Biomedical subjects

D M Johnson

Publications and source records attributed to D M Johnson.

At least 19 recordsLinked to original sources

PubMed2006

Non-haem iron transport in the rat proximal colon.

BACKGROUND: Only 10% of dietary iron is absorbed in the duodenum which implies that 90% (approximately 9 mg day(-1)) reaches the lower small intestine and colon. Therefore the purpose of this study was to assess the iron transport capacity of the rat proximal colon and to determine whether iron absorption is regulated by changes in dietary iron content. MATERIALS AND METHODS: Rats were fed for 14 days on either iron adequate (44 mg Fe kg(-1) diet) or iron-deficient (< 0.5 mg Fe kg(-1) diet) diets. The 59Fe transport across the colonic epithelium and its subsequent appearance in the blood were measured in vivo. In separate studies the colon was excised and used to measure divalent metal transporter expression. RESULTS: Divalent metal transporter (DMT1) was expressed at the apical membrane of the surface epithelium in rat proximal colon. In animals fed an iron-deficient diet, DMT1 mRNA and protein expression were increased. This was accompanied by a significant increase in tissue 59Fe uptake. CONCLUSIONS: The proximal colon can absorb non-haem iron from the intestinal lumen. The purpose of this mechanism remains to be elucidated.

Animals↗

PubMed2003

Susceptibility trends of haemophilus influenzae and Moraxella catarrhalis against orally administered antimicrobial agents: five-year report from the SENTRY Antimicrobial Surveillance Program.

The assessment of orally administered antimicrobial susceptibilities of common pathogens that cause community-acquired respiratory tract infections (CARTI) has become exceedingly important due to the number of office visits for this indication. Numerous local, regional and global studies have documented the susceptibilities of Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis, the most common CARTI pathogens. SENTRY Antimicrobial Surveillance Program sites in North and Latin America, and Europe were requested to send a combined total of 100 isolates of these pathogens to the local monitor for reference broth microdilution testing (1997-2001). This study compared the susceptibility profiles of H. influenzae and M. catarrhalis isolates (13,370 strains) from the three geographic regions over a five year period. beta-lactamase mediated ampicillin resistance among H. influenzae was highest among North American isolates (27.9%) compared to Latin America and Europe (16.2 to 16.3%), although it was noted that during the five year study period, ampicillin resistance was steadily increasing in the latter two regions. Cefprozil (84.3% susceptible) and clarithromycin (81.1% susceptible) were also less active against North American H. influenzae isolates. Latin American isolates were much less susceptible to trimethoprim/sulfamethoxazole (T/S; 59.3%) compared to the other regions (75.8 to 78.6%). M. catarrhalis isolates were also significantly less susceptible to T/S in Latin America (10.5% resistance). The production of beta-lactamase enzymes among the M. catarrhalis isolates exceeded >95% in all three regions during the five year period. The fluoroquinolones (FQ) remained very active against these two respiratory pathogens with rare isolates with elevated FQ MIC results. It is apparent from this investigation that many commonly prescribed empiric treatments remain viable therapeutic options for CARTI caused by these two Gram-negative respiratory tract pathogens.

Administration, Oral↗

PubMed2002

Infliximab and leflunomide combination therapy in rheumatoid arthritis: an open-label study.

OBJECTIVE: To study the safety and efficacy of infliximab plus leflunomide combination therapy in adult rheumatoid arthritis (RA). METHODS: Twenty patients with active RA received leflunomide 100 mg for 3 days followed by 20 mg daily for 32 weeks. At week 2 all patients started infliximab 3 mg/kg, and received a further four infusions at weeks 4, 8, 16 and 24. RESULTS: Adverse events led to 11 patients being withdrawn before the end of the study. The commonest adverse event was pruritus associated with an eczematous rash. Other serious reactions included infliximab infusion reactions in four patients and Stevens-Johnson syndrome in one. There was no relationship between the serum concentration of A77 1726, the active metabolite of leflunomide, and adverse events. The mean Disease Activity Score (DAS28) fell from 7.18 at week 0 to 5.18 (P<0.0001, paired t-test) at week 4 and remained between 3.85 and 4.85 up to week 32. In those patients remaining on treatment, more than 80% achieved an ACR20 response from week 8 to week 28, and up to 46% achieved an ACR70 response. CONCLUSION: Infliximab plus leflunomide combination therapy appears to be highly efficacious in the treatment of adult RA. However, widespread use may be limited by adverse events, which were common and in some cases severe.

Adult↗

PubMed2002

Watch what you say and how you say it: differential response to speech by participants with and without head injuries.

Previous research has shown that both prosodic and content variations in speech register are important when addressing all individuals. Motherese speech register has been associated with higher levels of perceived disability and is viewed more negatively by individuals with a history of head injury. This research was conducted to investigate the separate contributions of content and prosody in producing differential response to speech by individuals with and without a history of head injury. Participants included 210 introductory psychology students with and without head injuries. No significant demographic differences were found between these groups. Participants listened to 4 sets of audiotaped instructions from afictitious home economics teacher containing prosodic and content variations. Afterward, they rated the teacher on the following dimensions: liking, positive impact, negative impact, grade level being taught, and whether they would recommend hiring this teacher. Analysis of variance revealed there were no significant group differences between participants rating with normal speech. As expected, both groups favored the normal speech register over motherese. However, the group with head injuries consistently rated the speech with motherese content as more negative, less likable, less likely to hire, and aimed at a lower grade level. Participants with head injuries also rated the speech register with motherese prosody as less likable and less likely to hire. These results suggest that when addressing individuals with head injuries, both what you say and how you say it are important.

Adult↗

PubMed2001

A new subdivision of anterior piriform cortex and associated deep nucleus with novel features of interest for olfaction and epilepsy.

The anterior part of the piriform cortex (the APC) has been the focus of cortical-level studies of olfactory coding and associative processes and has attracted considerable attention as a result of a unique capacity to initiate generalized tonic-clonic seizures. Based on analysis of cytoarchitecture, connections, and immunocytochemical markers, a new subdivision of the APC and an associated deep nucleus are distinguished in the rat. As a result of its ventrorostral location in the APC, the new subdivision is termed the APC(VR). The deep nucleus is termed the pre-endopiriform nucleus (pEn) based on location and certain parallels to the endopiriform nucleus. The APC(VR) has unique features of interest for normal function: immunostaining suggests that it receives input from tufted cells in the olfactory bulb in addition to mitral cells, and it provides a heavy, rather selective projection from the piriform cortex to the ventrolateral orbital cortex (VLO), a prefrontal area where chemosensory, visual, and spatial information converges. The APC(VR) also has di- and tri-synaptic projections to the VLO via the pEn and the submedial thalamic nucleus. The pEn is of particular interest from a pathological standpoint because it corresponds in location to the physiologically defined "deep piriform cortex" ("area tempestas") from which convulsants initiate temporal lobe seizures, and blockade reduces ischemic damage to the hippocampus. Immunostaining revealed novel features of the pEn and APC(VR) that could alter excitability, including a near-absence of gamma-aminobutyric acid (GABA)ergic "cartridge" endings on axon initial segments, few cholecystokinin (CCK)-positive basket cells, and very low gamma-aminobutyric acid transporter-1 (GAT1)-like immunoreactivity. Normal functions of the APC(VR)-pEn may require a shaping of neuronal activity by inhibitory processes in a fashion that renders this region susceptible to pathological behavior.

Animals↗

PubMed2001

Factors predicting PTSD, depression, and dissociative severity in female treatment-seeking childhood sexual abuse survivors.

OBJECTIVE: Two main questions were asked: (1) what abuse characteristics relate to PTSD, depressive, and dissociative severity in adult survivors of child sexual abuse (CSA); and (2) what abuse characteristics influence the severity of dissociation during CSA. METHOD: 89 female CSA survivors' current symptoms of PTSD, depression, and dissociation were assessed with standardized measures. Additionally, abuse characteristics (e.g., age of onset, peritraumatic dissociation) were assessed with a structured interview. RESULTS: Correlational analyses indicated that peritraumatic dissociation was most strongly related to all three types of symptom severity. Additional posthoc correlational analyses revealed that women who experienced penile penetration, believed someone/thing else would be killed, and/or were injured as a result of the abuse exhibited more severe peritraumatic dissociation. Regression analyses indicated that peritraumatic dissociation was the only variable to significantly predict symptom severity across symptom type or disorder. Furthermore, different abuse characteristics predicted adult symptom severity and peritraumatic dissociation. CONCLUSIONS: The relation between peritraumatic dissociation and adult symptomatology was most intriguing and has two main clinical implications: (1) teaching engagement strategies to some CSA survivors in hopes of containing dissociative symptoms immediately following the abuse and (2) the inclusion of exposure-based interventions in the treatment of some adult CSA survivors where indicated.

Adolescent↗

PubMed2001

Retention of low income mothers in a parenting intervention study.

Women with inadequate prenatal care were recruited to a multi-component parenting intervention study. Because it was anticipated that this high-risk population might present challenges to retention, a variety of strategies were employed to maintain their participation in the study. This report reviews the results of these retention efforts and compares the population that completed the study versus those that terminated prior to study completion. Two hundred and eighty-six women were randomized to an intervention or control group. Careful tracking of the mothers, offering incentives for completing various study activities and providing a culturally competent staff were among the strategies employed to maintain participation. Comparison was made of those mothers terminating before study completion versus those retained, and of those terminating early in the study period versus later. Despite retention efforts, attrition at a level of 41% occurred. A few characteristics of mothers terminating early from the study were significant including older maternal age, a larger number of children, and incidence of no prenatal care. Despite comprehensive tracking procedures, some mothers were lost to follow up after change of residence. Other reasons for attrition included child outplacement and refusal of services or data collection procedures.

Adult↗

PubMed2001

Enhancing wellness in a high school: a community partnership.

Meeting the wellness needs of high school students reporting high-risk behaviors above national averages was the purpose of a community partnership between the county school district and West Virginia University School of Nursing. Although the school district and School of Nursing were the primary partners, other programs in the university provided additional support. The school nurse, school of nursing faculty, and nursing students provided wellness programs to students, faculty, and staff. Positive evaluations and high demand for the services demonstrated the school community's need for the program and the success of the partnership.

Adolescent↗

PubMed2001

In vitro evaluation of BI 397, a novel glycopeptide antimicrobial agent.

BI 397, a semi-synthetic amide derivative of the experimental glycopeptide, MDL 62,476 (A40926), has excellent in vitro activity against a wide range of Gram-positive organisms. In this extensive study, 630 contemporary (1998-2000) Gram-positive isolates were selected from various resistance surveillance studies for their resistance patterns to fluoroquinolones, macrolides-lincosamides-streptogramins, beta-lactams and glycopeptide agents. The BI 397 spectrum of activity was similar to that of other glycopeptides with a MIC90 of < or =0.5 microg/ml for all tested isolates with the exception of vancomycin-resistant enterococci Van A; (MIC90, 32 microg/ml). BI 397 was more potent than vancomycin and teicoplanin against Staphylococcus aureus (2- to 8-fold), beta-haemolytic streptococci (equal to >16-fold), viridans group streptococci (equal to >32-fold), and Corynebacterium spp. including C. jeikeium (8- to >16-fold). BI 397 was also more active than quinupristin/dalfopristin against all Gram-positive organisms tested with the exception of oxacillin-susceptible S. aureus, against which it had equal activity. BI 397 has little activity against Haemophilus influenzae (MIC90, 64 microg/ml) or other Gram-negative bacilli (MIC90, >64 microg/ml). BI 397 exhibited bacteriostatic activity (like the vancomycin control) versus most species, but was bactericidal against tested Streptococcus pneumoniae. In vitro testing conditions with blood supplemented or free protein containing media elevated BI 397 MIC results, and the 30-microg disk seems acceptable for further disk diffusion test development. Animal pharmacokinetic data published elsewhere suggest that BI 397 may be dosed less frequently than teicoplanin and the results of early studies in humans are awaited with interest, especially when treating teicoplanin-refractory coagulase-negative staphylococci.

Anti-Bacterial Agents↗

PubMed2001

Tandem mass spectrometric analysis for amino, organic, and fatty acid disorders in newborn dried blood spots: a two-year summary from the New England Newborn Screening Program.

BACKGROUND: Tandem mass spectrometry (MS/MS) is rapidly being adopted by newborn screening programs to screen dried blood spots for >20 markers of disease in a single assay. Limited information is available for setting the marker cutoffs and for the resulting positive predictive values. METHODS: We screened >160 000 newborns by MS/MS. The markers were extracted from blood spots into a methanol solution with deuterium-labeled internal standards and then were derivatized before analysis by MS/MS. Multiple reaction monitoring of each sample for the markers of interest was accomplished in approximately 1.9 min. Cutoffs for each marker were set at 6-13 SD above the population mean. RESULTS: We identified 22 babies with amino acid disorders (7 phenylketonuria, 11 hyperphenylalaninemia, 1 maple syrup urine disease, 1 hypermethioninemia, 1 arginosuccinate lyase deficiency, and 1 argininemia) and 20 infants with fatty and organic acid disorders (10 medium-chain acyl-CoA dehydrogenase deficiencies, 5 presumptive short-chain acyl-CoA dehydrogenase deficiencies, 2 propionic acidemias, 1 carnitine palmitoyltransferase II deficiency, 1 methylcrotonyl-CoA carboxylase deficiency, and 1 presumptive very-long chain acyl-CoA dehydrogenase deficiency). Approximately 0.3% of all newborns screened were flagged for either amino acid or acylcarnitine markers; approximately one-half of all the flagged infants were from the 5% of newborns who required neonatal intensive care or had birth weights <1500 g. CONCLUSIONS: In screening for 23 metabolic disorders by MS/MS, an mean positive predictive value of 8% can be achieved when using cutoffs for individual markers determined empirically on newborns.

Amino Acid Metabolism, Inborn Errors↗

PubMed2000

New features of connectivity in piriform cortex visualized by intracellular injection of pyramidal cells suggest that "primary" olfactory cortex functions like "association" cortex in other sensory systems.

Associational connections of pyramidal cells in rat posterior piriform cortex were studied by direct visualization of axons stained by intracellular injection in vivo. The results revealed that individual cells have widespread axonal arbors that extend over nearly the full length of the cerebral hemisphere. Within piriform cortex these arbors are highly distributed with no regularly arranged patchy concentrations like those associated with the columnar organization in other primary sensory areas (i.e., where periodically arranged sets of cells have common response properties, inputs, and outputs). A lack of columnar organization was also indicated by a marked disparity in the intrinsic projection patterns of neighboring injected cells. Analysis of axonal branching patterns, bouton distributions, and dendritic arbors suggested that each pyramidal cell makes a small number of synaptic contacts on a large number (>1000) of other cells in piriform cortex at disparate locations. Axons from individual pyramidal cells also arborize extensively within many neighboring cortical areas, most of which send strong projections back to piriform cortex. These include areas involved in high-order functions in prefrontal, amygdaloid, entorhinal, and perirhinal cortex, to which there are few projections from other primary sensory areas. Our results suggest that piriform cortex performs correlative functions analogous to those in association areas of neocortex rather than those typical of primary sensory areas with which it has been traditionally classed. Findings from other studies suggest that the olfactory bulb subserves functions performed by primary areas in other sensory systems.

Animals↗

PubMed2000

Acquisition, extinction, and reinstatement of Pavlovian fear conditioning: the roles of the NMDA receptor and nitric oxide.

The acquisition and extinction of Pavlovian conditioned fear have been shown to be mediated by the N-methyl-D-aspartate (NMDA) glutamate receptor. This study found that the NMDA antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine maleate (MK-801) blocked the reinstatement of Pavlovian conditioned fear in rats. The role of nitric oxide (NO) in the acquisition and extinction of Pavlovian fear conditioning was also examined. L-NAME, an NO synthase inhibitor, failed to block the acquisition or extinction of Pavlovian fear conditioning. The results are discussed in the context of hierarchical associations and the array of NMDA and calcium mediated mechanisms of synaptic strengthening.

Animals↗

PubMed2000

Cefditoren activity against nearly 1000 non-fastidious bacterial isolates and the development of in vitro susceptibility test methods.

Cefditoren (formerly ME-1206) is an investigational, orally administered cephalosporin ester with bactericidal activity against many Gram-positive and -negative organisms. Cefditoren potency against nearly 1000 non-fastidious species was determined by National Committee for Clinical Laboratory Standards (NCCLS) reference broth microdilution and standardized disk diffusion methods. Against staphylococci, usable cefditoren activity was completely correlated with oxacillin with respect to potency and susceptibility interpretation (mec A-negative strains). Cefditoren was very active against Klebsiella spp., Proteus mirabilis, Salmonella spp., and Escherichia coli (MIC(90) range, 0.12-1 microg/ml; median zone, 23-26 mm). Cefditoren had more limited activity against Citrobacter spp., Enterobacter spp., Serratia marcescens, and indole-positive Proteae (MIC(50) range, 0.12-1 microg/ml; MIC(90), > 16 microg/ml; median zone, 18-25 mm). Against Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Acinetobacter spp., and other non-fermentors, cefditoren was inactive (MIC(90), > 16 microg/ml; zone, 6 mm). Pharmacokinetic analysis of cefditoren showed that utilized dosages produce a plasma concentration that exceeds 0.5 microg/ml for 5 to 8 h and 1 microg/ml for 4 to 6 hours (T(1/2) ranges from 1.5-2 h). The following interpretive criteria were suggested: </= 2 microg/ml or >/= 15 mm (susceptible) and >/= 8 microg/ml or </= 11 mm (resistance) that yielded an intermethod categorical agreement of 95.8% and very major or major error rates of 0.7% and 0.3%, respectively. Alternatively, </= 1 microg/ml or >/= 18 mm (susceptible) and >/= 4 microg/ml or </= 14 mm (resistant) breakpoints resulted in 96.2% accuracy and combined serious errors of only 1.1%. Cefditoren was observed to be a very active cephalosporin ranking among the most potent available orally active beta-lactams for use against a wide variety of pathogens.

Cephalosporins↗

PubMed2000

Antimicrobial activity and in vitro susceptibility test development for cefditoren against Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus species.

Cefditoren, a third generation orally administered aminothiazolyl cephalosporin, has demonstrated bactericidal activity against many Gram positive and negative bacterial pathogens and stability against clinically important beta-lactamases. Cefditoren was compared to cefaclor, cefixime, and penicillins against 1 435 recently isolated strains of streptococci (312 Streptococcus pneumoniae, 165 viridans group streptococci, 142 beta-haemolytic streptococci), Haemophilus influenzae (521 strains), and Moraxella catarrhalis (295 strains). Streptococcus pneumoniae and viridans group streptococci had penicillin nonsusceptible rates of 37.8 and 35.8%, respectively. Cefditoren (MIC(90) in microg/ml/% susceptible) activity against all tested H. influenzae (0.03/100) and M. catarrhalis (0.06-0.5/100) was comparable to cefixime and significantly greater than cefaclor. Cefditoren (MIC(90), 0.5 microg/ml) was 4- to 128-fold more active than comparison beta-lactams against the pneumoococci and was the most potent beta-lactam (including penicillin) versus beta-haemolytic streptococci. Cefditoren pharmacokinetics demonstrate a T(1/2) of 1.5-2 h and C(max) values of 2.8 and 4.6 microg/ml, respectively with 200 or 400 mg doses of cefditoren pivoxil; plasma concentrations exceed 1 microg/ml for 4 to 6 hours (33-50% of dosing interval). Consequently, a susceptible MIC of </= 1 microg/ml or </= 2 microg/ml was proposed with zone diameter correlates of >/= 18 and >/= 15 mm (5-microg disk) for all cited fastidious species tested. Categorical agreement between MIC and disk tests was 94.6 to 100% with a correlation coefficient (r) range of 0.50 to 0.90 for streptococci. H. influenzae intermethod comparison results using the same interpretive criteria were in complete agreement, but exhibited a low r = 0.39. Cefditoren clearly possesses the most potent activity among currently studied oral cephalosporins or penicillin against commonly isolated bacterial pathogens causing bronchitis, pneumonia, sinusitis, or pharyngitis and was active against nearly all penicillin-resistant streptococci at </= 0.5 microg/ml. Expanded clinical investigations seem warranted.

Cefaclor↗

PubMed2000

Possible drug-associated pancreatitis after paclitaxel-cremophor administration.

Paclitaxel, a relatively new antineoplastic agent, is associated with numerous side effects, including two reported cases of pancreatitis. Our patient also developed paclitaxel-associated pancreatitis. Several companion drugs, including steroids, diphenhydramine, histamine2 blockers, serotonin type 3 antagonists, and other chemotherapeutic agents administered with paclitaxel, must be considered as possible causes of pancreatitis. In addition, paclitaxel is a hydrophobic agent that requires a vehicle, cremophor (CrEL), for solubility. Intravenous cyclosporine also requires CrEL and has been associated with pancreatitis. In the cerulein-induced pancreatitis rat model, paclitaxel with dimethyl sulfoxide as a vehicle prevents pancreatitis, suggesting that another causal agent is responsible. Animal studies of CrEL as a single agent may be required to settle this question, but for now, awareness that paclitaxel may be associated with pancreatitis may lead to earlier treatment of this potentially fatal complication.

Acute Disease↗

PubMed1999

Comparative antimicrobial activity of gatifloxacin tested against Streptococcus spp. including quality control guidelines and etest method validation. Quality Control Study Group.

Gatifloxacin (formerly AM-1155 or CG 5501) is a new 8-methoxy fluoroquinolone with enhanced activity against Gram-positive cocci, especially Streptococcus pneumoniae and other streptococci. Recent clinical strains (599 isolates) were tested against gatifloxacin, three comparison fluoroquinolones, and penicillin by the reference broth microdilution, Etest (AB BIODISK, Solna, Sweden) and standardized disk diffusion methods (5 micrograms gatifloxacin disk). Gatifloxacin (MIC90, 0.5 microgram/ml) activity was generally comparable to that of trovafloxacin (MIC90, 0.25 microgram/ml), or sparfloxacin (MIC90, 0.5 microgram/ ml) and markedly superior to ofloxacin (MIC90, 2-4 micrograms/ml) against the streptococci. Rates of penicillin non-susceptibility were 41.9, 38.0, and 16.2% for S. pneumoniae (301 strains), viridans group streptococci (150 strains), and beta-haemolytic streptococci (148 strains). Etest results correlated well (95.7-100.0% +/- one log2 dilution) with the reference MIC results, but Etest tended to have elevated gatifloxacin MIC results compared to the broth microdilution method for the highly resistant isolates (MICs, > 2 micrograms/ml). Gatifloxacin disk zone diameters correlate well to reference MICs for all streptococci and proposed interpretive criteria (susceptible at < or = 1 microgram/ml or > or = 18 mm, and resistant at > or = 4 micrograms/ml or < or = 14 mm) did not produce discords between method results (absolute agreement). A nine laboratory quality control (QC) study conforming to the National Committee for Clinical Laboratory Standards (NCCLS) Guideline M23-T3 studied S. pneumoniae ATCC 49619 and gatifloxacin. Proposed ranges for QC of NCCLS tests were 0.12-0.5 microgram/ml for the broth microdilution test and 24-31 mm for the disk diffusion method. These reported results indicate that gatifloxacin was a potent fluoroquinolone with extensive activity against streptococcal isolates. In vitro test methods to measure this activity appear accurate and comparable; and QC guidelines have been established for routine clinical laboratory use pending approval by the NCCLS and the Food and Drug Administration (FDA).

Anti-Infective Agents↗

PubMed1999

Anti-streptococcal activity of SB-265805 (LB20304), a novel fluoronaphthyridone, compared with five other compounds, including quality control guidelines.

SB-265805 (formerly LB20304) is a novel C-7 pyrrolidine-substituted naphthyridone that has a broad spectrum of activity, especially against Gram-positive cocci. SB-265805 activity was compared with ciprofloxacin, grepafloxacin, moxifloxacin, sparfloxacin, and penicillin against 599 Streptococcus spp. isolated recently from more than 30 medical centers in North and South America. These included 70 isolates with decreased susceptibility to recently released fluoroquinolones (levofloxacin MIC, > or = 4 micrograms/mL). All strains were tested by reference microdilution methods in lysed horse blood-supplemented Mueller-Hinton broth. Sixteen percent of 148 beta-haemolytic streptococci (strains of gr. B and C) were not susceptible to penicillin, whereas 38% and 42% of viridans group streptococci and Streptococcus pneumoniae were resistant to penicillin, respectively. SB-265805 potency against 301 pneumococci (MIC90, 0.06 microgram/mL) was fourfold more active than moxifloxacin and was > or = eightfold more potent than other quinolones. Against beta-haemolytic streptococci, SB-265805 and moxifloxacin were the most active (MIC90, 0.06 and 0.25 microgram/mL, respectively), whereas sparfloxacin, grepafloxacin, and ciprofloxacin (MIC90, 0.5-1 microgram/mL) were less potent. SB-265805 MICs versus viridans group streptococci (MIC90, 0.12 microgram/mL) were fourfold lower than sparfloxacin or grepafloxacin, and twofold more active than moxifloxacin. A nine-laboratory quality control (QC) protocol conforming to NCCLS M23-T3 guidelines demonstrated a modal SB-265805 MIC of 0.016 microgram/mL for S. pneumoniae ATCC 49619 (proposed QC range, 0.008 to 0.03 microgram/mL). The SB-265805 disk (5-microgram) QC range was 28-34 mm (97.3% of qualifying results). In general, SB-265805 in vitro activity against Streptococcus species was superior to sparfloxacin, grepafloxacin, and moxifloxacin and markedly greater than ciprofloxacin. This degree of antimicrobial potency warrants further investigation of this newer drug for its potential human clinical application against streptococcal infections.

Anti-Infective Agents↗

PubMed1999

Development of in vitro susceptibility testing methods for gemifloxacin (formerly LB20304a or SB-265805), an investigational fluoronaphthyridone.

Potent investigational fluoroquinolones require convenient, but accurate, diagnostic tests for initially applied clinical trials. For this purpose, gemifloxacin (formerly SB-265805, LB20304a) was tested by the reference dilution tests and standardized disk diffusion methods of the National Committee for Clinical Laboratory Standards (NCCLS) to establish interpretive criteria. For rapid-growing pathogens, 986 organisms were tested by broth microdilution MIC, and 5- and 10-microgram disk diffusion tests. Correlation (r) between 5- and 10-microgram disk zone diameters was 0.99 (y = -0.12 to 0.99x) and the preferred 5-microgram disk zone/MIC scattergram produced a regression of y = 14.8 to 0.41x (r = 0.93). At potential pharmacodynamics (Cmax = 1.3 micrograms/mL for 320 mg dose) validated breakpoints of < or = 0.5 microgram/mL for susceptible and > or = 2 micrograms/mL for resistant, correlate zones of > or = 17 mm and < or = 13 mm produced rare serious interpretive errors (0.1%) and 96.7% absolute categorical agreement. For 304 Streptococcus pneumoniae and 305 strains of other streptococci, the same breakpoints produced 100 and 99.1% categorical accuracy even when testing levofloxacin-resistant (MIC, > or = 4 micrograms/mL) strains. Interpretive breakpoints were proposed for Hemophilus influenzae (300 strains tested), with complete correlation between tests. Etest (AB BIODISK, Solna, Sweden) was compared in all experiments with the fastidious species and showed a trend toward higher values (twofold). Gemifloxacin in vitro susceptibility test methods seem to be accurate and with very acceptable intermethod agreement, supported by previously reported functional quality control guidelines.

Anti-Infective Agents↗