneous to Group 1, 21 patients (Group 2) not receiving TAP were studied in ICU I . A control group of patients admitted to another, identical, ICU (ICU II), where no TAP was administered, were studied simultaneously (Group 3a, n = 23) . A second control group (Group 3b, n = 31), was formed by collecting data from patients admitted to ICU I in Period II . Patients receiving TAP were less frequently colonized than patients not receiving prophylaxis . Moreover, of the patients not receiving TAP, those staying in the ICU where TAP was administered (Group 2) were less frequently colonized than patients in another ICU (Group 3) . Of the patients not colonized on admission, those staying in the ICU where TAP was administered remained free of colonization for a longer time . In the ICU where no TAP was administered, more patients were colonized simultaneously and cross-acquisition occurred more frequently . TAP significantly influenced colonization of oropharynx and trachea in patients receiving and not receiving prophylaxis within the same ICU as compared with patients not receiving prophylaxis in another identical ICU.

Ann Hematol, 1994 Nov, 69(5), 231 - 43
Interventional antimicrobial therapy in febrile neutropenic patients . Study Group of the Paul Ehrlich Society for Chemotherapy; Link H et al.; In this prospective multicenter trial, treatment strategies for 1573 patients with neutropenia < 1000/microliters and fever > or = 38.5 degrees C after cytotoxic chemotherapy were compared . Patients with unexplained fever were randomized to a three-phase sequential study for different established drug regimens . If an infection could be defined microbiologically or clinically, treatment modifications were determined . In phase I, treatment for all patients consisted of acylaminopenicillin (PEN) plus aminoglycoside (AMG); or third-generation cephalosporin (CEPH) plus AMG; or PEN plus CEPH . In 800 patients with unexplained fever the response rates were: PEN/AMG (n = 258): 74.4%, CEPH/AMG (n = 252): 73.4%; PEN/CEPH (n = 290): 70.0% . Total response rate was 72.5% . In phase II, patients not responding after 3 days received PEN/CEPH/vancomycin (n = 70) or PEN/CEPH/AMG (n = 74) . The respective response rates were 52.9% and 55.4%, total 54.2% . If fever did not resolve, the patients received either PEN/CEPH (n = 40) or imipenem/cilastatin (n = 59) both in combination with amphotericin-B/5-flucytosin/rifampin . The response rates were 62.5% and 79.7%, respectively (p = 0.07), total 72.7% . No significant differences between the treatment modalities compared were found . Analyzing all three phases together, 91.3% of patients with unexplained fever were cured . The response rate was also analyzed according to patients with gram-positive bacteremia (n = 183), response rate = 82.5%; gram-negative organisms (n = 145) 78.6%; fungemia (n = 51) 43.1% (p < 0.001); lung infiltrates (n = 269) 61.3% (p < 0.001); clinically documented infections (n = 198) 84.4%; and clinically and microbiologically documented infections (n = 84) 82.1% . If infections were diagnosed after at least 5 febrile days, more lung infiltrates and fungal infections occurred (p < 0.001) . Leukocytes rising above 500/mu during the infection predicted better response rates (p < 0.001): in unexplained fever 97.8% vs 86.5% and lower death rates 1.5% vs 8.5% . In documented infections the response rates were then 89.9% vs 62.3% and the death rates 7.0% vs 20.5% . Therapy of neutropenic fever and infections must be adapted according to risk factors and should include early empiric antifungal therapy . The therapeutic and prophylactic use of hematopoietic growth factors to overcome neutropenia should be evaluated.

Infect Immun, 1994 Nov, 62(11), 5040 - 7
Mouse Paneth cell defensins: primary structures and antibacterial activities of numerous cryptdin isoforms; Ouellette AJ et al.; Cryptdins are antimicrobial peptides of the defensin family that are produced by intestinal Paneth cells . mRNAs encoding 17 cryptdin isoforms have been characterized from a cDNA library generated from a single jejunal crypt . Six cryptdin cDNAs correspond to known peptides, and the remainder predict 11 novel Paneth cell defensins . Most cryptdin cDNAs have > or = 93% nucleotide sequence identity overall, except for cryptdin 4 and 5 cDNAs, whose respective mature peptide-encoding regions are only 74 and 78% identical to that of cryptdin 1 . Cryptdin cDNAs differ at a small number of nucleotide positions: frequent substitutions were found in codons 38 and 52 of the propiece and in codons 68, 73, 76, 87, and 89 of the deduced peptides; cDNA clones with changes in codons 74, 83, and 88 were found, but there were fewer of these . The antimicrobial activities of cryptdins 1 to 6 were tested against Escherichia coli ML35 in two assays . In an agar diffusion assay, the potencies of cryptdins 1 to 3, 5, and 6 were approximately equivalent to that of rabbit neutrophil defensin NP-1 but cryptdin 4 was 30 times more active than NP-1 . In a bactericidal assay system, cryptdins 1 and 3 to 6 were equally active at 10 micrograms/ml but cryptdin 2 and rabbit NP-1 were not active at this concentration . Since cryptdins 2 and 3 differ only at residue 10 (Thr and Lys, respectively), this amino acid appears to function in bactericidal interaction with E . coli . The demonstration that Paneth cells express a diverse population of microbicidal defensins further implicates cryptdins in restricting colonization or invasion of small intestinal epithelium by bacteria.

Clin Infect Dis, 1994 Nov, 19(5), 931 - 6
Effect of clinically relevant culture conditions on antimicrobial susceptibility of Chlamydia trachomatis; Wyrick PB et al.; Infection of polarized human endometrial-gland epithelial cells obtained at hysterectomy with Chlamydia trachomatis serovar E may provide a relevant in vitro model for studies of pharmacokinetics in genital chlamydial infections . The minimal bactericidal concentration of azithromycin against C . trachomatis was lower in this model than in studies with nonpolarized cells (0.125 and 0.5 mg/L, respectively) . Polarized cells also internalized more azithromycin over 24 hours . The results indicate that the eradication of chlamydial infections may be difficult to prove by antigen detection methods: the persistence of chlamydial envelope material within the intracellular vacuoles of azithromycin-treated cells may lead to a false-positive diagnosis of persisting chlamydial infection.

Clin Infect Dis, 1994 Nov, 19(5), 926 - 30
Tissue-directed antibiotics and intracellular parasites: complex interaction of phagocytes, pathogens, and drugs; Donowitz GR; Antibiotics with significant tissue penetration and intracellular accumulation may have an important role in the treatment of intracellular infections . However, clinically relevant evaluation of these antibiotics in vitro remains a challenge . Measurement of serum drug concentrations or serum bactericidal levels may not be relevant . Measurement of intracellular drug concentrations may be simplistic, given the complex interaction of drug, microbe, and phagocyte . The effect of an antibiotic on an intracellular organism depends on the drug's penetration into the cell, its intracellular location, its metabolism within the cell, and its antimicrobial activity within the organism's specific intracellular microenvironment . Legionella micdadei, an intracellular parasite that grows within monocytes, has been used for the evaluation of drugs like azithromycin that are concentrated intracellularly.

Clin Infect Dis, 1994 Nov, 19(5), 910 - 5
Challenges to antibiotic activity in tissue; Barza M; The most important determinants of antibiotic efficacy in infectious sites are the pharmacokinetic profile of the drug, the biochemical characteristics of the local environment, and the susceptibility of the infecting microorganisms under local growth conditions . The role of these variables is fairly clear for extracellular infections but not for intracellular infections or tissues as a whole . Many agents, including the macrolides, azalides, lincosamides, and quinolones, are concentrated within cells--notably, phagocytic cells . The mechanisms and pharmacokinetics of accumulation as well as the subcellular localization of accumulated drug are poorly understood in most instances . High intracellular drug concentrations do not necessarily translate into potent anti-infective activity . Many drugs with high intracellular concentrations are weak bases that accumulate within acidic lysosomes, where their activity may be reduced; the site at which drug accumulation is greatest may differ from that at which the microbe is found; and slow rates of intracellular growth may lessen the susceptibility of microbes to a variety of agents . Nevertheless, some drugs display good antimicrobial activity within cells . Future studies must better identify the determinants of this activity and clarify the clinical utility of drugs that reach high intracellular levels.

Clin Infect Dis, 1994 Nov, 19(5), 891 - 6
Subacute multiple-site osteomyelitis caused by Borrelia burgdorferi; Oksi J et al.; In a pediatric case of severe multiple-site osteomyelitis caused by Borrelia burgdorferi, the presence of spirochetes in a bone lesion was documented both by culture and by the polymerase chain reaction (PCR) . Positive PCR results were also obtained with culture fluid yielding spirochetal growth and with acute-phase serum . Although the disease evidently was a late manifestation of Lyme borreliosis, antibodies to B . burgdorferi were low in titer and were restricted to the IgM class . The distribution of osteomyelitic lesions in multiple bones and the positive PCR results obtained with serum argue for hematogenous spread of the spirochetes . Before the specific diagnosis was established, the patient received several potent antimicrobial drugs, without a favorable outcome . In contrast, therapy with ceftriaxone led to a rapid cure that persisted thereafter . We conclude that infection due to B . burgdorferi must be considered a possible cause of subacute pediatric osteomyelitis.

Clin Infect Dis, 1994 Nov, 19(5), 823 - 33
Otitis media; Klein JO; Otitis media is the most common respiratory tract infection of infancy and early childhood that is managed with antibacterial agents . A bacterial pathogen is isolated from the middle ear fluids of approximately two-thirds of children with acute otitis media; S . pneumoniae is the leading bacterial pathogen followed by nontypable strains of H . influenzae and M . catarrhalis . Clearance of bacteria from middle ear fluid without use of antibacterial drugs is evident in studies in which a placebo is used . Whereas pneumococci continued to be isolated from middle ear fluids when the infection was not treated, approximately one-half of infections due to nontypable H . influenzae and up to 80% of those due to M . catarrhalis cleared . The microbiological data suggest that only one-third of patients with acute otitis media require antibacterial therapy for resolution of clinical signs and symptoms . However, without the results of prior tympanocentesis, the physician cannot identify the patients for whom the infection will resolve . Thus, the data support use of antibacterial agents for all episodes of acute otitis media to cover adequately the one-third of children who will need the antimicrobial agent to recover from the infection . Effusion persists in the middle ear for weeks to months after every episode of acute otitis media . Conductive hearing loss of some degree occurs whenever the middle ear space is filled with effusion . Decreased scores in tests of speech and cognitive abilities for infants and children who had prolonged middle ear effusion has stimulated investigators to seek means to reduce the duration of middle ear effusion following acute otitis media . Because the pathogenesis of persistent middle ear effusion is uncertain, the results with medical therapies, including antibiotics and steroids, have been inconsistent . Placement of ventilating or tympanostomy tubes to produce drainage and ventilation of the middle ear and to restore hearing is effective and is now the second most frequent surgical procedure in children (after circumcision), but the criteria for placement of tubes are controversial . Prevention of otitis media is possible by use of chemoprophylaxis or vaccines . Chemoprophylaxis has been effective in children with recurrent acute otitis media by reducing new episodes by 40%-90% . A serum antibody response that is age- and type-specific follows pneumococcal infection and protects against subsequent homotypic infection . Polysaccharide pneumococcal vaccines are not consistently immunogenic in children > 2 years of age, but experimental conjugate polysaccharide vaccines are immunogenic in infants as young as 2 months.(ABSTRACT TRUNCATED AT 400 WORDS)

Diagn Microbiol Infect Dis, 1994 Nov, 20(3), 159 - 62
Evaluations of the Etest for antimicrobial susceptibility testing of Legionella pneumophila, including validation of the imipenem and sparfloxacin strips; Rhomberg PR et al.; Development of antimicrobial testing for Legionella spp . has been technically compromised by the fastidious growth requirements of this organism and by the most commonly used medium, buffered charcoal yeast extract agar (BCYE) that contains substances known to inhibit some antimicrobial agents . This study validated the potency of two newer antimicrobials (sparfloxacin and imipenem) and their Etest strip . The comparisons of antimicrobial minimum inhibitory concentration (MIC) values as determined by Etest on BCYE agar (98 Legionella pneumophila) demonstrated that sparfloxacin was the most potent drug (MIC90, 0.19 microgram/ml) among the fluoroquinolones, macrolides, tetracyclines, and beta-lactams tested . Imipenem MICs (MIC90, < or = 0.38 microgram/ml) were also determined by a reference agar dilution method and validated Etest strips on buffered yeast extract agar, buffered charcoal yeast extract agar, and buffered charcoal yeast extract agar with defined supplements . The non-Legionella control strains used to demonstrate medium component influences on the imipenem MICs demonstrated the addition of supplements (particularly L-cysteine) markedly elevated the MICs . These data indicate that the Etest was a simple and accurate quantitative method for susceptibility tests with Legionella isolates . Sparfloxacin among the fluoroquinolones and imipenem among the beta-lactams require further clinical studies for legionellosis therapy.

Antimicrob Agents Chemother, 1994 Nov, 38(11), 2671 - 5
Unilamellar liposomes modulate secretion of tumor necrosis factor by lipopolysaccharide-stimulated macrophages; Brisseau GF et al.; Liposomal encapsulation of antimicrobial agents has been used to improve drug delivery, particularly against intracellular pathogens . The effect of unilamellar liposomes on macrophage activation in response to Escherichia coli lipopolysaccharide was examined . Liposomes caused a dose- and time-dependent inhibition of tumor necrosis factor release by lipopolysaccharide-treated cells . The accumulation of tumor necrosis factor mRNA transcripts was unaffected, suggesting a posttranscriptional mechanism for this effect . However, induction of macrophage procoagulant activity was unaffected by liposomes, indicating a selective rather than a global inhibition . These data suggest that liposomes used for drug delivery may modulate the host response to infection.

Antimicrob Agents Chemother, 1994 Nov, 38(11), 2521 - 9
Effectiveness of various antimicrobial agents against Mycobacterium avium complex in the beige mouse model; Ji B et al.; The results of five chemotherapeutic experiments in beige mice infected with organisms of the Mycobacterium avium complex are presented . After monotherapy with various antimicrobial agents for 4 weeks, only clarithromycin, amikacin, and ethambutol displayed definite bactericidal effects; sparfloxacin and clofazimine showed modest bacteriostatic effects; and rifampin and rifabutin were totally inactive against the isolate tested . After treatment for 4 weeks, the large quantities of clofazimine that had accumulated in the organs of mice seriously interfered with the enumeration of the CFU and assessment of the efficacy of the treatment . The in vitro synergistic effects of drug combinations against M . avium complex were not confirmed in beige mice . In combination with clarithromycin, amikacin could prevent the selection of clarithromycin-resistant mutants, whereas minocycline could not.

Trends Microbiol, 1994 Nov, 2(11), 444 - 9
How bacteria resist killing by host-defense peptides; Groisman EA; Small cationic peptides with antimicrobial properties are part of the innate immune response of a wide variety of animal species, including insects, amphibians and mammals . Bacterial pathogens have evolved distinct mechanisms to avoid, inactivate or resist the killing effects of these peptides . Determinants necessary for resistance to peptides often contribute to the virulence properties of recognized pathogens.

Boll Chim Farm, 1994 Nov, 133(10), 643 - 50
{Antibiotic resistance: current problems and prospects}; Mazza P; In recent years the frequency and spectrum of antibiotic resistant microorganisms have dramatically increased worldwide . In same cases certain infections turned out to be essentially untreatable with antimicrobial drugs . The antibiotic resistance and its transmissibility among different microorganisms poses serious problems for the near future . It is thus important to search and develop rapidly new antimicrobial drugs with improved activity and able to overcome resistance mechanisms . A more prudent and appropriate use of antimicrobial drug in humans and animals is also recommend.

J Periodontol, 1994 Nov, 65(11), 1079 - 87
The vasculature of the periodontal ligament: a scanning electron microscopic study using corrosion casts in the rat; Selliseth NJ et al.; The purpose of this study was to examine the 3-dimensional architecture of the microvascular system of the rat periodontal ligament (PDL) . Vascular corrosion casts were prepared and examined by scanning electron microscopy . Cervically, arterioles and venules communicated with the profuse capillary network of the gingiva . The mid-root segment of the PDL contained arterioles and venules that mainly coursed occluso-apically near the alveolar wall, as well as capillary loops located closer to the root surface . Arterioles entered the PDL through vascular canals from the bone marrow, then coursed coronally and branched into an interconnected network of capillaries . The capillaries formed hairpin loops pointing coronally . At the tip, the capillary loops were enlarged in diameter and had an irregular luminar surface . The capillaries then coursed apically, anastomosing freely, until entering a venule . Large venules mainly followed a coronal-apical path, giving the PDL vasculature a palisade-like appearance . These vessels either left the PDL through vascular canals in the alveolar wall or connected in an apical, venous cap with venules exiting through the apical foramen . The results show that the microvasculature forms a highly organized system presumably related to the specialized functions of the periodontium . Cervically, a dense capillary system may be required for antimicrobial defense and rapid tissue turnover . The vasculature in the middle segment supports the suspensory structures, while the venous cap in the apical region may be designed to cushion masticatory forces.(ABSTRACT TRUNCATED AT 250 WORDS)

Ann Pharmacother, 1994 Nov, 28(11), 1255 - 63
New macrolide antibiotics: usefulness in infections caused by mycobacteria other than Mycobacterium tuberculosis; Rapp RP et al.; OBJECTIVE: To compare the pharmacology, in vitro activity, and clinical use of the new macrolide antibiotics, azithromycin and clarithromycin, in the treatment of infections caused by mycobacteria other than Mycobacterium tuberculosis . DATA IDENTIFICATION: An English-language literature search using MEDLINE (1987-1994), Index Medicus (1987-1994), Program and abstracts of the 31st (1991) and 32nd (1992) Interscience Conference on Antimicrobial Agents and Chemotherapy, and bibliographic reviews of related textbooks, review articles, and professional society publications . STUDY SELECTION: 105 articles were selected . In vitro and in vivo reports on the pharmacokinetics, microbiology, pharmacology, and effectiveness of clarithromycin and azithromycin were assessed to compare their effectiveness and safety . Emphasis was placed on the use of these new drugs in treating infections caused by Mycobacterium avium complex, Mycobacterium chelonae, and Mycobacterium fortuitum infections . RESULTS: A review of the in vitro activity of the new macrolides revealed moderate to very good activity against many strains of mycobacteria other than M . tuberculosis . Early clinical trials show promising results in pulmonary infections, lymphadenitis, cutaneous infections, and disseminated infections . CONCLUSIONS: The new macrolides, azithromycin and clarithromycin, show great promise for treating infections caused by these acid-fast bacteria . Clarithromycin is recommended as a component of combination therapy for the treatment of M . avium complex infections in patients with AIDS . The development of resistance in patients, particularly when these agents are used alone, has been reported.

J Pediatr Surg, 1994 Nov, 29(11), 1414 - 6
Necrotizing fasciitis: a serious complication of omphalitis in neonates; Samuel M et al.; Necrotizing fasciitis occurs when the inflammation (cellulitis) spreads beyond the umbilicus to include the subcutaneous tissue and underlying fascia . Presently, omphalitis is relatively uncommon because of aseptic delivery techniques and antimicrobial therapy . One hundred three neonates aged 7 to 28 days, with varying degrees of omphalitis, were treated on an outpatient or inpatient basis between 1989 and mid-1993 . The neonates were full-term and weighed at least 2.5 kg . Patients with necrotizing fasciitis initially appear deceptively well, which results in less-than-optimum treatment at the outset, followed by a rapid and fulminating downhill course, in turn resulting in death within 24 to 72 hours . Early recognition of the condition, with aggressive resuscitation, appropriate antibiotics, and early surgery are necessary to salvage this high-risk group . The risk factors that may predict the development of necrotizing fasciitis and its early detection are discussed.

Kekkaku, 1994 Nov, 69(11), 725 - 32
{Therapeutic efficacy of macrolide in pulmonary nontuberculous mycobacteriosis}; Tomono K; Clarithromycin (CAM) is semi-synthetic macrolide antimicrobial agent, differing from erythromycin by an O-methyl substitution at position 6 of the 14-membered lactate ring . CAM is one of the very few antimicrobial agents that show activity against that Mycobacterium avium complex (MAC) in vivo, in vitro, and in AIDS patients with disseminated infections . The purpose of the present study was to evaluate the therapeutic efficacy of CAM against MAC in patients with chronic pulmonary MAC infection . In vitro activity against clinically isolated MAC; MIC was evaluated by liquid medium dilution method . CAM was the most effective than other antitubercular drugs against M . avium, but less effective than RFP against M . intracellulare . Activity in animal model of infection; In vivo activity was evaluated by the murine models of hematogenous pulmonary MAC infection . A dose-related reduction in lung cell counts was noted with treatment at 10, 50, 150, and 300 mg/kg of body weight administrated daily . Histopathological examinations were revealed also the reduction of the numbers of granulomas in the lungs with treatment CAM at 300 mg/kg . Therapeutic efficacy of CAM in chronic pulmonary MAC infection; Thirty patients with chronic pulmonary MAC infection were given CAM with other antitubercular drugs . Nineteen of 30 patients had previously received combination antimycobacterial therapy . The overall efficacy rates were 23.3%, and ten patients (33.3%) had negative sputum culture for MAC . Eradication of MAC from sputum has been almost observed within 3 months of initiating treatment, and the patients those who had no cavitation were effective . In conclusion, CAM was considerably effective against chronic pulmonary MAC infection, and the effect was observed relatively rapid.

Kekkaku, 1994 Nov, 69(11), 703 - 10
{Studies on therapeutic efficacy of a new anti-tuberculous drug, benzoxazinorifamycin, against murine experimental mycobacterial infections: attempt at various regimens and protocols}; Tomioka H et al.; Because of the recent AIDS endemic, there is a worldwide increase in intractable mycobacterial infections including extrapulmonary tuberculosis due to multidrug-resistant M . tuberculosis and disseminated M . avium complex (MAC) infections . Therefore, development of new anti-tuberculous drugs having an excellent antimycobacterial activity and protocols for clinical use of presently available antimicrobials are urgently desired . In this study, we performed in vitro and in vivo experiments to assess the chemotherapeutic efficacy of a newly synthesized benzoxazinorifamycin derivative, KRM-1648 (KRM), against experimental infections due to MAC and M . tuberculosis . In addition, we attempted to improve the therapeutic efficacy of the KRM against MAC infections by changing its administration protocols and timing or by combined use with other antimicrobials, including clarithromycin (CAM), clofazimine (CFZ), sparfloxacin (SPFX), streptomycin (SM), and ethambutol (EB) . Furthermore, we examined therapeutic efficacy of KRM against rifampicin (RFP)-resistant M . tuberculosis in details . KRM showing much more potent in vitro activity against the MAC organisms compared to rifabutin (RBT) and RFP, also exerted markedly greater therapeutic efficacy against the MAC infections induced in mice or rabbits in terms of reducing the incidence and the extent of gross pulmonary lesions and the bacterial loads in the lungs and spleens . However, in the case of mouse experimental infections, regrowth of the organisms was initiated after week 4 to 6 even in the animals given KRM . Since KRM-resistant organisms could not be isolated from infected mice given continuous KRM administrations, some unknown mechanisms other than the acquisition of drug resistance by infected organisms may be important for the establishment of the regrowth of MAC organisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Br J Surg, 1994 Nov, 81(11), 1673 - 6
Prospective randomized trial of mechanical bowel preparation in patients undergoing elective colorectal surgery; Santos JC Jr et al.; A total of 149 patients admitted for elective colorectal surgery were randomly allocated to receive preoperative mechanical bowel preparation (group 1) or no mechanical bowel preparation (group 2) . All patients received antimicrobial prophylaxis with cephalothin and metronidazole . The overall incidence of wound infection was 17.4 per cent (24 per cent for group 1, 12 per cent for group 2) and that of dehiscence 7.4 per cent (10 per cent for group 1, 5 per cent for group 2) . The incidence of wound infection was significantly higher in group 1 (P < 0.05) but that of anastomotic dehiscence did not differ significantly between groups . Mechanical bowel preparation is unnecessary and may be harmful in terms of preventing wound infection and anastomotic dehiscence in patients undergoing elective colorectal surgery.

Arch Fam Med, 1994 Nov, 3(11), 975 - 80
A critical review of the new oral cephalosporins . Considerations and place in therapy; Rodman DP et al.; Oral cephalosporins are key antimicrobials in the family physician's therapeutic armamentarium . The list of available agents within this class has been recently expanded to include cefixime, cefprozil, cefpodoxime proxetil, and loracarbef . Each of these antibiotics has differing antimicrobial coverage patterns and approved therapeutic uses . Compared with older, more established antimicrobials such as penicillin, amoxicillin, cefaclor, a combination of amoxicillin and clavulanate potassium, and erythromycin, the newer cephalosporins offer little, if any, therapeutic advantage . Clinical efficacy has been shown to be equal in virtually all studies comparing the newer cephalosporins with traditional agents for various community-acquired infections . While the four newer agents may be given less often, they are relatively expensive . In light of the available clinical data, the newer oral cephalosporins should be reserved as second- or third-line choices.

Photochem Photobiol, 1994 Nov, 60(5), 450 - 4
Photochemistry of 2-mercaptopyridines . Part 2 . An EPR and spin-trapping investigation using 2-methyl-2-nitrosopropane and aci-nitromethane as spin traps in aqueous solutions; Reszka KJ et al.; Compounds possessing a pyridine-2-thione moiety show antimicrobial, antifungal and anticancer activities . Some of them are also photochemically active and upon UV irradiation generate free radicals . In this work, employing EPR and the spin traps 2-methyl-2-nitrosopropane (MNP) and aci-nitromethane (NM), we investigated the photochemistry in aqueous solutions of N-hydroxypyridine-2-thione (used here as a sodium salt, 2-S-PyrNONa), and pyridine-2-thione (2-S-PryH), as well as photochemistry of the respective disulfides, 2,2'-dithiobis(pyridine N-oxide) {(2-S-PyrN-->O)2} and 2,2'-dithiodipyridine {(2-S-Pyr)2} . We found that UV irradiation of 2-S-PyrNONa and of 2-S-PyrH in the presence of MNP and NM generates EPR signals of reduced spin traps in addition to signals of MNP and NM adducts with aryl-thiyl radicals, 2-.S-PyrN-->O and 2-.S-Pyr . The identification of the aromatic thiyl radicals was based on comparison of EPR spectra of spin adducts generated by irradiation of 2-S-PyrNONa and 2-S-PyrH with those produced by UV photolysis of the respective disulfides (2-S-PyrN-->O)2 and (2-S-Pyr)2 . It is concluded that pyridine-2-thione and N-hydroxypyridine-2-thione possess a photoreducing capacity and generate aromatic thiyl radicals upon UV activation . This property may be relevant to biological action of agents containing the pyridine-2-thione moiety.

J Chem Technol Biotechnol, 1994 Nov, 61(3), 225 - 9
Synthesis and antibacterial activity of thioglycolic amino acid derivatives and dipeptides containing the 2-methyl-3,4-dihydroquinazolin-4-one moiety; Atta FM; 3-(2'-Chloroethyl)-2-methyl-3,4-dihydroquinazolin-4-one (I) was reacted with sodio (sodium thioglycolate) in dry dioxane and yielded compound II . By using thionyl chloride, this compound was converted to the corresponding acid chloride (III) . The prepared acyl chloride (III) was allowed to interact with different alpha-amino acids such as Gly, L-Ala, L-B-Phe, DL-Asp, L-Glu, L-Thr and L-Val to give new amino acid derivatives (IVa-g) . A selected C-terminal derivative of glycine (IVa) was converted into acid chloride (V) . The acid chloride formed was reacted with L-Ala, L-B-Phe, DL-Asp, L-Glu, L-Thr and L-Val and yielded the new dipeptides VIa-f . The structures of the synthesized compounds were elucidated by elemental analysis and IR spectra . The prepared peptides were tested for their antimicrobial activities by comparison with tetra-cycline as a reference compound.

J Antimicrob Chemother, 1994 Nov, 34(5), 765 - 76
Pharmacokinetics of azithromycin and erythromycin in human endometrial epithelial cells and in cells infected with Chlamydia trachomatis; Raulston JE; The pharmacokinetics of azithromycin and erythromycin were examined in uninfected and Chlamydia trachomatis infected human endometrial epithelial cells in vitro . Cells which were grown in a polarized orientation showed a three-fold higher quantity of azithromycin uptake than did non-polarized cells . Cellular penetration profiles of azithromycin exceeded erythromycin by as much as eight-fold . In addition, approximately 20% of azithromycin remained cell-associated after 24 h in drug-free medium whereas erythromycin was not retained beyond 3 h . Hormone-responsive primary human endometrial gland epithelial cells, cultured directly after hysterectomy, showed enhanced uptake of both antimicrobials compared with laboratory adapted epithelial cell lines . Cells infected with a genital serovariant of C . trachomatis showed no significant difference in antibiotic uptake during the early stages of the chlamydial developmental cycle, and only a slight decrease in azithromycin uptake in the late stage of infection compared with non-infected cells . Morphological evidence of the bactericidal activity of azithromycin was evident in infected cells at most stages of the chlamydial developmental cycle, whereas the same concentration of erythromycin produced less evidence of marked bactericidal activity as observed by transmission electron microscopy.

Intensive Care Med, 1994 Nov, 20 Suppl 4, S23 - 9
Glycopeptides and nephrotoxicity; Chow AW et al.; Infections due to Gram-positive bacteria have become an increasing problem in the ICU . Furthermore, multidrug resistance among Gram-positive pathogens is increasingly recognized . Empirical therapy with antibiotic regimens that are effective against Gram-positive pathogens is often required in the ICU . Many critically ill patients in the ICU have multiorgan system failure, including acute renal failure, which further impedes optimal antimicrobial therapy . In this communication, the use of glycopeptides in the ICU is briefly reviewed, and the occurrence of associated nephrotoxicity during therapy with vancomycin or teicoplanin, alone or in combination with an aminoglycoside, is examined . Finally, existing recommendations regarding the dose regimens of these agents in patients with renal impairment are evaluated, and guide-lines for optimizing glycopeptide therapy through improved pharmacokinetic monitoring are presented.

Infection, 1994 Nov-Dec, 22(6), 430 - 6
Teicoplanin: 10 years of clinical experience; Trautmann M et al.; The teichomycin antibiotics have been discovered and chemically purified in the late 1970s . Teicoplanin, one of the major derivatives of this group, has been introduced into clinical use in 1984 . In Germany, teicoplanin was licensed in 1988 and now ranks among the antimicrobial agents most frequently used in intensive care units . Due to its reduced rate of side effects compared to vancomycin, its longer serum half-life and a simplified mode of application, teicoplanin has become the glycopeptide of choice in many hospitals . The present review summarizes in vitro activity data, pharmacokinetics, and clinical experience with teicoplanin, with special consideration of currently recommended doses and serum levels.

Eur J Clin Microbiol Infect Dis, 1994 Nov, 13(11), 942 - 52
Chemotherapy of lepromatous leprosy: recent developments and prospects for the future; Gelber RH; Leprosy is a major debilitating infectious disease, primarily of the developing world . In this paper the current status and future prospects of antimicrobial therapy of the severe anergic lepromatous form of the disease are reviewed . Until the last few years only dapsone, rifampicin, clofazimine and ethionamide have had practical application in its therapy, and only rifampicin was bactericidal . Recently, antibiotics from three different classes have been found to be bactericidal in lepromatous patients: a tetracycline (minocycline), a macrolide (clarithromycin), and several fluoroquinolones (including pefloxacin, ofloxacin and sparfloxacin) . Against a background of drug resistance and bacterial persistence, recommendations for multidrug therapy and the means to devise rationally based therapy for the future are discussed.

Eur J Clin Microbiol Infect Dis, 1994 Nov, 13(11), 937 - 41
Pulmonary infections caused by less frequently encountered slow-growing environmental mycobacteria; Hoffner SE; Pulmonary mycobacteriosis is usually caused by Mycobacterium tuberculosis or Mycobacterium avium complex . There are, however, other slow-growing mycobacteria that can cause pulmonary infection . Mycobacterium kansasii, Mycobacterium malmoense, Mycobacterium xenopi, Mycobacterium szulgai and Mycobacterium simiae typically infect middle-aged to elderly persons with preexisting lung disease . Differentiation of infection with these five mycobacteria from infection with Mycobacterium tuberculosis, by culture and determination of the antimicrobial susceptibility pattern of the organism are important for several reasons . All five organisms are found in water and soil . They probably infect humans from environmental habitats; human-to-human spread of infection is thought not to occur . Furthermore, isolation of the organisms in culture may represent contamination of the specimen or colonization of the patient, and not necessarily an infection . Finally, although the antituberculosis drugs-isoniazid, ethambutol, rifampin and streptomycin-have been used for treatment of infection with these five organisms, there are often differences between the antimycobacterial susceptibility patterns of Mycobacterium tuberculosis and those of the non-tuberculous mycobacteria . Thus, the optimal choice of drug therapy may differ from that used for tuberculosis.

Eur J Clin Microbiol Infect Dis, 1994 Nov, 13(11), 925 - 31
Mycobacterium haemophilum: an emerging pathogen; Kiehn TE et al.; Mycobacterium haemophilum is emerging as a pathogen of immunocompromised patients particularly those with AIDS and organ transplants . Infection has also occurred in healthy children . Adults usually present with cutaneous manifestations, septic arthritis or occasionally pneumonia . Children have perihilar, cervical or submandibular adenitis . The organism grows on mycobacterial media supplemented with ferric ammonium citrate or hemin, incubated at 30 degrees C to 32 degrees C, two to three weeks after inoculation . The most active antimicrobial agents in vitro are amikacin, ciprofloxacin, clarithromycin, rifabutin and rifampin . Development of resistance to the rifamycins has been demonstrated after patients were treated for several months with several antimycobacterial agents, including the rifamycins . Treatment for several months with at least two agents demonstrated to have low MICs for the organism has been shown to be effective.

Eur J Clin Microbiol Infect Dis, 1994 Nov, 13(11), 915 - 24
Mycobacterium avium complex: advances in therapy; Havlir DV; Disseminated Mycobacterium avium complex (MAC) is one of the most common opportunistic infections in AIDS patients and is increasingly recognized as a significant pathogen in chronic pulmonary disease in nonimmunocompromised patients . Important progress in therapy has occurred over the last several years . In AIDS patients, multidrug therapy has been shown to be beneficial in terms of reducing circulating bacteremia and improving clinical symptoms . Clarithromycin and azithromycin, two broad-spectrum antimicrobials with minimal activity against Mycobacterium tuberculosis, have emerged as potent, well tolerated agents pivotal to treatment regimens . In AIDS patients, rifabutin prophylaxis reduced the frequency of MAC bacteremia by 50% in two placebo controlled trials . Despite these advances, there remains a need for determining the optimal combination regimens for therapy, and more effective drugs for prophylaxis which are beneficial both in terms of survival and functional capacity of patients.

Chem Res Toxicol, 1994 Nov-Dec, 7(6), 868 - 76
The nitrosation of hexetidine and hexedine: characterization of the major nitrosamine from common antimicrobial agents; Bae JY et al.; The acidic nitrosation of hexetidine and hexedine, common antimicrobial agents and drug constituents, leads to a mixture of nitrosamines . The major nitrosamine product, "HEXNO", forms rapidly in yields as high as 60% over the pH range 1-4.8 at incubation times of 1 h at 37 degrees C with 40 mM NO2- and 10 mM hexetidine . On the basis of extensive spectroscopic characterization and independent synthesis HEXNO has been assigned the structure of 1-(2-ethylhexyl)-3-nitroso-4-methyl-4-{{N-(2-ethylhexyl)-N- nitrosoamino}methyl}imidazolidine (7) . The synthesis of HEXNO involves the novel interception by potassium nitrite in ether/18-crown-6 of an imminium ion produced from the reaction of hexedine with benzyl chloroformate . Collapse of the alpha-amino nitrous ester produced by this reaction yields the nitrosamine containing carbamate 8, which yields HEXNO after removal of the carbamate with trimethylsilyl iodide and subsequent nitrosation . The rapid formation of HEXNO from hexetidine and hexedine supports the hypothesis that tertiary geminal diamines will produce nitrosamines rapidly by a mechanism which involves the cleavage of a nitrosammonium ion with the assistance of the neighboring nitrogen atom . This process is deemed to be of possible importance in the endogenous production of potentially carcinogenic nitrosamines because of its low nitrite requirement and high nitrosation rate . The available data suggest the probable formation of HEXNO and other nitrosamines from hexetidine under conditions of its use.

Chem Res Toxicol, 1994 Nov-Dec, 7(6), 861 - 7
An aziridinium ion intermediate in the nitrosation of a hexetidine model; Loeppky RN et al.; The nitrosation chemistry of 1,3,5-trimethyl-5-aminohexahydropyrimidine (2) has been investigated as a model for the behavior of the antimicrobial agent hexetidine (1) under similar conditions . The reaction of 2 with sodium nitrite in glacial acetic acid gives 4-methyl-4-{(methylnitrosamino)methyl}-3-nitroso-1,3-oxazolidine (4) as the major nitrosamine . This compound arises from a molecular rearrangement which proceeds through the diazotization of the primary amino group followed by intramolecular displacement of nitrogen to generate an aziridinium ion . The N-nitrosooxazolidine 4 forms from the nitrosation of an imidazolidine produced from the aziridinium ring hydrolytic opening . The N-nitrosooxazolidine 4, an isomer, 5-methyl-5-{(methylnitrosamino)methyl}-3-nitroso-1,3-oxazolidine (14), which is not formed in the nitrosation of 2, and an analog 4-methyl-4-{{(2-ethylhexyl)nitrosamino}methyl}-3-nitroso-1,3-oxazolidine (22) have been independently synthesized . The N-nitrosooxazolidine 22 which would be formed from hexetidine is not present in its nitrosation mixture, suggesting the absence of reactive aziridinium ions in that case . The dissimilar nitrosation chemistry of 2 and 1 are discussed.

Circ Shock, 1994 Nov, 44(3), 115 - 20
Molecular mechanisms of natural resistance to mycobacterial infections; Radzioch D et al.; Natural resistance to infection with intracellular parasites is controlled by a dominant gene on mouse chromosome 1, called Bcg . Bcg affects the capacity of macrophages to destroy ingested intracellular parasites early during infection . Reactive nitrogen intermediates (RNI) have been implicated in the interferon-gamma (IFN-gamma)-induced antimicrobial action of macrophages against a wide variety of pathogens . To determine whether Bcg (Nramp) is involved in the production of RNI, these studies have taken advantage of the recent cloning of the Bcg candidate gene, designated Nramp . The expression of Bcg has been down-regulated in the B10R (Bcgr) macrophage cell line using a ribozyme hybrid to site-specifically cleave the Nramp mRNA . Following activation with IFN-gamma, the secretory activity {nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha)} and surface marker expression (la antigen) of these Bcg(Nramp) ribozyme-transfected macrophages were markedly lower than in activated control mock-transfected macrophages (B10R-CTL) . However, there was no difference in NO production of B10R-Bcg(Nramp)Rb and B10R-CTL macrophages if the treatment with IFN-gamma occurred in the presence of lipopolysaccharide (LPS) . These studies support the hypothesis that the Bcg(Nramp) gene is involved in the regulation of early signaling that occurs in macrophages activated with IFN-gamma . Furthermore, it seems that IFN-gamma, but not LPS-induced activation is affected by the inhibition of Bcg(Nramp) gene expression . Definitive evidence will be provided by transfection experiments that will show whether the Bcgr allele of Bcg(Nramp) can restore NO production of the Bcgs macrophage.

Chem Pharm Bull (Tokyo), 1994 Nov, 42(11), 2225 - 30
Development of bioactive functions in hydrangeae dulcis folium . III . On the antiallergic and antimicrobial principles of hydrangeae dulcis folium . (1) . Thunberginols A, B, and F; Yoshikawa M et al.; From the less polar fraction of Hydrangeae Dulcis Folium, the fermented and dried leaves of Hydrangea macrophylla Seringe var . thunbergii Makino, Eight antiallergic and antimicrobial principles were isolated together with several known compounds . Among the newly isolated bioactive constituents, the chemical structures of thunberginols A, B, and F have been determined on the basis of chemical and physicochemical evidence . Thunberginols A, B, and F were found to exhibit more potent antiallergic activity than phyllodulcin, hydrangenol, disodium cromoglycate (DSCG), and tranilast . In addition, these thunberginols showed antimicrobial activity against oral bacteria.

Proc Natl Acad Sci U S A, 1994 Oct 25, 91(22), 10335 - 9
Paneth cell differentiation in the developing intestine of normal and transgenic mice; Bry L et al.; Paneth cells represent one of the four major epithelial lineages in the mouse small intestine . It is the only lineage that migrates downward from the stem-cell zone located in the lower portion of the crypt of Lieberkuhn to the crypt base . Mature Paneth cells release growth factors, digestive enzymes, and antimicrobial peptides from their apical secretory granules . Some of these factors may affect the crypt stem cell, its transit-cell descendants, differentiating villus-associated epithelial lineages, and/or the gut microflora . We used single and multilabel immunocytochemical methods to study Paneth cell differentiation during and after completion of gut morphogenesis in normal, gnotobiotic, and transgenic mice as well as in intestinal isografts . This lineage emerges coincident with cytodifferentiation of the fetal small intestinal endoderm, formation of crypts from an intervillus epithelium, and establishment of a stem-cell hierarchy . The initial differentiation program involves sequential expression of cryptdins, a phospholipase A2 (enhancing factor), and lysozyme . A dramatic increase in Paneth cell number per crypt occurs during postnatal days 14-28, when crypts proliferate by fission . Accumulation of fucosylated and sialylated glycoconjugates during this period represents the final evolution of the lineage's differentiation program . Establishment of this lineage is not dependent upon instructive interactions from the microflora . Transgenic mice containing nucleotides -6500 to +34 of the Paneth cell-specific mouse cryptdin 2 gene linked to the human growth hormone gene beginning at its nucleotide +3 inappropriately express human growth hormone in a large population of proliferating and nonproliferating cells in the intervillus epithelium up to postnatal day 5 . Transgene expression subsequently becomes restricted to the Paneth cell lineage in the developing crypt . Cryptdin 2 nucleotides -6500 to +34 should be a useful marker of crypt morphogenesis and a valuable tool for conducting gain-of-function or loss-of-function experiments in Paneth cells.

FEMS Microbiol Lett, 1994 Oct 15, 123(1-2), 37 - 42
Susceptibility of various purple and green sulfur bacteria to different antimicrobial agents; Nogales B et al.; Several purple and green sulfur bacteria (genera Chromatium, Thiocapsa and Chlorobium) were tested for their sensitivity to different antimicrobial agents by a disc diffusion assay, using thioacetamide as a source of hydrogen sulfide for plate growth . Chlorobium limicola strains were more sensitive to amoxicillin, erythromycin and nalidixic acid, whereas gentamicin and netilmicin were more active against the purple bacteria tested . None of the organisms were sensitive to oxacillin and trimethoprim+sulfamethoxazole . The critical concentrations at the edge of the inhibition zone were also calculated for three organisms and the antimicrobials colistin, mitomycin C, penicillin G, rifampicin, and streptomycin . The results obtained suggest that colistin, mitomycin C, penicillin G would provide selective conditions against the growth of Chlorobium limicola strains, while streptomycin and other aminoglycoside antibiotics would select against purple bacteria.

J Med Chem, 1994 Oct 14, 37(21), 3503 - 10
Synthesis and structure-activity relationship of methyl-substituted indolo{2,3-b}quinolines: novel cytotoxic, DNA topoisomerase II inhibitors; Peczynska-Czoch W et al.; In furtherance of our SAR study on the chemistry and antitumor activity of fused nitrogen heteroaromatic compounds, a series of linear, methyl-substituted derivatives of 5H- and 6H-indolo{2,3-b}quinolines were synthesized according to the modified Graebe-Ullmann reaction . To establish the relationship between the physicochemical and biological activities of indolo{2,3-b}quinolines, their lipophilic properties, cytotoxic and antimicrobial activity, and ability to induce topoisomerase II dependent pSP65 DNA cleavage in vitro were investigated . We found that the antimicrobial and cytotoxic activity of indolo{2,3-b}quinolines was strongly influenced by the position, and the number of methyl substituents and the presence of methyl group at pyridine nitrogen was essential for the cytotoxicity of these compounds . All indolo{2,3-b}quinolines belonging to the 5H series, i.e., bearing a methyl group on the pyridine nitrogen, showed significant activity against procaryotic and eucaryotic organisms . They inhibited the growth of Gram-positive bacteria and pathogenic fungi at MIC range 3 x 10(-2) to 2.5 x 10(-1) mumol/mL, displayed cytotoxicity against KB cells ID50 in the range 2 x 10(-3) to 9 x 10(-3) mumol/mL, and stimulated the formation of calf thymus topoisomerase II mediated DNA cleavage at concentration between 0.4 and 10 microM . None of the indolo{2,3-b}quinolines belonging to the 6H series, i.e., lacking a methyl group on the pyridine nitrogen, was active in analogous tests . Of the investigated compounds, the most active was 2,5,9,11-tetramethyl-5H-indolo{2,3-b}quinoline, a compound bearing the highest number of symmetrically distributed methyl groups . The interaction of indolo{2,3-b}quinolines with DNA was studied by measuring the increase of calf thymus DNA denaturating temperature (Tm) . The delta Tm values for the 5H series were found to be about 10 times as high as those for the 6H compounds . Indolo{2,3-b}quinolines with the highest number of methyl groups had the greatest contribution to the increase in the Tm of calf thymus DNA . The values of delta Tm reached 19 degrees C and 1.6 degrees C for the most substituted compounds of both series.

Schweiz Med Wochenschr, 1994 Oct 8, 124(40), 1775 - 81
{Low-grade MALT-type non-Hodgkin lymphoma of the stomach with local recurrence 14 years following resection . Demonstration of clonal identity using polymerase-chain-reaction (PCR)}; Maurer R et al.; So-called low grade B-cell lymphomas of MALT type occurring mainly in the gastrointestinal tract but also in the salivary glands, the thyroid and the lungs are indolent neoplasms with a prolonged clinical course and persistent localized disease at the site of origin . This behaviour sets them apart from their nodal counterparts, which are frequently generalized from onset . Their recognition within and their separation from accompanying reactive processes (e.g . chronic gastritis) is important but may be difficult on morphology alone . In the immediate past there have been reports on regression of gastric MALT type lymphomas after eradication of Helicobacter pylori . We observed a 68-year-old male patient who underwent partial gastric resection for persistent ulcer disease in 1979 . A histological diagnosis of pseudolymphoma was established at that time . In 1993 he again had gastrointestinal bleeding . Endoscopy revealed ulcerations at the anastomosis . Biopsies showed a monoclonal infiltrate of centrocytoid B-cells with typical lymphoepithelial lesions, suggesting the diagnosis of low grade B-cell lymphoma of MALT type which was seen focally in multiple biopsies randomly taken from the gastric remnant . Review of the 1979 specimen revealed identical lesions . Polymerase chain reaction (PCR) on both specimens demonstrated identical products of rearranged Ig-heavy chain genes, thus confirming the monoclonality and establishing the clonal relationship of both lesions . Staging revealed no extragastric disease . Two courses of chemotherapy did not affect the mucosal infiltrates . Although the patient had been under antacid medication and the presence of Helicobacter pylori could not be demonstrated, antimicrobial treatment was given, after which follow-up biopsies were free of tumor and bacteria after 4 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Biochem Pharmacol, 1994 Oct 7, 48(7), 1379 - 85
Fusidic acid suppresses nitric oxide toxicity in pancreatic islet cells; Burkart V et al.; Earlier preclinical and clinical trials indicate that fusidic acid, a triterpenoid compound originally described as an antimicrobial drug may protect islet beta cells from destruction in type I (insulin-dependent) diabetes mellitus . Since nitric oxide appears to be an important mediator of inflammatory islet cell death we analyzed whether fusidic acid interferes with nitric oxide production or action . We report here that fusidic acid dose-dependently inhibits lysis of isolated islet cells by activated macrophages, a process mediated by nitric oxide . In the presence of 100 microM fusidic acid macrophage-mediated islet cell lysis was reduced from 52.5 to 1.7% (P < 0.001) . Fusidic acid only slightly affected macrophage function and did not inhibit the release of nitric oxide . We therefore tested whether fusidic acid suppresses nitric oxide toxicity in target cells . Isolated islet cells were exposed to the nitric oxide donor nitroprusside which led to DNA strand breaks and plasma membrane lysis . DNA strand breaks were reduced from 54.6 to 34.9% (P < 0.001) in the presence of 100 microM fusidic acid and cell lysis was reduced from 60.1 to 27.5% with 100 microM (P < 0.001) . In the presence of 500 microM fusidic acid DNA strand breaks and cell lysis were reduced further to 27.1 and 10.7%, respectively (P < 0.001) . No protection by fusidic acid was observed when cells were exposed to oxygen radicals or the alkylating beta cell toxin streptozotocin . The suppression of nitric oxide toxicity by fusidic acid was not due to its known inhibitory action on protein biosynthesis and thus represents a hitherto unknown activity of this drug.

Burns, 1994 Oct, 20(5), 426 - 9
Agar well diffusion assay testing of bacterial susceptibility to various antimicrobials in concentrations non-toxic for human cells in culture; Holder IA et al.; Previously, we showed that microbial susceptibility to antimicrobials in concentrations non-toxic for human cells in culture could be tested using the wet disc topical antimicrobial assay . In this report, wet disc assay and agar well diffusion assay results were compared testing the susceptibility of Ps . aeruginosa isolates from burn patients to concentrations of Polymyxin B non-toxic for cultured cells . Both assays were performed on the same agar plates . No differences in results were observed . Further agar well diffusion assay testing showed that susceptibility/resistance could be demonstrated when testing several antimicrobials in concentrations non-toxic for cultured cells against a variety of bacteria isolated from burn patients . Therefore, the more familiar agar well diffusion as well as the wet disc assay can be used to test microbial susceptibility to these concentrations of antimicrobials.

Rinsho Byori, 1994 Oct, 42(10), 1062 - 8
{The correlation between the MICs deduced from Showa disk method and the MICs determined by micro-dilution method}; Moroizumi S et al.; Disc diffusion technique is useful to routine drug susceptibility testing for bacteria in clinical laboratories because of the advantages on simplicity and cost . Kirby-Bauer (KB) method recommended by NCCLS is using widely as a standard method of disk diffusion test, and simply categorize microorganisms as being susceptible, moderately susceptible, intermediate or resistant to different antimicrobial agents by the use of break point . In the determination of breakpoints, the relationship between MICs and clinical results and pharmacokinetics parameters (Cmax, T1/2 and AUC) are significantly considered . However, there are variance of pharmacokinetics among a race, moreover, breakpoint is not yet established in Japan . In report to doctor from clinical laboratory, the MIC might be better than that by breakpoint since there are such problems of breakpoint . Showa disk was developed as mono-disk method being able to deduce MIC from the linear regression between MIC and zone diameter . Therefore, it is thought that Showa disk is one of valuable methods for the routine drug susceptibility testing for bacteria in Japan . There is one problem, which is that MIC deduced by Showa disk is based on the relationship with agar dilution method although the determination method of MIC is going to turn into micro-dilution method, so we compared the MICs deduced from zone diameter of Showa disk method with the MICs determined by broth micro-dilution method by using a challenge set of 110 gram-positive and gram-negative bacteria for 7 antimicrobial agents . The total agreement of MIC within 1-log2 dilution difference was 77% and the correlation coefficient was 0.929 . As results, a good relationship was obtained except the results of tetracycline and ofloxacin for beta-lactamase non-producing H . influenzae, and ceftizoxime for E . coli, and K . pneumoniae.

J Antibiot (Tokyo), 1994 Oct, 47(10), 1153 - 9
Novel antibiotics, amythiamicins . III . Structure elucidations of amythiamicins A, B and C; Shimanaka K et al.; The structures of novel antimicrobial antibiotics, amythiamicins A, B and C, were elucidated by chemical degradations and NMR spectral analyses . The main frame from C-1 to C-41 of these antibiotics was the same as that of amythiamicin D . Amino acid autoanalyses of amythiamicins A, B and C showed that these have another one mole of serine and proline in comparison with amythiamicin D . Stereochemistries of both amino acids were determined to be L by chiral HPLC . These seryl-prolyl residues in amythiamicins A, B and C are attached at C-41 through an oxazoline ring, amide and ester bond, respectively.

Scand J Immunol, 1994 Oct, 40(4), 403 - 9
Interleukin-10 inhibits antimicrobial activity against Leishmania major in murine macrophages; Vieth M et al.; The stimulation of macrophages is of importance to the defense against intracellularly replicating microorganisms such as Leishmania . In this study the direct effect of recombinant interleukin-10 (IL-10) on the leishmanicidal effector functions of murine peritoneal or bone marrow derived macrophages was investigated . IL-10 almost completely inhibited the killing of intracellular leishmania at concentrations above 10 ng/ml . This inhibitory effect was independent of the stimulus used as the activation of macrophages by IFN-gamma and IL-7, recently shown to possess macrophage activating properties, were suppressed by IL-10 . Kinetic experiments revealed that IL-10 must be present during the process of macrophage activation and that the leishmanicidal effector function of fully activated macrophages was not influenced . Furthermore, in the absence of exogenously added IL-10, the addition of neutralizing antibodies against IL-10 or IL-10-specific antisense phosphorothioate DNA-oligonucleotide led to an enhanced killing of parasites after stimulation with either IFN-gamma or IL-7 . In accordance with this, IL-10 mRNA was readily detectable in murine macrophages by PCR with reverse transcribed mRNA . These results indicate that IL-10, which is endogenously produced by macrophages, acts as an autocrine deactivating factor supporting the survival of the parasite.

Mayo Clin Proc, 1994 Oct, 69(10), 962 - 8
Diagnosing ventilator-associated pneumonia: the role of bronchoscopy; Allen RM et al.; OBJECTIVE: To discuss the two diagnostic procedures used most frequently to obtain uncontaminated lower airway secretions during bronchoscopy . DESIGN: This article reviews the contributing risk factors of ventilator-associated pneumonia (VAP) and the recent studies that have assessed the usefulness of the protected specimen brush (PSB) and bronchoalveolar lavage (BAL) in the nonimmunocompromised host . RESULTS: A prompt, accurate diagnosis of VAP, including specific identification of the bacterial pathogen, remains a common challenge in the intensive-care unit . Standard clinical criteria are of suboptimal specificity for making decisions, including selecting antibiotic therapy . Bronchoscopic techniques of lung secretion sampling can be used in the intensive-care unit in an effort to overcome the effects of oropharyngeal contamination . The PSB and BAL, used appropriately, can help intensive-care clinicians formulate specific antimicrobial therapy . Evaluation of intracellular bacteria obtained by BAL has been reported to be useful in guiding empiric antibiotic therapy while the final results of cultures obtained with the PSB are pending . Prior antibiotic therapy, however, may confound the interpretation and clinical utility of results . CONCLUSION: Currently, for a patient taking antibiotic therapy, no reliable technique nor quantitative culture threshold exists to help in diagnosing suspected VAP or in guiding antibiotic therapy . If the clinical situation allows, antibiotic therapy should be discontinued for 48 hours; then, the PSB, BAL, protected BAL, or endobronchial aspiration should be used . These contemporary modalities, however, necessitate further clinical trials before widespread use is warranted.

J Pediatr, 1994 Oct, 125(4), 649 - 51
Treatment of chronic neutropenia with chloramphenicol; Feder HM Jr et al.; We describe a patient with chronic congenital idiopathic neutropenia whose neutropenia resolved on four occasions during chloramphenicol therapy . This is the second report of chloramphenicol-responsive chronic neutropenia . Chloramphenicol, in addition to its antimicrobial action, has immune-modulating activity, which may explain the reversal of neutropenia.

Crit Care Med, 1994 Oct, 22(10), 1683 - 91
Problems in diagnosing nosocomial pneumonia in mechanically ventilated patients: a review; Bonten MJ et al.; OBJECTIVE: To review the available information about diagnosing nosocomial pneumonia in mechanically ventilated intensive care unit patients . DATA SOURCES: The National Library of Medicine MEDLINE database and bibliographies of the reviewed articles . STUDY SELECTION AND DATA EXTRACTION: Studies were selected from the English literature, with an emphasis on recent studies . Studies were selected on the basis of their historical value and originality . A total of 82 articles was considered relevant . DATA SYNTHESIS: Many efforts have been made to diagnose nosocomial pneumonia with more accuracy . Two promising new diagnostic modalities are the protected specimen brush and bronchoalveolar lavage, both performed via flexible bronchoscopy . Depending on the study design and patient selection, sensitivity and specificity of bronchoalveolar lavage and protected specimen brush differ widely, ranging from 50% to 100% . However, interpretation of study results is seriously hampered because a standardized diagnostic threshold is not available, the influence of previous antimicrobial therapy on culture results remains unclear, and, most importantly, a well-defined gold standard to study the value of both methods is lacking . CONCLUSIONS: Because studies of bronchoalveolar lavage and protected specimen brush are seriously hampered by several pitfalls, these studies as well as clinical results must be interpreted with caution.

Clin Exp Immunol, 1994 Oct, 98(1), 66 - 70
Use of methyl prednisolone and antioxidants in mercuric chloride-induced experimental vasculitis; Qasim FJ et al.; The systemic vasculitides are characterized by necrotizing inflammation of blood vessels . Neutrophils are implicated in tissue damage by their presence at the site of injury . They can mediate injury by release of cellular contents including proteinases, cytokines and reactive oxygen species . Antioxidants such as vitamin E and N-acetyl cysteine (NAC) may therefore be predicted to ameliorate oxidative damage in vivo and could be a cheap and non-toxic form of therapy . We examined this hypothesis in an experimental model of vasculitis which has some similarities to human disease, and in which depletion of neutrophils ameliorates tissue injury . Mercuric chloride (HgCl2) treatment induces an autoimmune syndrome and necrotizing leucocytoclastic vasculitis in the Brown Norway (BN) rat; anti-myeloperoxidase (MPO) and anti-glomerular basement (GBM) antibodies are present, and vasculitis is reduced by antimicrobials . Methyl prednisolone given intravenously was effective in reducing tissue injury, demonstrating that the model was responsive to a treatment used in man . Vitamin E and NAC were given as daily injections intraperitoneally to BN rats either before, during or after HgCl2 administration . Serial blood samples were taken for anti-MPO and IgE antibodies, which were assayed by ELISA . Necropsies were performed on animals killed at peak disease . At doses of 50-200 mg/kg per day vitamin E had no beneficial effect on tissue injury, regardless of timing of treatment . NAC at 100 or 200 mg/kg also had no significant protective effect on vasculitis . Autoantibody and IgE levels were not affected by either methyl prednisolone or the antioxidants . The lack of benefit of vitamin E and NAC suggests that oxidative damage, whether generated by neutrophils or other cells, does not play a major role in the pathogenesis of vasculitis, and that antioxidant therapy is unlikely to be of benefit in systemic vasculitis in man.

CMAJ, 1994 Oct 1, 151(7), 925 - 31
Antimicrobial prophylaxis in surgery . Committee on Antimicrobial Agents, Canadian Infectious Disease Society; Waddell TK et al.; OBJECTIVE: To provide guidelines for antimicrobial prophylaxis on the basis of the type of surgical procedure . OPTIONS: Standard drug regimens for prophylaxis of infection in a variety of surgical procedures were considered, including a first-generation cephalosporin; an aminoglycoside in combination with metronidazole, clindamycin or erythromycin; a second-generation cephalosporin; and trimethoprim-sulfamethoxazole . OUTCOMES: In order of importance: efficacy, side effects and cost . EVIDENCE: A MEDLINE search of articles published between January 1980 and December 1991 . For clinical trial data, greatest emphasis was placed on randomized, double-blind studies using appropriate controls . VALUES: The Committee on Antimicrobial Agents of the Canadian Infectious Disease Society (CIDS) and two recognized experts (T.K.W . and O.D.R.) recommended antimicrobial regimens suitable for prophylaxis of infections in surgery . Whenever possible, recommendations were based on data from randomized controlled trials . BENEFITS, HARMS AND COSTS: Implementation of the guidelines is expected to reduce the incidence of postoperative infections, the inappropriate use of antibiotics and costs to hospitals . RECOMMENDATIONS: Antibiotic prophylaxis is recommended for operations with a high risk of postoperative wound infection or with a low risk of infection but significant consequences if infection occurs . These operations include clean-contaminated procedures and certain clean procedures . Drugs should be administered intravenously immediately before the operation . In colorectal operations oral administration also appears to be effective . A single dose is sufficient for most procedures . The regimen chosen depends on the pathogens usually associated with wound infection in a given operation, the serum half-life of the drugs, the antimicrobial susceptibility patterns in the local hospital and the cost of the drugs . VALIDATION: The guidelines were compared with others in standard textbooks of surgery and peer-reviewed articles . The guidelines were prepared and revised by the Committee on Antimicrobial Agents of the CIDS . They were then reviewed and revised further by the Council of the CIDS . SPONSOR: The CIDS was solely responsible for developing, funding and endorsing these guidelines.

J Antimicrob Chemother, 1994 Oct, 34(4), 465 - 83
Interaction of divalent cations, quinolones and bacteria; Marshall AJ et al.; The interaction between divalent cations and quinolones and the mechanism by which the former antagonizes the antimicrobial activities of the latter were investigated . In the presence of either magnesium or calcium chloride, the MICs of 18 quinolones for Gram-positive and Gram-negative bacteria increased . Accumulation of and inhibition of DNA synthesis by quinolones were decreased in the presence of magnesium chloride while, in the presence of EDTA, there was no increase in the concentration of accumulated quinolone for any of the agents tested . Only with nalidixic acid was there enhancement of the inhibition of DNA synthesis . Chelation of selected quinolones by magnesium was demonstrated with a fluorescence assay which showed that the extent to which fluorescence (consistent with chelation) was enhanced varied with the quinolone . Assessment of the strength of the magnesium-quinolone complexes with the chelating agent EDTA demonstrated that some of the complexes could be broken . Thin layer chromatography of quinolones and quinolone-magnesium complexes provided evidence that the components of the complex were probably combined in a ratio of 1:1 and that reduced intracellular accumulation of the quinolones in the presence of magnesium was unlikely to be due to a complex being too bulky to be taken through the porin channels . In contrast with permeabilizers which are known to utilize the self-promoted uptake pathway, none of the quinolones studied permeabilized Gram-negative bacteria to lysozyme, caused enhanced fluorescence to 1-N-phenyl-naphthylamine (NPN) or increased the leakage of periplasmic beta-lactamase into the culture medium . The reduced activities of the quinolones in the presence of divalent cations may be the result of the chelation of exogenous ions and, possibly, lipopolysaccharide- or lipoteichoic acid-associated magnesium ions, thereby resulting in less drug being available to enter the bacterium . Alternatively, reduced activity may be due to a fundamental effect on the interaction between quinolones and their target DNA gyrase.

New Microbiol, 1994 Oct, 17(4), 313 - 8
Investigation on several phenotypic features in two strains of Mycobacterium genavense; Tortoli E et al.; The newly recognized species Mycobacterium genavense causes disseminated infections in AIDS patients, but its prevalence is difficult to assess because of its inability to grow on standard solid media . For the same reason, very little is known about the phenotypic traits of its isolates . We report here the results of our studies on two such strains isolated from AIDS patients and subcultured on a non-standard solid medium . Besides several features conventionally explored for mycobacterial speciation, we tested the isolates for 19 enzymatic activities and determined their mycolic acids profiles by means of high performance liquid chromatography . We also compare our findings with the scanty literature data on the laboratory characteristic and antimicrobial susceptibility of M . genavense.

New Microbiol, 1994 Oct, 17(4), 281 - 9
Systemic infection with Herpes bovis virus 2 evokes a biphasic immune response in the mouse; Puliti M et al.; We evaluated the effects of systemic infection by Herpes bovis virus 2 (HBV-2) on a murine experimental system . We provide evidence that such infection is lethal for the immunocompromised but not for the immunocompetent mouse in which a biphasic immune response is elicited . In particular, 1 day post-infection, we observed a rapid transient depression induced by the virus, as documented by a decrease in peripheral leukocyte counts, mitogenic spleen cell response and resistance to a secondary microbial challenge . Later, HBV-2 infection boosted cytokine secretion and enhanced antimicrobial and antitumoral activities by the splenic district . In conclusion, our experimental model discloses some immunological aspects underlying the complex host-virus interaction.

What is Food Microbiology?, What Is Anthrax?, What Is Cell Biology?, What Is Bioassay?, What Is Salmonella?, n, Microorganism, r, Microorganisms, c, Microbiology, n, Microbes, e, Bacteria, c, Prokaryotes, e, Cell suspensions, o, Bacteriological, o, Yeasts, o, Streptococci, r, Bacteriological, r, Microbiological, a, Minimum inhibiting concentration, s, Pediococci, e, Enterobacters, s, Antimicrobial, c, Bacteroides, e, Staphylococcus aureus, s, S. cerevisiae, c, Antibiotic prophylaxis, c, Cephalosporin, s, Meningococcus, r, Microorganisms, r, Yeasts, e, Sepsis, i, Salmonella

Scientific Publications - Work Done by Microbiology Reader Bioscreen C
Agricultural Microbiology Anaerobic Microbiology Antimicrobial Susceptibility Artificial Atmosphere Bioassay of Antibiotics Biofilm Microbiology Bioreactor Technology Biotechnology Cell Biology Clinical Microbiology Environmental Microbiology Experiments with Yeast	Fermentation Food Microbiology Functional Genomics Gene Technology Growth Media Development Growth Rate and Lag Time Industrial Microbiology Medical/Pharmaceutical Field Microbiological Assay Microbiological Research Microbiology of Cosmetics go to a specific theme...	Military Microbiology Molecular Microbiology Mutagenicity and Genotoxicity Oral Microbiology Patents Postantibiotic Studies Soil Microbiology Spore Microbiology Veterinary Microbiology Waste/Wastewater Treatment Water Microbiology Wine Microbiology

� 2005 Transgalactic Ltd (manufacturer of Bioscreen C software) | Privacy Statement | P.O. Box 1393, 00101 Helsinki, Finland, phone: +358 9 85172920, fax: +358 9 8749481, e-mail: microbiology@bionewsonline.com

Last modified: May 25, 2005