Intrinsic resistance of Pseudomonas aeruginosa.
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Anti-Bacterial Agents↗
Biomedical subjects
C W Stratton
Publications and source records attributed to C W Stratton.
Sensitivity, specificity, and predictive value of body surface cultures in a neonatal intensive care unit.
We analyzed 24,584 cultures obtained from 3371 infants during a three-year period to determine how frequently body surface culture isolates matched those obtained subsequently from body fluids. The sensitivity, specificity, and predictive values of surface cultures were calculated daily for the two weeks up to and including the day that a body fluid culture was obtained. Isolates from cultures of material from the ear canal, nasopharynx, axilla, umbilicus, groin, rectum, stomach, and endotracheal tube were rarely the same as those recovered from blood or fluids of the cerebrospinal, joint, pleural, pericardial, and peritoneal spaces. With a frequency of sepsis of 3.3% among patients in our neonatal intensive care unit, the optimum sensitivity, specificity, and positive predictive values of surface cultures were 56%, 82%, and 7.5%, respectively. These values did not improve substantially for any specific times of surface cultures prior to sepsis, for anatomic sites cultured, or for pathogens recovered. We conclude that surface cultures are of limited value in predicting the etiology of sepsis in neonates.
Algorithms↗
Comparison of the bactericidal activity of ciprofloxacin alone and in combination with selected antipseudomonal beta-lactam agents against clinical isolates of Pseudomonas aeruginosa.
The bactericidal activity of ciprofloxacin against 60 clinical isolates of Pseudomonas aeruginosa was evaluated by exposing replicating microorganisms to concentrations ranging from 0.12 to 2 micrograms/ml for 48 hr. In addition, ciprofloxacin was combined with selected antipseudomonal beta-lactams using subinhibitory concentrations (1/4 x MIC, 1/2 x MIC) of each. We found that a concentration of 2 micrograms/ml of ciprofloxacin resulted in bactericidal activity (greater than or equal to 99.9% killing of the final inoculum) at 8 and 12 hr for the highest percentage of isolates (95 and 96.7%, respectively). At the breakpoint concentration (1 micrograms/ml), there was bactericidal activity against 81.7% of these isolates at 8 hr and 78.7% at 12 hr. By 24 and 48 hr, regrowth was frequently seen for concentrations of 1 and 2 micrograms/m (76.7 and 41.7%, respectively). This regrowth represented limited progression of resistance (4- to 16-fold increase in MICs) to ciprofloxacin without cross-resistance to other classes of antibiotics. The combinations containing ciprofloxacin and beta-lactam agent were synergistic for isolates that were susceptible to both agents. Moreover, the combinations prevented the emergence of resistance to either drug.
Anti-Bacterial Agents↗
The problem of selecting antimicrobial agents before (or without) the results of susceptibility testing.
The appropriate selection of an antimicrobial regimen depends upon more factors than merely the results of susceptibility testing. It is a task more difficult today because of the recent development of many new antimicrobial agents. Clinicians who prescribe antibiotics need to invest time and energy beyond reading a package insert in order to gain familiarity with antimicrobial agents. Understanding the antimicrobial and pharmacologic properties of a few agents from each class of antimicrobial agents will help make the selection of empiric regimens less difficult. Essential to empiric therapy is frequent and habitual reassessment of antimicrobial regimens with possible application of cost-effective modifications kept in mind. Once the pathogen is isolated, the empiric regimen can be modified. The very last factor that is used in modification of the antimicrobial regimen is the result of susceptibility testing. Prior to (or without) this information, the clinical outcome of serious infections most often will depend upon the early institution of appropriate empiric therapy.
Anti-Infective Agents↗
Susceptibility testing today: myth, reality, and new direction.
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Animals↗
Activity of beta-lactamases against beta-lactams.
Resistance mediated by beta-lactamases is an important mechanism which has evolved in both Gram-positive and Gram-negative bacteria. There are a large number of different beta-lactamases produced by micro-organisms. Synthesis can be mediated by chromosomes, plasmids, or transposons. Enzyme kinetics for these different beta-lactamases are expressed as affinity of the enzyme for the substrate (1/Km) and rate of hydrolysis of the substrate by the enzyme (Vmax). Such kinetics at physiological concentrations of the enzyme and substrate are important factors in determining the activity of beta-lactam agents. Other factors include the cellular location and amount of enzyme. The clinical importance of subtle differences in beta-lactamase-mediated resistance for both Gram-positive and Gram-negative bacteria is becoming apparent. Antagonism of beta-lactams by beta-lactamases becomes increasingly more important as a resistance mechanism as our knowledge and understanding of this phenomenon grows.
Anti-Bacterial Agents↗
A review of ceftriaxone: a long-acting cephalosporin.
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Ceftriaxone↗
Serum bactericidal test.
The serum bactericidal test represents one of the few in vitro tests performed in the clinical microbiology laboratory that combines the interaction of the pathogen, the antimicrobial agent, and the patient. Although the use of such a test antedates the antimicrobial era, its performance, results, and interpretation have been subject to question and controversy. Much of the confusion concerning the serum bactericidal test can be avoided by an understanding of the various factors which influence bactericidal testing. In addition, the methodologic aspects of the serum bactericidal test have recently been addressed and should place this test on firmer ground. New information on the clinical utility of this test is becoming available; additional data are needed to establish more clearly the usefulness of the serum bactericidal test in specific infections. Such clinical trials from multiple centers will enable firmer recommendations for the future use of the serum bactericidal test.
Anti-Bacterial Agents↗
Controlled evaluation of blood culture medium containing gelatin and V-factor-analog for detection of septicemia in children.
Both Neisseria meningitidis and Haemophilus influenzae are important isolates recovered in blood cultures from septicemic children. Sodium polyanetholsulfonate is present in most blood culture media and can inhibit the growth of certain bacteria, including N. meningitidis. The addition of gelatin to blood culture media neutralizes this inhibition. The growth of H. influenzae is enhanced by specific growth factors such as hemin and NAD. The addition of gelatin and V-factor-analog (a proprietary supplement for enhancing the growth of H. influenzae) might have a positive effect on the yield and on the speed of detection of septicemia in children. To evaluate this possibility, we did 4,565 paired comparisons of blood cultured in BACTEC 6B (aerobic) medium with and without the addition of both 1.2% gelatin and V-factor-analog. More aerobic and facultative bacteria grew in the 6B than in the 6B-gelatin-V-factor-analog medium (P less than 0.01). Only seven isolates of Neisseria spp. were recovered during this study period, with the 6B medium performing as well as the supplemented medium. When microorganisms grew in both bottles, they did so at the same time except for H. influenzae and Candida albicans. H. influenzae was recovered earlier from the 6B-gelatin-V-factor-analog bottle (P less than 0.01), with a mean time to detection of 8.5 h compared with 15.9 h for the 6B bottle. C. albicans was recovered earlier from the 6B bottle (P less than 0.02), with a mean time to detection of 34.9 h compared with 71.6 h for the 6B-gelatin-V-factor-analog bottle. We conclude that the 6B medium in its present formulation is superior to bB supplemented with gelatin and V-factor-analog.
Adolescent↗
The role of the microbiology laboratory in guiding formulary decisions.
Typically, P & T Committee antibiotic selection criteria have included such factors as cost, pharmacokinetics, side effects profile, spectrum of activity, and relative activity against specific pathogens. The microbiology laboratory can provide the P & T Committee with other useful information to help guide them in making even more appropriate and cost-effective formulary decisions. This information includes specific susceptibility data (including prevalence of pathogens, source of infection [community or nosocomial], anatomical site of isolates, specific unit or service where isolated, type of culture specimen, total number of pathogens in the hospital), resistance trends data, an evaluation of microbiologic data presented in published studies, further data regarding an antimicrobial's spectrum of activity and activity against specific pathogens, and the relevance and limitations of in vitro data. With this information in hand, P & T Committee should be in a much better position to optimize formulary decision-making.
Anti-Bacterial Agents↗
Beta-lactamase alteration of beta-lactam inhibitory zones.
A disk approximation test, in which the inhibitory zone of one beta-lactam antibiotic is truncated under influence of another beta-lactam (e.g. cefoxitin), was used as a screen for the presence of inducible beta-lactamase. By using beta-lactamase extracts and a specific inhibitor, it was shown that chromosomal beta-lactamase can indeed be the sole cause of truncated beta-lactam inhibitory zones.
Anti-Bacterial Agents↗
Multicenter collaborative evaluation of a standardized serum bactericidal test as a predictor of therapeutic efficacy in acute and chronic osteomyelitis.
Forty-eight episodes of osteomyelitis, 30 acute and 18 chronic, were evaluated in a prospective multicenter collaborative study to determine whether a standardized serum bactericidal test could predict outcome of infection. All centers used a microdilution test method that defined the recognized important test variables, including inoculum size, culture medium, dilution technique, incubation time, method of subculture, and bactericidal endpoint. In patients with acute osteomyelitis, peak serum bactericidal titers had no predictive value; however, trough titers of 1:2 or greater accurately predicted cure, whereas trough titers of less than 1:2 predicted therapeutic failure. In patients with chronic osteomyelitis, peak serum bactericidal titers of 1:16 or greater and trough titers of 1:4 or greater accurately predicted cure, whereas peak titers of less than 1:16 and trough titers of less than 1:2 accurately predicted failure. It is concluded that this standardized serum bactericidal test provides good prognostic information in patients with osteomyelitis, and it is recommended that patients with acute osteomyelitis have serum bactericidal titers of 1:2 or greater at all times and that patients with chronic osteomyelitis have serum bactericidal titers of 1:4 or greater at all times.
Acute Disease↗
Beta-lactamase induction and aminoglycoside susceptibility in Pseudomonas aeruginosa.
Recent clinical reports have described the emergence of cross-resistance to aminoglycosides during beta-lactam therapy. We therefore studied the effect of imipenem-mediated beta-lactamase induction on the susceptibilities of 92 clinical isolates of Pseudomonas aeruginosa to gentamicin, tobramycin, and amikacin. We performed a disc approximation test to look for truncation by imipenem of the inhibitory zone sizes of the aminoglycosides. We also compared aminoglycoside inhibitory zone sizes of strains grown in the presence and absence of subinhibitory concentrations of imipenem. Finally, we compared aminoglycoside MIC values determined with and without subinhibitory concentrations of imipenem. The results showed that simultaneous emergence of resistance to beta-lactams and aminoglycosides is very rare.
Amikacin↗
Synergistic resistance mechanisms in Pseudomonas aeruginosa.
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Anti-Bacterial Agents↗
The role of the microbiology laboratory in the treatment of infective endocarditis.
The antibiotic era has greatly improved the prognosis for patients with infective endocarditis. The need for bactericidal activity against the infecting organism has created an additional role for the clinical microbiology laboratory. This role involves the selection and performance of the proper in-vitro susceptible tests in order to ensure bactericidal activity. However, there are problems in both the performance and the interpretation of bactericidal tests; these include persisters, the 'paradoxical effect', tolerance and the development of resistance. Technical factors include inoculum size, growth phase of the inoculum, insufficient contact between the test organism and the antimicrobial agent, and the volume of transfer for the count of survivors. Appreciation of these factors is important for the laboratory performing bactericidal tests, which include time-kill curves, minimal bactericidal concentrations and the serum bactericidal test. Of these tests, the serum bactericidal test offers the most logical approach. However, the performance of this test and the interpretation of the results has been controversial. Recent attempts at standardization should allow better utilization. In addition to the serum bactericidal test, the clinical microbiology laboratory can offer time-kill curves and minimal bactericidal activity and can offer serum assays of antibiotics to ensure adequate levels without toxicity. The use of any or all of these methods must be tempered by clinical judgement in each individual case. Application of the proper tests can assist in the optimal therapy of infective endocarditis.
Blood Bactericidal Activity↗
Vancomycin entry into lung lymph in sheep.
The distribution of antibiotics into target tissues is a crucial factor in therapeutic efficacy. To estimate the availability of systemically administered vancomycin to the interstitial fluid in the lung, we have used a sheep model with a chronic pulmonary lymph fistula to collect simultaneously series of plasma and pulmonary lymph specimens during a 6-h period after an intravenous dose of vancomycin (7 mg/kg). After a minor delay in transit from blood to lymph, vancomycin was completely distributed to pulmonary lymph with a ratio of free drug in lymph to free drug in plasma of 0.9. This suggests that vancomycin is an excellent choice for treating pulmonary infections by susceptible organisms.
Animals↗
Bactericidal activity of deptomycin (LY146032) compared with those of ciprofloxacin, vancomycin, and ampicillin against enterococci as determined by kill-kinetic studies.
This study used kill-kinetic methods to provide data on the bactericidal activity of subinhibitory (1/2 X MIC), inhibitory (1 x MIC), and suprainhibitory (4X, 6X, and 8X MIC) concentrations of deptomycin (LY146032) against strains of enterococci compared with those of ciprofloxacin, vancomycin, and ampicillin. Deptomycin was the most active agent tested, as determined by broth microdilution methods, with all strains being inhibited at concentrations less than or equal to 2 micrograms/ml. The kill-kinetic demonstrated that deptomycin had greater activity at all concentrations tested than the other cell wall-active agents; regrowth was seen, however, at lower concentrations. At higher concentrations (6X and 8X MIC), all agents tested demonstrated the same or less bactericidal activity than at 4X MIC, presumably due to the Eagle effect. Nevertheless, these results suggest that further evaluation of deptomycin as a therapeutic agent for serious enterococcal infections is warranted.
Ampicillin↗
Activity of LY146032 compared with that of methicillin, cefazolin, cefamandole, cefuroxime, ciprofloxacin, and vancomycin against staphylococci as determined by kill-kinetic studies.
Kill-kinetic methods were used to provide data on the bactericidal activity of subinhibitory (0.5x MIC), inhibitory (1x MIC), and suprainhibitory (4x MIC) concentrations of LY146032 against methicillin-susceptible and -resistant Staphylococcus aureus and Staphylococcus epidermidis. These bactericidal activities were compared with those of methicillin, cefazolin, cefamandole, cefuroxime, ciprofloxacin, and vancomycin. LY146032 was among the most active of the antistaphylococcal agents tested, as determined by broth microdilution methods, with all strains being inhibited at concentrations of less than or equal to 1 microgram/ml. Time kill-kinetic studies demonstrated that at 4x MIC, LY146032 was rapidly bactericidal against all strains of staphylococci. Our data show that LY146032 has significant bactericidal activity against staphylococci in comparison with other antistaphylococcal agents. Further evaluation of LY146032 against serious staphylococcal infections is warranted.
Anti-Bacterial Agents↗