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PubMed1984

Antimicrobial susceptibility patterns of canine Staphylococcus intermedius isolates from veterinary clinical specimens.

Sixty-six Staphylococcus intermedius isolates from canine clinical specimens were tested for susceptibility to various antimicrobial agents by the Bauer-Kirby disk diffusion method and a commercial microdilution system. All isolates were susceptible to cephalothin, cloxacillin, gentamicin, methicillin, and vancomycin. Resistance to ampicillin, penicillin G, and tetracycline was frequent. There was an overall 87% agreement of results from the disk diffusion and microdilution methods for 10 antimicrobial agents. There was greater than or equal to 94% agreement between the 2 methods for 7 antimicrobics; discrepancies were minor.

Animals↗

PubMed1979

Comparison of direct and standard antimicrobial disk susceptibility testing for bacteria isolated from blood.

To determine the reliability of early antimicrobial susceptibility testing, we compared the results of direct and standard single-disk diffusion methods for 581 positive blood cultures processed routinely by the clinical microbiology laboratory. The direct procedure differed from the standard one only in that the 0.5 McFarland inoculum was prepared from 1 ml of turbid broth rather than five isolated colonies from a subculture plate. A major discrepancy in results was defined as a change from susceptible to resistant or vice versa according to interpretive standards for zone diameters, whereas a minor discrepancy was defined as a shift to or from the intermediate category when paired direct and standard tests were compared. The overall agreement between the two methods was 94.6% of 2,308 comparisons. There were 119 minor (5.2%) and 6 major (0.3%) discrepancies. The major discrepancies were seen with three strains of Staphylococcus epidermidis and one strain each of S. aureus, Escherichia coli, and Enterobacter sp. Direct susceptibility testing of positive blood cultures that were pure by gram-stained smear provided reliable results 24 to 36 h earlier than conventional procedures; therefore, we recommended this procedure to guide early antimicrobial therapy in patients with bacterial sepsis.

Anti-Bacterial Agents↗

PubMed1992

[Evaluation of in vitro antimicrobial activity of cefazolin alone and in combination with cefmetazole or flomoxef using agar dilution method and disk diffusion method].

Antimicrobial activities of cefazolin (CEZ) against 251 strains of various clinical isolates obtained during 1989 and 1990 were determined using the Mueller-Hinton agar dilution method at an inoculum level 10(6) CFU/ml. The reliability of the disk susceptility test was also studied using Mueller-Hinton agar and various disks at inoculum levels of 10(3-4) CFU/cm2 in estimating approximate values of MICs. In addition, antimicrobial activities of CEZ and cefmetazole (CMZ) or flomoxef (FMOX) in combination were investigated against methicillin-sensitive and -resistant Staphylococcus aureus (MSSA and MRSA) using the checkerboard agar dilution MIC method and the disk diffusion test either with the disks contained CEZ, CMZ, and FMOX alone, or CEZ, and CMZ or FMOX in combination. In this study, the MICs of CEZ against S. aureus were distributed with the 3 peak values at 0.39 microgram/ml, 3.13 micrograms/ml and > 100 micrograms/ml. MICs against MSSA were 0.39 microgram/ml to 0.78 microgram/ml, whereas those against MRSA were greater than 0.78 microgram/ml. MICs against majority of strains of Enterococcus faecalis were 25 micrograms/ml. Over 90% of strains of Escherichia coli and Klebsiella pneumoniae were inhibited at the level of 3.13 micrograms/ml. About 60% of isolates of indole negative Proteus spp. were inhibited at the levels of less than 3.13 micrograms/ml and 100% at 6.25 micrograms/ml, but MICs against indole positive Proteus spp., Serratia spp. and Pseudomonas aeruginosa were over 100 micrograms/ml. The antimicrobial activities of CEZ against these clinical isolates were not significantly different compared to those reported about 15-20 years ago, except for S. aureus. Highly resistant strains of S. aureus to CEZ were more prevalent in this study. The inhibitory zones obtained with the disk test were compared with MICs. The results of CEZ disk susceptibility test with 30 micrograms disk (Showa) or 10 micrograms disk (prepared in this laboratory) were well correlated with MICs (r = -0.837 and -0.814, respectively), showing the reliavility of the disk method in estimating approximate values of MICs. In the 4 category classification system currently used in Japan, break points in MIC values proposed are () MIC < or = 3 micrograms/ml, (++) > 3-15 micrograms/ml, (+) > 15-60 micrograms/ml, (-) > 60 micrograms/ml. The results obtained with 30 micrograms disks showed false positive in 7.7% and false negative in 6.8% of the samples. The disk results with E. faecalis showed a higher ratio of false positive results.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacteria↗

PubMed1999

Diffusion through agar blocks of finite dimensions: a theoretical analysis of three systems of practical significance in microbiology.

A number of experimental methods in biology depend on the kinetics of diffusion of a substance through a gel. This paper reviews the diffusion equations, gives the experimental limitations for some useful cases, and presents computer simulations for cases that cannot be treated analytically. While double diffusion is not considered, three single-diffusion situations are treated. (1) Systems for the study of chemotaxis in the gliding bacterium Myxococcus xanthus. Experimental designs used for this in many cases in the literature were inappropriate and mathematical analysis of these is presented. (2) The development of gradient plates. The time necessary for vertical diffusion to become substantially complete and before diffusion in the direction of the original slant has proceeded significantly is calculated. (3) The application to antimicrobial disk susceptibility tests. The basis of the measurement of antibiotic sensitivities with disks containing antimicrobial agents, as routinely used in clinical microbiological and testing laboratories, is analysed and the limitations are assessed and improvements suggested.

Agar↗

PubMed1980

Antimicrobial susceptibility of Aeromonas hydrophila.

Minimal inhibitory concentration determinations and disk diffusion and Autobac 1 susceptibility tests were performed on 22 strains of Aeromonas hydrophila. Eleven of the strains had discrepancies between Autobac and disk diffusion or minimal inhibitory concentration results. These discrepancies occurred with the beta-lactam antibiotics, primarily carbenicillin and cephalothin. It is recommended that any strain of A. hydrophila found to be susceptible to any of the beta-lactam antibiotics by using Autobac 1 should be retested by a disk diffusion or minimal inhibitory concentration method.

Aeromonas↗

PubMed1985

Imipenem-induced resistance to antipseudomonal beta-lactams in Pseudomonas aeruginosa.

Using clinical isolates of Pseudomonas aeruginosa, we studied the ability of imipenem to antagonize the activity of nine other antipseudomonal beta-lactam antimicrobial agents. Imipenem caused truncation of the zones of inhibition in a disk diffusion test for 91 to 100% of the strains, depending on the beta-lactam tested. Addition of subinhibitory concentrations of imipenem caused a fourfold or greater increase in MICs for 72 of 74 isolates and in 20 to 87% of the tests, again depending on the antibiotic tested. beta-Lactamase assays with both whole-cell suspensions and cell sonicates showed that exposure to subinhibitory concentrations of imipenem resulted in a beta-lactamase production supported the hypothesis that induction of beta-lactamase was responsible for antagonism. In hydrolysis studies with a beta-lactamase extract, most of the antagonized drugs were either not hydrolyzed or only poorly hydrolyzed. We conclude that imipenem induces significantly elevated levels of beta-lactamase in P. aeruginosa. This increase in beta-lactamase is associated with increased resistance of the organism to many other beta-lactam agents.

Anti-Bacterial Agents↗

PubMed2003

Methicillin (Oxacillin)-resistant Staphylococcus aureus strains isolated from major food animals and their potential transmission to humans.

From May 2001 to April 2003, various types of specimens from cattle, pigs, and chickens were collected and examined for the presence of methicillin (oxacillin)-resistant Staphylococcus aureus (MRSA). S. aureus was isolated and positively identified by using Gram staining, colony morphology, tests for coagulase and urease activities, and an API Staph Ident system. Among 1,913 specimens collected from the animals, 421 contained S. aureus; of these, 28 contained S. aureus resistant to concentrations of oxacillin higher than 2 micro g/ml. Isolates from 15 of the 28 specimens were positive by PCR for the mecA gene. Of the 15 mecA-positive MRSA isolates, 12 were from dairy cows and 3 were from chickens. Antimicrobial susceptibility tests of mecA-positive MRSA strains were performed by the disk diffusion method. All isolates were resistant to members of the penicillin family, such as ampicillin, oxacillin, and penicillin. All isolates were also susceptible to amikacin, vancomycin, and trimethoprim-sulfamethoxazole. To determine molecular epidemiological relatedness of these 15 animal MRSA isolates to isolates from humans, random amplified polymorphic DNA (RAPD) patterns were generated by arbitrarily primed PCR. The RAPD patterns of six of the isolates from animals were identical to the patterns of certain isolates from humans. The antibiotypes of the six animal isolates revealed types similar to those of the human isolates. These data suggested that the genomes of the six animal MRSA isolates were very closely related to those of some human MRSA isolates and were a possible source of human infections caused by consuming contaminated food products made from these animals.

Animals↗

PubMed1989

New datum handling methods for the quality control of antibiotic solutions and plates used in the antimicrobial susceptibility test.

Quality control programs are described for monitoring both the antibiotic solutions and the plates used in the dilution antimicrobial susceptibility test. For the quality control of antibiotic solutions, a simple comparative disk diffusion assay is used in which the data are expressed as zone ratios calculated from the following formula: zone ratios = mean zones of inhibition for disks impregnated with antibiotic under test/mean zones of inhibition of previously prepared quality control disks impregnated with the same antibiotic. The rejection limits set for this method are twice as stringent as for MIC estimation, and its precision is four times greater. For quality control of the antibiotic agar plates, fluid was absorbed directly into filter paper disks placed on the surface of the medium. These disks were then transferred to a seeded plate to produce zones of inhibition. These zones of inhibition were then converted to zone ratios by dividing the zone of inhibition for the individual antibiotics by the mean of the total zones of inhibition for all the antibiotics tested on the same plate. We further normalized these data by expressing each entry as a standard normal deviate calculated from the mean and standard deviation of the cumulative data for each individual antibiotic. The use of zone ratios reduced batch-to-batch variation, and standard normal deviate values gave a uniform result for convenience. The method has a sensitivity equal to that of an MIC estimation if it were possible to estimate the MICs of antibiotics at these low levels.

Anti-Bacterial Agents↗

PubMed2004

Use of 1,4-naphthoquinones for control of Erwinia carotovora.

The antimicrobial effect of 5 naphthoquinones was tested against the phytopathogenic bacteria Erwinia carotovora. Disk diffusion tests and determination of minimal inhibitory concentrations (MIC) indicate that the compound naphthazarin (NTZ) has the best antibacterial activity among the naphthoquinones tested. Studies on the mode of action indicate the effect of NTZ was bactericidal at 10 microg/mL. When cultivation was done in the presence of sodium ascorbate, the restoration of E. carotovora growth was observed with 3 microg/mL NTZ, but not when a 10 microg/mL dose was used. The incubation of NTZ with bacterial suspension of E. carotovora resulted in important changes in the absorption spectra of this naphthoquinone, indicating that a redox reaction takes place. These results may suggest that NTZ induces an increase of reactive oxygen species that are toxic to the cell. The compound NTZ was also effective in preventing E. carotovora growth on potato tubers, inhibiting the soft rot development at a concentration of 2 mg/mL.

Anti-Bacterial Agents↗

PubMed2002

Comparative antimicrobial spectrum and activity of BMS284756 (T-3811; a desfluoroquinolone) tested against an international collection of staphylococci and enterococci, including in vitro test development and intermethod comparisons.

The study was initiated to determine the in vitro activity and MIC/disk test comparisons of BMS284756, a new des-fluoro(6)-quinolone, against isolates of staphylococci and enterococci from the SENTRY Antimicrobial Surveillance Program, 2000. Isolates were tested by reference broth microdilution and standardized disk diffusion methods. Against 3,789 strains of gram-positive cocci from the SENTRY Program (2000), the BMS284756 MIC90 and percentage susceptible at < or = 2 and < or = 4 microg/ml were: Staphylococcus aureus (4 microg/ml; 89.3 and 97.1%), coagulase-negative staphylococci (CoNS; 4 microg/ml; 86.1 and 96.0%) and enterococci (> 4 microg/ml; 62.0 and 76.2%). Also tested were selected staphylococci (300 strains) and enterococci (102 strains) by two standardized methods. The activity of BMS284756 was highly correlated with oxacillin resistance among staphylococci. Oxacillin-susceptible staphylococci were all inhibited by BMS284756 at < or = 0.5 microg/ml, whereas oxacillin-resistant strains required inhibitory concentrations of > or = 1 microg/ml. Excellent correlation was observed between the MIC and 5-microg disk zone diameter for staphylococci and enterococci (r=0.91 to 0.93). Among vancomycin-susceptible enterococci, 67% of Enterococcus faecalis, 25% of E. faecium, and 76% of other Enterococcus spp. isolates were inhibited by BMS284756 at < or = 2 microg/ml. All vancomycin-resistant enterococci (VRE; 11 E. faecalis and 15 E. faecium) were inhibited by > or = 2 microg/ml of BMS284756. Among the non-VRE, non-faecium enterococcal isolates (n=64), 62% were inhibited by < or = 0.5 microg/ml. BMS284756 showed excellent activity against oxacillin-susceptible staphylococci and moderate activity against enterococci other than VRE and E. faecium. Acceptable correlations were observed between MIC and disk test results for both tested genus groups.

Anti-Infective Agents↗

PubMedDate not supplied

The prevalence of staphylococcal resistance to penicillinase-resistant penicillins. A retrospective and prospective national surveillance trial of isolates from 40 medical centers.

In a retrospective survey of resistance to penicillinase-resistant penicillins (PRPs) in 152,076 clinical staphylococcal strains isolated in 40 United States Hospitals in 1985 and 1986, rates of resistance to oxacillin were found to be 11 and 13%, respectively, among Staphylococcus aureus isolates. The rates were approximately four times higher among coagulase-negative staphylococcal strains. In a prospective study of 1,408 wound or bacteremia isolates from the participant hospitals, oxacillin and methicillin agar screening, disk diffusion, and broth microdilution testing were conducted at a single reference laboratory. These tests yielded PRP resistance rates of 15% among S. aureus, 75% among S. epidermidis, and 48% among other coagulase-negative strains. No major changes in the distribution of resistance rates among hospitals or by hospital type were observed. Dilution susceptibility testing of several antimicrobial agents against PRP-resistant isolates and species-matched susceptible isolates from the same hospital showed that teicoplanin and vancomycin were the most active drugs (100% of S. aureus isolates were susceptible). Teicoplanin and vancomycin disk diffusion testing of all PRP-resistant staphylococcal strains also showed that these isolates were susceptible to the glycopeptides. However, agar dilution screening and broth microdilution tests revealed that several coagulase-negative strains, predominantly S. haemolyticus, had teicoplanin MICs greater than or equal to 8 micrograms/ml. S. haemolyticus isolates represented a very small number of the total stains tested. Teicoplanin and vancomycin were also the most active drugs when tested against older (1962-82) clinical PRP-resistant S. aureus strains from the reference laboratory collection. The methods found to be superior in detecting PRP-resistant strains were the oxacillin 6 micrograms/ml agar screening test in 4% NaCl-supplemented Mueller-Hinton agar and the 1 microgram oxacillin disk test. By reference laboratory standards, participant laboratories were incorrect in only 2.3% of species identifications and 4.5% of oxacillin-susceptibility determinations, indicating acceptable contemporary agreement and accuracy.

Anti-Bacterial Agents↗

PubMed1988

Susceptibility testing of Nocardia species for the clinical laboratory.

Not all patients are able to tolerate or show a favorable response to the treatment of choice for Nocardia, the sulfonamides. Many new drugs are available with good activity against N. asteroides, the most common pathogenic species, although susceptibility to these agents, including amikacin, amoxicillin/clavulanic acid, and the third generation cephalosporins, is variable. For these and other reasons, we recommend routine susceptibility testing of Nocardia. Disk diffusion testing on Mueller Hinton agar is the best currently available clinical method. A suggested control strain and tentative susceptible and resistant breakpoints for 12 antimicrobial agents are provided. This includes agents not previously evaluated, including cefotaxime, amikacin, ciprofloxacin, and doxycycline. The zones of inhibition were all larger than those currently used by the NCCLS for rapidly growing bacteria, and the disk breakpoints generally fit best with the MIC breakpoints used with the dilution susceptibility method (M7-T). A broth microdilution MIC method is described that showed good correlation with disk diffusion results, but need additional study. Because of limited experience in most laboratories with this species, reliance on a good reference laboratory for confirmatory susceptibility testing is recommended. Beta-lactamase testing is not helpful, as almost all Nocardia produce beta-lactamase, although many isolates retain susceptibility to selected beta-lactams.

Culture Media↗

PubMed2006

[Mutations of gyrA gene and parC gene in fluoroquinolone-resistant Escherichia coli isolates from sporadic diarrheal cases].

We studied 107 isolates of Escherichia coli O153 from sporadic diarrhea cases in Fukui, Toyama, Aichi, and Saga prefectures from 1991 to 2005 for antimicrobial susceptibility and mechanisms of fluoroquinolone resistance, based on standard disk diffusion. Of 12 drugs tested, ampicillin displayed resistance to 72.9% of isolates, streptomycin to 48.6%, tetracycline to 46.7%, sulfisoxazole to 46.7%, trimethoprim/sulfamethoxazole to 29.9%, nalidixic acid (NA) to 29.9%, and ciprofloxacin (CPFX) to 24.3%. Ten of 32 isolates resistant to 3-6 drugs and 16 of 18 isolates resistant to 7-10 drugs were resistant both to NA and CPFX. Mutations of amino acid in quinolone resistance-determining regions of gyrA and parC genes were detected in 24 isolates resistant both to NA and CPFX, and in 1 isolate resistant to NA. The former possessed a combination of double substitution (S83L and D87L) in GyrA and a single substitution (S80I) in ParC. Some 12 of 24 isolates possessed another single substitution (E84V or E84G or A108T) in ParC. The 25 isolates were classified into 4 types as follows. 1 isolate as type 1: GyrA (S83L) and ParC (S80I); 12 isolates as type 2: GyrA (S83L and D87N) and ParC (S80I); 8 isolates as type 3: GyrA (S83L and D87N) and ParC (S80I and E84G/S80R and E84V); and 4 isolate as type 4: GyrA (S83L and D87N) and ParC (S80I and A108T). In the relationship between amino acid mutations and minimal inhibitory concentrations (MIC) of fluoroquinolone, MICs of CPFX, ofloxacin, and norfloxacin showed 1microg/mL, 2microg/mL and 8microg/mL in type 1; 8 approximately 32microg/mL, 8 approximately 32microg/mL and 16 approximately 256microg/mL in type 2; and 32 approximately 256microg/mL' 32 approximately 128microg/mL and 128-->512microg/ mL in types 3 and 4. These results suggest that most of multiple-antimicrobial-resitant E. coli O153 isolates from sporadic diarrhea cases were resistant to fluoroquinolones and possessed mutations at gyrA and parC genes associated with fluoroquinolone resistance.

DNA Gyrase↗

PubMed2004

Detection and susceptibility testing of hypermutable Pseudomonas aeruginosa strains with the Etest and disk diffusion.

Resistance development in Pseudomonas aeruginosa from chronically colonized cystic fibrosis (CF) patients has been linked to the presence of a high proportion of mismatch repair-deficient hypermutable strains. The detection of hypermutable strains by microbiology laboratories may be useful for establishing adequate antimicrobial therapies. In this work, we find that the Etest and disk diffusion can be used as simple methods for the detection and susceptibility testing of hypermutable P. aeruginosa isolates. Strain PAO1 and its hypermutable derivative strain PAODeltamutS were used to standardize the procedure, which was tested with 35 P. aeruginosa isolates from 21 CF patients. Mutation frequencies were estimated by standard methods, and 29% of the isolates were found to be hypermutable. MICs and inhibition zone diameters were determined for ceftazidime, imipenem, meropenem, ciprofloxacin, and tobramycin by using Etest strips and conventional disks, respectively. The presence (or absence) of resistant mutant subpopulations, as well as their relative numbers and the highest MICs for them (or smallest inhibition zone diameters), was recorded. The presence of resistant mutant subpopulations within the inhibition zones of three or more antibiotics clearly identified the strains as hypermutable (they were present in 10 of 10 hypermutable strains and 0 of 25 nonhypermutable strains) with both methods. Additionally, these methods allowed us to differentiate between dual effects of hypermutation in antibiotic resistance, namely, that (i) hypermutable isolates were substantially more resistant than nonhypermutable isolates and that (ii) the resistance of hypermutable isolates was dramatically increased by the presence of resistant mutant subpopulations. This differentiation may be relevant for the design of adequate treatments, since the second effect, in contrast to the first, may be overcome by antibiotic combinations.

Anti-Bacterial Agents↗

PubMed1982

[Effect of temperature on the results of the antibiotic sensitivity test performed by the diffusion method in fish pathology].

The sensitivity disk method is currently used in fish pathology to assess the efficacy of antimicrobial drugs. However, it is generally performed at temperatures lower than 37 degrees C, at which standard procedures were recommended by WHO. In order to check up the reliability of the results, selected strains and antibiotic substances were at once studied at 37 degrees C and 22 degrees C. In the last case, two readings of the zones of inhibition were done, after 24 and 48 h of incubation. Minimal inhibitory concentrations (MIC) had been determined using an agar-plate dilution method. Each association drug-bacterial strain provided three samplings of 30 measures which were compared by variance analysis and mean comparison tests. Variances did not differ, except with chloramphenicol and tetracyclines. But the mean values of the diameters significantly differed according to the incubation temperature. The variations could reach 7 to 8 mm, in any way. So, it appears that the disk method fails to allow any quantitative interpretation when performed at 22 degrees C. Consequences in diagnostic of fish diseases are stressed.

Animals↗

PubMed1996

Reevaluation of contemporary laboratory methods for detection of antimicrobial resistance among enterococci.

OBJECTIVE: To evaluate broth microdilution, disk diffusion, Etest and Vitek Systems for susceptibility testing of enterococci. METHODS: Susceptibility testing of a panel of 149 enterococci (99 vancomycin-resistant) strains, using the study methods, was performed and the results compared. RESULTS: For vancomycin susceptibility testing, categorical agreement of disk diffusion, Etest and Vitek with the reference broth microdilution test was > 95%. For aminoglycoside and ampicillin testing, categorical agreement between Etest and Vitek was 98 to 100%. CONCLUSIONS: Disk diffusion, Etest and Vitek have acceptable performance for detection of vancomycin resistance of Van A and Van B phenotypes among enterococci.

Journal Article↗

PubMed1994

[The correlation between the MICs deduced from Showa disk method and the MICs determined by micro-dilution method].

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

Anti-Bacterial Agents↗

PubMed1980

Comparative in vitro appraisal of piperacillin, including its activity against Salmonella typhi.

Piperacillin was evaluated in vitro against 711 clinical isolates of aerobic and anerobic gram-positive and gram-negative bacteria, including 76 isolates of Salmonella typhi. Piperacillin minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were compared with those of a range of beta-lactam, aminoglycoside, and other antimicrobial agents, and inoculum size effects were considered. The relationship between dilution and disk diffusion tests was studied by regression analysis. In addition, piperacillin was assessed in combination with aminoglycoside and other beta-lactam drugs. This investigation has confirmed the activity of piperacillin against a broad range of bacteria, including Pseudomonas, Enterobacteriaceae, Neisseria, beta-lactamase-negative Haemophilus influenzae, and Staphylococcus aureus as well as enterococci, Bacteroides fragilis, and other anaerobes. All strains of Pseudomonas aeruginosa were inhibited by </=32 mug/ml or less, demonstrating again the potential usefulness of piperacillin in the treatment of pseudomonal infections. S. typhi proved susceptible to piperacillin, all isolates being inhibited by 1 mug/ml. Inoculum size experiments showed that inocula of 10(8) CFU resulted in MICs and MBCs appreciably higher than those resulting from inocula of 10(6) CFU, and inocula of 10(2) CFU resulted in MICs and MBCs appreciably lower than those resulting from inocula of 10(4) CFU. Piperacillin was active against all gentamicin-resistant pseudomonads tested, but not against gentamicin-resistant klebsiellas and enterobacters. Combinations of piperacillin with tobramycin and amikacin were consistently synergistic against Pseudomonas and Serratia isolates. Less consistent results were shown when piperacillin was combined with aminoglycosides or cephalothin against Klebsiella and indole-positive Proteus isolates, although synergy was observed in most cases. Occasional antagonistic reactions were encountered with piperacillin-cephalothin or piperacillin-tobramycin combinations against the latter isolates.

Anti-Bacterial Agents↗