Biomedical subjects

C Carbon

Publications and source records attributed to C Carbon.

At least 37 records · Page 2Linked to original sources

PubMed2001

Consequences of VanE-type resistance on efficacy of glycopeptides in vitro and in experimental endocarditis due to Enterococcus faecalis.

The consequences on glycopeptide activity of low-level resistance to vancomycin due to VanE-type resistance were evaluated in vitro and in experimental endocarditis caused by Enterococcus faecalis BM4405 (MICs of vancomycin and teicoplanin: 16 and 0.5 microg/ml, respectively), its susceptible derivative BM4405-1, and susceptible E. faecalis JH2-2. After 24 h of incubation, vancomycin at 8 microg/ml was not active against E. faecalis BM4405 whereas it was bacteriostatic against strains BM4405-1 and JH2-2. Against all three strains, vancomycin at 30 microg/ml and teicoplanin at 8 or 30 microg/ml were bacteriostatic but bactericidal when combined with gentamicin. In rabbits with aortic endocarditis due to VanE-type resistant strain BM4405, treatment with a standard dose of vancomycin generated subinhibitory plasma concentrations (i.e., peak of 36.3 +/- 2.1 microg/ml and trough of 6.0 +/- 2.2 microg/ml) and led to no significant reduction in mean aortic valve vegetation counts compared to no treatment of control animals. In contrast, a higher dosing regimen of vancomycin (i.e., resulting in a peak of 38.3 +/- 5.2 microg/ml and a trough of 15.0 +/- 8.3 microg/ml), providing plasma concentrations above the MIC for the entire dosing interval, led to significant and similar activities against all three strains, which were enhanced by combination with gentamicin. Treatment with teicoplanin led to results similar to those obtained with vancomycin at a high dose. No subpopulations with increased resistance to glycopeptides were selected in vitro or in vivo. In conclusion, the use of a high dose of vancomycin was necessary for the treatment of experimental enterococcal endocarditis due to VanE-type strains.

Animals↗

PubMed2001

Differential selection of multidrug efflux mutants by trovafloxacin and ciprofloxacin in an experimental model of Pseudomonas aeruginosa acute pneumonia in rats.

The ability of trovafloxacin and ciprofloxacin to select efflux mutants in vivo was studied in a model of acute Pseudomonas aeruginosa pneumonia in rats. Twelve hours after intratracheal inoculation of 10(6) CFU of P. aeruginosa strain PAO1 enmeshed in agar beads, two groups of 12 rats were treated by three intraperitoneal injections of each antibiotic given every 5 h. Dosing regimens were chosen to obtain a comparable area under the concentration-time curve from 0 to infinity/MIC ratio of 27.9 min for trovafloxacin (75 mg/kg of body weight) and of 32.6 min for ciprofloxacin (12.5 mg/kg). Twelve rats were left untreated and served as controls. Rats were sacrificed 12 h after the last injection (34 h after infection) for lung bacteriological studies. Selection of resistant bacteria was determined by plating lung homogenates on Trypticase soy agar plates containing antibiotic. In untreated animals, the frequency of resistant colonies was 10-fold higher than in agar beads. Compared to controls, both treatment regimens resulted in a 2-log reduction of lung bacterial load. The frequency of resistant colonies was 10-fold less with trovafloxacin than with ciprofloxacin at twice the MIC (7.4 x 10(-5) versus 8.4 x 10(-4), respectively) (P < 0.05) and at four times the MIC (6.2 x 10(-4) versus 5.0 x 10(-5), respectively) (P < 0.05). A multidrug resistance phenotype typical of efflux mutants was observed in all 41 randomly tested colonies obtained from treated and untreated rats. In agreement with in vitro results, trovafloxacin and ciprofloxacin preferentially selected MexCD-OprJ and MexEF-OprN overproducers, respectively. These results demonstrate the differential ability of trovafloxacin and ciprofloxacin to select efflux mutants in vivo and highlight the rapid emergence of those mutants, even without treatment.

Acute Disease↗

PubMed2001

Activities of the combination of quinupristin-dalfopristin with rifampin in vitro and in experimental endocarditis due to Staphylococcus aureus strains with various phenotypes of resistance to macrolide-lincosamide-streptogramin antibiotics.

We evaluated the activities of quinupristin-dalfopristin (Q-D), alone or in combination with rifampin, against three strains of Staphylococcus aureus susceptible to rifampin (MIC, 0.06 microg/ml) and to Q-D (MICs, 0.5 to 1 microg/ml) but displaying various phenotypes of resistance to macrolide-lincosamide-streptogramin antibiotics: S. aureus HM1054 was susceptible to quinupristin and dalfopristin (MICs of 8 and 4 microg/ml, respectively); for S. aureus RP13, the MIC of dalfopristin was high (MICs of quinupristin and dalfopristin for strain RP13, 8 and 32 microg/ml, respectively); and S. aureus HM1054R was obtained after conjugative transfer of macrolide-lincosamide-streptogramin B constitutive resistance to HM1054, and the MIC of quinupristin for this strain was high (MICs of quinupristin and dalfopristin, 64 and 4 microg/ml, respectively). In vitro time-kill curve studies showed an additive effect [corrected] between Q-D and rifampin, at a concentration of four times the MIC, against the three strains. Rabbits with aortic endocarditis were treated 4 days with Q-D, rifampin, or their combination. In vivo, the combination was highly bactericidal and synergistic against strains susceptible to quinupristin (HM1054 and RP13) and sterilized 94% of the animals. In contrast, the combination was neither synergistic nor bactericidal against the quinupristin-resistant strain (HM1054R) and did not prevent the emergence of mutants resistant to rifampin. We conclude that the in vivo synergistic and bactericidal activity of the combination of Q-D and rifampin against S. aureus is predicted by the absence of resistance to quinupristin but not by in vitro combination studies.

Animals↗

PubMed2001

Optimal treatment strategies for community-acquired pneumonia: high-risk patients (geriatric and with comorbidity).

The four major factors predisposing individuals to community-acquired pneumonia (CAP) are chronic obstructive pulmonary disease, congestive heart failure, diabetes, and a high alcohol intake. The elderly are also at increased risk of severe infection. The introduction of fluoroquinolones with increased activity against Streptococcus pneumoniae and other CAP pathogens has been an important development, with recent guidelines recommending the use of respiratory fluoroquinolones as a first-line choice in outpatients with modifying factors, nursing home residents, and hospitalised patients in medical wards. Of the fluoroquinolones currently available that have antipneumococcal activity, levofloxacin is well tolerated and effective. It has been approved by the Food and Drug Administration (FDA) for treatment of CAP and widespread use has shown it to be very safe.

Age Factors↗

PubMed2001

Comparison of side effects of levofloxacin versus other fluoroquinolones.

The side-effect profile of levofloxacin was compared with that of other fluoroquinolones based on European and international data from approximately 130 million prescriptions. Levofloxacin was found to be very safe with a low rate of hepatic abnormalities (1/650,000). In contrast, 140 trovafloxacin-treated patients developed hepatic problems, 14 of which were severe, and 8 required transplantation. The main CNS problems associated with fluoroquinolones include dizziness, convulsions, psychosis, and insomnia. Levofloxacin, ofloxacin, and moxifloxacin reportedly have the lowest potential of inducing central nervous system (CNS) adverse events among the fluoroquinolones currently available. Cardiovascular problems were seen in 1/15 million levofloxacin prescriptions compared to 1-3% of sparfloxacin patients having QTc prolongation of greater than 500 msec. Moxifloxacin was also associated with QTc prolongation when compared to non-fluoroquinolone comparators. Nausea, vomiting, and diarrhoea remain the main adverse drug reactions (ADRs) associated with levofloxacin. However, the ADR rate for levofloxacin is still one of the lowest of any fluoroquinolone at 2% (compared to 2-10% for other fluoroquinolones). Ofloxacin and levofloxacin have a very low phototoxic potential, whereas this is a problem for sparfloxacin, enoxacin, and pefloxacin. The tolerance profile of levofloxacin can be considered to be very good, and better than most, if not all of the fluoroquinolones available.

Anti-Infective Agents↗

PubMed2001

Clinical evaluation of the management of community-acquired pneumonia by general practitioners in France.

STUDY OBJECTIVES: To evaluate the management of community-acquired pneumonia (CAP) by general practitioners (GPs) in terms of clinical efficiency and adherence to official recommendations. DESIGN: Prospective cohort study. SETTING: Community-based study from 11 French counties. PATIENTS: Adult patients clinically suspected of having CAP who were seen by GPs were included after confirmation of the presence of an infiltrate on chest radiographs. INTERVENTION: The management of the patients was left to the discretion of the GP. MEASUREMENTS AND RESULTS: One hundred thirty patients were included in the study, and 13 patients (10%) were immediately hospitalized because of the severity of the pneumonia. The remaining 117 patients were treated as outpatients: 108 of 117 patients (92%) were cured, and 9 patients were subsequently hospitalized because of the failure of ambulatory treatment. Diagnostic error (n = 6) rather than antibiotic failure (n = 3) was the most frequent cause of the failure of ambulatory treatment. Only 40% of the patients received an initial antibiotic treatment that was in agreement with French recommendations. However, the rate of antibiotic failure leading to hospitalization was low (3 of 117 patients; 2.6%) and similar for patients treated or not according to recommendations (p > 0.5). Overall, five patients (4%) died; all deaths occurred during hospitalization and were related to the severity of the underlying disease but not to the choice of antibiotic treatment. CONCLUSIONS: The management of CAP by GPs was clinically effective despite a poor adherence to official recommendations. Our results suggest that adequate assessment of severity rather than adherence to recommendations for antibiotic treatment had an impact on clinical outcome of CAP managed by GPs.

AIDS-Related Opportunistic Infections↗

PubMed2000

[Telithromycin, a once-a-day ketolide in the treatment of community acquired pneumonia].

KETOLIDES: The principal advantage of this series of original compounds elaborated from macrolides is their activity against pneumococci and against macrolide-resistant streptococci while preserving the remainder of the macrolide spectrum of activity, particularly for intracellular germs. TELITHROMYCIN: To date, the main indications have been assessed in adults: pneumonia, super-infection of chronic bronchitis, sinusitis and pharyngitis. The recommended dose is 800 mg once a day. The safety of this dose has been validated for patients treated for 7 to 10 days for community-acquired pneumonia. CONTRIBUTION TO CURRENT STRATEGIES: Should telithromycin be proposed as first line treatment for community-acquired respiratory tract infections or should it be used as an alternative treatment for situations where no other antibiotic can be used?

Anti-Bacterial Agents↗

PubMed2000

[Undergraduate medical education. Students' perspective and medical school policy].

OBJECTIVES: Student attendance to lectures in French medical schools is often poor. We surveyed undergraduate medical students in our medical school, repeating a similar survey conducted ten years earlier. The results are presented with the conclusions of the faculty seminar that followed this survey. METHODS: A closed item questionnaire was distributed in June, 1998, through the hospital wards where the students were posted. After two reminders, the final response rate was 71% (247/348). RESULTS: Overall, 71% of the students declared that they never, or only occasionally, attended lectures in the medical school. Reasons included lack of time (75%), the curriculum diverging from the program of the selective examination that gives access to graduate specialization programs (59%), or insufficient practical clinical content (36%); 46% believed that this teaching prepared them to practice family medicine (11% some specially), and 92% that the way it was organized was not compatible with preparing for the selective examination. On the other hand, 75% of the students in the final two years of the curriculum declared that attending regularly special preparation seminars for the selective examination, to succeed at this test (91%), but also to prepare for family practice (25%). Respectively, 75%, 68% and 66% declared that undergraduate medical courses should, ideally, prepare them for the selective examination, but also for the practice of family medicine, and for graduate medical education. CONCLUSIONS: These results echoed the difficulties of the faculty of the medical school to reconcile preparing students both for their future medical practice and for the selective examination. Two working groups were asked to identify independently appropriate educational objectives according to each perspective: their conclusions appeared to be quite compatible. Based on these conclusions, institutional objectives were ratified to guide the educational policy of our medical school, including the following: to reinforce the consistency and progressiveness of the curriculum; to promote active and autonomous student learning approaches; to develop faculty teaching skills, curriculum evaluation and recognition of teaching activities.

Curriculum↗

PubMed2000

MRSA and MRSE: is there an answer?

Explore the source record for details and available documents.

Anti-Bacterial Agents↗

PubMed2000

Dramatic improvement of renal dysfunction in a human immunodeficiency virus-infected woman treated with highly active antiretroviral therapy.

We report a single case documenting substantial improvement in the course of human immunodeficiency virus (HIV)-associated, biopsy-proven nephropathy after introduction of highly active antiretroviral therapy. Our case report joins several others recording improvement or stabilization in the course of nephropathy following better control of HIV replication.

Adult↗

PubMed2000

Antibiotic use in developing countries.

Antimicrobials have been used successfully for over 6 decades, but genes expressing resistance to them have emerged in strains of bacteria and have disseminated through the global ecosystem to reach infecting microorganisms, produce disease, and seriously interfere with therapy, allowing infections to progress and kill despite antibiotic administration. The upsurge in prevalence of such resistance genes in the bacterial population that colonize and infect humans involves two processes, emergence and dissemination, in both of which there have been contributions from the developing world, where resistance is common and increasing. The emergence of pneumococcal isolates noted in Papua New Guinea and later in South Africa that 1 decade later spread to most of the world and the intercontinental spread between the United States and Venezuela of a new gentamicin resistance gene carried on an epidemic plasmid are examples of the ability of bacteria to travel freely, without regard to borders. Complex societal issues such as the misuse of antibiotics by physicians, pharmacists, and the public; the suboptimal quality of the drugs (emergence); and conditions such as crowding, lack of hygiene, poor or nonexistent hospital infection control practices, or insufficient surveillance (dissemination) play a largely unmeasured role that requires study and solutions. In the meantime, we may intervene to delay the emergence of resistance and to limit its spread by promoting the judicious use of antibiotics both at the local level as well as from multinational organized cooperative efforts. Education and improvement of surveillance and socioeconomic conditions are integral parts of any solution strategy.

Anti-Bacterial Agents↗

PubMed2000

In vivo activity of levofloxacin alone or in combination with imipenem or amikacin in a mouse model of Acinetobacter baumannii pneumonia.

We evaluated the in vivo activity of levofloxacin alone or in combination with imipenem or amikacin in a mouse model of Acinetobacter baumannii pneumonia using a susceptible strain and one with low-level resistance (MIC/MBC of levofloxacin: 0.06/0.06 and 4/4 mg/L, respectively). As demonstrated previously with other pathogens, the AUC/MIC ratio predicted the efficacy of fluoroquinolones against A. baumannii. This parameter correlated with bactericidal effect and survival. Combination therapy did not enhance the efficacy of levofloxacin.

Acinetobacter Infections↗

PubMed2000

Nuclear factor-kappaB activation in mouse lung lavage cells in response to Streptococcus pneumoniae pulmonary infection.

OBJECTIVES: To assess the state and activation kinetics of the nuclear transcription regulatory protein nuclear factor-kappB (NF-kappaB) in lung lavage cells in a murine pneumococcal pneumonia model and to determine how the virulence of the infecting organisms altered the activation state of NF-kappaB. DESIGN: Experimental, comparative study of three Streptococcus pneumoniae strains that induced three distinct pulmonary diseases. SETTING: Experimental laboratory in a university-based medical center. SUBJECTS: Female BALB/cby mice, 8-10 wks of age. INTERVENTIONS: We randomly divided the mice into the following five groups: a) the control group; b) animals infected by virulent encapsulated S. pneumoniae P4241 strain; c) animals infected by avirulent encapsulated S. pneumoniae P15986 strain; d) animals infected by avirulent unencapsulated S. pneumoniae R6 strain; e) animals infected by virulent lysed S. pneumoniae P4241 strain. Animals were anesthetized and infected by intratracheal delivery of 4 x 10(5) colony-forming units (CFU) of S. pneumoniae per mouse or bacterial components equivalent to 4 x 10(5) CFU for lysed S. pneumoniae challenge. After intratracheal challenge with virulent encapsulated strain P4241, mice developed acute pneumonia, became bacteremic, and died within 3 to 5 days. None of the mice infected with the avirulent encapsulated strain P15986 or the avirulent unencapsulated strain R6 died. After collection of lung lavage cells and nuclear extraction, NF-kappaB activation was determined 1 hr, 4 hrs, 6 hrs and 24 hrs after pneumococcal infection. At the same time, pulmonary and blood clearance, bronchoalveolar lavage cells population, and tumor necrosis factor-alpha production were assessed (six mice per time point). MEASUREMENTS AND MAIN RESULTS: NF-kappaB was constitutively expressed within nuclear extracts of lung lavage cells from uninfected control mice. A significant increase in NF-kappaB activation was detected within 1 hr after injection of virulent lysed S. pneumoniae P4241 strain (bacterial components equivalent to 4 x 10(5) CFU), and was still present 24 hrs after the injection. After live pneumococcal challenge, significant NF-kappaB activation was detected within 4 hrs with a peak at 24 hrs. Responses to all three strains (P4241, P15986 and R6) were time-dependent (p < .0001), as NF-kappaB activation gradually increased during the first 24 hrs. Moreover, compared with the control uninfected mice, the intensity of the retarded KB oligonucleotide, as determined by densitometry, was increased approximately four- to five-fold and seven-fold in reactions containing nuclear extracts isolated 24 hrs after infection with the avirulent strains P15986 or R6 and the virulent strain P4241, respectively. With the virulent strain P4241, responses were significantly stronger than with the avirulent strains P15986 and R6 (p < .01). Responses were of similar order with avirulent strains P15986 and R6 (p > .05). CONCLUSION: Pulmonary infection by S. pneumoniae induced delayed and time-dependent activation of NF-kappaB in mouse lung lavage cells. The degree of NF-kappaB activation in lung lavage cells correlated with the virulence of the infecting organisms. Our results suggest that the more severe the infection, the higher the rise in NF-kappaB.

Animals↗

PubMed2000

Activity of LY333328 combined with gentamicin in vitro and in rabbit experimental endocarditis due to vancomycin-susceptible or -resistant Enterococcus faecalis.

We investigated the activity of LY333328 alone and combined with gentamicin, both in vitro and in a rabbit model of experimental endocarditis, against the susceptible strain Enterococcus faecalis JH2-2 and its two glycopeptide-resistant transconjugants, BM4316 (VanA) and BM4275 (VanB). MICs of LY333328 and gentamicin were 2 and 16 microgram/ml, respectively, for the three strains. In vitro, LY333328 alone was bactericidal at 24 h against JH2-2 at a concentration of 2 microgram/ml and against BM4316 and BM4275 at a concentration of 30 microgram/ml. The combination of LY333328 and gentamicin (4 microgram/ml) was synergistic and bactericidal after 24 h of incubation against the three strains at LY333328 concentrations of 2 microgram/ml for JH2-2 and 8 microgram/ml for BM4275 and BM4316. The combination of LY333328 and gentamicin was the only regimen demonstrating in vitro bactericidal activity against BM4316. In vivo, intravenous treatment with LY333328 alone, providing peak and trough serum levels of 83.3 +/- 1.3 and 3.8 +/- 0.2 microgram/ml, respectively, was inactive against BM4316 and BM4275 and selected mutants resistant to LY333328 in half of the rabbits infected with the VanA-type strain (MICs, 8 to 20 microgram/ml). However, the LY333328-gentamicin combination was active against the three strains and prevented the emergence of mutants resistant to both components of the combination. We conclude that the LY333328-gentamicin combination might be of interest for the treatment of enterococcal infections, particularly against VanA-type strains.

Animals↗

PubMed2000

Influence of resistance to streptogramin A type antibiotics on the activity of quinupristin-dalfopristin in vitro and in experimental endocarditis due to Staphylococcus aureus.

We evaluated the activity of quinupristin-dalfopristin (Q-D) against three clinical strains of Staphylococcus aureus susceptible to Q (MIC, 8 microg/ml) and Q-D (MICs, 0.5 to 1 microg/ml) but displaying various levels of susceptibility to D. D was active against S. aureus HM 1054 (MIC, 4 microg/ml) and had reduced activity against S. aureus RP 13 and S. aureus N 95 (MICs, 32 and 64 microg/ml, respectively). In vitro, Q-D at a concentration two times the MIC (2xMIC) produced reductions of 4.3, 3.9, and 5.8 log(10) CFU/ml after 24 h of incubation for HM 1054, RP 13, and N 95, respectively. Comparable killing was obtained at 8xMIC. Q-D-resistant mutants were selected in vitro at a frequency of 2 x 10(-8) to 2 x 10(-7) for the three strains on agar containing 2xMIC of Q-D; no resistant bacteria were detected at 4xMIC. Rabbits with aortic endocarditis were treated for 4 days with Q-D at 30 mg/kg of body weight intramuscularly (i.m.) three times a day (t.i.d.) or vancomycin at 50 mg/kg i.m. t.i.d. In vivo, Q-D and vancomycin were similarly active and bactericidal against the three tested strains compared to the results for control animals (P < 0.01). Among animals infected with RP 13 and treated with Q-D, one rabbit retained Q-D-resistant mutants that were resistant to Q and to high levels of D (MICs, 64, >256, and 8 microg/ml for Q, D, and Q-D, respectively). We conclude that the bactericidal activity of Q-D against strains with reduced susceptibility to D and susceptible to Q-D is retained and is comparable to that of vancomycin. Acquisition of resistance to both Q and D is necessary to select resistance to Q-D.

Animals↗

PubMed2000

Relationship between capsular type, penicillin susceptibility, and virulence of human Streptococcus pneumoniae isolates in mice.

We examined the relationship between penicillin susceptibility, peritoneal virulence in Swiss mice, and capsular type in a selection of 122 clinical Streptococcus pneumoniae isolates belonging to 24 serotypes. Regardless of the serotype, all 32 virulent strains were susceptible to penicillin, and all 41 strains with diminished susceptibility or resistance to penicillin were avirulent. The remaining 49 strains were both susceptible to penicillin and avirulent, irrespective of the serotype. On the basis of their capsular type and pathogenic behavior, strains fell into one of four groups. In the group consisting of serotypes 1, 3, and 4 (n = 16), strains were predominantly virulent (81.3%), and all were penicillin susceptible. In the serotype 6 group (n = 32), the frequency of virulence was significantly lower (34.4 versus 81.3%, P = 0.002), and strains were predominantly penicillin susceptible (71.9%). In the group composed of serotypes 9, 14, 19, and 23 (n = 50), all strains were avirulent, and 56% had decreased susceptibility (n = 12) or resistance to (n = 16) penicillin. The fourth group was heterogenous, as it pooled 24 strains of 15 different serotypes; in this group the frequency of virulence was 33.3%, and strains were predominantly penicillin susceptible (83.3%). These data point to a complex relationship between penicillin susceptibility and virulence in mice but do not entirely separate these characteristics from the role of the capsular type. The possibility that the mechanisms conferring penicillin resistance are related to those leading to a loss of virulence is supported by these findings.

Animals↗

PubMed2000

Monotherapy with a broad-spectrum beta-lactam is as effective as its combination with an aminoglycoside in treatment of severe generalized peritonitis: a multicenter randomized controlled trial. The Severe Generalized Peritonitis Study Group.

In a randomized trial conducted in 35 centers, we compared the clinical efficacy and safety of piperacillin plus tazobactam (TAZ) alone (monotherapy [MT]) versus those of TAZ combined with amikacin (AMK) (combined therapy [CT]) for the treatment of severe generalized peritonitis (SGP). Primary analysis consisted of blind assessment by an independent committee of the failure rate 30 days after the end of treatment in the modified intent-to-treat (ITT) analysis (mITT) population. Of the 241 patients with suspected SGP randomized into the study, 227 were eligible for ITT analysis, including 204 (99 in the MT group and 105 in the CT group) with confirmed SGP (mITT population). A total of 159 patients were eligible for per-protocol (PP) analysis. The clinical failure rates were equivalent in the mITT and PP populations (MT versus CT): 56 versus 52%, (odds ratio [OR] 0.87, 90% confidence interval [CI] = 0. 6 to 1.27) for mITT and 49 versus 49% (OR = 1.03, 90% CI = 0.67 to 1. 59) for PP analysis. Mortality rates (ITT population, 19%; PP population, 21%) and overall adverse event rates (ITT population, 55%; PP population, 54%) were also similar. Six patients (three in MT group and three in the CT group) developed acute renal failure. In conclusion, the addition of AMK to TAZ does not seem to be necessary for the treatment of SGP, even after adjustment for the simplified acute physiology score (SAPS II) and type of SGP.

Adolescent↗

PubMed2000

Bactericidal activity of gentamicin against Enterococcus faecalis in vitro and in vivo.

The activity of gentamicin at various concentrations against two strains of Enterococcus faecalis was investigated in vitro and in a rabbit model of aortic endocarditis. In vitro, gentamicin at 0.5 to 4 times the MIC failed to reduce the number of bacteria at 24 h. Rabbit or human serum dramatically increased gentamicin activity, leading to a >/=3-log(10) CFU/ml decrease in bacterial counts when the drug concentration exceeded the MIC. Susceptibility testing in the presence of serum was predictive of in vivo activity, since gentamicin alone significantly reduced the number of surviving bacteria in the vegetations if the peak-to-MIC ratio was greater than 1. However, gentamicin selected resistant mutants in rabbits. The intrinsic activity of gentamicin should be taken into account in evaluation of combinations of gentamicin and cell wall-active agents against enterococci.

Animals↗