Gen Dent, 2000 Jan-Feb, 48(1), 54 - 60 Drug use for the pregnant or lactating patient; Haas DA et al.; The dental patient who is pregnant or lactating may require management involving the administration or prescription of drugs . The approach of completely avoiding all drugs may not permit appropriate treatment of the patient and most often is not warranted . This article reviews the current considerations in the use of drugs in the dental patient who is either pregnant or lactating . The safety of the local anesthetics, vasoconstrictors, analgesics, antimicrobials, and sedatives used in dentistry is discussed. Planta Med, 2000 Dec, 66(8), 768 - 9 Antimicrobial triterpenoids from Licania heteromorpha; Braca A et al.; Six triterpenoids having a lupane and oleane skeleton were isolated from the leaves and young branches of Licania heteromorpha Bentham var . heteromorpha and were identified as: betulinic acid 1, alphitolic acid 2, 3 beta-O-trans-p-coumaroyl alphitolic acid 3, 3 beta-O-cis-p-coumaroyl alphitolic acid 4, 3 beta-O-trans-p-coumaroyl maslinic acid 5, 3 beta-O-cis-p-coumaroyl maslinic acid 6 . The antimicrobial activity of these compounds was evaluated in vitro on clinically isolated microorganisms employing a microdilution method . Compounds 2, 3, 5, and 6 showed antimicrobial activity on Gram-positive bacteria and yeasts, whereas none of the six triterpenoids were active against Gram-negative organisms. Planta Med, 2000 Dec, 66(8), 687 - 93 Antioxidant and antimicrobial activity of Foeniculum vulgare and Crithmum maritimum essential oils; Ruberto G et al.; The essential oils obtained from Crithmum maritimum L . (marine fennel) and two samples of Foeniculum vulgare Miller (common fennel) were analysed by GC and GC-MS and assayed for their antioxidant and antibacterial activities . The antioxidant activity of the oils was evaluated by two lipid model systems: a modified thiobarbituric acid reactive species (TBARS) assay and a spectrophotometric detection of hydroperoxydienes from linoleic acid in a micellar system . The oils demonstrated antioxidant capacities, comparable in some cases to that of alpha-tocopherol and butylated hydroxytoluene (BHT), used as reference antioxidants . Concerning the antimicrobial tests the essential oils were assayed against twenty-five genera of bacteria, including animal and plant pathogens, food poisoning and spoilage bacteria . Oils from the two samples of F . vulgare showed a higher and broader degree of inhibition than that of C . maritimum. J Pharm Belg, 2000 Nov-Dec, 55(6), 137 - 41 {Multiple bacterial resistance in daily practice}; Sternon J; Present and future solutions to the problem of bacterial multiple resistance involve physicians, patients and veterinarians . Their behaviour should evolve to take into account the medical and economical issues of antibiotic prescription . The clinical diagnosis requires a more rigorous assessment, based on bacteriological and rapid antigenic tests . Vaccination in both young people and the elderly, is an essential prophylactic tool, which is too often neglected . When a bacterial infection is suspected or proven, priority should be given to a targeted antimicrobial therapy with a bactericidal activity, in order to quickly eradicate pathogens . Therapies should be shorter and questionable antibioprophylaxis should also be avoided . A watch laboratory network should provide physicians with an adequate information on local bacterial resistance patterns on a regular basis, in order to allow them adjusting their prescription. Inorg Chem, 2000 Jul 24, 39(15), 3301 - 11 Synthesis and characterization of water-soluble silver(I) complexes with L-histidine (H2his) and (S)-(-)-2-pyrrolidone-5-carboxylic acid (H2pyrrld) showing a wide spectrum of effective antibacterial and antifungal activities . Crystal structures of chiral helical polymers {Ag(Hhis)}n and ({Ag(Hpyrrld)}2)n in the solid state; Nomiya K et al.; Two water-soluble, silver(I) complexes showing a wide spectrum of effective antibacterial and antifungal activities, i.e., ({Ag(Hhis)}.0.2EtOH)2 (1; H2his = L-histidine) and {Ag(Hpyrrld)}2 (3; H2pyrrld = (S)-(-)-2-pyrrolidone-5-carboxylic acid) were prepared . In aqueous solution 1 and 3 were present as dimers, whereas in the solid state they were polymers . Crystallization of 1 by slow evaporation and/or vapor diffusion gave water-insoluble crystals of {Ag(Hhis)}n (2) showing modest antimicrobial activities . The complex 1 in the solid state is a polymer formed by intermolecular hydrogen-bonding interactions between dimeric {Ag(Hhis)}2 cores, while 2 is a different polymer without a core complex . X-ray crystallography revealed that 2 was a left-handed helical polymer consisting of a bent, 2-coordinate silver(I) atom bonding to the Namino atom of one Hhis- ligand and the N pi atom of a different Hhis- ligand . Of particular note is the fact that Ocarboxyl atoms do not participate in the coordination . X-ray crystallography also revealed that 3 was a left-handed helical polymer formed by self-assembly of dimeric {Ag(Hpyrrld)}2 cores with an intramolecular metal(I)-metal(I) interaction (Ag-Ag distance, 2.9022(7) A) . The FT-IR and the solid-state 13C and 15N NMR spectra showed that the dimeric core of 1 was formed through Ag-N bonds, while that of 3 was formed through Ag-O bonds . The molecular ions of 1 and 3 were detected by the positive-ion electrospray ionization (ESI) mass spectrometry . For 1-3, characterization by elemental analysis, TG/DTA, FT-IR, and variable-temperature solid-state 13C NMR and room-temperature 15N NMR measurements was performed, and for 1 and 3, that by solution molecular weight measurements and solution (109Ag, 1H, and 13C) NMR spectroscopies was also carried out . The antibacterial and antifungal activities of 1 and 3 were remarkable and comparable to those of the previous silver(I)-N-heterocycle complexes. Methods Find Exp Clin Pharmacol, 2000 Sep, 22(7), 581 - 4 Effect of clarithromycin on the pharmacokinetics of carbamazepine in rhesus monkeys; Badyal DK et al.; Clarithromycin, an advanced-generation macrolide antimicrobial, is less prone to drug interactions as compared to erythromycin . Based on two case reports in which increased carbamazepine (CBZ) plasma concentrations were observed in patients receiving clarithromycin, a crossover multiple dose study was designed to find out the pharmacokinetic interaction between CBZ and clarithromycin in rhesus monkeys . CBZ (46 mg/kg/d) was administered to the monkeys alone and along with clarithromycin (20 mg/kg/d) . Blood samples were collected from 0-24 h . Plasma concentrations of CBZ were measured by HPLC technique . Pharmacokinetic data revealed an increase in plasma concentrations, AUC(0-24) and t1/2e of CBZ when coadministered with clarithromycin, but the increase was not statistically significant . These findings suggest careful administration and plasma monitoring of CBZ concentrations when coadministered with clarithromycin. Avian Dis, 2000 Oct-Dec, 44(4), 963 - 7 Presence of fluoroquinolone-resistant coliforms in poultry litter; Hofacre CL et al.; Litter was collected from four turkey farms (eight houses) with a history of fluoroquinolone (FQ) treatment failure, 10 adult broiler breeder chicken farms (43 houses) with one having a history of FQ treatment, and 30 broiler chicken farms (110 houses) with 24 having a history of FQ treatment . In the turkey litter, the percentage of nalidixic acid-resistant (at 100 microg/ml) coliforms/total number of coliforms ranged from 0.6% to 61.9% . Two of the four farms had houses containing coliforms resistant to the two FQs, enrofloxacin (1 microg/ml) and sarafloxacin (1 microg/ml) . There was also multiple resistance to other antimicrobials on all four turkey farms (ampicillin, tetracycline, chloramphenicol, kanamycin) . The level of total coliforms from the adult broiler breeder litter was low, and there were no nalidixic acid-resistant isolates from any of the 10 farms . In the broiler chickens, 7 of 91 houses with a history of FQ usage contained coliforms resistant to nalidixic acid; however, 2 of the 19 houses on farms with no history of FQ usage had nalidixic acid-resistant coliforms . All of the broiler farms with nalidixic acid-resistant isolates were also resistant to the FQ sarafloxacin, whereas only 3 of the 24 treatment history farms and 1 of the no-treatment history farms exhibited enrofloxacin-resistant coliforms in the litter. J Fam Pract, 2001 Jan, 50(1), 26 - 31 The common cold in patients with a history of recurrent sinusitis: increased symptoms and radiologic sinusitislike findings; Alho OP et al.; BACKGROUND: We evaluated whether the symptoms and signs and radiologic findings during a common cold are similar in patients who have and have not suffered from recurrent sinusitis . METHODS: We recruited 2 series of volunteer cases from February 1, 1996, to December 31, 1996 . Twenty-three adults who claimed to have suffered from recurrent sinusitis and 25 who had never had sinusitis were examined during the period of a self-diagnosed cold of 48 to 96 hours' duration and again after 21 days . Symptom scores were recorded, nasoendoscopy and computed tomography scans were performed, and viral and bacterial specimens were taken . RESULTS: The patients with a history of sinusitis had significantly higher symptom scores than the control patients (P=.04) and had radiologic sinusitislike changes more often (65% {15} vs 36% {9}; difference 29% {95% confidence interval, 2%-56%}; P=.04) . The viral etiology of the common cold (verified in 67% of the episodes) was similar in both groups . Pathogenic bacteria were isolated from the middle meatus in 24% (6) of the control patients and only 9% (2) of the sinusitis-prone patients (P=.15) . On the basis of the symptomatology, radiologic findings, and bacterial cultures only 2 patients in the sinusitis-prone group should have been treated with antimicrobials . CONCLUSIONS: Some patients are susceptible to both sinusitislike symptoms and radiologic findings during viral common colds . This may cause them to consult their physicians earlier and more often during viral colds, which may result in unnecessary antibiotic treatments . Nasopharyngeal bacteriological cultures may prove to be useful in ruling out bacterial sinusitis. Am J Health Syst Pharm, 2001 Jan 1, 58(1), 41 - 50; quiz 51-3 Treatment strategies for recurrent oral aphthous ulcers; Barrons RW; The clinical features, etiology, and treatment of recurrent aphthous ulcers (RAU) are discussed . Aphthous ulcers are among the most common oral lesions in the general population, with a frequency of up to 25% and three-month recurrence rates as high as 50% . The ulcers, which usually occur on the nonkeratinized oral mucosa, can cause considerable pain and may interfere with eating, speaking, and swallowing . RAU is classified as minor, major, and herpetiform on the basis of ulcer size and number . The cause of RAU is idiopathic in most patients . The most likely precipitating factors are local trauma and stress . Other associated factors include systemic diseases and nutritional deficiencies, food allergies, genetic predisposition, immune disorders, the use of certain medications, and HIV infection . The primary goals of therapy for RAU are relief of pain, reduction of ulcer duration, and restoration of normal oral function . Secondary goals include reduction in the frequency and severity of recurrences and maintenance of remission . Topical medications, such as antimicrobial mouthwashes and topical corticosteroids, can achieve the primary goals but have not been shown to alter recurrence or remission rates . Systemic medications can be tried if topical therapy is ineffective . Levamisole has shown variable efficacy in reducing ulcer frequency and duration in patients with minor RAU . Oral corticosteroids should be reserved for severe cases of major RAU that do not respond to topical agents . Thalidomide is effective but, because of its toxicity and cost, should be used only as an alternative to oral corticosteroids . RAU can be effectively managed with a variety of topical and systemic medications. Poult Sci, 2000 Dec, 79(12), 1857 - 60 Validation of thiosulfate for neutralization of acidified sodium chlorite in microbiological testing; Kemp GK et al.; At low pH, acidified sodium chlorite (ASC) has antimicrobial activity against a variety of foodborne contaminants . To evaluate the antimicrobial efficacy of ASC at specific time points posttreatment, it is necessary to halt the action of the disinfectant by removing residual chlorite or by increasing the pH . In this study, thiosulfate was investigated at varying concentrations for its effect on microbial survival and was investigated at a concentration of 0.1% in the presence of ASC for its effect on the antimicrobial and chemical activity of the test solution . Additionally, sodium thiosulfate was tested in two buffering systems, buffered peptone water (BPW) and Butterfield's phopshate buffer (BPB), for its ability to inactivate ASC chemistry . The results of this study show that, at a concentration of 0.1%, sodium thiosulfate has no deleterious effect on Escherichia coli survival and is effective in halting the antimicrobial action of ASC by eliminating the production of residual chlorite . The BPW alone and BPB in combination with thiosulfate were found to be effective inactivators of ASC chemistry. Nihon Kokyuki Gakkai Zasshi, 2000 Nov, 38(11), 844 - 9 {Pulmonary Nocardia otitidiscaviarum infection in an immunocompetent host}; Matsuo K et al.; A rare case of pulmonary Nocardia otitidiscaviarum (N . otitidiscaviarum) was encountered in an immunocompetent host . A 74-year-old man was admitted to our hospital with a high fever and a productive cough . His chest radiograph and CT scan revealed infiltrative shadows in the right middle and lower lung fields . Although several antibiotics (third-generation cephalosporin, minocycline, imipenem) were administered, the fever and cough persisted, and C-reactive protein remained elevated . Repeated sputum cultures showed normal flora, so a transbronchial lung biopsy and bronchoalveolar lavage (BAL) were performed bronchoscopically at the right S5 . The BAL fluid contained acid-fast, branching filamentous structures . The microorganism was identified as N . otitidiscaviarum by the Research Center for Pathogenic Fungi and Microbial Toxicoses (Chiba University) . Trimethoprim-sulfamethoxazole was therefore administered, but the fever continued to rise daily, and C-reactive protein remained elevated . This isolated N . otitidiscaviarum showed resistance to multiple antimicrobial agents in vitro when examined by the disk diffusion method, and so, on the basis of the antibiogram, the patient was treated with clarithromycin (oral, 600 mg/day) plus amikacin (400 mg/day), which proved successful . Testing for pulmonary nocardiosis should be added to the differential diagnosis procedures for refractory pneumonia as an opportunistic infection and for community-acquired pneumonia. Eur J Ophthalmol, 2000 Oct-Dec, 10(4), 286 - 92 Preoperative gentamicin eye drops and chlorhexidine solution in cataract surgery . Experimental and clinical results; Montan PG et al.; PURPOSE: 1) To evaluate the effects on the conjunctival flora of gentamicin ophthalmic eye drops 0.3%, given four times in 45 minutes, and a conjunctival rinse with 10 ml chlorhexidine 0.05% solution . 2) To investigate retrospectively the rate of endophthalmitis after cataract operations when these antimicrobials were applied preoperatively . METHODS: Seventy-six patients undergoing standard phacoemulsification operations were enrolled in the experimental part of the study . Cultures were taken preoperatively, 5 minutes after prophylaxis with either chlorhexidine or gentamicin . To assess the combined effects of chlorhexidine and gentamicin, cultures were taken after the cataract operation . Hospital charts were reviewed for cases of endophthalmitis in 1994 and 1995, when this prophylactic protocol was used at the St Erik's cataract surgery department . RESULTS: The conjunctival microflora was significantly suppressed by chlorhexidine rinsing alone (p = 0.001), while no other significant anti-bacterial effects were observed with the experimental prophylaxis . The endophthalmitis rate was 32/12 . 806 operations (0.25%) . CONCLUSIONS: Topical rinsing with chlorhexidine solution suppresses conjunctival flora in the short term . Combined topical chlorhexidine and gentamicin prophylaxis does not eliminate postoperative endophthalmitis caused by gram-positive bacteria. J Inorg Biochem, 2001 Jan 1, 83(1), 7 - 16 Copper(II) complexes with phenoxyalkanoic acids and nitrogen donor heterocyclic ligands: structure and bioactivity; Dendrinou-Samara C et al.; The copper complexes with the phenoxyalkanoic acids MCPA, 2,4-D, 2,4,5-T and 2,4-DP in the presence of a nitrogen donor heterocyclic ligand, phen or bipyam, were prepared and characterized . Interaction of Cu(II) with phenoxyalkanoic acids and bipyam leads to dinuclear or uninuclear neutral complexes while in the presence of phen uninuclear neutral or cationic forms have been isolated . The crystal structure of bis(1,10-phenanthroline)(2-methyl-4-chloro-phenoxyacetato)copper(ll) chloride-methanol(1/1)-water(1/0.6), 1 has been determined and refined by least-squares methods using three-dimensional MoK, data . 1 crystallizes in space group P1, in a cell of dimensions a = 14.577(6)A, b = 1 1.665(5) A, c = 12.249(6) A, alpha = 98.38( 1)degrees, beta = 112.18( 1) degrees, gamma = 104.56(1 ) degrees, V= 1,798( 1) A3 and Z= 2 . The cyclic voltammograms of uninuclear cationic complexes in dmf exhibit an extra cathodic wave due to the chloride ion . The available evidence supports an increasing antimicrobial effeciency for the cationic complexes. Ann Plast Surg, 2001 Jan, 46(1), 55 - 8 Actinomycosis of the frontal and parotid regions; Ermis I et al.; Cervicofacial actinomycosis still occurs infrequently and should be included in the differential diagnosis of neoplasms, and chronic suppurative and granulomatous lesions of the head and neck region . The authors present two cases of actinomycosis . Patient 1 was a 32-year-old man who was first seen with a firm, suppurative mass at his left frontal region . Patient 2 was a 36-year-old woman with an indurated mass at her left parotid area . Both patients were diagnosed histopathologically with cervicofacial actinomycosis, but each patient had a different clinical course and different response to antimicrobial and surgical treatments. J Parasitol, 2000 Dec, 86(6), 1355 - 9 Effect of the antimicrobial peptide, D-hecate, on trichomonads; Mutwiri GK et al.; Tritrichomonas foetus and Trichomonas vaginalis are protozoan parasites that cause sexually transmitted diseases in cattle and humans, respectively . There is a need for new antimicrobial agents to treat or prevent trichomoniasis because there are currently no approved chemotherapeutic agents against T . foetus and resistance of T . vaginalis to metronidazole does occur . Therefore, we evaluated the effect of a novel antimicrobial peptide, D-hecate, on the viability of 6 isolates of T . foetus and T . vaginalis in vitro . Tritrichomonas foetus and T . vaginalis were grown to mid log phase (24 hr) or late log/stationary phase (48 hr) . Parasites at 10(6)/ml were mixed with equal volumes of D-hecate to final concentrations of 10 microM, 20 microM . and 40 microM of D-hecate . Controls had minimal essential medium (MEM) alone . The numbers of viable parasites were determined microscopically after 10, 20, and 30 min of incubation at 37 C with D-hecate or MEM . Our results show that D-hecate killed all 6 isolates of T . foetus and T . vaginalis evaluated . The killing effect was dependent on the concentration of the peptide, incubation time, and phase of growth of the parasites . Ultrastructural studies of parasites treated with 10 microM of D-hecate revealed extensive damage to the plasma membrane of most T . foetus and T . vaginalis cells, while a few cells were distorted but remained intact . D-Hecate may be a useful chemotherapeutic agent for the treatment of trichomoniasis. Methods Inf Med, 2000 Dec, 39(4-5), 303 - 10 A data mining system for infection control surveillance; Brossette SE et al.; Nosocomial infections and antimicrobial resistance are problems of enormous magnitude that impact the morbidity and mortality of hospitalized patients as well as their cost of care . The Data Mining Surveillance System (DMSS) uses novel data mining techniques to discover unsuspected, useful patterns of nosocomial infections and antimicrobial resistance from the analysis of hospital laboratory data . This report details a mature version of DMSS as well as an experiment in which DMSS was used to analyze all inpatient culture data, collected over 15 months at the University of Alabama at Birmingham Hospital. Nahrung, 2000 Dec, 44(6), 407 - 10 Improvement in the yield of lipophilized lysozyme by the combination with Maillard-type glycosylation; Liu S et al.; Hen egg white lysozyme was modified using the Maillard-type glycosylation method prior to the lipophilization with palmitic acid . The yield of lipophilized lysozyme significantly increased by the pre-glycosylation of the protein . The lipophilized lysozyme derivative was separated into two main fractions with different level of glycosylation . All fractions showed a strong antimicrobial activity against Gram-negative bacteria, Escherichia coli . The lipophilization of the lysozyme combined with glycosylation is a promising method for potential industrial applications of the lysozyme due to the enhanced antimicrobial activity and the improved yield. Arzneimittelforschung, 2000 Dec, 50(12), 1115 - 9 New thiazolo{4,5-d}pyrimidine derivatives as potential antimicrobial agents; Urgun H et al.; In this study, by starting from ethyl 4-amino-2,3-dihydro-3-phenyl-2-thioxothiazole-5-carboxylate (1), three compounds having 2,3-dihydro-3-phenyl-5-mercapto-6-alkyl/phenyl-2-thioxothiazolo{4,5- d}pyrimidin-7(6H)-one (2a-c) structure and their 5-(4'-nonsubstituted/-substituted benzoylmethyl)thio derivatives (3a-l) were synthesized . The antimicrobial activities of the synthesized compounds were investigated against some bacteria and fungi using the microdilution method . 2,3-Dihydro-3,6-diphenyl-5-(4'-bromobenzoylmethyl)thio-2-thioxothiazolo {4,5-d}pyrimidin-7(6H) one (3k) possessing remarkable activity against Gram-positive bacteria and yeast like fungi was found to be the most active compound in this series. Zentralbl Chir, 2000, 125 Suppl 2, 196 - 8 {Value of non-randomized prospective multicenter studies of perioperative antibiotic prophylaxis}; Hell K; Non-randomized prospective multicenter studies involving a large number of patients are often capable to prove effectiveness of perioperative antimicrobial prophylaxis in situations where it is not feasible to carry out highly sophisticated clinical trials due to limitations in logistical or financial resources . Furthermore, these studies tend to give a true picture of the daily work and procedures in hospitals, contrary to controlled trials in clinical research which might suffer of multitudes of restrictions and exclusions . Some non-randomized studies each involving more than 1,000 patients on antibiotic prophylaxis in colonic and biliary surgery as well as appendectomy are discussed and its usefulness demonstrated. Med Clin North Am, 2001 Jan, 85(1), 79 - 114 Nosocomial pneumonia . Diagnostic and therapeutic considerations; Cunha BA; Many patients with presumed nosocomial pneumonia probably have infiltrates on the chest radiograph, fever, and leukocytosis resulting from noninfectious causes . Because of the high mortality and morbidity associated with nosocomial pneumonias, however, most clinicians treat such patients with a 2-week empiric trial of antibiotics . Before therapy is initiated, the clinician should rule out other causes of pulmonary infiltrates, fever, and leukocytosis that mimic a nosocomial pneumonia (e.g., pre-existing interstitial lung disease, primary or metastatic lung carcinomas, pulmonary emboli, pulmonary drug reactions, pulmonary hemorrhage, collagen vascular disease affecting the lungs, or congestive heart failure) . If these disorders can be eliminated from diagnostic consideration, a 2-week trial of empiric monotherapy is indicated . The clinician should treat cases of presumed nosocomial pneumonia as if P . aeruginosa were the pathogen . Although P . aeruginosa is not the most common cause of nosocomial pneumonia, it is the most virulent pulmonary pathogen associated with nosocomial pneumonia . Coverage directed against P . aeruginosa is effective against all other aerobic gram-negative bacillary pathogens causing hospital-acquired pneumonia . The clinician should select an antibiotic for empiric monotherapy that is highly effective against P . aeruginosa, has a good side-effect profile, has a low resistance potential, and is relatively inexpensive in terms of its cost to the institution . The preferred agents for empiric monotherapy for nosocomial pneumonia are cefepime, meropenem, and piperacillin . Single organisms are responsible for nosocomial pneumonia, not multiple pathogens . S . aureus rarely, if ever, causes nosocomial pneumonia but is mentioned frequently in studies based on cultures of respiratory tract secretions . S . aureus, unless accompanied by a necrotizing pneumonia with rapid cavitation within 72 hours, in the sputum indicates colonization rather than infection and should not be addressed therapeutically . Antibiotics associated with a high resistance potential should not be used as monotherapy or included in combination therapy regimens (i.e., ceftazidime, ciprofloxacin, imipenem, or gentamicin) . Combination therapy is more expensive than monotherapy and is indicated only when P . aeruginosa is extremely likely, based on its characteristic clinical presentation, or is proved by tissue biopsy . Therapy should not be based on respiratory secretion cultures regardless of technique . Optimal combination regimens include cefepime or meropenem plus levofloxacin or piperacillin or aztreonam or amikacin . Nosocomial pneumonias usually are treated for 14 days . Lack of radiographic or clinical response to appropriate empiric nosocomial pneumonia monotherapy after 14 days suggests an alternate diagnosis . In these patients, a tissue biopsy specimen should be obtained to determine the cause of the persistence of pulmonary infiltrates unresponsive to appropriate antimicrobial therapy. Med Clin North Am, 2001 Jan, 85(1), 43 - 77 Community-acquired pneumonia . Diagnostic and therapeutic approach; Cunha BA; Optimal empiric therapy of CAP is with appropriate monotherapy (e.g., doxycycline, levofloxacin) . Combination therapy is problematic because of potential side effects and high cost . Empiric coverage should have a high degree of activity against both typical and atypical pathogens . The antibiotic selected should have an excellent side-effect profile and be relatively inexpensive . Clinicians should be selective in their choice of antibiotic for CAP and choose an antimicrobial that has little or no resistance potential, is relatively inexpensive, and permits i.v.-to-PO switch monotherapy. Med Clin North Am, 2001 Jan, 85(1), 149 - 85 Antibiotic side effects; Cunha BA; Antibiotic side effects are approached best from an individual agent perspective rather than from a class-related standpoint . As this article indicates, with the exception of drug fevers and drug rashes, most antibiotic side effects are related to individual agents and not class side effects . Clinicians should view antimicrobial side effects as related to each organ system and be aware that more often a nonmicrobial medication is the explanation for the drug side effect rather than the antimicrobial . Nonantimicrobial medications are the most common cause of drug fever; among antimicrobials, beta-lactams and sulfonamides are the most common causes of drug-induced fevers . Antimicrobial side effects have important implications for the patient, legal and economic implications for the hospital, and medicolegal implications for the physician . Antibiotic side effects that prolong hospitalization in today's managed care environment have important economic implications . Clinicians should be familiar with the most common side effects of the most frequently used antimicrobials, to minimize the potential of having adverse reactions occur in patients . Most adverse events related to antimicrobials are reversible rapidly on cessation of the medication . Irreversible toxicities include aminoglycoside-induced ototoxicity, Stevens-Johnson syndrome, and toxicity secondary to nitrofurantoin . The most common acute fatal drug reactions include hypersensitivity reactions resulting in anaphylaxis or the Stevens-Johnson syndrome and fatal hepatic necrosis secondary to trovafloxacin . Clinicians should eliminate the use of drugs associated with chronic or fatal toxicities because multiple therapeutic alternatives exist for virtually every potential infection. Med Clin North Am, 2001 Jan, 85(1), 133 - 47, vii Antimicrobial therapy in the elderly; Rajagopalan S et al.; This article focuses on the special characteristics of infection in the elderly and provides an update of the principles of antibiotic selection, use of specific antibiotics, and empiric use of antimicrobials in the treatment of infectious diseases in this particularly vulnerable group . Antituberculous, antifungal, and antiviral agents are mentioned briefly; detailed information regarding these classes of agents in reference to aging can be found in standard reviews of antimicrobial therapy in the elderly. Med Clin North Am, 2001 Jan, 85(1), 125 - 32 New uses of older antibiotics; Klein NC et al.; Despite the development of extended-spectrum penicillins, cephalosporins, and quinolones, the older antimicrobial agents, doxycycline, minocycline, TMP-SMX, clindamycin, and metronidazole, still play an important role in the treatment of infectious diseases . All of these older drugs are well absorbed by the oral route, attaining serum levels equivalent to those achieved by parenteral administration . The availability of generic forms of the older drugs reduces their cost . Besides traditional uses, some older drugs have become the preferred therapy for newly recognized infectious diseases . Doxycycline is the preferred drug for rickettsial tickborne diseases, ehrlichiosis and early Lyme disease . TMP-SMX is the preferred drug for I . belli and Cyclospora . Minocycline has been used to treat MRSA and MRSE infections . Clindamycin or metronidazole combined with a quinolone is an excellent oral regimen for polymicrobial infections . {table: see text} Med Clin North Am, 2001 Jan, 85(1), 115 - 23, vii Oral antibiotic treatment of infectious diseases; Sensakovic JW et al.; The use of antimicrobial agents (i.e., penicillins, cephalosporins, macrolides, aminoglycosides, tetracyclines, quinolones) have continued to grow at an astounding rate . Centers for Disease Control and Prevention estimates are of some 150 million prescriptions annually in the United States, amounting to some 50 millions pounds of antibiotics annually being used in the United States with some 15 to 17 million pounds being used in livestock and agriculture alone . These large numbers serve as indicators for caution and concern . Most oral antibiotics are prescribed for respiratory tract infections, more than half of which are probably viral, for which antimicrobials are not necessary . This overprescribing is noted at a time when increasing antimicrobial resistance is being recognized in hospital settings as well as in the community . The dilemma for the practitioner is to be able to use antibiotics efficaciously and prevent overusage and overprescribing. Gastroenterol Clin North Am, 2000 Dec, 29(4), 895 - 902 Accurate diagnosis of Helicobacter pylori . 14C-urea breath test; Chey WD; The 14C-urea breath test is an accurate means of identifying the presence of H . pylori infection before and after antimicrobial therapy . Several issues, including out of office analysis, the need for a support structure to perform the test, concerns regarding radiation exposure, and inconsistent reimbursement, have slowed the widespread acceptance of the 14C-urea breath test in clinical practice . Despite these problems, the 14C-urea breath test is simple, rapid, and relatively inexpensive compared with the currently available version of the 13C-urea breath test . As such, the 14C-urea breath test provides an attractive, nonendoscopic means of identifying active H . pylori infection. Gastroenterol Clin North Am, 2000 Dec, 29(4), 759 - 73, vii How to treat Helicobacter pylori . First-line, second-line, and future therapies; Megraud F et al.; Numerous trials were performed in the 1990s to define the optimal therapy for Helicobacter pylori infections . The proposed proton-pump inhibitor (PPI)-based and ranitidine bismuth citrate (RBC)-based triple therapies led to satisfactory results . Their first drawback is cost, and, for this reason, many people worldwide cannot benefit from these regimens . Failures of first-line therapies essentially are because of antimicrobial resistance, which increases with the selection pressure resulting from the use of these drugs . Second-line treatments using antimicrobial agents for which H . pylori resistance is low or nonexistent are being tested to find alternatives to the quadruple therapy . There is a need for new drugs, which should be highly effective, nonselective of resistant strains, and without side effects, to improve current regimens . These drugs may be the results of postgenomic studies. Cornea, 2001 Jan, 20(1), 112 - 6 Corneal co-infection with Scedosporium apiospermum and Acanthamoeba after sewage-contaminated ocular injury; Rumelt S et al.; PURPOSE: To describe a corneal co-infection with the fungus Scedosporium apiospermum and Acanthamoeba that result in spontaneous corneal perforation . METHODS: A 27-year-old man presented due to severe ocular pain in his left eye caused by a corneal ulcer . The patient was injured 7 days before presentation by metallic thread contaminated by sewage . Corneal scrapping and deep stromal biopsy were obtained and stained for microscopic evaluation with periodic acid-Schiff, Giemsa, and Gomori's methenamine silver stains . Samples were sent for aerobic and anaerobic bacterial and fungal cultures . RESULTS: Corneal biopsy and corneal scrapping showed viable Acanthamoeba cysts in the corneal stroma and S . apiospermum micelle, respectively . The fungal culture was sensitive to ketoconazole, miconazole, econasole, and traconazole . Devastating corneal perforation occurred despite aggressive antifungal and antiamoebic topical and systemic treatment initiated after diagnosis . The corneal button showed a necrotic tissue devoid of inflammatory cells and microorganisms . CONCLUSION: S . apiospermum and Acanthamoeba may co-infect immune privilege sites, such as the cornea, in immunocompetent hosts . Compromised corneal surface, e.g., after trauma by sewage-contaminated objects, may increase the susceptibility for such devastating coinfection . Prevention may be possible by use of protective eyewear by high-risk individuals . Treatment should be initiated promptly with broad-spectrum antimicrobial agents after ocular injury by sewage-contaminated objects . Repeated corneal cultures and biopsies, if the cultures are negative, are warranted . Corticosteroids should be withheld until the causative agents are identified and targeted treatment is initiated. Am J Manag Care, 2000 Dec, 6(23 Suppl), S1202 - 10 Antibiotic kinetic and dynamic attributes for community-acquired respiratory tract infections; Nicolau DP; Factors, including the age of the treatment population, this population's multiple comorbidities, the greater severity of their illness, and the considerable change in the pathogens in their epidemiology and resistance patterns, affect the management of community-acquired respiratory tract infections in the outpatient setting . Moreover, outcome is affected by the host, etiologic agent, and the selection of the antimicrobial treatment . The challenge of selecting appropriate antimicrobial therapy is often at the discretion of the prescriber . The nature of respiratory tract infections and the relationship of antimicrobial therapy to the resolution of infection are described. Am J Manag Care, 2000 Dec, 6(23 Suppl), S1178 - 88 Clinical choices of antibiotics: judging judicious use; Steinberg I; Scientific literature widely documents the current overuse of antibiotics but often does not address the issue of the judicious use of antibiotics . Multiple analyses of prescribing patterns consistently reveal inappropriate prescribing of antibiotics, even when the clinician is aware of appropriate antibiotic use . In addition to overprescribing antibiotics, providers frequently address therapy failures by switching to same-class antibiotic agents . Additional investigations report that prescribing of antibiotics at the first office visit tends to increase, rather than decrease, costs and has marginal impact on patient outcomes . Patient education interventions, delivered prior to illness, can significantly reduce inappropriate use of antibiotics and reverse resistance trends . A variety of developments in antimicrobial use and resistance and newer antibiotic and respiratory infection management strategies are discussed. J Pharm Pharmacol, 2000 Nov, 52(11), 1355 - 9 Determination of the salivary retention of hexetidine in-vivo by high-performance liquid chromatography; McCoy CP et al.; The non-antibiotic antimicrobial agent hexetidine is widely used at a concentration of 0.1% w/v as an oral rinse to reduce the number of viable microorganisms within the oral cavity . However, following use, the available concentration of hexetidine in the oral cavity declines with time, thus compromising the resultant antimicrobial activity . It is, therefore, desirable to determine the persistence of the agent in the oral cavity by quantification of the drug concentration in saliva, thus enabling prediction of its antimicrobial activity in the oral environment . A rapid reverse-phase HPLC method was therefore developed and validated for hexetidine in aqueous solution (Oraldene) and in saliva samples collected from volunteers post-rinsing with 15 mL of hexetidine oral rinse for 30s . The HPLC assay was sufficiently sensitive to accurately detect hexetidine in saliva up to 25 min after in-vivo use of a commercial oral rinse . Furthermore, it was possible to detect hexetidine below the published minimum inhibitory concentrations (MICs) for a selection of microorganisms . From these data a first-order elimination rate constant of hexetidine from the oral cavity was determined post-rinsing in each of six volunteers . The validated HPLC assay method presented is useful for the assay of hexetidine in the oral cavity both at and below MICs . The first-order elimination rate constant shows significant variation between volunteers. Int J Hematol, 2000 Oct, 72(3), 358 - 61 Necrotizing enterocolitis: experience of 27 cases from a single Korean institution; Choi JH et al.; Necrotizing enterocolitis (NEC) can involve any site in the gastrointestinal tract and is a fatal complication of immunosuppression . To characterize NEC, clinical and radiological characteristics were analyzed . A total of 27 cases of NEC were identified from January 1993 to August 1998, and medical records were reviewed . NEC was diagnosed by clinical and radiological criteria, and other mimicking conditions were excluded . Of the NEC cases, 22 (81.5%) occurred in patients with underlying hematologic malignancy . All patients complained of abdominal pain and fever at the time of inclusion . Escherichia coli was the most common pathogen identified . The most common finding by computed tomography was single-layered diffuse bowel wall thickening with variable density . Other findings were ascites, fascial thickening, pneumatosis, and mesenteric lymphadenopathy . Of the patients, 25 were treated with antimicrobials with or without recombinant hematopoietic growth factors, and 2 were treated with surgery because of perforation and profound bleeding . Among the 12 patients who died, NEC was the direct cause of death in 7 patients . In conclusion, computed tomography is an effective tool for early diagnosis of NEC . Bowel rest, broad-spectrum antimicrobials, and recombinant hematopoietic growth factors are important aspects of treatment . Surgery should be reserved for complicated cases. Phytomedicine, 2000 Jun, 7(3), 239 - 43 Allylsulfide constituents of garlic volatile oil as antimicrobial agents; Avato P et al.; Six different mixtures of garlic distilled oils containing diallyl disulfide (DDS) and diallyl trisulfide (DTS), ranging from 1 to 51% and 88 to 38% respectively, have been assayed against a number of yeasts (C . albicans, C . tropicalis and B . capitatus), gram-positive bacteria (S . aureus and B . subtilis) and gram-negative bacteria (P . aeruginosa and E . coli) . Results obtained support a specific antifungal more than an antibacterial activity and implicate DDS as the active constituent . Incubation of garlic extracts made up of 1% DDS and 88% DTS resulted, in fact, in the absence of growth inhibition against all the tested microorganisms, whereas garlic oils with higher quantities of DDS showed significant inhibitory activity, increasing with the increase of DDS amount. Can J Gastroenterol, 2000 Sep, 14(8), 676 - 80 Appropriateness of omeprazole prescribing in Quebec's senior population; Gregoire JP et al.; BACKGROUND: Prescribing omeprazole for the treatment of digestive disorders accounts for an important part of the costs in Quebec's drug benefit plan . In July 1993, the Quebec drug program listed omeprazole, with restriction, in its formulary . On January 1, 1994, this restriction was lifted; since then, omeprazole has been listed in the regular provincial formulary . OBJECTIVE: To describe the appropriateness of initial omeprazole prescribing in the ambulatory senior population of Quebec in the 27 months after being listed without restriction . SUBJECTS AND METHODS: A retrospective population-based cohort study was performed using prescription and medical services claims databases of the Quebec drug program . Data were extracted for elderly patients who received their first omeprazole prescription between July 1, 1994 and March 31, 1996 . RESULTS: Among the 47,140 first-time users of omeprazole identified, 7516 (15.9%) had had an endoscopy in the previous six months, 2308 (4.9%) were given an antimicrobial agent and omeprazole simultaneously, and 22,730 (48.2%) received omeprazole after prior use of an H2 receptor antagonist (H2RA) or a prokinetic drug . A total of 26,525 (56.3%) first-time users were prescribed omeprazole based on at least one of the three criteria listed above . Among these users, 729 (2.8%) received an H2RA concurrently with omeprazole . Altogether, 25,796 (54.7%) first-time users received omeprazole appropriately . CONCLUSIONS: Although reimbursement for omeprazole prescriptions has not been restricted in Quebec since January 1, 1994, it was prescribed appropriately for elderly patients in the majority of cases studied. Int J Antimicrob Agents, 2000 Sep, 16(1), 25 - 9 Antimicrobial activities of levofloxacin, clarithromycin, and KRM-1648 against Mycobacterium tuberculosis and Mycobacterium avium complex replicating within Mono Mac 6 human macrophage and A-549 type II alveolar cell lines; Sato K et al.; The antimicrobial activities of levofloxacin, clarithromycin and KRM-1648 against Mycobacterium tuberculosis (MTB) and Mycobacterium avium complex (MAC) residing in Mono Mac 6 human macrophage-like cells (MM6-Mphis) and A-549 human type II alveolar epithelial cells (A-549 cells) were studied . We measured the antimicrobial activity of test drugs in terms of effects on the behaviour of intracellular organisms during a 7-day cultivation of MTB- or MAC-infected cells in the medium containing the drugs at Cmax doses . Microbicidal action of levofloxacin against intracellular MTB within A-549 cells was markedly less than its activity against the same organisms in MM6-Mphis . The same effect was also noted for the action of KRM-1648 against MAC organisms but this did not occur with clarithromycin . The MIC of KRM-1648 for MAC multiplying within A-549 cells was 32 times larger than that for MAC residing in MM6-Mphis . These findings indicate that MTB and MAC organisms replicating in the type II lung epithelial cells resist the action of certain antimycobacterial agents such as quinolones and rifamycin derivatives but not when the organisms are contained in macrophages . It appears that the antimicrobial action of certain drugs against intracellular mycobacteria is differentially manifested depending on the types of host cells, i.e . professional phagocytes (MM6-Mphis) or non-professional phagocytes (A-549cells), in which the organisms are contained. Adv Ther, 2000 May-Jun, 17(3), 148 - 51 Effect of anti-infective ophthalmic solutions on corneal cells in vitro; Matsumoto S et al.; External ocular infections caused by susceptible strains of bacteria have recently been treated with potent broad-spectrum antimicrobial solutions . This study was conducted to compare the in vitro biologic effects of three anti-infective ophthalmic solutions (Ocuflox, Ciloxan, and Tobramycin) on rabbit corneal epithelial cell cultures . Epithelial cell layers from albino rabbit eyes were isolated and incubated in culture media for 9 days, following which the cultures were rinsed and treated with the anti-infective solutions . Ciloxan and Tobramycin caused extensive ethidium bromide staining of the corneal epithelial cell layer after 5, 10, and 15 minutes, indicating acute cell membrane damage . Ocuflox ophthalmic solution caused less ethidium bromide staining at all evaluated times and, therefore, less cell membrane damage than the comparator solutions. Thorax, 2001 Feb, 56(2), 121 - 5 Leucocyte response and anti-inflammatory cytokines in community acquired pneumonia; Kolling UK et al.; BACKGROUND: In the host defence of the lung neutrophils (PMN) play a central role . Apart from antimicrobial properties, recent data indicate that PMN also exert anti-inflammatory effects by stimulation and release of cytokine antagonists such as interleukin-1 receptor antagonist (IL-1ra) . METHODS: Cytokine release from lipopolysaccharide stimulated whole blood was studied in 18 patients with community acquired pneumonia (CAP) and severe co-morbidities at admission and after 24 hours . Release of IL-1ra, interleukin-1beta (IL-1beta), tumour necrosis factor alpha (TNFalpha), soluble TNF receptor type I (sTNF-RI), and IL-8 was determined by ELISA . RESULTS: The mean (SD) leucocyte level at admission was 12.5 (4.1)/nl . There was a significant correlation between the release of anti-inflammatory cytokines such as IL-1ra and sTNF-RI and the leucocyte count at admission and after 24 hours . Additional in vitro experiments showed that co-incubation of peripheral blood mononuclear cells with autologous PMN led to a marked dose dependent increase in IL-1ra and sTNF-RI release . CONCLUSION: These results indicate that PMN may be responsible for the increase in anti-inflammatory cytokines in CAP . Strategies to increase neutrophil counts may exert beneficial effects, not only by augmenting the antimicrobial activity but also by modulating the inflammatory cytokine response. Thorax, 2001 Feb, 56(2), 115 - 20 Role of bronchoalveolar lavage in immunocompromised patients with pneumonia treated with a broad spectrum antibiotic and antifungal regimen; Hohenadel IA et al.; BACKGROUND: In a retrospective study the value of bronchoalveolar lavage (BAL) in the diagnosis of pneumonia was investigated in 95 immunocompromised patients suffering from haematological disorders and receiving a regimen of broad spectrum antibiotics and antifungal agents (BSAR) . METHODS: With the exception of four afebrile patients, all had fever, raised C reactive protein (CRP) levels, and new infiltrates visible on chest radiography . All patients underwent BAL to identify the organism causing the pneumonia and surveillance cultures were performed regularly for pathogens at different sites . Following classification of the isolates, patients with positive cultures were subdivided into two groups, pathogenic or contaminated . We investigated whether relevant pathogens were cultured only from the BAL fluid and whether they were susceptible to BSAR . RESULTS: Although 77 of the 95 patients were thrombocytopenic, bleeding during BAL occurred in only 15% of all patients . Ten days after the procedure the fever improved in 88% of patients, radiographic findings improved in 71%, and CRP levels improved in 75% of patients; 22% of patients died within 28 days . Pathologically relevant isolates were found in 65% of all patients . Respiratory pathogens were detected only in the BAL fluid of 29 of the 95 patients (35% Gram positive species, 40% Gram negative species, 11% Mycobacterium, 11% fungi, and 3% cytomegalovirus) . In 16 of these 29 patients (55%) the pathogens cultured only from the BAL fluid were resistant to treatment . Pathogens detected only in the BAL fluid were not susceptible to a standard broad spectrum antibiotic and antifungal regimen including teicoplanin, ceftriaxon, tobramycin, and amphotericin B in 12 of the 29 patients (41%) . CONCLUSIONS: Our data suggest that 12 patients were treated with broad spectrum antimicrobial agents which were not directed at the appropriate organism on in vitro sensitivity tests without BAL . BAL is a relatively safe procedure in the diagnosis of pneumonia, supplying important information in immunocompromised patients as well as in immunocompromised patients receiving BSAR. Am J Physiol Cell Physiol, 2001 Feb, 280(2), C296 - 302 Cryptdin-3 induces novel apical conductance(s) in Cl- secretory, including cystic fibrosis, epithelia; Merlin D et al.; Opening of anion-conductive pathways in apical membranes of secretory cells lining mucosal surfaces is a critical step in salt and water secretion and, thus, hydration of sites including airway and intestine . In intestine, Paneth cells are positioned at the base of the secretory gland (crypt) and release defensin peptide, in mice termed cryptdins, into the crypt lumen . Because at least some defensins have been shown to form anion-conductive channels in phospholipid bilayers, we tested whether these endogenous antimicrobial peptides could act as soluble inducers of channel-like activity when applied to apical membranes . To directly evaluate the possibility of cryptdin-3-mediated apical anion conductance (G(ap)), we have utilized amphotericin B to selectively permeabilize basolateral membranes of electrically tight monolayers of polarized human intestinal secretory epithelia (T84 cells), thus isolating the apical membrane for study . Cryptdin-3 induces G(ap) that is voltage independent (deltaG(ap) = 1.90 +/- 0.60 mS/cm2) and exhibits ion selectivity contrasting to that elicited by forskolin or thapsigargin (for cryptdin-3, Cl- = gluconate; for forskolin and thapsigargin, Cl- >> gluconate) . We cannot exclude the possibility that the macroscopic current induced by cryptdin could be the sum of cation and Cl- currents . Cryptdin-3 induces a current in basolaterally permeabilized epithelial monolayers derived from airway cells harboring the deltaF508 mutation of cystic fibrosis (CF; deltaG(ap) = 0.80 +/- 0.06 mS/cm2), demonstrating that cryptdin-3 restores anion secretion in CF cells; this occurs independently of the CF transmembrane conductance regulator channel . These results support the idea that cryptdin-3 may associate with apical membranes of Cl--secreting epithelia and self-assemble into conducting channels capable of mediating a physiological response. J Am Geriatr Soc, 2001 Jan, 49(1), 85 - 90 Interventions to prevent pneumonia among older adults; Yamaya M et al.; Pneumonia is a common cause of death in older people . Antimicrobial drugs do not prevent pneumonia and, because of increasingly resistant organisms, their value in curing infection will become more limited . Establishing new strategies to prevent pneumonia through consideration of the mechanisms of this devastating illness is essential . The purpose of this review is to discuss how pneumonia develops in older people and to suggest preventive strategies that may reduce the incidence of pneumonia among older adults . Aspiration of oropharyngeal bacterial pathogens to the lower respiratory tract is one of the most important risk factors for pneumonia; impairments in swallowing and cough reflexes among older adults, e.g., related to cerebrovascular disease, increase the risk for the development of pneumonia . Thus, strategies to reduce the volumes and pathogenicity of aspirated material should be pursued . For example, since both swallowing and cough reflexes are mediated by endogenous substance P, pharmacologic therapy using angiotensin-converting enzyme inhibitors, which decrease substance P catabolism, may improve both reflexes and result in the lowering of the risk of pneumonia . Similarly, since the production of substance P is regulated by dopaminergic neurons in the cerebral basal ganglia, treatment with dopamine analogs or potentiating drugs such as amantadine (and, of course, prevention of cerebral vascular disease, which can result in basal ganglia strokes) should affect the incidence of pneumonia . The purpose of this review is to consider promising pharmacologic treatments as methods of preventing pneumonia in older adults and to review other proven strategies, e.g., infection control and cerebrovascular disease prevention that will lessen the incidence of pneumonia. Cell Microbiol, 2001 Feb, 3(2), 115 - 23 Helicobacter pylori-mediated transcriptional regulation of the human beta-defensin 2 gene requires NF-kappaB; Wada A et al.; Human beta-defensin 2 (hBD-2) is an antimicrobial peptide involved in host defence against bacterial infection in epithelial tissues . Its levels are dramatically increased after bacterial infection . The involvement of NF-kappaB in Helicobacter pylori-mediated induction of hBD-2 promoter activity was examined . A luciferase reporter plasmid containing the hBD-2 promoter extending from -2110 base pairs to -1 was transiently expressed in MKN45 cells, and promoter activity was determined after incubation with H . pylori for 6 h . Deletion or mutation of the NF-kappaB site at -208 abolished activation of the hBD-2 promoter . Only H . pylori strains carrying a cag pathogenicity island (PAI) induced activation of the NF-kappaB site of the hBD-2 promoter gene . By gel retardation analyses, H . pylori increased NF-kappaB binding to hBD-2 promoter gene sequences . Supershift analysis demonstrated that whereas H . pylori activated NF-kappaB p65-p65 and p50-p50 homodimers, and the p65-p50 heterodimer of NF-kappaB, only the p65-p65 homodimer bound to the NF-kappaB site of the hBD-2 promoter . Thus, specific NF-kappaB proteins are important cis-elements for induction of hBD-2 gene transcription by H . pylori. Ann Intern Med, 2001 Feb 20, 134(4), 298 - 314 Antibiotic resistance in the intensive care unit; Kollef MH et al.; Antimicrobial resistance has emerged as an important determinant of outcome for patients in the intensive care unit (ICU) . This is largely due to the administration of inadequate antimicrobial treatment, which is most often related to bacterial antibiotic resistance . In addition, the escalating problem of antimicrobial resistance has substantially increased overall health care costs . This increase is a result of prolonged hospitalizations and convalescence associated with antibiotic treatment failures, the need to develop new antimicrobial agents, and the implementation of broader infection control and public health interventions aimed at curbing the spread of antibiotic-resistant pathogens . Intensive care units are unique because they house seriously ill patients in confined environments where antibiotic use is extremely common . They have been focal points for the emergence and spread of antibiotic-resistant pathogens . Effective strategies for the prevention of antimicrobial resistance in ICUs have focused on limiting the unnecessary use of antibiotics and increasing compliance with infection control practices . Clinicians caring for critically ill patients should consider antimicrobial resistance as part of their routine treatment plans . Careful, focused attention to this problem at the local ICU level, using a multidisciplinary approach, will have the greatest likelihood of limiting the development and dissemination of antibiotic-resistant infections. Chem Biol, 2001 Jan, 8(1), 17 - 31 Energetic, structural, and antimicrobial analyses of beta-lactam side chain recognition by beta-lactamases; Caselli E et al.; BACKGROUND: Penicillins and cephalosporins are among the most widely used and successful antibiotics . The emergence of resistance to these beta-lactams, most often through bacterial expression of beta-lactamases, threatens public health . To understand how beta-lactamases recognize their substrates, it would be helpful to know their binding energies . Unfortunately, these have been difficult to measure because beta-lactams form covalent adducts with beta-lactamases . This has complicated functional analyses and inhibitor design . RESULTS: To investigate the contribution to interaction energy of the key amide (R1) side chain of beta-lactam antibiotics, eight acylglycineboronic acids that bear the side chains of characteristic penicillins and cephalosporins, as well as four other analogs, were synthesized . These transition-state analogs form reversible adducts with serine beta-lactamases . Therefore, binding energies can be calculated directly from K(i) values . The K(i) values measured span four orders of magnitude against the Group I beta-lactamase AmpC and three orders of magnitude against the Group II beta-lactamase TEM-1 . The acylglycineboronic acids have K(i) values as low as 20 nM against AmpC and as low as 390 nM against TEM-1 . The inhibitors showed little activity against serine proteases, such as chymotrypsin . R1 side chains characteristic of beta-lactam inhibitors did not have better affinity for AmpC than did side chains characteristic of beta-lactam substrates . Two of the inhibitors reversed the resistance of pathogenic bacteria to beta-lactams in cell culture . Structures of two inhibitors in their complexes with AmpC were determined by X-ray crystallography to 1.90 A and 1.75 A resolution; these structures suggest interactions that are important to the affinity of the inhibitors . CONCLUSIONS: Acylglycineboronic acids allow us to begin to dissect interaction energies between beta-lactam side chains and beta-lactamases . Surprisingly, there is little correlation between the affinity contributed by R1 side chains and their occurrence in beta-lactam inhibitors or beta-lactam substrates of serine beta-lactamases . Nevertheless, presented in acylglycineboronic acids, these side chains can lead to inhibitors with high affinities and specificities . The structures of their complexes with AmpC give a molecular context to their affinities and may guide the design of anti-resistance compounds in this series. Thorax, 2001 Mar, 56(3), 223 - 7 Similarities and differences in lectin cytochemistry of laryngeal and tracheal epithelium and subepithelial seromucous glands in cases of sudden infant death and controls; Paulsen FP et al.; BACKGROUND: It has been speculated that non-specific defence mechanisms of the epithelium and subepithelial seromucous glands play a role in the larynx and lungs in cases of sudden infant death . METHODS: The larynx and trachea from five children who had died of sudden infant death (SID) syndrome and five control cases of comparable age were compared for the presence of lectin binding sites (12 different lectins tested) . RESULTS: The secretory product of mucin producing cells contained carbohydrates including galactose and sialic acids . Binding sites for fucose and N-acetyl-galactosamine were only present in some of the specimens and distribution revealed no correlation between cases of SID and controls . Epithelial cells and serous cells of seromucous glands contained binding sites for sialic acid in cases of SID and controls . Moreover, binding sites for mannose were detected in these cells but were only present in SID cases . The difference between the SID and control groups as to the presence/expression of concanavalin A was highly significant . CONCLUSIONS: It is suggested that mucus hypersecretion in SID occurs in response to bacterial toxins or viral infection and is not specific . The different binding sites for mannose in cases of SID and controls could indicate differences in the production of antimicrobial peptides . A disturbed expression pattern of antimicrobial peptides in children who later succumb to SID could be responsible for an imbalance of the local microflora with a higher density of microorganisms on the mucosa . Further studies are required to elucidate the pattern of expression of antimicrobial peptides in subsequent SID victims. Hum Mol Genet, 2001 Mar 1, 10(5), 445 - 56 Ulcerative colitis and Crohn's disease: distinctive gene expression profiles and novel susceptibility candidate genes; Lawrance IC et al.; To elucidate the biological dysregulation underlying two forms of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD), we examined global gene expression profiles of inflamed colonic tissue using DNA microarrays . Our results identified several genes with altered expression not previously linked to IBD . In addition to the expected upregulation of various cytokine and chemokine genes, novel immune function-related genes such as IGHG3, IGLL2 and CD74, inflammation-related lipocalins HNL and NGAL, and proliferation-related GRO genes were over-expressed in UC . Certain cancer-related genes such as DD96, DRAL and MXI1 were differentially expressed only in UC . Other genes over-expressed in both UC and CD included the REG gene family and the calcium-binding S100 protein genes S100A9 and S100P . The natural antimicrobial defensin DEFA5 and DEFA6 genes were particularly over-expressed in CD . Overall, significant differences in the expression profiles of 170 genes identified UC and CD as distinct molecular entities . The genomic map locations of the dysregulated genes may identify novel candidates for UC and CD genetic susceptibility. Antimicrob Agents Chemother, 2001 Mar, 45(3), 786 - 8 Antimicrobial susceptibility of Ehrlichia phagocytophila; Horowitz HW et al.; Human granulocytic ehrlichiosis is a recently described disease caused by an obligate intracellular gram-negative organism recently named Ehrlichia phagocytophila . To expand our knowledge of the susceptibility of E . phagocytophila, we tested six New York State isolates for susceptibility to 12 antimicrobials using an HL-60 cell culture system . All of the isolates were susceptible to doxycycline (MIC, < or =0.125 microg/ml; minimum bactericidal concentration {MBC}, 0.125 to 0.5 microg/ml), rifampin (MIC, < or =0.125 microg/ml; MBC, < or =0.125 microg/ml), ofloxacin (MIC, < or =2 microg/ml; MBC, < or =2 microg/ml), levofloxacin (MIC, < or =1 microg/ml; MBC, < or =1 microg/ml), and trovafloxacin (MIC, < or =0.032 microg/ml; MBC, < or =0.032 microg/ml) . Isolates were uniformly resistant to amoxicillin, ceftriaxone, erythromycin, azithromycin, clarithromycin, and amikacin . For one strain, the MBC of chloramphenicol was < or =8 microg/ml . These data suggest that quinolone antibiotics and rifampin may be alternative agents for patients with intolerance to tetracyclines. Antimicrob Agents Chemother, 2001 Mar, 45(3), 768 - 75 Novel scintillation proximity assay for measuring membrane-associated steps of peptidoglycan biosynthesis in Escherichia coli; Chandrakala B et al.; We have developed a novel, high-throughput scintillation proximity assay to measure the membrane-associated steps (stages 2 and 3) of peptidoglycan synthesis in Escherichia coli . At least five enzymes are involved in these two stages, all of which are thought to be essential for the survival of the cell . The individual enzymes are difficult to assay since the substrates are lipidic and difficult to isolate in large quantities and analysis is done by paper chromatography . We have assayed all five enzymes in a single mixture by monitoring synthesis of cross-linked peptidoglycan, which is the final product of the pathway . E . coli membranes are incubated with the two sugar precursors, UDP-N-acetyl muramylpentapeptide and UDP-{(3)H}-N-acetylglucosamine . The radiolabel is incorporated into peptidoglycan, which is captured using wheat germ agglutinin-coated scintillation proximity assay beads . The assay monitors the activity of the translocase (MraY), the transferase (MurG), the lipid pyrophosphorylase, and the transglycosylase and transpeptidase activities of the penicillin-binding proteins . Vancomyin, tunicamycin, nisin, moenomycin, bacitracin, and penicillin inhibit the assay, and these inhibitors have been used to validate the assay . The search for new antimicrobial agents that act via the late stages of peptidoglycan biosynthesis can now be performed in high throughput in a microtiter plate. Clin Infect Dis, 2001 Feb 15, 32(4), 660 - 1 Epub 2001 Feb 07. Nocardia asteroides native valve endocarditis; Watson A et al.; A 39-year-old man with a history of injection drug abuse was given a diagnosis of Nocardia asteroides native aortic valve endocarditis, and he required valve replacement therapy, despite having received potent antimicrobial therapy . This is the first reported proven case of native valve endocarditis due to Nocardia species. Clin Infect Dis, 2001 Feb 15, 32(4), 605 - 11 Epub 2001 Feb 07. Role of clinical microbiology laboratories in the management and control of infectious diseases and the delivery of health care; Peterson LR et al.; Modern medicine has led to dramatic changes in infectious diseases practice . Vaccination and antibiotic therapy have benefited millions of persons . However, constrained resources now threaten our ability to adequately manage threats of infectious diseases by placing clinical microbiology services and expertise distant from the patient and their infectious diseases physician . Continuing in such a direction threatens quality of laboratory results, timeliness of diagnosis, appropriateness of treatment, effective communication, reduction of health care-associated infections, advances in infectious diseases practice, and training of future practitioners . Microbiology laboratories are the first lines of defense for detection of new antibiotic resistance, outbreaks of foodborne infection, and a possible bioterrorism event . Maintaining high-quality clinical microbiology laboratories on the site of the institution that they serve is the current best approach for managing today's problems of emerging infectious diseases and antimicrobial agent resistance by providing good patient care outcomes that actually save money. Clin Infect Dis, 2001 Feb 15, 32(4), 546 - 51 Epub 2001 Feb 09. Low infectious morbidity after intensive chemotherapy and autologous peripheral blood progenitor cell transplantation in the outpatient setting for women with breast cancer; Chandrasekar PH et al.; Autologous peripheral blood progenitor cell (PBPC) transplantation is increasingly employed in the outpatient setting, yet data on early complications following PBPC transplantation are scant . We evaluated 105 women with high-risk primary or metastatic breast cancer who were treated at a single institution during 1996--1997 . The mean duration of neutropenia (absolute neutrophil count, <500 cells/mm(3)) was 7.5 days . Twenty-nine percent of women remained afebrile throughout the neutropenic period . Of the remaining 71%, most (64 of 75) had fever of unknown origin . Infections, mostly of mild severity, occurred in 34% of women; these infections included bacteremia due to gram-positive organisms, catheter site infection, cellulitis, pneumonia, oral candidiasis, herpes simplex virus infection, and vaginitis . Fifty percent of PBPC transplant recipients required hospital admission, usually because of persistent fever; the mean duration of hospitalization was 3 days . No deaths or serious adverse events occurred . Such reduced infectious morbidity may be a consequence of minimal oral and/or gastrointestinal mucositis associated with the conditioning regimen and broad-spectrum antimicrobial prophylaxis used for this patient population. Toxicol Appl Pharmacol, 2001 Feb 15, 171(1), 20 - 6 Human alveolar macrophage responses to air pollution particulates are associated with insoluble components of coarse material, including particulate endotoxin; Soukup JM et al.; Inhalation of particulate matter in the ambient air has been shown to cause pulmonary morbidity and exacerbate asthma . Alveolar macrophage (AM) are essential for effective removal of inhaled particles and microbes in the lower airways . While some particles minimally effect AM function others inhibit antimicrobial activity or cause cytokine and growth factor production leading to inflammation and tissue remodeling . This study has investigated the effects of water soluble (s) and insoluble (is) components of Chapel Hill, North Carolina ambient particulate matter in the size ranges 0.1-2.5 microm (PM2.5) and 2.5-10 microm (PM10) diameter, on human AM IL-6, TNFalpha, and MCP-1 cytokine production and host defense mechanisms including phagocytosis and oxidant production . Cytokines were found to be induced by isPM10 to a much higher extent (>50-fold) than sPM10, which in turn stimulated production better than isPM2.5, while sPM2.5 was inactive . Previous studies have indicated that endotoxin (ETOX) is a component of sPM10 responsible for cytokine production . Here, it is shown that inhibition of isPM10-induced cytokine production was partially achieved with polymyxin B and LPS-binding protein (LBP), but not with a metal chelator, implicating ETOX as a cytokine-inducing moiety also in isPM10 . In addition to inducing cytokines, exposure to isPM10, but not the other PM fractions, also inhibited phagocytosis and oxidant generation in response to yeast . This inhibition was ETOX independent . The decrease in host defenses may be the result of apoptosis in the AM population, which was also found to be specifically caused by isPM10 . These results show that the functional capacity of AM is selectively modulated by insoluble components of coarse PM, including the biocontaminant ETOX. Exp Eye Res, 2001 Mar, 72(3), 289 - 99 Ocular pharmacokinetics in rabbits using a novel dual probe microdialysis technique; Macha S et al.; Ocular infections involve delicate internal structures of the eye that often require treatment with antimicrobial agents . A major constraint to the study of ocular drug absorption from systemic administration is the inaccessibility of the vitreous for continuous serial sampling . A novel dual probe microdialysis technique has been employed in our laboratory, which will enable the delineation of complete ocular pharmacokinetics of a drug . New Zealand albino rabbits weighing 2--2.5 kg were used . The animals were kept under anesthesia throughout the experiment . A concentric probe was implanted in the vitreous chamber about 3 mm below the corneal scleral limbus . Simultaneously a linear probe was implanted in the anterior chamber across the cornea . Intraocular pressure (IOP) was measured using Schiotz tonometer . The total protein concentrations in the aqueous and vitreous humors were determined using the Bio-Rad protein assay method . The aqueous and vitreous elimination kinetics of fluorescein were studied after intravitreal and systemic administrations over a period of 10 hr . Microdialysis technique was also compared to the conventional direct sampling technique by determining the intravitreal kinetics of fluorescein . Results suggest that IOP reverted to normal within 2 hr after the implantation of the probes . The increase in the vitreal total protein concentration was not significantly different from the baseline . The increase in the aqueous total protein concentration was less than five times the basal concentration throughout the experiment . The blood-aqueous and blood-retinal barrier integrity was delineated by determining the permeability index for fluorescein and were found to be 9.48 +/- 4.25% and 1.99 +/- 0.66% for the anterior and vitreous chamber, respectively . The rate constant of penetration of fluorescein into the anterior chamber was found to be 8.48 +/- 1.33 x 10(-2) min(-1), which was significantly higher than into the vitreous i.e . 4.34 +/- 2.82 x 10(-2) min(-1) . The terminal elimination rate constant of fluorescein from the anterior chamber (1.48 +/- 0.79 x 10(-2) min(-1)) was found to be similar to that of the plasma terminal elimination rate constant (1.57 +/- 0.25 x 10(-2) min(-1)), but significantly higher than from the vitreous (3.0 +/- 0.7 x 10(-3) min(-1)) . The terminal vitreal elimination rate constant of fluorescein after intravitreal administration was found to be similar by both microdialysis (3.98 +/- 0.6 x 10(-3) min(-1)) and direct sampling (4.38 +/- 1.4 x 10(-3) min(-1)) techniques . In case of direct sampling technique the area under the vitreous concentration-time curve was higher compared to that obtained by the microdialysis technique . There was no breakdown of the blood ocular barriers as shown by a very small change in the intraocular fluid protein concentrations . This was also confirmed by the fluorescein kinetics, which were in accordance with the previous studies . IOP data suggests that the intraocular fluid dynamics were not affected and the animals stabilized within 2 hr after the implantation of the probes . Fluorescein data suggests that the vitreous compartment is surrounded by a tighter barrier compared to the anterior chamber . This technique appears to be more sensitive, reproducible and requires only one animal for the determination of entire ocular pharmacokinetic profile . Int J Infect Dis, 2000, 4(3), 140 - 7 Genetic diversity and evidence for acquired antimicrobial resistance in Mycobacterium tuberculosis at a large hospital in South India; Harris KA Jr et al.; OBJECTIVE: To assess genetic diversity and drug resistance of Mycobacterium tuberculosis isolates collected at Christian Medical College Hospital (CMCH), Vellore, India, between July 1995 and May 1996 . MATERIALS AND METHODS: Isolates were subjected to IS6110-based restriction fragment length polymorphism (RFLP) analysis and tested for resistance to isoniazid, rifampin, ethambutol, streptomycin, and pyrazinamide, and DNA from selected strains was sequenced in regions associated with drug resistance . RESULTS: One hundred and one M . tuberculosis isolates were collected from 87 patients with pulmonary tuberculosis . Charts of 69 patients were reviewed for history of tuberculosis illness and treatment . DNA from 29 strains was sequenced in katG, rpoB, and gyrA, and sometimes pncA regions . Analysis by RFLP revealed a high degree of genetic diversity, with no identifiable clusters of infection . Of the strains tested, 51% were resistant to at least one antibiotic, and 43% were resistant to more than one drug . There was a high rate of resistance observed in patients whose charts indicated a history of improperly administered tuberculosis treatment, whereas little drug resistance was observed in patients never previously treated for tuberculosis . Sequencing of genes associated with drug resistance revealed several previously unreported mutations in resistant strains . CONCLUSIONS: This analysis suggests that the cases of tuberculosis in the sample are largely reactivation of long-standing infections and that the drug resistance among patients in CMCH is largely acquired or secondary rather than attributable to the spread of drug-resistant strains. Infect Immun, 2001 Mar, 69(3), 1402 - 8 Salivary histatin 5 is an inhibitor of both host and bacterial enzymes implicated in periodontal disease; Gusman H et al.; One of the salient features of periodontitis and gingivitis is the increase in the levels of bacterial and host-derived proteolytic enzymes in oral inflammatory exudates . This study evaluated the potential of histatin 5, a 24-residue histidine-rich salivary antimicrobial protein, to inhibit these enzymes . Using biotinylated gelatin as a substrate, histatin 5 was found to inhibit the activity of the host matrix metalloproteinases MMP-2 and MMP-9 with 50% inhibitory concentrations (IC50s) of 0.57 and 0.25 microM, respectively . To localize the domain responsible for this inhibition, three peptides containing different regions of histatin 5 were synthesized and tested as inhibitors of MMP-9 . Peptides comprising residues 1 to 14 and residues 4 to 15 of histatin 5 showed much lower inhibitory activities (IC50, 21.4 and 20.5 microM, respectively), while a peptide comprising residues 9 to 22 showed identical activity to histatin 5 against MMP-9 . These results point to a functional domain localized in the C-terminal part of histatin 5 . To evaluate the effect of histatin 5 on bacterial proteases, a detailed characterization of histatin 5 inhibition of gingipains from Porphyromonas gingivalis was carried out using purified Arg- and Lys-specific enzymes . Kinetic analysis of the inhibition of the Arg-gingipain revealed that histatin 5 is a competitive inhibitor, affecting only the Km with a K(i) of 15 microM . In contrast, inhibition of Lys-gingipain affected both the Km and Vmax, suggesting that both competitive and noncompetitive competitive processes underlie this inhibition . The inhibitory activity of histatin 5 against host and bacterial proteases at physiological concentrations points to a new potential biological function of histatin in the oral cavity. Expert Opin Investig Drugs, 2001 Feb, 10(2), 321 - 9 Granulysin: a novel antimicrobial; Kumar J et al.; Granulysin is a novel lytic molecule produced by human cytolytic T-lymphocytes (CTLs) and natural killer (NK) cells . It is active against a broad range of microbes, including Gram-positive and -negative bacteria, parasites and Mycobacterium tuberculosis . It is functionally related to other antibacterial peptides, like defensins and magainins, but is structurally distinct . It has structural similarity to porcine NK-lysin and to amoebapores made by Entamoeba histolytica . Synthetic peptides derived from granulysin have differential activity against eukaryotic cells and bacteria . Selective bactericidal peptides may have therapeutic roles as novel antibiotics. Expert Opin Investig Drugs, 2001 Feb, 10(2), 309 - 20 Antimicrobial properties of porphyrins; Stojiljkovic I et al.; A large number of natural and synthetic porphyrins of diverse chemical compositions and characteristics can be isolated from nature or synthesised in the laboratory . Antimicrobial and antiviral activities of porphyrins are based on their ability to catalyse peroxidase and oxidase reactions, absorb photons and generate reactive oxygen species (ROS) and partition into lipids of bacterial membranes . Light-dependent, photodynamic activity of natural and synthetic porphyrins and pthalocyanines against Gram-positive and Gram-negative bacteria has been well demonstrated . Some non-iron metalloporphyrins (MPs) possess a powerful light-independent antimicrobial activity that is based on the ability of these compounds to increase the sensitivity of bacteria to ROS or directly produce ROS . MPs mimic haem in their molecular structure and are actively accumulated by bacteria via high affinity haem-uptake systems . The same uptake systems can be used to deliver antibiotic-porphyrin and antibacterial peptide-porphyrin conjugates . Haemin, the most well known natural porphyrin, possesses a significant antibacterial activity that is augmented by the presence of physiological concentrations of hydrogen peroxide or a reducing agent . Natural and synthetic porphyrins have relatively low toxicity in vitro and in vivo . The ability for numerous chemical modifications and the large number of different mechanisms by which porphyrins affect microbial and viral pathogens place porphyrins into a group of compounds with an outstanding potential for discovery of novel agents, procedures and materials active against pathogenic microorganisms. Curr Infect Dis Rep, 2001 Feb, 3(1), 50 - 58 Preparation of the HIV-infected Traveler to the Tropics; Karp CL; Pre-travel advice and planning can help the HIV-infected traveler minimize the unavoidable risks of tropical travel . Issues to cover: the diagnosis, staging, and stabilization of HIV infection and its sequelae; adequacy of the supply of medications currently used; optimal sources of medical care in planned destinations; potential HIV-related legal restrictions on travel; special risks associated with the medical geography of the traveler's route and planned activities; the need to avoid food-, water-, and vector-borne diseases; any appropriate vaccination, chemoprophylaxis, and antimicrobial agents; and arrangement for adequate medical follow-up upon the traveler's return. Pediatr Infect Dis J, 2001 Jan, 20(1), 98 - 101; discussion 120-2 Historical perspective on the use of otic antimicrobial agents; Myer CM 3rd; Treatment of otorrhea has been described in the literature since 1500 BC . A multitude of therapeutic options have been described, including the use of astringents, antiseptics, alcohol, benzoin and various powders . Since the middle of the 20th century, antibiotic usage has been promoted as the most effective means of therapy . Until recently none of the agents that were used was found to be safe for middle ear use . Since 1990 there have been publications describing the safety and efficacy of fluoroquinolone drops for acute and chronic otorrhea . This article details the transition from treatment of otorrhea with nonspecific means to an era of antimicrobial therapy based on sound scientific evidence. Pediatr Infect Dis J, 2001 Jan, 20(1), 1 - 5 Compliance issues related to the selection of antibiotic suspensions for children; Steele RW et al.; OBJECTIVE: To evaluate the palatability, cost and other compliance issues as variables in the selection of antibiotic suspensions for children . METHODS: Eighty-six physicians and health care personnel randomly sampled amoxicillin (used as a standard for comparison) and 11 other antibiotics, evaluating them in categories of appearance, smell, texture, taste and aftertaste . Overall scoring was then adjusted for cost, duration of therapy and dosing intervals . RESULTS: Overall taste (palatability) ranking of antibiotics, highest to lowest, was as follows: loracarbef, cefdinir, cefixime, azithromycin, ciprofloxacin, trimethoprim-sulfamethoxazole, clarithromycin, trimethoprim, amoxicillin/clavulanate, cefpodoxime and cefuroxime . Overall rating of antibiotics was greatly influenced by other compliance variables, in order of their impact: cost; duration of therapy (5 vs . 10 days); and dosing intervals . Cost was not judged to be a major factor by most participants unless antibiotic expense was >$50.00 for treatment of otitis media in our hypothetical 2-year-old, 13-kg child . Taking all variables into consideration, final ranking from highest to lowest was azithromycin, cefdinir, loracarbef, cefixime, amoxicillin, trimethoprim-sulfamethoxazole, cefpodoxime, trimethoprim, clarithromycin, ciprofloxacin, cefuroxime and amoxicillin/clavulanate . CONCLUSIONS: Variables related to compliance for families filling antibiotic prescriptions and children taking these products are important in the selection of antimicrobial therapy . Because final assessment is likely to vary considerably among health care personnel, decisions must be made on an individual basis. Nat Med, 2001 Feb, 7(2), 174 - 9 T-cell release of granulysin contributes to host defense in leprosy; Ochoa MT et al.; A novel mechanism by which T cells contribute to host defense against microbial pathogens is release of the antimicrobial protein granulysin . We investigated the role of granulysin in human infectious disease using leprosy as a model . Granulysin-expressing T cells were detected in cutaneous leprosy lesions at a six-fold greater frequency in patients with the localized tuberculoid as compared with the disseminated lepromatous form of the disease . In contrast, perforin, a cytolytic molecule that colocalizes with granulysin in cytotoxic granules, was expressed at similar levels across the spectrum of disease . Within leprosy lesions, granulysin colocalized in CD4+ T cells and was expressed in CD4+ T-cell lines derived from skin lesions . These CD4+ T-cell lines lysed targets by the granule exocytosis pathway and reduced the viability of mycobacteria in infected targets . Given the broad antimicrobial spectrum of granulysin, these data provide evidence that T-cell release of granulysin contributes to host defense in human infectious disease. Nat Med, 2001 Feb, 7(2), 167 - 73 Triclosan offers protection against blood stages of malaria by inhibiting enoyl-ACP reductase of Plasmodium falciparum; Surolia N et al.; The antimicrobial biocide triclosan {5-chloro-2-(2,4-dichlorophenoxy)phenol} potently inhibits the growth of Plasmodium falciparum in vitro and, in a mouse model, Plasmodium berghei in vivo . Inhibition of {14C}acetate and {14C}malonyl-CoA incorporation into fatty acids in vivo and in vitro, respectively, by triclosan implicate FabI as its target . Here we demonstrate that the enoyl-ACP reductase purified from P . falciparum is triclosan sensitive . Also, we present the evidence for the existence of FabI gene in P . falciparum . We establish the existence of the de novo fatty acid biosynthetic pathway in this parasite, and identify a key enzyme of this pathway for the development of new antimalarials. Rev Soc Bras Med Trop, 2000 Nov-Dec, 33(6), 609 - 12 {Brain abscess caused by Nocardia sp in immunosuppressed patient}; Barata CH et al.; Patient with autoimmune haemolytic anaemia and thrombocytopenic purpura (Evans Syndrome), treated with immunosuppressive therapy (prednisone and azathioprine) developed brain abscess unresponsive to antimicrobial therapy, in spite of its 23 days duration . Diagnosis could be possible after recover secretion of peribulbar abscess and maintenance of this material over seven days in incubation. Echocardiography, 1998 Jul, 15(5), 489 - 492 Spontaneous Echo Contrast in Purulent Pericardial Effusion due to Non-Gas-Forming Organisms; Hung MJ et al.; We present the case of a 55-year-old man who developed massive pericardial effusion with tamponade within a 5-day period . During transthoracic two-dimensional echocardiographic examination, spontaneous echo contrast was visualized in pericardial effusion . A diagnosis of polymicrobial pyopericarditis was made when urgent pericardiocentesis revealed a significantly foul odor and purulent fluid that grew a culture of aerobes . After surgical drainage and appropriate antimicrobial therapy, this patient's pyopericarditis resolved . It was suggested that spontaneous echo contrast in pericardial effusion could be induced by non-gas-forming pyogenic cells. Acta Crystallogr D Biol Crystallogr, 2001 Feb, 57(Pt 2), 306 - 9 Identification of many crystal forms of Aspergillus nidulans dehydroquinate synthase; Nichols CE et al.; Extensive crystallization trials of Aspergillus nidulans dehydroquinate synthase, a potential novel target for antimicrobial drugs, in complexes with different ligands have resulted in the identification of nine crystal forms . Crystals of unliganded DHQS, binary complexes with either the substrate analogue, carbaphosphonate or the cofactor NADH, as well as the ternary DHQS-carbaphosphonate-cofactor complex, were obtained . The ternary complex crystallizes from ammonium sulfate and CoCl(2) in space group P2(1)2(1)2, with unit-cell parameters a = 133.8, b = 86.6, c = 74.9 A . The binary carbaphosphonate complex crystallizes from PEG 6000 in space group P2(1)2(1)2(1), with a = 70.0, b = 64.0, c = 197.6 A, and the binary cofactor complex crystallizes from PEG 3350 and sodium potassium tartrate in space group P2(1), with a = 83.7, b = 70.4, c = 144.3 A, beta = 89.2 degrees . DHQS in the absence of ligands crystallizes in space group P2(1), with a = 41.0, b = 68.9, c = 137.7 A, beta = 94.8 degrees . Each of these crystal forms are suitable for high-resolution structure determination . Structures of a range of DHQS-ligand complexes will be of value in the structure-based design of novel antimicrobial drugs. Acta Crystallogr D Biol Crystallogr, 2001 Feb, 57(Pt 2), 263 - 5 Crystallization and preliminary crystallographic studies of an antimicrobial protein from Pharbitis nil; Ha SC et al.; An antimicrobial protein from seeds of Pharbitis nil (Pn-AMP) which shows an antifungal activity towards several agriculturally important plant pathogens has been crystallized in the presence of equimolar N-acetylglucosamine with sodium citrate as precipitant . The crystal belongs to the hexagonal space group P6(1)22 (or P6(5)22), with unit-cell parameters a = b = 29.33 (5), c = 133.44 (12) A . Native data were collected using a crystal at 100 K to a resolution of 1.78 A. Curr Med Chem, 2001 Mar, 8(4), 371 - 84 Adverse reactions to fluoroquinolones . an overview on mechanistic aspects; De Sarro A et al.; This review focuses on the most recent research findings on adverse reactions caused by quinolone antibiotics . Reactions of the gastrointestinal tract, the central nervous system (CNS) and the skin are the most often observed adverse effects . Occasionally major events such as phototoxicity, cardiotoxicity, arthropathy and tendinitis occur, leading to significant tolerability problems . Over the years, several structure-activity and side-effect relationships have been developed, in an effort to improve overall antimicrobial efficacy while reducing undesirable side-effects . In this article we review the toxicity of fluoroquinolones, including the newer derivatives such levofloxacin, sparfloxacin, graepafloxacin and the 7-azabicyclo derivatives, trovafloxacin and moxifloxacin . A special attention is given to new data on mechanistic aspects, particularly those regarding CNS effects . In recent years extensive in vivo and in vitro experiments have been performed in an attempt to explain the neurotoxic effects of quinolones sometimes observed under therapeutic conditions . However, the molecular target or receptor for such effects is still not exactly known . Several mechanisms are thought to be responsible . The involvement of gamma-aminobutyric acid (GABA) and excitatory amino acid (EAA) neurotransmission and the kinetics of quinolones distribution in brain tissue are discussed . In addition, quinolones may interact with other drugs--theophylline and nonsteroidal antiflammatory drugs (NSAID(s))--in producing CNS effects This article provides information about the different mechanisms responsible of quinolones interaction with NSAID(s), methylxanthines, warfarin and antiacids. Curr Med Chem, 2001 Feb, 8(3), 305 - 16 Excessive matrix metalloproteinase activity in diabetes: inhibition by tetracycline analogues with zinc reactivity; Ryan ME et al.; Diabetes mellitus in rats is characterized by excessive activity of several matrix metalloproteinases (MMPs), notably collagenase(s) and gelatinase(s), in skin, gingiva, and other tissues . A number of tetracyclines (TCs), both antimicrobial compounds as well as chemically modified non-antimicrobial TC analogues (CMTs) are known to possess potent inhibitory activity against these enzymes . Three conventional antimicrobial TCs and six CMTs were used in this study . In vitro, doxycycline was shown to possess higher inhibitory capacity (i.e . lower IC(max)) against diabetic rat skin collagenase than either minocycline or tetracycline HCl . Addition of excess zinc partially reversed the proteinase inhibition by TCs . In vivo, using rats made diabetic with streptozotocin (STZ), oral administration of various TCs led to decreased weight loss and substantial reductions in the activity of both skin collagenase and skin gelatinase (primarily MMP-9, 92 kDa) without affecting blood glucose . Using an in vitro spectrophotometric technique, the Zn(++) reactivity of several CMTs was assessed and found to be positively related to the potency of these compounds as MMP inhibitors . One particular CMT (CMT-5, pyrazole analogue), which is neither antimicrobial nor capable of binding metal cations, did not inhibit the MMPs . TCs have potential utility in management of diabetic complications mediated by excessive activity of MMPs. Curr Med Chem, 2001 Feb, 8(3), 295 - 303 A combination of subtherapeutic doses of chemically modified doxycycline (CMT-8) and a bisphosphonate (clodronate) inhibits bone loss in the ovariectomized rat: a dynamic histomorphometric and gene expression study; Ramamurthy N et al.; Recent studies have demonstrated that tetracyclines can reduce bone loss in the ovariectomized (OVX) rat model of osteoporosis . In the current study, a non-antimicrobial, chemically modified doxycycline (CMT-8), alone or in combination with a bisphosphonate (Clodronate), was evaluated in this model . Forty-two, 6month old, female rats were randomly assigned to the following groups, (6/ group): a) sham/vehicle, b) OVX/vehicle; c) OVX/1 mg/day CMT-8; d) OVX/2 mg/day CMT-8, e) OVX/1 mg/week Clodronate; and f) OVX/1 mg/day CMT-8 + 1 mg/week Clodronate, CMT-8 was administered by oral gavage, Clodronate injected S/C . Following sham surgery or OVX, the rats were treated for 90 days with CMT-8 or vehicle alone, injected at three different times with fluorochrome labels, the rats were sacrificed, and the tibiae excised for analysis by dynamic bone histomorphometry . Femurs were aseptically removed and analyzed for collagen, collagenase and osteopontin mRNAs by Northern and dot blot analysis . As expected, OVX decreased trabecular bone volume (BV/TV by 73.8% vs . sham p<.01), and also reduced trabecular thickness, numbers, and increased spacing . Bone loss in the OVX animals was partially prevented with either 2 mg/day CMT-8 or 1 mg/wk Clodronate (p<.01), while the 1 mg/day CMT-8 had no effect . Interestingly, the efficacy of the combination therapy of CMT-8 and Clodronate was significantly better than either treatment by itself, maintaining bone mass and structural indices at levels identical to sham values . OVX rats mRNA for collagen, collagenase and osteopontin were elevated indicating high-turnover bone loss . Only COMBO therapy significantly reduced the collagenase and osteopontin mRNA . In summary, CMT-8 mono-therapy (2 mg) alone partially inhibited bone loss in this animal model of osteoporosis . However, 1 mg/day (CMT-8) monotherapy had no effect on bone loss or bone mRNA levels and when combined with Clodronate, interacted to increase efficacy . Thus, a combination of a suboptimal dose of CMT-8 and a bisphosphonate appears to increase the amount of bone by suppressing resorption in a model of osteoporosis. Curr Med Chem, 2001 Feb, 8(3), 271 - 9 Cytotoxic activity and inhibition of tumor cell invasion by derivatives of a chemically modified tetracycline CMT-3 (COL-3); Lokeshwar BL et al.; Tetracyclines such as chlortetracycline and doxycycline with antimicrobial activity were reported to possess cytostatic and cytotoxic activity against mammalian tumor cells, often at high doses . Non-antimicrobial chemically modified tetracyclines (CMTs), with limited systemic toxicity but with significant tumor cell toxicity and antimetastatic activity, are attractive for long term treatment for cancer . We recently reported one such CMT, 6-deoxy,6-demethyl 4-dedimethylamino tetracycline (CMT-3) is a potent anti-tumor and anti-metastatic drug . Here we report on the anti-cell proliferation and anti-invasive activity of five nitro derivatives of CMT-3 (CMT-3N).All the five CMT-3Ns (CMT-302, CMT-303, CMT-306, CMT-308 and CMT-316) inhibited in vitro cell proliferation of prostate cancer cells . The 50% growth inhibition concentration (IC(50)) of CMT-3Ns was similar to that of CMT-3 . Although CMT-3 was by far the most potent anti-cell proliferation drug, all CMT-3Ns except CMT-303 and CMT-308 had similar anti-cell proliferation activity (IC(50): 2.5 -5.7 microg/ml) . IC(50)s for CMT-303 and CMT-308 were approximately 8.1 and -12.4 microg/ml, respectively . Activity against tumor cell invasion was tested in vitro using the Matrigel invasion assay . All CMT-3Ns had similar anti- invasive activity . While cytotoxic activity of CMT-3 was strongly associated with cell death-effector caspase activation, mitochondrial permeablization and apoptosis, the CMT-3Ns weakly induced apoptosis and did not activate Caspase-3 . However, the CMT-3Ns were able to induce mitochondrial permeabilization . This dichotomous mechanism of cytotoxic activity of CMTs may have significance in their selection for clinical application. Curr Med Chem, 2001 Feb, 8(3), 257 - 60 CMT-3, a non-antimicrobial tetracycline (TC), inhibits MT1-MMP activity: relevance to cancer; Lee HM et al.; Tetracyclines (TCs) and their non-antimicrobial analogs (CMTs) have therapeutic potential to inhibit tissue destructive disease processes, such as cancer invasion and metastasis, by inhibiting certain matrix metalloproteinases . Enhanced matrix metalloproteinase-2 (MMP-2; gelatinase A) activity has been correlated to cancer invasiveness, and membrane type MMP (MT1-MMP) expressed by tumor cells is involved in localizing and activating pro-MMP-2, a pathway believed to mediate cancer induced tissue breakdown . CMT-3 (6-demethyl, 6-deoxy, 4-dedimethylamino TC) has been shown to experimentally suppress prostate cancer, colon adenocarcinoma and melanoma invasiveness in cell culture and to inhibit tumor growth and metastasis in vivo and was used in the current in vitro study . Confluent MT1-MMP transfected COS-1 cells were harvested, washed thoroughly, subjected to N(2) cavitation and cell membrane enriched fractions were isolated by sequential centrifugations . This MT1-MMP preparation exhibited (i) pro-MMP-2 activating activity as shown by molecular weight shift of this gelatinase from 72 kDa to 62 kDa using gelatin zymography, and (ii) the ability to degrade both {(3)H-methyl} gelatin and casein at 37 degrees C . Adding CMT-3 at final concentrations of 5--20microM inhibited MT1-MMP gelatinolytic and caseinolytic activity, blocked MT1-MMP activation of pro-MMP-2, and decreased invasiveness (using the Matrigel system) of HT-1080 fibrosarcoma cells . The inhibition of MT1-MMP by CMT-3 may partially explain the inhibition of cancer cell -mediated tissue breakdown and invasiveness by this non-antimicrobial tetracycline analog. Curr Med Chem, 2001 Feb, 8(3), 243 - 52 The lipophilicity, pharmacokinetics, and cellular uptake of different chemically-modified tetracyclines (CMTs); Liu Y et al.; CMTs are analogs of tetracyclines, which are chemically modified to eliminate their antimicrobial efficacy but which retain their inhibitory activity against matrix metalloproteinases . These compounds have been found to inhibit connective tissue breakdown in animal models of diseases such as periodontitis, arthritis and cancer . Because CMTs exhibit different in vivo efficacy in these various models of disease, the current study compared their pharmacokinetics and other properties as follows: Adult male Sprague-Dawley rats were administered by oral gavage a single dose of 5mg of different CMTs suspended in 1 ml 2% carboxymethyl-cellulose, and blood samples were collected from 1-48 hours after dosing . The sera were extracted, then analyzed by HPLC using a C-18 reverse-phase column . The results showed that the peak concentrations (C(max)) in rat sera 1-12 hours after oral administration of CMTs -1, -2,-3, -4,-5,-6,-7,-8 and doxycycline were 5.5, 0.7, 4.6, 6.2, 0.8, 0.7, 9.0 (note: the 3 peaks detected for CMT-7 were combined), 15.0 and 0.9 microg/ml, respectively . Their in vivo half-lives (t(1/2)) were 11, 5, 22, 11, 32, 15, 37, 38, and 17 hours, respectively . Of the anticollagenase CMTs tested, CMT-8 showed the greatest C(max) and t(1/2)values, followed by CMTs-3, -1, -4, and perhaps -7; CMTs-2, -5, and -6 exhibited much lower levels in serum . The relative lipophilicities of the 8 CMTs and doxycycline were tested by examining their extractability in octanol . The results showed that CMT-2, -5, and -6 had the lowest partition coefficients using this organic solvent, while CMT-3 was the most lipophilic . The lipophilicity of the different CMTs was also positively correlated (r(2)=0.767, P<0.05) to peak serum concentrations (C(max)), but not to their serum half-lives (r(2)=0.25,P=0.49) . This property of the different CMTs was also found to be positively correlated to their ability to enter into human whole blood cells in vitro (r2=0.95, P<0.001) . Since CMT-8, as well as CMTs-3 and -1, consistently exhibited the greatest in vivo efficacy in animal models of tissue breakdown, this may reflect, at least in part, their favorable pharmacokinetics and tissue uptake. Curr Med Chem, 2001 Feb, 8(3), 237 - 42 Biologic properties of non-antibiotic, chemically modified tetracyclines (CMTs): a structured, annotated bibliography; Greenwald R et al.; The first paper reporting on a potentially important medical property of a non-antimicrobial tetracycline appeared in 1987 . Since then, a literature of over 75 papers has supported the therapeutic potential of this class of compounds . In this review, this literature is grouped and organized with commentary on the data which has been published to date . The biomedical applicability of these discoveries obviously covers a wide range of medical conditions and clearly justifies their continued development. Am J Otolaryngol, 2001 Jan-Feb, 22(1), 19 - 32 Nitric oxide in the nasal airway: a new dimension in otorhinolaryngology; Djupesland PG et al.; The discovery that the gas nitric oxide (NO) is an important signaling molecule in the cardiovascular system earned its Nobel prize in 1998 . NO has since been found to play important roles in a variety of physiologic and pathophysiologic processes in the body including vasoregulation, hemostasis, neurotransmission, immune defense, and respiration . The surprisingly high concentrations of NO in the nasal airway and paranasal sinuses has important implications for the field of otorhinolaryngology . NO provides a first-line defense against micro-organisms through its antiviral and antimicrobial activity and by its upregulation of ciliary motility . Nasal treatments such as polypectomy, sinus surgery, removal of hypertrophic adenoids and tonsils, and treatment of allergic rhinitis may alter NO output and, therefore, the microbial colonization of the upper airways . Nasal surgery aimed at relieving nasal obstruction may do the same but would also be expected to improve pulmonary function in patients with asthma and upper airway obstruction . NO output rises in a number of conditions associated with chronic airway inflammation, but not all of them . Concentrations are increased in asthma, allergic rhinitis, and viral respiratory infections, but reduced in sinusitis, cystic fibrosis, primary ciliary dysfunction, chronic cough, and after exposure to tobacco and alcohol . Therefore, NO, similar to several other inflammatory mediators, probably subserves different functions as local conditions dictate . At present, it seems that the measurement of NO in the upper airway may prove valuable as a simple, noninvasive diagnostic marker of airway pathologies . The objective of this review is to highlight some aspects of the origin, physiology, and functions of upper airway NO, and to discuss the particular methodological problems that result from the complex anatomy. N Engl J Med, 2001 Jan 18, 344(3), 205 - 11 Acute pharyngitis; Bisno AL; The primary care physician needs to identify those patients with acute pharyngitis who require specific antimicrobial therapy and to avoid unnecessary and potentially deleterious treatment in the large majority of patients who have a benign, self-limited infection that is usually viral . In most cases, differentiating between these two types of infection can be accomplished easily if the physician considers the epidemiologic setting, the history, and the physical findings, plus the results of a few readily available laboratory tests . When antimicrobial therapy is required, the safest, narrowest-spectrum, and most cost-effective drugs should be used . Despite agreement on these principles by expert advisory committees, data from national surveys of ambulatory care indicate that antimicrobial agents continue to be prescribed indiscriminately for upper respiratory infections. Chest, 2001 Feb, 119(2 Suppl), 412S - 418S Guidelines and critical pathways for severe hospital-acquired pneumonia; Fiel S; Hospital-acquired pneumonia (HAP) is associated with high morbidity and mortality . Early, appropriate, and adequate empiric therapy can increase the chance of survival . In 1995, the American Thoracic Society provided guidelines for the initial treatment of immunocompetent HAP patients, which is one of the principal HAP management approaches available to physicians today . However, these guidelines have several important limitations, including a lack of recommendations for duration of therapy and no recognition of newer drugs such as cefepime, trovafloxacin, and meropenem . Furthermore, they fail to distinguish among similar compounds (ie, beta-lactam/beta-lactamase inhibitor combinations) or to recommend specific antibiotics . The clinician using these guidelines needs to address local patterns of antimicrobial resistance, especially in ICUs . Effective computerized antibiotic management programs that incorporate information on local patterns of antimicrobial resistance can assist physicians in empiric therapy decision making, improve patient quality of care, and reduce medical costs. J Hosp Infect, 2000 Dec, 46(4), 304 - 8 Virucidal efficacy of a combination of 0.2% peracetic acid and 80% (v/v) ethanol (PAA-ethanol) as a potential hand disinfectant; Wutzler P et al.; The formulation PAA-ethanol, consisting of 0.2% paracetic acid (PAA) and 80% ethanol, was tested for its virucidal activity on the enveloped vaccinia virus and papova virus SV 40 and the non-enveloped adenovirus type 2 and poliovirus type 1 . All test viruses were inactivated by PAA-ethanol within an exposure time of 1 minute, as measured by a log(10)reduction of 4 in virus titres . It was shown that poliovirus type 1 can be inactivated by PAA-ethanol within 1 min, whilst for the aqueous 0.2% PAA solution, an exposure time of 5 min is necessary . As shown by electron microscopic observation, the structure of virus particles was completely destroyed by 0.2% PAA within 15 min.The broad antimicrobial spectrum including a high virucidal activity, short exposure time and no toxic or allergenic decomposition products are favourable prerequisites for the medical use of PAA-ethanol and it warrants further investigation as a hand disinfectant . J Cell Physiol, 2001 Mar, 186(3), 380 - 6 Altered macrophage-like functions of preadipocytes in inflammation and genetic obesity; Cousin B et al.; We recently demonstrated that preadipocytes exhibit functional features of macrophages, such as phagocytosis and anti-microbial activity, suggesting that preadipose cells could play a role in the inflammatory process or immune response . The aim of this study was to compare these functions of both macrophages and cells from stroma-vascular fraction (SVF) of the adipose tissue in two different situations, obesity and inflammation, characterized by alterations in immune responsiveness . We demonstrated that ob/ob mice exhibited strong decrease in antimicrobial activity of both macrophages and SVF . This defect is compensated in SVF, at least in part, by an enhancement of phagocytosis that does not seem to be due to an increased macrophage number . In vitro leptin treatment of SVF and macrophages from obese mice did not restore their immune defects . Thioglycollate treatment of lean and obese mice induced an inflammatory process that led to an increase in macrophage activity in both strains . This stimulation also observed in SVF from lean mice is not present in obese ones . This work demonstrated that SVF immune functions could be modified in different pathological situations such as inflammation and obesity and sustained the new physiological role of preadipocytes in these processes . Oral Microbiol Immunol, 2001 Feb, 16(1), 10 - 5 Incidence of beta-lactamase production and antimicrobial susceptibility of anaerobic gram-negative rods isolated from pus specimens of orofacial odontogenic infections; Kuriyama T et al.; The incidence of beta-lactamase production in anaerobic gram-negative rods isolated from 93 pus specimens of orofacial odontogenic infections and the antimicrobial susceptibility of these isolates against 11 antibiotics were determined . A total of 191 anaerobic gram-negative rods were isolated from the specimens . Beta-lactamase was detected in 35.6% of the black-pigmented Prevotella and 31.9% of the nonpigmented Prevotella . However, no strains among the other species isolated produced beta-lactamase . Ampicillin, cefazolin and cefotaxime showed decreased activity as regards beta-lactamase-positive Prevotella strains, whereas the activity of ampicillin/sulbactam, cefmetazole, and imipenem continued to be effective against such strains . All tested beta-lactam antibiotics were effective against Porphyromonas and Fusobacterium . Erythromycin showed decreased activity against nonpigmented Prevotella and Fusobacterium . Clindamycin, minocycline and metronidazole were powerful antibiotics against which anaerobic gram-negative rods could be tested . The present study showed that beta-lactamase-positive strains were found more frequently in the Prevotella strains than in any of the other species of anaerobic gram-negative rods . The effectiveness of adding sulbactam to ampicillin was demonstrated, as well as the difference in cephalosporin activity against beta-lactamase-positive strains. J Pept Res, 2001 Jan, 57(1), 59 - 67 Biological activities of retro and diastereo analogs of a 13-residue peptide with antimicrobial and hemolytic activities; Subbalakshmi C et al.; The biological activities of synthetic retro and diastereo analogs of PKLLKTFLSKWIG (SPFK), a 13-residue peptide with antimicrobial and hemolytic activities, have been investigated . Retro peptides with C-terminal acid and amide exhibited antibacterial activities comparable with those of SPFK . Their hemolytic activities were, however, only marginally lower . The diastereo analog with C-terminal acid was not antibacterial and