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Results for “Synergy”

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PubMed1994

The influence of a bilateral peripheral vestibular deficit on postural synergies.

The role of vestibular sensory information in the triggering, selection and modulation of postural response synergies was evaluated by comparing the EMG responses of normal subjects to balance perturbations with those of subjects with a bilateral peripheral vestibular deficit. The balance perturbations were a rotation and/or a translation of a support surface on which the test subjects stood with eyes open. Onset latencies and most timing patterns of muscle responses were not altered in vestibular-loss subjects. Major changes were observed, however, in the muscle amplitude synergy. Responses between 120 and 240 ms in tibialis anterior, soleus, and quadriceps muscles were reduced more than 50% with respect to normal amplitudes. In contrast, responses in paraspinal muscles were enhanced nearly 100% with respect to normal values. These changes in muscle amplitudes with accompanying vestibular loss were highest for rotation and lowest for translation perturbations. The identification of a bilateral vestibular loss using EMG amplitudes was always 100% correct for rotation perturbations and between 75 to 85% correct for translation perturbations. Multivariate linear correlations between muscle EMG response areas, and the amplitudes of initial link velocities revealed an increased contribution of afferent signals from the upper leg and a decreased dependence on signals from the trunk and head to postural synergies in vestibular-loss subjects. The afferent modulation of the muscle amplitude synergy correcting a balance disturbance to the stance of normal subjects is, on the basis of these findings, highly dependent on vestibular afferent signals. Our results indicate that vestibular afferent signals are used to enhance the amplitude of responses in tibialis anterior, quadriceps, and soleus muscles; and inhibit the responses of paraspinal muscles, once the response timing has been triggered and selected by proprioceptive signals. Lacking this modulation, bilateral vestibular deficit subjects respond to balance perturbations under eyes-open conditions as if the perturbation were 50% slower. Clinically, our results document that the perturbation of choice, when testing vestibular deficit patients, is a rotation (greater than 3 degrees in amplitude and 15 degrees/s in velocity) and not a translation of the support surface.

Adult↗

PubMed1997

The alpha2a adrenergic receptor subtype mediates spinal analgesia evoked by alpha2 agonists and is necessary for spinal adrenergic-opioid synergy.

Agonists acting at alpha2 adrenergic and opioid receptors have analgesic properties and act synergistically when co-administered in the spinal cord; this synergy may also contribute to the potency and efficacy of spinally administered morphine. The lack of subtype-selective pharmacological agents has previously impeded the definition of the adrenergic receptor subtype(s) mediating these effects. We therefore exploited a genetically modified mouse line expressing a point mutation (D79N) in the alpha2a adrenergic receptor (alpha2aAR) to investigate the role of the alpha2aAR in alpha2 agonist-evoked analgesia and adrenergic-opioid synergy. In the tail-flick test, intrathecal administration of UK 14,304, a nonsubtype-selective alpha2AR agonist, had no analgesic effect in D79N mice, whereas the analgesic potency of morphine (intrathecal) in this assay was not affected by the mutation. The mutation also decreased alpha2-agonist-mediated spinal analgesia and blocked the synergy seen in wild-type mice with both the delta-opioid agonist deltorphin II and the micro-opioid agonist [D-ALA2,N-Me-Phe4, Gly-ol5]-Enkephalin (DAMGO) in the substance P behavioral test. In addition, the potency of spinally administered morphine was decreased in this test, suggesting that activation of descending noradrenergic systems impinging on the alpha2aAR contributes to morphine-induced spinal inhibition in this model. These results demonstrate that the alpha2aAR subtype is the primary mediator of alpha2 adrenergic spinal analgesia and is necessary for analgesic synergy with opioids. Thus, combination therapies targeting the alpha2aAR and opioid receptors may prove useful in maximizing the analgesic efficacy of opioids while decreasing total dose requirements.

Adrenergic alpha-Agonists↗

PubMed1998

Super in vitro synergy between inhibitors of dihydrofolate reductase and inhibitors of other folate-requiring enzymes: the critical role of polyglutamylation.

The combined action among polyglutamylatable and nonpolyglutamylatable antifolates, directed against dihydrofolate reductase (DHFR), glycinamide ribonucleotide formyltransferase (GARFT), 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase (AICARFT), and thymidylate synthase (TS), in human ileocecal HCT-8 cells was examined in a 96-well plate growth inhibition assay (96-h continuous drug exposure). An interaction parameter, alpha, was estimated for each of 95 experiments by fitting a seven-parameter model to data with weighted nonlinear regression. In a representative experiment, raising the folic acid concentration in the medium dramatically increased the Loewe synergy for the combination of trimetrexate (TMTX) and the GARFT inhibitor AG2034 (from a mean alpha +/- SE of 1.50 +/- 0.25 at 2.3 microM folic acid to 146 +/- 20 at 78 microM folic acid). Enhancements were also found for combinations of TMTX with the GARFT inhibitors AG2032, Lometrexol, and LY309887, the AICARFT inhibitor AG2009, and the TS inhibitors LY231514 and Tomudex but not with the GARFT inhibitor LL95509 or with the TS inhibitors AG337, ZD9331, and BW1843U89. Replacing TMTX with methotrexate in two-drug mixtures decreased the intensity of Loewe synergy. Examination of isobolograms at different effect levels revealed informative reproducible changes in isobol patterns. No two-drug combinations among inhibitors of GARFT, AICARFT, and TS exhibited Loewe synergy at either 2.3 or 78 microM folic acid. Thus, the ideal requirement for the folic acid-enhanced synergy is that a nonpolyglutamylatable DHFR inhibitor be combined with a polyglutamylatable inhibitor of another folate-requiring enzyme. A hypothesis to explain this general phenomenon involves the critical role of folylpoly-gamma-glutamate synthetase and the effect of the DHFR inhibitor in decreasing the protection by folic acid of cells to the other antifolates.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

A correlation with type of sulfonamide resistance gene in Escherichia coli and synergy between trimethoprim and sulfamethoxazole.

Plasmids carrying type I or II sulfonamide-resistance (Sur) genes were evaluated for their effect on synergy between trimethoprim (Tmp) and sulfamethoxyzole (Smx) in E. coli. Strain J53 containing each of three plasmids (R1, pSa, and R388) with the type I Sur gene displayed a synergistic response to Tmp/Smx; strain LE392 containing a plasmid (RSF1010) with the type II Sur gene displayed no synergy. The difference in synergy between type I and type II Sur genes might be explained by the difference in amount of resistant enzyme produced.

Drug Synergism↗

PubMedDate not supplied

Synergy between TLR2 and TLR4: a safety mechanism.

BACKGROUND: The Toll (Tlr) receptors facilitate innate immunity by detecting products that are unique to invading microorganisms. Stimulation of these receptors can produce severe reactions and death. We propose that synergy between receptors for different microbial products would provide a safety mechanism, preventing inappropriate, potentially fatal reactions by reacting to low concentrations of ligands when more than a single ligand is present. RESULTS: Striking synergy is noted between the ligand for Tlr4, lipopolysaccharide (LPS), and a ligand for Tlr2, muramyl dipeptide (MDP), in the release of tumor necrosis factor from RAW cells. CONCLUSIONS: Synergy between a ligand for Tlr2 and Tlr4 can be demonstrated in a simple in vitro system. The greater sensitivity of MDP-stimulated cells to LPS may explain the data that were once interpreted incorrectly as indicating that Tlr2 is the endotoxin receptor.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed2003

Muscle synergies during shifts of the center of pressure by standing persons.

Movements by a standing person are commonly associated with adjustments in the activity of postural muscles to cause a desired shift of the center of pressure (COP) and keep balance. We hypothesize that such COP shifts are controlled (stabilized) using a small set of central variables (muscle modes, M-modes), while each M-mode induces changes in the activity of a subgroup of postural muscles. The main purpose of this study has been to explore the possibility of identification of muscle synergies in a postural task using the framework of the uncontrolled manifold (UCM) hypothesis employing the following three steps in data analysis: (i) Identification of M-modes: Subjects were asked to release a load from extended arms through a pulley system, resulting in a COP shift forward prior to load release. Electromyographic (EMG) activity of eleven postural muscles on one side of the body was integrated over a 100 ms interval corresponding to the early stage of the COP shift, and subjected to a principal component (PC) analysis across multiple repetitions of each task. Three PCs were identified and associated with a 'push-back M-mode', a 'push-forward M-mode' and a 'mixed M-mode'. (ii) Calculation of the Jacobian of the system, which relates changes in the magnitude of M-modes to COP shifts using regression techniques: Subjects performed three different tasks (releasing different loads at the back, voluntarily shifting body weight forward and backward, at different speeds) to verify if the relationship between magnitudes of M-modes and COP shifts is task or direction specific. (iii) UCM analysis: Three tasks were chosen (load release in the front, arm movement forward and backward) which were associated with an early shift in COP. A manifold was identified in the M-mode space corresponding to a certain average (across trials) shift of the COP and variance per degree of freedom within the UCM (V(UCM)) and orthogonal (V(ORT)) to the UCM was computed. Across subjects, V(UCM) was significantly higher than V(ORT) when analysis at the third step was performed using a Jacobian computed based on a set of tasks associated with a COP shift in the same direction but not in the opposite direction. This result confirms our hypothesis that the M-modes work together as a synergy to stabilize a desired shift of the COP. Forward and backward COP shifts are associated with different synergies based on the same three M-modes.

Adult↗

PubMed2000

Force synergies for multifingered grasping.

Compared with the control of precision grips involving the thumb and one or two fingers, the control of grasping using the entire hand involves a larger number of degrees of freedom that has to be controlled simultaneously, and it introduces indeterminacies in the distribution of grip forces suitable for holding an object. We studied the control of five-digit grasping by measuring contact forces when subjects lifted, held, and replaced a manipulandum. This study focused primarily on the patterns of coordination among the normal forces exerted by each of the digits, assessed by varying the center of mass of the manipulandum. The force patterns during the lift and hold phases were modulated as a function of the location of the center of mass. A frequency domain analysis revealed a consistent temporal synergy by which digits tended to exert normal forces in phase with each other across all experimental conditions. This tendency for in-phase covariations by the normal forces exerted by the digits extended over the entire functional frequency range (up to 10 Hz). When the effect of thumb force was removed, a second synergy was revealed in which forces in two fingers could be modulated 180 degrees out of phase (also prevailing throughout the range of frequencies studied). The first synergy suggests the presence of a "common drive" to all of the extrinsic finger muscles, whereas the second one suggests another input, ultimately resulting in a reciprocally organized pattern of activity of some of these muscles.

Analysis of Variance↗

PubMed2005

A central back-coupling hypothesis on the organization of motor synergies: a physical metaphor and a neural model.

We offer a hypothesis on the organization of multi-effector motor synergies and illustrate it with the task of force production with a set of fingers. A physical metaphor, a leaking bucket, is analyzed to demonstrate that an inanimate structure can show apparent error compensation among its elements. A neural model is developed using tunable back-coupling loops as means of assuring error compensation in a task-specific way. The model demonstrates non-trivial features of multi-finger interaction such as delayed emergence of force stabilizing synergies and simultaneous stabilization of the total force and total moment produced by the fingers. The hypothesis suggests that neurophysiological structures involving short-latency feedback may play a central role in the formation of motor synergies.

Afferent Pathways↗

PubMed2002

Adapting portfolio theory for the evaluation of multiple investments in health with a multiplicative extension for treatment synergies.

Portfolio theory is central to the analysis of risk in many areas of economics but is seldom used appropriately in health economics. This contribution examines the use of portfolio theory in the context of cost-effectiveness analysis (CEA). A number of modifications are needed to apply portfolio analysis to the economic evaluation of health care interventions. First, the method of reporting the results of a CEA, and consequently some of the underlying assumptions, needs to be modified. Second, portfolio theory needs to be expressed in terms of effects on individuals aggregated to a population. Finally, one needs to allow for the possibility of synergy between the various health interventions. This paper derives a general formula for a portfolio of health care interventions that allows for synergies between interventions where the population effects are aggregated from individual effects. A number of special cases are also derived to highlight the nature of the formulation of the modified portfolio theory. We conclude that, while modified portfolio theory adds a theoretical foundation to health care evaluations, it may not be operational until estimates of the correlation between interventions are available, and the question of uncertainty is resolved in health care evaluation. Also, while a synergy may be present at the individual level, when aggregated over a large population it may not be significant given the standard assumption of constant returns to scale.

Journal Article↗

PubMed1986

Aminoglycosides plus beta-lactams against gram-negative organisms. Evaluation of in vitro synergy and chemical interactions.

Combination antibiotic therapy has been used mainly to broaden the antibacterial spectrum and prevent the development of resistance. Antibiotic combinations proven to be synergistic in vitro are associated with a significantly better in vivo response, particularly in the compromised host in whom traditional treatment combines an antipseudomonal penicillin plus an aminoglycoside. Several investigators have examined combining new agents, such as the third-generation cephalosporins (cefotaxime, ceftriaxone, ceftizoxime, ceftazidime, cefoperazone, and moxalactam), aztreonam, or the ureidopenicillins, with amikacin. When compared with combinations of an older cephalosporin, carbenicillin or ticarcillin, plus gentamicin or tobramycin, these newer combinations produce higher rates of clinically meaningful synergy and rapid enhancement of in vitro bactericidal activity against the difficult-to-treat Enterobacteriaceae (i.e., Serratia, Citrobacter, Enterobacter, Providencia, and indole-positive Proteus species). This effect, without any evidence of antagonism, has been reported even for strains moderately or completely resistant to the former antibiotics. Unsatisfactory and unpredictable synergistic interactions against both resistant and susceptible strains of Pseudomonas aeruginosa--the most difficult nosocomial pathogen to treat--have been noted with combinations of tobramycin or gentamicin plus cefotaxime, moxalactam, or cefoperazone. Conversely, the use of amikacin plus various beta-lactams against multi-resistant strains is more frequently synergistic. Agents have been observed to exhibit such synergy in the following order of activity, from most to least synergistic: ceftazidime, ceftriaxone, moxalactam, aztreonam, cefotaxime, azlocillin, cefoperazone, cefsulodin, and carbenicillin. The combination of amikacin plus imipenem or ciprofloxacin against strains of P. aeruginosa resistant to the former and moderately resistant to the latter was recently reported to have a low probability of synergy; the combination of two of the newer beta-lactams had mostly an unpredictable or even antagonistic result. In vitro studies have also demonstrated that high concentrations of the antipseudomonal penicillins can inactivate the aminoglycosides. Among the latter compounds, the inactivation order, from most to least inactivated, was as follows: tobramycin, gentamicin, netilmicin, and amikacin. To date, the reports of aminoglycoside inactivation by the newer cephalosporins have been rather contradictory; only moxalactam has been shown produce a significant decrease in activity.

Amikacin↗

PubMed1994

Mu and delta opioid synergy between the periaqueductal gray and the rostro-ventral medulla.

Microinjection of [D-Ala2,MePhe4,Gly(ol)5]enkephalin (DAMGO) into either the periaqueductal gray (PAG) or the rostral ventral medulla (RVM) elicits analgesia in the tailflick assay in the rat. Co-administration of DAMGO into both regions together results in a profound synergistic interaction similar to that we previously reported with morphine. U50,488H and DPDPE are inactive when given into either region. [D-Ala2,Glu4]Deltorphin (deltorphin), on the other hand, elicits an analgesic response, although the maximal response is less than than mu agonists. Co-administration of DAMGO into one region with deltorphin in the other also results in a significant synergy. However, co-administration of DAMGO and deltorphin together in the same region gives only additive effects. These results confirm the existence of mu/mu synergy between the PAG and RVM. kappa 1 and delta 1 agents are inactive, but the delta 2 agonist deltorphin is active in both regions. Our results indicate the presence of mu/delta 2 synergy between the PAG and RVM which appears to involve interactions of pathways rather than receptor interactions at the cellular level.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1989

Activation of human peripheral blood-derived monocytes by OK-432 (Streptococcus pyogenes): augmented cytotoxicity and secretion of TNF and synergy with rIFN-gamma.

The biological response modifier OK-432 has been shown both to exert the enhancement of several immunological activities and to have a direct anti-tumor effect. The present study examines the immunopotentiating effect of OK-432 on peripheral blood monocytes (PBM) derived from normal humans. Monocyte activation was assessed by examining direct cell-mediated cytotoxic activity (CMC) and secretion of cytotoxic factors in the supernatant by the 51Cr release assay and secretion of tumor necrosis factor (TNF)-alpha detected by a sensitive radioimmunoassay. The OK-432-augmented activity was compared to that achieved by recombinant interferon-gamma (rIFN-gamma). Coculture of PBM with OK-432 overnight resulted in significant augmentation of CMC and secretion of cytotoxic factors and TNF in the supernatant. The effects observed were dose dependent and the resulting activity was much more pronounced than that achieved with an optimal concentration of IFN-gamma. The monocyte- and supernatant-mediated cytotoxic activities were in a large part attributed to TNF as both activities were inhibited by anti-TNF antibody. Several parameters of monocyte activation by OK-432 were examined. The kinetics of monocyte activation revealed that a short time exposure (2-6 hr) was sufficient for activation but maximal activation was detected after 18 hr. However, the kinetics of the cytotoxic assay were not shortened and 16-20 hr was necessary for optimal cytotoxic activity. Significant synergy was obtained when suboptimal concentrations of OK-432 and IFN-gamma were used. The synergy was noted in CMC, supernatant activity, and TNF concentration. These results demonstrate that OK-432 is a potent activator of monocyte cytotoxicity and also activates secretion of TNF. Also, OK-432 is a much more potent activator than rIFN-gamma. The synergy with OK-432 and IFN-gamma suggests that OK-432-mediated activation of monocytes takes place by a different mechanism than that mediated by rIFN-gamma. Thus, monocytes and products thereof may actively participate in the in vivo anti-tumor effect mediated by OK-432.

Biological Products↗

PubMed1977

The stability of synergy in agonists during the execution of a simple voluntary movement.

The characteristics of muscular synergy between the main elbow flexors (biceps brachii, brachialis, brachoradialis were considered. The activities of these different muscles were recorded simultaneously with surface and wire electrodes. A quantitative analysis of the activity of each of these muscles and of their excitation levels was carried out during movements performed at various velocities and against different inertias. It was shown that: (1) the onset as well as the cessation of activity in the different muscles occur practically simultaneously and independently of the velocity and inertia of the movement; (2) the well-known linear relation between the integrated EMG of biceps brachii and the work can be extended to the other main flexors. This implies that the relation between the activities of the main flexors remains constant whatever the velocity and inertia may be. These results confirm the notion of 'Flexor Equivalent'. They also demonstrate a stability of the synergy between agonist muscles which must be distinguished particularly from the synergy between agonists and antagonists.

Adult↗

PubMed1989

Growth hormone release from chicken anterior pituitary cells in primary culture: TRH and hpGRF synergy, protein synthesis, and cyclic adenosine 3'5'-monophosphate.

Our earlier work showed that the effects of thyrotropin-releasing hormone (TRH) and human pancreatic growth hormone-releasing factor (hpGRF) on growth hormone (GH) release are synergistic (greater than additive) in a primary culture of chicken adenohypophyseal cells. The purpose of the present studies was to investigate the possible participation of protein synthesis and cyclic adenosine 3'5'-monophosphate (cAMP) in GH release. Following culture (48 hr), cells were incubated for 2 hr with test agents. Cycloheximide (an inhibitor of protein synthesis) had no effect on basal (absence of test agent) GH release or hpGRF-induced GH release. However, cycloheximide abolished the synergy between TRH and hpGRF. Although neither TRH nor hpGRF alone stimulated GH production (intracellular GH plus GH release) during a 2-hr incubation period, in combination these secretagogues increased total GH. These findings suggest that GH release from the chicken somatotroph under conditions of TRH and hpGRF synergy requires protein synthesis. In other studies, cells were exposed to agents inducing the formation of cAMP and either TRH or hpGRF. 8 Br-cAMP (10(-3) M), forskolin (10(-6) M), or isobutylmethylxanthine (IBMX; 10(-3) M) alone stimulated GH release to values between 30 and 50% over the basal value. The combined effects of each of these agents and TRH on GH release were synergistic. Similarly, IBMX and hpGRF exerted synergistic effects on GH release. In contrast, no synergy was shown between hpGRF and either 8 Br-cAMP or forskolin; their combined actions were less than additive.

1-Methyl-3-isobutylxanthine↗

PubMed1989

Correlation of intracellular and extracellular calcium ion concentrations with synergy between 1,2-dioctanoyl-sn-glycerol and ionomycin in platelet arachidonic acid mobilization.

The potentiation by 1,2-dioctanoyl-sn-glycerol (DiC8) of ionomycin-induced platelet production of 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) was investigated in correlation with extracellular Ca2+ concentrations and increases in [Ca2+]i, as detected with aequorin and fura-2. Extracellular Ca2+ concentrations greatly influenced the production of arachidonic acid metabolites induced by DiC8 and ionomycin, while that induced by ionomycin alone was minimally affected by variation of the extracellular Ca2+ concentration. In the synergy between ionomycin and 20 microM DiC8, the optimal concentrations of ionomycin shifted from high to low with increasing concentrations of extracellular Ca2+, suggesting that there might be a range of optimal [Ca2+]i for the production of the arachidonic acid metabolites. This hypothesis was confirmed by simultaneous measurements of [Ca2+]i increases, and the production of the arachidonic acid metabolites. With the aequorin method, the optimal concentrations of [Ca2+]i fell to between 10 microM and 20 microM, and with the fura-2 method, it fell to between 800 nM and 1800 nM. Direct measurements of [14C]arachidonic acid release suggested that the DiC8-potentiated production of arachidonic acid metabolites induced by ionomycin was attributable to increased arachidonic acid release. Since ionomycin and DiC8 induced relatively low levels of phosphatidic acid production, an indicator of phospholipase C activation, it was suggested that the increased arachidonic acid release was largely dependent upon phospholipase A2. Synergy between DiC8 and ionomycin was also observed with aggregation and serotonin release. Aggregation was induced by lower concentrations of ionomycin, and appeared to be more dependent upon extracellular Ca2+, while serotonin release required higher concentrations of ionomycin, and variations in extracellular Ca2+ affected the response minimally. These findings suggest that the mechanisms underlying the synergy between protein kinase C activation and Ca2+ mobilization differ among the three functions evaluated in this study.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

PubMed1989

Unexpected synergy between N-phosphonacetyl-L-aspartate and cytidine against human tumor cells.

Cytidine, a non-toxic endogenous nucleoside, was found unexpectedly to augment the cytotoxicity of a pyrimidine antimetabolite N-phosphonacetyl-L-aspartate (PALA) in human ovarian carcinoma cells. The PALA/cytidine synergy is confirmed here in other human tumor cells (T242 melanoma, HL60 promyelocytic leukemia and SKOV3 ovarian carcinoma) in the cytidine concentration range of 1-10 micromolar. The synergy was not observed in Chinese hamster ovary (CHO) cells. Exogenous uridine (5-50 microM) completely reversed the PALA/cytidine cytotoxicity in a concentration-dependent manner. Measurements of cellular ribonucleotide levels revealed that the PALA treated cells had reduced UTP and CTP pools (10% and 40% of control respectively); and the PALA/cytidine treated cells had elevated CTP and GTP levels while their UTP levels remained at 10% of control. Deoxyribonucleotide levels were unremarkable except for a slight elevation of dCTP in the PALA/cytidine treated cells. Uridine competitively inhibited radioactive cytidine transport into 2008 cells, which may explain its ability to antagonize the PALA/cytidine synergy. These results suggest that the ribonucleotide biosynthetic mechanism is the primary cellular target for PALA/cytidine activity, and that the ratio of ribonucleotides to each other is an important determinant of tumor cell viability. The use of non-cytotoxic nucleosides to augment the activity of antimetabolites may have clinical relevance in cancer therapy.

Antimetabolites, Antineoplastic↗

PubMed1984

Cefotaxime, cephalothin, and cephapirin: antimicrobial activity and synergy studies of cephalosporins with significant in vivo desacetyl metabolite concentrations.

The desacetyl metabolites of cefotaxime, cephalothin, and cephapirin were 5-55% as active as the parent drug, depending upon the bacterial species tested. Synergy or partial synergy was demonstrated in 64% of 25 strains of Enterobacteriaceae and Staphylococcus aureus tested against cephalothin/desacetylcephalothin and cephapirin/desacetylcephapirin combinations. Some species variations were identified that influenced synergy rates, particularly among the S. aureus strains (for example, highest rates for cephapirin).

Bacteria↗

PubMedDate not supplied

Activity of cefotaxime/desacetylcefotaxime with two aminoglycosides against gram-negative pathogens: an example of interactive synergy.

The susceptibility patterns of clinical Gram-negative isolates were determined to cefotaxime (CTX) and desacetylcefotaxime (dCTX) alone and in combination with gentamicin (GENT) or tobramycin (TOB) by an agar dilution technique. A constant ratio of 1:1 (CTX to dCTX) was tested throughout the study. Isolates were challenged with subinhibitory levels of TOB or GENT in combination with clinically achievable levels of CTX, dCTX and CTX/dCTX to examine the interactions of the agents. Results of this study demonstrate that CTX/dCTX interacts synergistically with aminoglycosides against many Gram-negative pathogens. Synergy (defined as a fourfold or greater decrease in minimum inhibitory concentration (MIC) when CTX/dCTX was compared to CTX/dCTX/TOB) was demonstrable for 55% of isolates tested. Similarly, 45% were synergistically inhibited by CTX/dCTX/GENT. Additivism (a 2-fold decrease in MIC with the same comparisons) was evident for an additional 18 isolates for CTX/dCTX/TOB and 19 with CTX/dCTX/GENT. When data for Pseudomonas spp. were excluded from the analysis, synergy or additivism was evident with CTX/dCTX/TOB for 88% of the organisms tested and 72% with CTX/dCTX/GENT. Synergistic synergy for CTX/dCTX/TOB (an 8- to greater than 16-fold decrease in MIC for CTX) was demonstrable for 35 and 32 of 82 nonspeudomonal isolates respectively with the TOB and GENT combinations. Ninety nine percent of the nonspeudomonal isolates were inhibited by less than 4 micrograms/ml of CTX, 4 micrograms/ml of dCTX and 0.12 micrograms/ml of TOB, or 0.25 micrograms/ml of GENT, respectively.

Cefotaxime↗