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PubMed2001

Effect of inoculum size on the antibacterial activity of cefpirome and cefepime against Klebsiella pneumoniae strains producing SHV extended-spectrum beta-lactamases.

OBJECTIVE: To determine the effects of varying inoculum size on in vitro susceptibility of SHV extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae isolates to cefepime and cefpirome compared to previously established cephalosporins and aztreonam. METHODS: Antibiotic susceptibilities were determined by disk diffusion test, the MIC broth microdilution method, and time-kill studies with two different inocula of 10(5) and 10(7) CFU/mL. The strains were classified into four groups according to the type of beta-lactamase they produce: SHV-2, SHV-5, SHV-12, and ESBL-negative klebsiellae. RESULTS: The antibacterial activities of cefpirome and cefepime were comparable to that of cefotaxime, but were significantly greater than those of ceftazidime and aztreonam. An inoculum effect was detected for all broad-spectrum cephalosporins, but it was more pronounced with cefpirome and cefepime compared to older cephalosporins. The disk diffusion test proved to be not sensitive enough for the detection of an inoculum effect, particularly for cefepime. CONCLUSIONS: The present study found that most SHV-producing klebsiellae have MICs of cefpirome that imply susceptibility at the moderate inoculum size, in spite of the fact that, according to the NCCLS, all ESBL producers should be considered resistant to all cephalosporins, independent of MIC values. With a high inoculum, most of the strains seemed to be resistant to both antibiotics. Furthermore, the bactericidal activities of cefpirome and cefepime against isogenic Escherichia coli strains producing SHV-2, SHV-4 and SHV-5 beta-lactamases, respectively, were also inoculum dependent. Bactericidal activity against SHV-4 and SHV-5 beta-lactamase producers was obtained only at the moderate inoculum, whereas the SHV-2 beta-lactamase producer was efficiently killed with both antibiotics, regardless of the inoculum size.

Cefepime↗

PubMed2004

Cefepime and the inoculum effect in tests with Klebsiella pneumoniae producing plasmid-mediated AmpC-type beta-lactamase.

OBJECTIVE: In the past decade, a new problem in Klebsiella pneumoniae strains has emerged: plasmid-mediated AmpC enzymes. This study was conducted to investigate the activity of cefepime against clinical isolates by determining the activities of cefepime and three other parenteral beta-lactam agents in standard and high inoculum MIC tests. METHODS: A total of 61 K. pneumoniae blood isolates, including 28 isolates producing AmpC-type beta-lactamases (14 isolates of DHA-1 and 14 isolates of CMY-1-like) and 33 isolates producing extended-spectrum beta-lactamases (ESBLs) (32 isolates of TEM- or SHV-related and one isolate of CTX-M-14-like), were included in the study. Antimicrobial susceptibilities were determined using broth microdilution MIC tests with standard and 100-fold-higher inocula. The inoculum effect was defined as an eight-fold or greater MIC increase on testing with the higher inoculum. RESULTS: In tests with AmpC beta-lactamase-producing K. pneumoniae isolates and their transconjugants, the inoculum effect was most consistently detected with cefepime, cefotaxime and ceftazidime, as inoculum effects were consistently detected in ESBL-producing isolates. However, the inoculum effect was least frequently detected with imipenem. CONCLUSION: Although the inoculum effect is an in vitro laboratory phenomenon, these results suggest that cefepime may be a less than reliable agent for therapy in cases of high inoculum infections caused by AmpC beta-lactamase-producing K. pneumoniae.

Anti-Bacterial Agents↗

PubMed1991

Comparison of the inoculum effect of cefoxitin and other cephalosporins and of beta-lactamase inhibitors and their penicillin-derived components on the Bacteroides fragilis group.

We compared the inoculum effects for 109 recent clinical isolates of the Bacteroides fragilis group of cefoxitin, cefotetan, ceftizoxime, ceftriaxone, and three beta-lactamase inhibitors (clavulanic acid, sulbactam, and tazobactam) and their penicillin-derived components. Bactericidal activity was assayed and morphologic changes were monitored for selected strains exhibiting a large inoculum effect. Ceftizoxime demonstrated the largest inoculum effect, followed by cefotetan and ceftriaxone. The large inoculum effect of ceftizoxime and ceftriaxone was correlated with filamentous transformation at the high inoculum (10(8) CFU/ml) and lack of bactericidal activity suggesting drug destruction or inactivation. Cefotetan was bactericidal for B. fragilis isolates but not for other members of the B. fragilis group. Cefoxitin showed the least inoculum effect and was consistently bactericidal at high (10(8) CFU/ml), standard (10(6) CFU/ml), and low (10(4) CFU/ml) inocula, followed by ampicillin-sulbactam. Piperacillin-tazobactam and ticarcillin-clavulanic acid showed an intermediate inoculum effect. The degree of inoculum effect observed generally correlated with bactericidal activity at all inocula.

Anti-Bacterial Agents↗

PubMed2003

Inoculum size influences bacterial cross contamination between surfaces.

Many factors have been shown to influence bacterial transfer between surfaces, including surface type, bacterial species, moisture level, pressure, and friction, but the effect of inoculum size on bacterial transfer has not yet been established. Bacterial cross contamination rates during performance of common food service tasks were previously determined in our laboratory using nalidixic acid-resistant Enterobacter aerogenes. Eight different transfer rates were determined, each involving a minimum of 30 volunteers. The influence of source inoculum level on the percentage of bacteria transferred (percent transfer rates) and log10 CFU per recipient surface was determined using statistical analysis. The effect of inoculum size on transfer rate was highly statistically significant (P < 0.0001) for all transfer rate data combined (352 observations) and for each individual cross contamination rate, except for data on contamination via transfer from chicken to hand through a glove barrier (P = 0.1643). Where inoculum size on the source was greater, transfer rates were lower, and where inoculum size on the source was less, transfer rates were higher. The negative linear trend was more obvious for activities that had a larger range of inoculum sizes on the source surface. This phenomenon has serious implications for research seeking to determine bacterial cross contamination rates, since the different transfer efficiencies that were previously shown to be associated with certain activities may actually be the result of differing initial inoculum levels. The initial inoculum size on the source and the amount of bacteria transferred must both be considered to accurately determine bacterial transfer rates.

Animals↗

PubMed2004

Effects of inoculum and beta-lactamase activity in AmpC- and extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae clinical isolates tested by using NCCLS ESBL methodology.

Escherichia coli and Klebsiella pneumoniae isolates with extended-spectrum beta-lactamases (ESBLs) or AmpC cephalosporinases generally respond as predicted to NCCLS tests for ESBL production. However, inoculum size may affect MICs. The effect of inoculum level in clinical isolates expressing beta-lactamases were studied at inocula within 0.5 log unit of the standard inoculum, using broth microdilution methodology with ceftazidime, cefotaxime, cefepime, cefpodoxime, and aztreonam. Strains with TEM-1 or no beta-lactamases gave consistent MIC results with inocula of 10(5) and 10(6) CFU/ml. When the bacteria were screened for ESBL production and the lower inoculum was used, several strains with ESBLs, including CTX-M-10, TEM-3, TEM-10, TEM-12, TEM-6, SHV-18, and K1, gave false-negative results for one or more antimicrobial agents (MICs below the NCCLS screening concentration for detecting suspected ESBLs). When the higher inoculum was used, MICs of at least one antimicrobial agent increased at least fourfold in strains producing TEM-3, TEM-10, TEM-28, TEM-43, SHV-5, SHV-18, and K1. All antimicrobial agents showed an inoculum effect with at least one ESBL producer. Confirmatory clavulanate effects were seen for both inocula for all ESBL-producing strains with all antimicrobial agents tested, except for the CTX-M-10-producing E. coli with ceftazidime and the SHV-18-producing K. pneumoniae with cefotaxime. In kinetic studies, cefpodoxime and cefepime were hydrolyzed by ESBLs in a manner similar to that of cefotaxime. When total beta-lactamase activity and hydrolysis parameters were evaluated, however, no single factor was predictive of inoculum effects. These results indicate that the NCCLS screening and confirmation tests are generally predictive of ESBL production, but false-negative results can arise when a lower inoculum is used in testing.

Bacterial Proteins↗

PubMed2000

The effect of inoculum density and conditioned medium on the production of ajmalicine and catharanthine from immobilized Catharanthus roseus cells.

The effect of the cell-inoculum size and the addition of conditioned medium on ajmalicine and catharanthine production were studied using immobilized Catharanthus roseus cells. Higher specific-uptake rates of ammonium, nitrate, and sugars were observed in the low-inoculum-density cultures (50 g FW/L) compared to the high-inoculum-density cultures (100 g FW/L). Alkaloid production was not correlated with the exhaustion of a particular nutrient from the medium. The high-inoculum-density cultures produced higher ajmalicine concentrations throughout the experiment. Catharanthine production was similar between the two inoculum-density cultures. The addition of conditioned medium to MS-production medium dramatically improved the production of ajmalicine and catharanthine. The addition of conditioned medium enhanced ajmalicine production from immobilized Catharanthus roseus cultures on day 15 by at least two- to fourfold compared to media without the conditioning factors. Catharanthine production was increased by nearly fivefold in cultures with conditioned medium compared to those without conditioned medium. The enhancing effects of conditioned medium on alkaloid production were attributed to an unidentified factor produced and secreted by suspension cultures of C. roseus. The presence of conditioned medium also decreased the sucrose hydrolysis rate. The ajmalicine concentration in these immobilized cell cultures was found to be a function of the fresh-weight concentration, irrespective of the inoculum density or the culture medium. The medium choice and the inoculum density determined how rapidly fresh weight was accumulated and thus, how quickly ajmalicine was produced. Ajmalicine production correlated positively with fresh-weight concentration, but catharanthine production was not correlated with fresh-weight concentration.

Biotechnology↗

PubMed2005

Effect of inoculum size on the combined temperature, pH and aw limits for growth of Listeria monocytogenes.

The growth/no growth responses of Listeria monocytogenes inoculated at four levels (0.90, 2.58, 4.20 and 6.81 log cfu/well; 300 microl medium/well) into tryptic soy broth (TSB) were monitored at different combinations of temperature (4 to 30 degrees C), pH (3.76 to 6.44) and aw (0.888 to 0.997) for 60 days. The study was conducted in 96-well microtiter plates and growth was monitored visually and by recording the turbidity of the medium with an automated microplate reader. The growth limits of the pathogen and hence the position of the growth boundary were found to be affected by the size of the inoculum. For example, at 25 degrees C and aw 0.997 the minimum pH values that allowed growth were 4.45 and 3.94 for inoculum levels of 0.90 and 6.81 log cfu/well, respectively. Similarly, at 25 degrees C and pH 6.44 the minimum aw values where growth was observed ranged from 0.900 to 0.928 depending on the inoculum level. The results showed that at temperatures from 10 to 30 degrees C the difference in the growth limits between the tested inoculum levels was higher in environments where a single factor (pH or aw) was inhibitory than in environments where pH and aw together were inhibitory. The data were used to develop a growth/no growth interface model for each inoculum level tested, using logistic polynomial regression. The concordance indices of the models ranged from 99.8% to 99.9% and showed a good fit to the observed data in all models. This study indicates the importance of inoculum size for microbial growth initiation and provides quantitative data that show how the combinations of hurdles which prevent growth vary with inoculum size.

Colony Count, Microbial↗

PubMed2003

Effect of increasing inoculum sizes of Aspergillus hyphae on MICs and MFCs of antifungal agents by broth microdilution method.

In order to investigate the influence of different hyphal inoculum sizes on minimal inhibition concentrations (MICs) and minimum fungicidal concentrations (MFCs) of amphotericin B (AMB), voriconazole and itraconazole, five isolates each of Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger and Aspergillus terreus were studied using a broth microdilution method. Three inoculum sizes were used: 1 x 10(3)-5 x 10(3), 1 x 10(4)-5 x 10(4) and 1 x 10(5)-5 x 10(5) cfu/ml. MICs and MFCs were read at 24 and 48 h at 35 degrees C. For all species tested, AMB MICs and MFCs were minimally affected by inoculum size on. However inoculum size significantly affected MICs and MFCs of voriconazole and itraconazole; there was an increase of up to 6-fold in MICs and MFCs for the various aspergilli when the inoculum increased from 10(3) to 10(5) cfu/ml (P<0.05). Thus azoles showed significant inoculum effects, while AMB showed comparatively minimum inoculum effects against Aspergillus spp.

Amphotericin B↗

PubMed2002

Bacillus megaterium spore germination is influenced by inoculum size.

AIMS: The effect of spore density on the germination (time-to-germination, percent germination) of Bacillus megaterium spores on tryptic soy agar was determined using direct microscopic observation. METHODS AND RESULTS: Inoculum size varied from approximately 10(3) to 10(8) cfu ml(-1) in a medium where pH=7 and the sodium chloride concentration was 0.5% w/v. Inoculum size was measured by global inoculum size (the concentration of spores on a microscope slide) and local inoculum size (the number of spores observed in a given microscope field of observation). Both global and local inoculum sizes had a significant effect on time-to-germination (TTG), but only the global inoculum size influenced the percentage germination of the observed spores. CONCLUSIONS: These results show that higher concentrations of Bacillus megaterium spores encourage more rapid germination and more spores to germinate, indicating that low spore populations do not behave similarly to high spore populations. SIGNIFICANCE AND IMPACT OF THE STUDY: A likely explanation for the inoculum size-dependency of germination would be chemical signalling or quorum sensing between Bacillus spores.

Bacillus megaterium↗

PubMed1980

Influence of inoculum size on activity of cefoperazone, cefotaxime, moxalactam, piperacillin, and N-formimidoyl thienamycin (MK0787) against Pseudomonas aeruginosa.

Forty clinical isolates of Pseudomonas aeruginosa were tested for their susceptibility to cefoperazone, cefotaxime, moxalactam, piperacillin, N-formimidoyl thienamycin (MK0787), and gentamicin at three different inocula. At an inoculum of 5 x 10(3) colony-forming units (CFU) per ml, the minimum inhibitory concentrations (in micrograms per milliliter) for 90% of isolates (MIC90) were as follows: gentamicin, 1; N-formimidoyl thienamycin, 2; cefoperazone, 4; piperacillin, 8; moxalactam, 16; and cefotaxime, 16. When the inoculum was increased to 5 x 10(5) CFU/ml, the MIC90 for all drugs tested increased. Among the beta-lactam antibiotics, N-formimidoyl thienamycin and cefoperazone had the lowest MIC90 (8 micrograms/ml) at this inoculum. When the inoculum was increased further to 5 x 10(7) CFU/ml, an MIC90 could be determined only for gentamicin and N-formimidoyl thienamycin (4 and 8 micrograms/ml, respectively). Indeed, the MIC50 for moxalactam, cefotaxime, cefoperazone, and piperacillin was 128 micrograms/ml or more at this inoculum. The minimum bactericidal concentration for 90% of isolates (MBC90) at an inoculum of 5 x 10(5) CFU/ml ranged from 8 micrograms/ml for gentamicin and N-formimidoyl thienamycin to 128 micrograms/ml for cefotaxime. At the highest inoculum, however, whereas the MBC90 for gentamicin and N-formimidoyl thienamycin remained at 8 micrograms/ml, the MBC90 for each of the other drugs was greater than 128 micrograms/ml. N-Formimidoyl thienamycin was the only drug tested for which an MIC100 and MBC100 (MIC and MBC for 100% of isolates) could be determined, and these were not significantly different from the MIC90 and MCB90.

Anti-Bacterial Agents↗

PubMed1999

Influence of incubation time, inoculum size, and glucose concentrations on spectrophotometric endpoint determinations for amphotericin B, fluconazole, and itraconazole.

We addressed the influence of the incubation time (24 h versus 48 h), starting inoculum size (standard inoculum size, approximately 10(3) CFU/ml, versus large inoculum size, approximately 10(4) CFU/ml), and supplementation with 2% glucose of RPMI 1640 medium on the spectrophotometric determination of the MICs of amphotericin B, fluconazole, and itraconazole. We compared the MICs determined spectrophotometrically with those determined by the standard broth macrodilution method (National Committee for Clinical Laboratory Standards approved guideline M27-A). The agreement between the results of the spectrophotometric and standard methods for amphotericin B testing was 100%; this agreement was independent of the inoculum size and incubation time. On the other hand, the agreement for the results for fluconazole testing and itraconazole testing was dependent on the inoculum size and incubation time. With large inoculum size, excellent agreement can be achieved at 24 h. With standard inoculum size, acceptable agreement can be achieved only at 48 h. In contrast to previous observations, the addition of 2% glucose did not have any significant impact on the growth density at 24 h, nor did it improve the agreement with the standard method. Furthermore, supplemental glucose might falsely elevate the MIC at 48 h.

Amphotericin B↗

PubMed1990

Survival and inoculum potential of conidia and chlamydospores of Fusarium oxysporum f.sp. lini in soil.

The kinetics of survival and inoculum potential of Fusarium oxysporum f.sp. lini were studied in soil. Two types of inoculum were compared: microconidia freshly harvested from a laboratory-grown culture and microchlamydospores produced in sterilized soil. Introduced at the same inoculum densities into a natural soil, the two types of inoculum showed similar behavior; the inoculum densities changed little with time, at least during 100 days. However, the two types of inoculum did differ in disease potential. A higher percentage of microchlamydospores than microconidia germinated in the rhizosphere of flax seedlings, and the heterotrophic fluorescein diacetate hydrolysing activity of the microchlamydospores was 100 times higher than that of microconidia. Moreover, the microchlamydospores produced more disease on flax than the microconidia even at a much lower inoculum density.

Fusarium↗

PubMed2006

Influence of different histories of the inoculum on lag phase and growth of Listeria monocytogenes in meat models.

The aim of this study was to determine the effect of history of inoculum and preservatives on the lag phase and growth rate of Listeria monocytogenes strains in meat products packaged under modified atmosphere conditions. Inocula with different histories were added to meat models, and growth rate and lag phase of two strains of L. monocytogenes were measured at 5 and 10 degrees C. The meat model stored at 10 degrees C contained sodium lactate, but the model stored at 5 degrees C did not. The five different histories of the inocula included cold propagation, biofilm formation, and starvation. The lag phase ranged from 1 to 10 days and was affected by the history of the inoculum, whereas the growth rate was constant except for one combination of history of inoculum and strain, where growth did not start during the incubation period. In a second series of experiments, the growth rate and lag phase of the two Listeria strains and the effects of two different histories of inoculum were tested in meat models with pH 5.7 or 6.5 and increasing amounts of NaCl. The growth rate depended on salt concentration, bacterial strain, and pH, whereas lag phase duration depended on history of inoculum, salt concentration, and pH. The lag phase duration was highly dependent on the history of the inoculum, and higher amounts of preservative (NaCl) made these effects even more noticeable. The results of this study underline the importance of the effects of the history of the inoculum on lag phase duration and could be used to predict lag phase in industrial meat products.

Animals↗

PubMed2006

Dry-thermophilic anaerobic digestion of organic fraction of the municipal solid waste: focusing on the inoculum sources.

The effect of inoculum source on anaerobic thermophilic digestion of separately collected organic fraction of municipal solid wastes (SC_OFMSW) has been studied. Performance of laboratory scale reactors (V: 1.1 L) were evaluated using six different inoculums sources: (1) corn silage (CS); (2) restaurant waste digested mixed with rice hulls (RH_OFMSW); (3) cattle excrement (CATTLE); (4) swine excrement (SWINE); (5) digested sludge (SLUDGE); and (6) SWINE mixed with SLUDGE (1:1) (SWINE/SLUDGE). The SC_OFMSW was separately and collected from university restaurant. The selected conditions were: 25% of inoculum, 30% of total solid and 55 degrees C of temperature, optimum in the thermophilic range. The six inoculum sources showed an initial start-up phase in the range between 2 and 4 days and the initial methane generation began over 10 days operational process. Results indicated that SLUDGE is the best inoculum source for anaerobic thermophilic digestion of the treatment of organic fraction of municipal solid waste at dry conditions (30%TS). Over 60 days operating period, it was confirmed that SLUDGE reactor can achieve 44.0%COD removal efficiency and 43.0%VS removal. In stabilization phase, SLUDGE reactor showed higher volumetric biogas generated of 78.9 mL/day (or 35.6 mLCH(4)/day) reaching a methane yield of 0.53 LCH(4)/gVS. Also, SWINE/SLUDGE and SWINE were good inoculums at these experimental conditions.

Anaerobiosis↗

PubMed2001

The effect of inoculum size and sublethal injury on the ability of Listeria monocytogenes to initiate growth under suboptimal conditions.

AIMS: To investigate the effect of inoculum size and physiological state on the ability of Listeria monocytogenes cells to initiate growth under suboptimal conditions of salt concentration and pH. METHODS AND RESULTS: Cell suspensions were serially diluted in media of different salt concentration or pH and replicate inocula distributed into 96-well microplates. The proportion of wells showing growth at each dilution level was determined after incubation for 6 weeks for each set of conditions. Growth occurred from single cells up to a concentration of 1.2 mol l-1 NaCl; above this threshold, the inoculum size needed to initiate growth became progressively larger. A similar effect was seen with decreasing pH but only very close to the growth/no growth boundary. The threshold for inoculum-dependent growth was lower in exponential phase cells than in stationary phase ones and sublethal injury greatly decreased the probability of growth from small inocula. CONCLUSIONS: The growth/no growth boundary for L. monocytogenes is not an absolute cut-off point but represents a region where the probability of growth rapidly decreases as conditions become more extreme. We interpret the requirement for a critical inoculum size for growth as being due to death of a proportion of cells in the inoculum rather than to co-operative population effects. SIGNIFICANCE AND IMPACT OF THE STUDY: Physiological heterogeneity within the cell population and inoculum size will affect the risk of L. monocytogenes growing in food.

Adaptation, Physiological↗

PubMed1987

The use of the Prompt Inoculation System in preparing a standardized yeast inoculum.

One of the most important steps in performing broth dilution susceptibility testing of yeast isolates is the preparation of the starting inoculum. Although not specifically developed for yeast inoculum preparation, the Prompt Inoculation System (3M) provides a novel alternative approach that may provide a more standardized yeast inoculum than previously employed methods. The authors examined the relationship between the number of colonies picked with the Prompt Inoculation Wand and the hemacytometer and viable colony counts for each of six test organisms, including Candida albicans, Candida tropicalis, Candida krusei, Candida parapsilosis, Candida glabrata, and Cryptococcus neoformans. They found that by picking five colonies 1-2 mm in diameter, inoculum densities of 1 to 5 X 10(6) CFU/mL were obtained with most of the test organisms. A considerably higher inoculum density was observed with C. glabrata (1 to 2 X 10(7) CFU/mL) because of the small size of this organism. No overfilling of the Inoculation Wand was observed when more colonies were touched. This study indicates that the Prompt Inoculation System offers a convenient and simple method for yeast inoculum preparation.

Candida↗

PubMed1989

In-vitro susceptibility of the Bacteroides fragilis group and the inoculum effect of newer beta-lactam antibiotics on this group of organisms.

The susceptibility and inoculum effect of 190 selected Bacteroides fragilis group isolates were determined with six beta-lactam antibiotics by two different methods: agar dilution and broth microdilution. The results were analysed by species within this group of pathogens. The evaluation showed that imipenem had superior activity and was very stable to increased inoculum concentration. Cefoxitin and piperacillin exhibited very good activity and very small inoculum effect; latamoxef showed stability to changes in the inoculum concentration but only intermediate activity; while ceftizoxime and cefoperazone exhibited a marked inoculum effect and relatively poor activity. Resistance among the species was as follows: B. distasonis greater than B. thetaiotaomicron greater than B. ovatus greater than B. fragilis. The inoculum effect was higher when tests were performed in broth rather than in agar. In general, the effect was more pronounced among B. ovatus and less among B. distasonis isolates.

Anti-Bacterial Agents↗

PubMed1990

Relevance of the inoculum effect of antibiotics in the outcome of experimental infections caused by Escherichia coli.

The minimum dosage of antibiotics that reduced mortality in bacteraemic rats inoculated with two different Escherichia coli isolates was determined in an attempt to study the therapeutic importance of the inoculum effect. Low mortality rates (0-5%) at 48 h were obtained when antibiotics with minimal or no inoculum effect (ampicillin, cefuroxime, cefoxitin and gentamicin) were administered to yield serum levels 5 to 14 times the MIC, while antibiotics with a pronounced inoculum effect (piperacillin, cefotaxime and aztreonam) had to be administered to yield serum levels 57 to more than 1000 times the MIC determined with a standard (low) inoculum. All of the antibiotics with inoculum effect studied here are administered empirically in clinical practice at a higher dose than the microbiological and pharmacokinetic data would indicate (in order to reach peak serum concentrations exceeding the MICs of the pathogens by 4-10 times). Our experiment suggests that such high and empirical doses of antibiotics with inoculum effect may be justified.

Animals↗