Antimicrobial action and pharmacokinetics/pharmacodynamics: the use of AUIC to improve efficacy and avoid resistance

In in-vitro and in animal models, antibiotics show good relationships between concentration and response, when response is quantified as the rate of bacterial eradication. The strength of these in-vitro relationships promises their utility for dosage regimen design and predictable cure of human infections. Resistance is also predictable from these parameters, fostering a rational means of using dosing adjustments to avoid or minimize the development of resistant organisms. Newly developed computerized methods for the quantitation of susceptibility allow testing of integrated kinetic-susceptibility models in patients. Our attention has focused recently on fluoroquinolones, since they are relatively non-toxic and provide the necessary range of dosage needed to elucidate correlations between concentration and response in the Intensive Care Unit patient. Studies conducted in patients with nosocomial gram-negative pneumonia reveal good correlations between bacterial eradication and integration of concentration with bacterial susceptibility. In patients, the best correlation parameters are time over MIC, and the ratio of 24-hour AUC to MIC (AUIC). Patients with serious infections like nosocomial pneumonia require bactericidal antimicrobial activity. Studies in our laboratory demonstrate that the minimum effective antimicrobial action is an area under the inhibitory titer (AUIC) of 125, where AUIC is calculated as the 24-hour serum AUC divided by the MIC of the pathogen. This target AUIC may be achieved with either a single antibiotic or it can be the sum of AUIC values of two or more antibiotics. There is considerable variability in the actual AUIC value for patients when antibiotics are given in their usually recommended dosages. Examples of this variance will be provided using aminoglycosides, fluoroquinolones, beta-lactams, macrolides and vancomycin. The achievement of minimally effective antibiotic action, consisting of an AUIC of at least 125, is associated with bacterial eradication in about 7 days for beta-lactams and quinolones. When AUIC is increased to 250, the quinolone ciprofloxacin (which displays in vivo concentration dependent bacterial killing) can eliminate the bacterial pathogen in 1-2 days. Beta lactams, even when dosed to an AUIC of 250, often require longer treatment duration to eliminate the bacterial pathogen, because the in vivo bacterial killing rate is slower with beta-lactams than with the quinolones. This remains true even at AUIC values of 250 for both compounds, which is theoretically identical dosing. Antibiotic activity indices allow clinicians to evaluate individualized patient regimens. Furthermore, antibiotic activity is a predictable clinical endpoint with predictable clinical outcome. This value is also highly predictive of the development of bacterial resistance. Antimicrobial regimens that do not achieve an AUIC of at least 125 cannot prevent the selective pressure that leads to overgrowth of resistant bacterial sub-populations. Indeed, there is considerable anxiety that conventional respiratory tract infection management strategies, which prescribe antibacterial dosages that may attain AUIC values below 125, are contributing to the pandemic rise in bacterial resistance levels.     

A Review of the Antimicrobial Activity of the Fluoroquinolones

Summary

The evolution of the fluoroquinolones is described, and structure-activity relationships outlined. The in-vitro antimicrobial activities of ciprofloxacin, enoxacin, norfloxacin, ofloxacin and pefloxacin against a wide range of organisms are critically reviewed. In-vitro factors influencing fluoroquinolone activity are discussed. Reports of the acquisition of resistance to the fluoroquinolones are evaluated. Finally, possible future directions for this group of antibiotics are discussed.     

The Integration of Four Major Determinants of Antibiotic Action: Bactericidal Activity,Postantibiotic Effect,Susceptibility, and Pharmacokinetics

Abstract

A functional pharmacokinetic/pharmacodynamic (PK/PD) index that could simultaneously describe three controlling PD variables, i.e., bactericidal activity, postantibiotic effect (PAE), and susceptibility, in relation to pharmacokinetics, was designed using an in vitro kinetic model. Tobramycin was tested against one standard and five clinical strains of Pseudomonas aeruginosa. The organisms showed minimum inhibitory concentrations (MICs) ranging between 1 and >1000 μg/ml. The model allowed antibiotic concentrations to be reduced exponentially from initial concentrations at fixed multiples of MIC. Antibiotic removal was performed when the decreasing concentrations hit the MIC of individual strain to provide a wide range of AUC_>MIC within an identical frame of AUC_>MIC/MIC (AUIC) values. Viable counts were measured at antibiotic addition and before/after its removal for bactericidal activity and PAE assessments. A linear relationship was observed between PAE and bactericidal rate constants, though the pattern varied among different strains. Characterization of the exposure (AUC_>MIC)-effect relationships using the E_max model revealed that the less susceptible strains displayed lower E_max and higher EC₅₀ for both antimicrobial effects. By employing the AUIC as a common frame of reference, regression analysis showed a significant linear correlation (p<0.05) between the mean PAE and bactericidal rate data and, thereby simultaneously defining the four contributing factors of the PK/PD system. It appears that the AUIC, by conveying the pharmacokinetic and susceptibility information, could serve as a PK/PD index in bridging the interdependency of PAE and bactericidal activity. More importantly, the collective assessment of these four factors would allow more optimal evaluation of dosage regimens.     

Cefaclor: A Contemporary Look at Susceptibility of Key Pathogens from Around the Globe

Abstract

The orally administered cephalosporin antibiotic, cefaclor, has been available for clinical use in many countries since 1979. Because widespread antibiotic use is often cited as a factor in the emergence of bacterial resistance to antibiotics, we sought to determine the degrees of resistance to cefaclor expressed by key pathogens recently isolated in 10 countries widely distributed around the world. Using the E-test ®, minimal inhibitory concentrations (MIC) were determined for cefaclor and several comparator antibiotics against approximately 700 fresh clinical isolates of each of six bacterial species. The results demonstrated that > 90% of Haemophilus influenzae (β-lactamase producing and non-producing), Haemophilus parainfluenzae (β-lactamase producing and non-producing), Moraxella catarrhalis (> 90% β-lactamase producing), and methicillin-susceptible Staphylococcus aureus, and 85% of Escherichia coli were susceptible to cefaclor at the NCCLS interpretive breakpoints. MIC distributions showed that there has been no change in the activity of cefaclor against penicillin-susceptible strains of Streptococcus pneumoniae since 1977.     

High-Dose Intravenous Fluoroquinolones in the Treatment of Severe Infections

Abstract

A bacterial infection should be considered “serious” in case of underlying disease, nosocomial origin, antibiotic resistant pathogen, and/or poor delivery of antibiotics at the site of infection. Treatment of most serious infections requires parenteral administration of antimicrobial agents. Intravenous fluoroquinolones are a class of antimicrobial agents from which physicians must choose when treating nosocomial infections. Fluoroquinolones are bactericidal antimicrobial agents that act by inhibiting DNA gyrase. They are active in vitro against most Gram-negative bacteria and methicillin-susceptible staphylococci. Activity against anaerobic bacteria and streptococci is poor. The rapid development of bacterial resistance in centers with high quinolone usage is of great concern. Resistance develops most commonly in Pseudomonas aeruginosa and staphylococci. Most clinical trials with ciprofloxacin, ofloxacin, pefloxacin, the fluroquinolones currently available in France for parenteral use, are almost 10 years old. There are few studies with higher dosage and most of them have been carried out with ciprofloxacin. The findings of these studies indicate that higher dosage regimens of i.v. ciprofloxacin are much more effective against severe nososcomial infections than is the dosage of 200 mg twice daily. The higher dosage regimens resulted in greater rates of clinical cure and improvement in both monomicrobial and polymicrobial infections. Although the overall frequency of side effects to fluoroquinolones is low, seizures and allergic reactions have been attributed to their use.     

What is the role of fluoroquinolones in intensive care?

Fluoroquinolones are a class of antibiotics that are widely used in the treatment of a number of severe infections frequently observed in intensive care units (ICU). From a pharmacodynamic point of view, the optimal conditions for guaranteeing clinical recovery and preventing the occurrence of resistance to this class of antibiotics are represented by the ratios of C(max)/MIC > 12.2 and AUC(24h)/MIC equal to 100-125 hours for Gram-negative bacteria, and about 30-40 hours for Gram-positive cocci. Taking this into consideration, the pharmacokinetics and pharmacodynamics shown in healthy volunteers suggest that with the use of standard doses of the various fluoroquinolones, an optimal AUC(free)/MIC ratio for Gram-negative bacteria may be ensured with a minimum inhibitory concentration (MIC) < 0.25-0.5 mg/L and for Gram-positive bacteria with an MIC < 0.5-1 mg/L. The need to increase the dosage, or to combine them with other antibiotics is therefore recognized, when it is necessary to ensure adequate coverage of intermediately sensitive microorganisms (MIC 1-2 mg/L). In addition, patients recovered in the ICU often present some peculiar pathophysiological conditions that increase the distribution volume and/or the renal clearance of the drug. Thus it is likely that in this situation it would be reasonable to increase daily dosages, independent of the in vitro pattern of drug sensitivity (e.g. 500 mg b.i.d. for levofloxacin). Data from various clinical and pharmacological studies suggesting a potential role for fluoroquinolones both in monotherapy and combination therapy in the treatment of different clinically severe conditions are presented and discussed. This offers the dual opportunity to evaluate the role of quinolones as an alternative to aminoglycosides in combination with a beta-lactam and, at the same time, to consider their use in a periodic rotation program of anti-Gram-negative antibiotic therapy when there is a high risk of resistance selection, such as in the ICU. In conclusion, the role of fluoroquinolones in the treatment of multiple infectious diseases, such as bacteremia/sepsis, pneumonia and severe urinary tract infections in an environment such as the ICU is growing stronger, while there are convincing data indicating that these molecules might play a role in the treatment of meningitis in the near future.     

Hepatocyte growth factor protects the liver against hepatitis C virus in patients on regular hemodialysis

Abstract

Propolis is produced by bees and is reported to have several pharmaceutical properties. Its antibacterial activity against strains causing upper respiratory tract infections is particularly important: Propolis might be used as a therapeutic agent to prevent the bacterial infections that sometimes overlap viral infections.

In this study the in vitro activity of both an alcoholic solution and a hydroglyceric extract of Propolis as well as its active principles, was tested against bacteria responsible for respiratory infections (Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis and Streptococcus pyogenes).

We also evaluated the in vitro activity of a combination of propolis and its active principles and some beta-lactams, macrolides and fluoroquinolones. Our results, though not demonstrating a clearly synergistic activity between antibiotics and Propolis and its constituents, show the possibility of using natural preparations, due to their antimicrobial and anti-inflammatory properties, to enhance antibacterial therapy.     

Pharmacological aspects of the antibiotics used for urological diagnostic procedures

Abstract

Surgical antimicrobial prophylaxis is the use of an antibiotic before, during, or shortly after a urological procedure to prevent postoperative infections such as urinary tract or wound infection. The optimal antimicrobial drug must be microbiologically active against the most frequent potential pathogens and have good pharmacological properties.

Correct timing of antimicrobial prophylaxis is the first critical issue in determining treatment efficacy. The antibiotic must be administered before the start of the surgical procedure in order to ensure a high tissue level at the time of microbial contamination. If using an oral antibiotic, this must be administered 1–3 hours before the operation and a parenteral antibiotic should be administered at the induction of anaesthesia.

The antibiotics potentially useful for antimicrobial prophylaxis are the beta-lactams, cotrimoxazole, fluoroquinolones, and fosfomycin trometamol. The criteria for choosing the optimal antibiotic include an appropriate antimicrobial spectrum, favourable pharmacokinetic parameters (especially good tissue penetration), and elevated safety or tolerability. The use of cotrimoxazole must be restricted due to increasing chemoresistance. Unfortunately fluoroquinolone-based regimens, once the mainstay of prophylaxis guidelines, are increasingly ineffective due to a constant increase in multidrug-resistant (MDR) Gram-negative bacteria. The same concerns apply with regard to the second and third generation cephalosporins that have problems of resistance and, if administered orally, do not sufficiently penetrate prostatic tissue. An appropriate beta-lactam could be an aminopenicillin combined with a beta-lactamase inhibitor.

Fosfomycin trometamol can also be a good potential choice due to its elevated activity against MDR Gram-negative bacteria and its favourable pharmacokinetic parameters, including an elevated penetration into prostatic tissue.     

Natural Antibiotic Susceptibility of Ewingella americana Strains

Abstract

The natural susceptibility of 20 Ewingella americana strains to 72 antibiotics was examined. MIC values were determined using a microdilution procedure in cation-adjusted Mueller-Hinton broth. Evaluation of natural antibiotic susceptibility was performed applying the German standard (where applicable). β-Lactamases were examined with a conventional nitrocefin colony testing procedure, activity and induction assays, and SDS-PAGE. Ewingella strains were naturally resistant or of intermediate susceptibility to cefaclor, loracarbef, cefazoline, cefuroxime, cefoxitin, benzylpenicillin, oxacillin, fosfomycin, erythromycin, roxithromycin, clarithromycin, lincosamides, dalfopristin-quinupristin, ketolides, linezolid, glycopeptides, fusidic acid and rifampicin. Uniform natural sensitivity was found with acylureidopenicillins except for azlocillin, ticarcillin, several cephalosporins, carbapenems, aztreonam, tetracyclines, aminoglycosides, quinolones, azithromycin, folate-pathway inhibitors and chloramphenicol. Strains of E. americana were naturally sensitive or of intermediate susceptibility to aminopenicillins (with and without β-lactamase inhibitors), azlocillin and nitrofurantoin. All ewingellae yielded β-lactamases; testing of representative strains revealed that these enzymes belong to Ambler class C. Inducibility of β-lactamase was shown for E. americana ATCC 33852^T, CCUG 35675 and CCUG 42782.

The present study describes a database concerning the natural susceptibility of E. americana strains to a range of antibiotics, which can be applied to validate forthcoming antibiotic susceptibility tests of these bacteria. It enlarges the number of Enterobacteriaceae expressing naturally-occurring AmpC β-lactamases.     

Oral Ciprofloxacin for Treatment of Acute Bacterial Pharyngotonsillitis

Summary

The clinical efficacy and tolerability of ciprofloxacin orally administered at the dosage of 250 mg twice a day was evaluated in 25 patients affected by acute bacterial pharyngotonsillitis. All patients were non-responders to previous conventional antibiotic therapies due to in vitro resistance of the responsible bacteria, or possibly the low antibiotic concentration at the infection site. None of the patients had infections caused by group A β-haemolyticus streptococcus. Treatment with ciprofloxacin lasted for 5-10 days (mean 6.7). A favorable clinical response was observed in 92% of patients (15 resolutions and 7 improvements) at the end of the therapy and two weeks later (follow-up). One patient was not evaluable because of the unfortunate onset of glossitis that caused the interruption of the treatment. No other side-effects were recorded in the other 24 patients. The bacteriological response was excellent: 83% bacteriological eradication, 13% persistence and superinfection in only one patient (4%).

Ciprofloxacin administered orally at low dosages is highly effective in the treatment of bacterial pharyngotonsillitis and is also well tolerated.     

Antibiotic Resistance and Adherence Properties of Hafnia alvei Clinical Isolates: A 19-Month Study in the Hospital of Orléans,France

Abstract

We studied the epidemiology of antibiotic resistance and adherence properties among all Hafnia alvei clinical isolates collected from August 2003 to February 2005 from patients hospitalized in the hospital of Orléans, France. The isolates were typed by random amplified polymorphic DNA (RAPD), screened for antibiotic resistance and bacterial adherence to A549 respiratory and T24 bladder cells. Six intestinal, 3 respiratory, and 8 isolates from different body sites were collected. A total of 12 RAPD profiles were found, demonstrating a high genetic diversity. All the isolates were resistant to amoxicillin + clavulanate and cephalothin and sensitive to aminoglycosides, fluoroquinolones, cefepime and imipenem. Six isolates had a high-level and constitutive cephalosporinase production phenotype. Three independent isolates were resistant or had intermediate sensitivity to nalidixic acid, sulfonamide and trimethoprim or chloramphenicol. All the isolates adhered efficiently to the two cell lines with a higher effectiveness of adherence to bladder cells. The respiratory isolates adhered more efficiently to epithelial cells than intestinal isolates. No relationship was found between antibiotic resistance phenotypes, adherence properties, and RAPD types. In conclusion, H. alvei is an unusual nosocomial pathogen with little acquired antibiotic resistance able to adhere to human epithelial cells from different human body compartments.     

Antibiotic Susceptibility of Respiratory Pathogens Recently Isolated in Italy: Focus on Cefditoren

Abstract

The aim of this study was to evaluate the in vitro antibiotic susceptibility of respiratory pathogens recently isolated in italy to commonly used antibiotics including cefditoren. Six clinical microbiological laboratories collected, between January and September 2009, a total of 2,510 respiratory pathogens from subjects with community- acquired respiratory tract infections (CARTI). Cefditoren, out of all the beta-lactams studied, had the lowest MIC₉₀ against 965 strains of Streptococcus pneumoniae examined, followed by cefotaxime and ceftriaxone (2% resistance in penicillin-resistant S. pneumoniae (PRSP)). Against 470 Haemophilus influenzae, independently of their production of beta-lactamases or ampicillin resistance, cefditoren was the oral cephalosporin with the best in vitro activity, comparable to that of the injectable cephalosporins and levofloxacin. Higher MIC₉₀s were found for the macrolides (4 - 16 mg/L) and cefaclor (4 - 32 mg/L). As was foreseeable, Streptococcus pyogenes (225 strains) was uniformly sensitive to all the beta-lactam antibiotics, but the elevated miC90 values reduced (<75%) susceptibility of this pathogen to macrolides. Beta-lactamase-negative Moraxella catarrhalis (100 strains) had reduced susceptibility only to the macrolides, while the 250 beta-lactamase-producing strains also had reduced susceptibility to cefuroxime. Levofloxacin showed the lowest MIC₅₀/MIC₉₀ values in the producing strains, whereas cefditoren, cefotaxime and ceftriaxone in the non-producers. As regards the enterobacteriaceae, cefditoren and levofloxacin had the lowest MIC₉₀s against Klebsiella pneumoniae. Cefditoren and the third-generation injectable cephalosporins had the lowest MIC₉₀s against Escherichia coli (100% susceptibility) while levofloxacin was less active (86% susceptibility).

In conclusion, cefditoren's wide spectrum and high intrinsic activity, as well as its capacity to overcome most of the resistance that has become consolidated in some classes of antibiotics widely used as empiric therapy for CARTI, allows us to suggest that cefditoren might be included in the european guidelines as one of the first-choice antibiotics in the treatment of CARTI.     

Evaluation of Ciprofloxacin’s Activity against Recent Clinical Isolates

Summary

The in vitro antibacterial activity of ciprofloxacin, a new quinoline carboxylic acid, was tested against 1671 recendy clinically isolated bacterial strains, by measuring the minimum inhibitory concentrations (MIC). Comparisons were made with other quinolones: nalidixic acid, norfloxacin, and other drugs: piperacillin, cefoxitin, cefotetan, ceftazidime, tobramycin, rifampin, tetracycline, chloramphenicol.

Ciprofloxacin was very active against the tested species and was the most active drug against all the bacterial strains, with a geometric mean, a MIC₅₀ and MIC₉₀ of 0.27, 0.12 and 2 μg/ml, respectively.     

Influence of Subinhibitory Concentrations of Ceftazidime,Ciprofloxacin and Azithromycin on the Morphology and Adherence of P-Fimbriated Escherichia coli

Abstract

The influence of subinhibitory concentrations (1/2, 1/4, 1/8, 1/16 and 1/32 × MIC) of ceftazidime, ciprofloxacin and azithromycin on the morphology and adherence of 29 wild-type P-fimbriated strains of Escherichia coli was studied. Bacterial adherence to the Buffalo green monkey (BGM) cell line was tested before and after treatment with antibiotics and detected by means of an immunofluorescence staining. Significant dose dependent reduction of bacterial adherence was observed, which correlated with the alterations in bacterial cell morphology. After exposure of strains to sub-MICs of antibiotics, normal shapes, spherical forms and filaments were noted. The greatest filamentation and the greatest loss of adherence ability occurred at 1/2 × MIC of ceftazidime. Treatment with sub-MICs of ciprofloxacin resulted in shorter filaments, while filamentation did not occur after bacterial exposure to sub-MICs of azithromycin. Azithromycin was least damaging to the adherence ability of E.coli and at a concentration of 1/2 × MIC caused globoid cell formation.     

In- Vitro Sensitivity of Amoxicillin/Clavulanic Acid (Augmentin®) to Isolated Beta-Lactamases and In- Vitro Antibacterial Activity

Summary

The in vitro sensitivity of amoxicillin alone and combined with clavulanic acid (ratio 4:1) as been studied by a spectrophotometric method utilizing crude extract of the following enzymes: TEMI, TEM2, SHV1, SHV2, TLE1, HMS1, LXA, P99, ENT208. The in-vitro antibacterial activity of ampicillin, amoxicillin alone and associated with clavulanic acid was also determined by an agar dilution method.

Clavulanate protects amoxicillin from the hydrolytic activity of plasmid mediated beta-lactamase, conferring a stability on the beta-lactam comparable with that of cefotaxime.

The protection of amoxicillin by means of clavulanic acid reduces the minimal concentration of antibiotic necessary to inhibit most bacterial species and allows bacteria to remain sensitive to the drug which might otherwise be resistant.     

In Vitro Bacterial Adherence to Teicoplanin and Calcium Sulfate-Soaked Bone Cement

Abstract

The aim of this study was to assess In Vitro the improvement in release kinetics for teicoplanin and the inhibition of bacterial adhesion on calcium sulfate-soaked PMMA discs. Calcium sulfate has been used in vivo and shown to be biocompatible, and prevention of bacterial adhesion may be expected with calcium sulfatesoaked polymethylmethacrylate (PMMA). Discs were made by adding teicoplanin and calcium sulfate in powder form to PMMA powder.

The antibiotic concentration eluted from PMMA discs was assayed by agar diffusion assay. Nonadherent bacteria were removed by washing and adherent bacteria were detached by sonication. The suspension including nonadherent bacteria was seeded on sheep blood agar plate and incubated for 24 h at 37°C for the growth of microorganisms.

The teicoplanin released from discs containing calcium sulfate was higher than that released from discs which had not been soaked with calcium sulfate. The count of bacteria adhering to the calcium sulfate-soaked discs was lower than that from the discs without calcium sulfate.

In conclusion, the addition of calcium sulfate to teicoplanin-loaded PMMA bone cement may provide local antibiotic concentrations higher than MIC values due to increased antibiotic release. Furthermore, calcium sulfate was found to be effective in reducing bacterial adherence to treated discs.     

Inhibitory and Bactericidal Activity of Rokitamycin against Helicobacter pylori and Morphological Alterations

Abstract

Rokitamycin is a macrolide antibiotic, recently entered into clinical use. Its in vitro activity and kill kinetics against Helicobater pylori have been evaluated at 1 x the minimum inhibitory concentration (MIC), 2×MIC and 4×MIC at 2, 4, 8, 24 hours and compared with those of clarithromycin, erythromycin and amoxicillin. Morphological changes in H. pylori induced by rokitamycin incubation at these MICs and times were also investigated by scanning electron microscopy. All the antibiotics tested had good inhibitory activity against H. pylori, a slow growing microorganism. The order of MIC activity was clarithromycin > amoxicillin > rokitamycin > erythromycin. Rokitamycin killed more rapidly than the other antibiotics, in fact H. pylori strains were totally killed at 8 h (2×MIC) and 4 h ( 4×MIC) and after only 2h incubation all concentrations greatly decreased the CFU/ml. These effects were also confirmed by the rapid appearance of surface and morphological alterations (focal blebs, constrictions, rounded forms) in the normal structure of H. pylori observed by scanning electron microscopy. Clinical studies should be conducted to investigate the in vivo activity of rokitamycin, as an agent to be used in the combination therapies against H. pylori.     

Pharmacokinetic and pharmacodynamic predictors of antimicrobial efficacy: moxifloxacin and Streptococcus pneumoniae

Infections caused by Streptococcus pneumoniae place a considerable personal and economic burden on both patients and healthcare systems. As the resistance of S. pneumoniae to older antimicrobial agents such as penicillin, cephalosporins, and macrolides has increased, new antimicrobials with good activity against S. pneumoniae have been developed. The newer fluoroquinolones, including levofloxacin, gatifloxacin and moxifloxacin provide a safe and easy tool in the treatment of S. pneumoniae infections. However, there have been recent reports of levofloxacin-resistant strains of S. pneumoniae. Pharmacokinetics and pharmacodynamics can be used to determine which fluoroquinolone delivers the best coverage against S. pneumoniae, and also the 24-h AUC/MIC ratio (the AUIC) required to impede the emergence of bacterial resistance. Monte Carlo analysis suggests that moxifloxacin, with 4-8-fold greater activity and higher AUIC against S. pneumoniae than levofloxacin or gatifloxacin, provides the best coverage in terms of probability of cure and probability of minimizing emergence of resistance.     

Antimicrobial susceptibility and the in vitro postantibiotic effects of vancomycin and ciprofloxacin against Bacillus cereus isolates

Background: Vancomycin and ciprofloxacin were often used in the therapy of infections associated with Bacillus cereus.

Methods: Four B. cereus food and clinical isolates were chosen for determination of time–kill curves and postantibiotic effects (PAE) of ciprofloxacin and vancomycin.

Results: According to the minimum inhibition concentration (MIC), breakpoints defined by CLSI for Staphylococcus spp. were all four strains intermediate for vancomycin (MIC?=?4?μg/ml) and sensitive to ciprofloxacin (MIC?=?0.2?μg/ml) except the strain Bc63 resistant to the last antimicrobial (MIC?=?1.6?μg/ml). The lowest CFU values of tested strains were reached after 3–5?hours of exposure to 4?× MIC of vancomycin, and after 6–7?hours exposure to 10?× MIC of ciprofloxacin. The maximum reduction of the CFU in the presence of vancomycin and ciprofloxacin was about 2.46 log₁₀ and 2.48 log₁₀, respectively. The average duration of the PAE of vancomycin and ciprofloxacin was 0.94 and 1.60?hours, respectively. The statistically significant differences between PAEs induced with 3?× MIC, 4?× MIC and 8?× MIC of vancomycin were observed (P?Conclusions: The differences in PAE duration were strain and antimicrobial dependent.