antibacterial drug therapy Flashcards
(22 cards)
minimum inhibitory concentration (MIC)
minimum inhibitory concentration (MIC)
In some tissues a lipid membrane (such as tight junctions on capillaries) presents a barrier to drug diffusion. In these tissues, a drug must be sufficiently lipid soluble or be actively carried across the membrane in order to reach effective concentrations in tissues. These tissues include the central nervous system, eye, and prostate.
A functional membrane pump (p-glycoprotein) also contributes to the barrier.
Only some drugs can diffuse into these tissues because of their high lipophilicity or because of trapping of charged species of the drug. For example, drugs that are weak bases (trimethoprim, macrolides, lincosamides) are lipophilic in the pH of the blood and readily diffuse into cells and across membranes.
Lipophilic drugs may be more likely to diffuse through the blood-bronchus barrier and reach effective drug concentrations in bronchial secretions.
In some tissues a lipid membrane (such as tight junctions on capillaries) presents a barrier to drug diffusion. In these tissues, a drug must be sufficiently lipid soluble or be actively carried across the membrane in order to reach effective concentrations in tissues. These tissues include the central nervous system, eye, and prostate.
A functional membrane pump (p-glycoprotein) also contributes to the barrier.
Only some drugs can diffuse into these tissues because of their high lipophilicity or because of trapping of charged species of the drug. For example, drugs that are weak bases (trimethoprim, macrolides, lincosamides) are lipophilic in the pH of the blood and readily diffuse into cells and across membranes.
Lipophilic drugs may be more likely to diffuse through the blood-bronchus barrier and reach effective drug concentrations in bronchial secretions.
To achieve a cure, the drug concentration in plasma, serum, or tissue fluid should be maintained above the MIC, or some multiple of the MIC, for at least a portion of the dose interval. Antibacterial dosage regimens are based on this assumption, but drugs vary with respect to the peak concentration and the time above the MIC that is needed for a clinical cure.
To achieve a cure, the drug concentration in plasma, serum, or tissue fluid should be maintained above the MIC, or some multiple of the MIC, for at least a portion of the dose interval. Antibacterial dosage regimens are based on this assumption, but drugs vary with respect to the peak concentration and the time above the MIC that is needed for a clinical cure.
Antibiotics have been classified as being either bactericidal (A bactericide is a substance that kills bacteria) or bacteriostatic (A bacteriostatic agent is a biological or chemical agent that stops bacteria from reproducing), while not necessarily harming them otherwise, depending on their action on the bacteria. However, the distinction between bactericidal and bacteriostatic has become more blurred in recent years.
Drugs traditionally considered bactericidal can be “static” if the concentrations are low. Alternatively, drugs traditionally considered “static” can be “cidal” against some bacteria and under optimal conditions.
Rather than “bacterio-static” or “bacteri-cidal,” drugs are now more frequently grouped as either concentration-dependent or time-dependent in their action. If concentration-dependent, one should administer a high enough dose to maximize the CMAX : MIC ratio or AUC : MIC ratio.
If time-dependent, the drug should be administered frequently enough to maximize the T > MIC. For some of these drugs the AUC/MIC also predicts clinical success. Examples of how these relationships affect drug regimens are described below.
Antibiotics have been classified as being either bactericidal (A bactericide is a substance that kills bacteria) or bacteriostatic (A bacteriostatic agent is a biological or chemical agent that stops bacteria from reproducing), while not necessarily harming them otherwise, depending on their action on the bacteria. However, the distinction between bactericidal and bacteriostatic has become more blurred in recent years.
Drugs traditionally considered bactericidal can be “static” if the concentrations are low. Alternatively, drugs traditionally considered “static” can be “cidal” against some bacteria and under optimal conditions.
Rather than “bacterio-static” or “bacteri-cidal,” drugs are now more frequently grouped as either concentration-dependent or time-dependent in their action. If concentration-dependent, one should administer a high enough dose to maximize the CMAX : MIC ratio or AUC : MIC ratio.
If time-dependent, the drug should be administered frequently enough to maximize the T > MIC. For some of these drugs the AUC/MIC also predicts clinical success. Examples of how these relationships affect drug regimens are described below.
Aminoglycosides
Aminoglycosides (e.g., gentamicin, or amikacin) are concentration-dependent bactericidal drugs, therefore the higher the drug concentration, the greater the bactericidal effect. An optimal bactericidal effect occurs if a high enough dose is administered to produce a peak plasma concentration of 8 to10 times the MIC. This can be accomplished by administering a single dose once daily. This regimen is at least as effective, and perhaps less nephrotoxic, than lower doses administered more frequently. If the animal is immunocompromised, one may consider a more frequent interval for administration. In animals with decreased renal function, longer intervals may be considered.
Aminoglycosides
Aminoglycosides (e.g., gentamicin, or amikacin) are concentration-dependent bactericidal drugs, therefore the higher the drug concentration, the greater the bactericidal effect. An optimal bactericidal effect occurs if a high enough dose is administered to produce a peak plasma concentration of 8 to10 times the MIC. This can be accomplished by administering a single dose once daily. This regimen is at least as effective, and perhaps less nephrotoxic, than lower doses administered more frequently. If the animal is immunocompromised, one may consider a more frequent interval for administration. In animals with decreased renal function, longer intervals may be considered.
Fluoroquinolones
For the fluoroquinolone antimicrobials, investigators have shown that either CMAX : MIC ratio or the AUC : MIC ratio may predict clinical cure in studies of laboratory animals, and in a limited number human clinical studies.32,34-36 The optimal value for these surrogate markers has not been determined for infections in dogs or cats, but values attained with clinically proven dosages agree with targets established in laboratory animals and people. These experiences have shown that a CMAX : MIC of 8 to 10 or an AUC : MIC of greater than 100 to 125 has been associated with a cure. The study that associated an AUC : MIC of greater than 125 with a cure involved critically ill human patients, but for some clinical situations AUC : MIC ratios as low as 30 to 55 have been associated with a clinical cure.35 This difference may also be organism specific. Gram-positive bacteria infection cures have been associated with AUC : MIC ratios of 35 to 50.
Because wild-type sensitive bacteria from small animals often have an MIC for fluoroquinolones in the range of 0.125 mg/mL, (± one dilution), the approved label doses of the currently available fluoroquinolones usually meets the goal of a CMAX : MIC ratio or a AUC : MIC ratio in the range cited above.37 To take advantage of the wide range of safe doses for fluoroquinolones, low doses have been administered to treat susceptible organisms with low MIC, such as E. coli or Pasteurella. But for bacteria with a higher MIC (for example, gram-positive cocci), a slightly larger dose can be used. To achieve the necessary peak concentration for a bacterium such as Pseudomonas aeruginosa, which usually has the highest MIC among susceptible bacteria, the highest dose within a safe range is recommended. Bacteria such as streptococci and anaerobes are more resistant, and even at high doses a sufficient peak concentration or AUC : MIC ratio will be difficult to achieve.
Fluoroquinolones
For the fluoroquinolone antimicrobials, investigators have shown that either CMAX : MIC ratio or the AUC : MIC ratio may predict clinical cure in studies of laboratory animals, and in a limited number human clinical studies.32,34-36 The optimal value for these surrogate markers has not been determined for infections in dogs or cats, but values attained with clinically proven dosages agree with targets established in laboratory animals and people. These experiences have shown that a CMAX : MIC of 8 to 10 or an AUC : MIC of greater than 100 to 125 has been associated with a cure. The study that associated an AUC : MIC of greater than 125 with a cure involved critically ill human patients, but for some clinical situations AUC : MIC ratios as low as 30 to 55 have been associated with a clinical cure.35 This difference may also be organism specific. Gram-positive bacteria infection cures have been associated with AUC : MIC ratios of 35 to 50.
Because wild-type sensitive bacteria from small animals often have an MIC for fluoroquinolones in the range of 0.125 mg/mL, (± one dilution), the approved label doses of the currently available fluoroquinolones usually meets the goal of a CMAX : MIC ratio or a AUC : MIC ratio in the range cited above.37 To take advantage of the wide range of safe doses for fluoroquinolones, low doses have been administered to treat susceptible organisms with low MIC, such as E. coli or Pasteurella. But for bacteria with a higher MIC (for example, gram-positive cocci), a slightly larger dose can be used. To achieve the necessary peak concentration for a bacterium such as Pseudomonas aeruginosa, which usually has the highest MIC among susceptible bacteria, the highest dose within a safe range is recommended. Bacteria such as streptococci and anaerobes are more resistant, and even at high doses a sufficient peak concentration or AUC : MIC ratio will be difficult to achieve.
β-Lactam Antibiotics
β-lactam antibiotics such as penicillins, potentiated-aminopenicillins, and cephalosporins are slowly bactericidal. Their concentration should be kept above the MIC throughout as much of the dosing interval as possible (long T>MIC) for the optimal bactericidal effect. The time above MIC should exceed at least 30% to 50% of the dosing interval. Dosage regimens for the β-lactam antibiotics should consider these pharmacodynamic relationships. Therefore, for treating a gram-negative infection, especially a serious one, some regimens for penicillins and cephalosporins require administration 3 to 4 times per day. Gram-positive organisms are more susceptible to the β-lactams than are gram-negative bacteria, and lower doses and longer intervals are possible when treating these bacteria. Additionally, because antibacterial effects occur at concentrations below the MIC (postantibiotic effect or PAE) for Staphylococcus, longer dose intervals may be possible for staphylococcal infections. For example, cephalexin or amoxicillin-clavulanate has been used successfully to treat staphylococcal infections when administered only once daily (although twice-daily administration is recommended to obtain maximum response).
β-Lactam Antibiotics
β-lactam antibiotics such as penicillins, potentiated-aminopenicillins, and cephalosporins are slowly bactericidal. Their concentration should be kept above the MIC throughout as much of the dosing interval as possible (long T>MIC) for the optimal bactericidal effect. The time above MIC should exceed at least 30% to 50% of the dosing interval. Dosage regimens for the β-lactam antibiotics should consider these pharmacodynamic relationships. Therefore, for treating a gram-negative infection, especially a serious one, some regimens for penicillins and cephalosporins require administration 3 to 4 times per day. Gram-positive organisms are more susceptible to the β-lactams than are gram-negative bacteria, and lower doses and longer intervals are possible when treating these bacteria. Additionally, because antibacterial effects occur at concentrations below the MIC (postantibiotic effect or PAE) for Staphylococcus, longer dose intervals may be possible for staphylococcal infections. For example, cephalexin or amoxicillin-clavulanate has been used successfully to treat staphylococcal infections when administered only once daily (although twice-daily administration is recommended to obtain maximum response).
Other Time-Dependent Drugs
The drugs such as tetracyclines, macrolides (erythromycin and derivatives), sulfonamides, lincosamides (lincomycin and clindamycin), and chloramphenicol derivatives act in a time-dependent manner against most bacteria. Either time above MIC (T>MIC) or total drug exposure, measured as AUC/MIC, has been used to predict clinical success for these drugs.
The drugs such as tetracyclines, macrolides (erythromycin and derivatives), sulfonamides, lincosamides (lincomycin and clindamycin), and chloramphenicol derivatives act in a time-dependent manner against most bacteria. Either time above MIC (T>MIC) or total drug exposure, measured as AUC/MIC, has been used to predict clinical success for these drugs.
Glucocorticoid drug preparations are derivatives of the endogenously produced adrenal hormone cortisol. Cortisol and other glucocorticoid compounds move passively into cells and then bind intracytoplasmic receptors. Receptor numbers vary with tissue and cell type. Bound receptors translocate to the nucleus, where they modify gene transcription. Proteins are either up- or down-regulated by glucocorticoids, which leads to specific cellular actions. Together, these actions affect the function of nearly every tissue type and result in a wide variety of effects (Box 157-1).
Glucocorticoid drug preparations are derivatives of the endogenously produced adrenal hormone cortisol. Cortisol and other glucocorticoid compounds move passively into cells and then bind intracytoplasmic receptors. Receptor numbers vary with tissue and cell type. Bound receptors translocate to the nucleus, where they modify gene transcription. Proteins are either up- or down-regulated by glucocorticoids, which leads to specific cellular actions. Together, these actions affect the function of nearly every tissue type and result in a wide variety of effects (Box 157-1).
Selected Physiologic Effects of Glucocorticoids
Metabolic Effects
Increase gluconeogenesis
Increase protein catabolism
Antagonize insulin
Mobilize free fatty acids
Redistribute adipose tissue
Metabolic Effects
Increase gluconeogenesis
Increase protein catabolism
Antagonize insulin
Mobilize free fatty acids
Redistribute adipose tissue
Inflammatory and Immunologic Effects
Decreased eicosanoid (prostaglandin and leukotriene) formation
Inhibit mononuclear phagocytosis and chemotaxis
Decrease or increase cytokine production
Depress cell-mediated immunity
Diminish humoral immunity (secondary effect)
Inflammatory and Immunologic Effects
Decreased eicosanoid (prostaglandin and leukotriene) formation
Inhibit mononuclear phagocytosis and chemotaxis
Decrease or increase cytokine production
Depress cell-mediated immunity
Diminish humoral immunity (secondary effect)
Metabolic, antiinflammatory, and immunosuppressive effects of glucocorticoids are particularly relevant to their therapeutic use. Metabolic effects are primarily catabolic and include insulin antagonism, increased glycogen formation, and increased gluconeogenesis. Glucocorticoids inhibit liberation of arachidonic acid to diminish production of eicosanoid proinflammatory mediators, and they increase production of antiinflammatory proteins.
Many antiinflammatory effects of glucocorticoids overlap with immunosuppressive effects. The glucocorticoid-induced stress leukogram (mature neutrophilia, lymphopenia and eosinopenia, and variable monocytosis) results from altered membrane expression of cellular adhesion molecules. Although glucocorticoids are typically described as “immunosuppressive” and are used to good effect in the treatment of immune-mediated disease, their actions are not so simple as to suppress all immune function. In fact, glucocorticoids can prime the innate immune response and promote humoral immunity at the same time that they dampen inflammation and suppress cellular immunity.1 Dogs and cats are considered steroid-resistant species in that glucocorticoids induce apoptosis of only neoplastic or activated lymphocytes and not of resting lymphocytes.2
Metabolic, antiinflammatory, and immunosuppressive effects of glucocorticoids are particularly relevant to their therapeutic use. Metabolic effects are primarily catabolic and include insulin antagonism, increased glycogen formation, and increased gluconeogenesis. Glucocorticoids inhibit liberation of arachidonic acid to diminish production of eicosanoid proinflammatory mediators, and they increase production of antiinflammatory proteins.
Many antiinflammatory effects of glucocorticoids overlap with immunosuppressive effects. The glucocorticoid-induced stress leukogram (mature neutrophilia, lymphopenia and eosinopenia, and variable monocytosis) results from altered membrane expression of cellular adhesion molecules. Although glucocorticoids are typically described as “immunosuppressive” and are used to good effect in the treatment of immune-mediated disease, their actions are not so simple as to suppress all immune function. In fact, glucocorticoids can prime the innate immune response and promote humoral immunity at the same time that they dampen inflammation and suppress cellular immunity.1 Dogs and cats are considered steroid-resistant species in that glucocorticoids induce apoptosis of only neoplastic or activated lymphocytes and not of resting lymphocytes.2
The release of endogenous glucocorticoids is controlled by an endocrine feedback axis consisting of the hypothalamus, the pituitary gland, and the adrenal gland (HPA axis) (Web Figure 157-1). The hypothalamus produces corticotropin-releasing hormone (CRH), which stimulates production of adrenocorticotropic hormone (ACTH) from the anterior pituitary gland. In turn, ACTH causes production and release of cortisol from the zona fasciculata and zona reticularis of the adrenal cortex. Cortisol then inhibits release of CRH and ACTH and dampens further glucocorticoid production. Pharmacologic derivatives of cortisol exert a similar negative feedback, but degree of suppression varies with glucocorticoid potency.
The release of endogenous glucocorticoids is controlled by an endocrine feedback axis consisting of the hypothalamus, the pituitary gland, and the adrenal gland (HPA axis) (Web Figure 157-1). The hypothalamus produces corticotropin-releasing hormone (CRH), which stimulates production of adrenocorticotropic hormone (ACTH) from the anterior pituitary gland. In turn, ACTH causes production and release of cortisol from the zona fasciculata and zona reticularis of the adrenal cortex. Cortisol then inhibits release of CRH and ACTH and dampens further glucocorticoid production. Pharmacologic derivatives of cortisol exert a similar negative feedback, but degree of suppression varies with glucocorticoid potency.
Pharmacology
Numerous modifications of the 17-carbon atom steroid nucleus have been developed to enhance or diminish particular glucocorticoid drug properties (e.g., mineralocorticoid or glucocorticoid potency, receptor binding strength). Intense efforts are currently underway to identify glucocorticoid receptor ligands that might retain desired actions while minimizing adverse events, but resulting drugs are not yet available commercially.3 The majority of glucocorticoid in plasma is bound to proteins, but binding affinity varies with the particular product. Corticosteroid-binding globulin, and to a lesser extent other proteins including albumin, hold glucocorticoid unavailable for diffusion into the cell. Only glucocorticoid in excess of this binding capacity enters the cell and exerts a biologic effect.
Pharmacology
Numerous modifications of the 17-carbon atom steroid nucleus have been developed to enhance or diminish particular glucocorticoid drug properties (e.g., mineralocorticoid or glucocorticoid potency, receptor binding strength). Intense efforts are currently underway to identify glucocorticoid receptor ligands that might retain desired actions while minimizing adverse events, but resulting drugs are not yet available commercially.3 The majority of glucocorticoid in plasma is bound to proteins, but binding affinity varies with the particular product. Corticosteroid-binding globulin, and to a lesser extent other proteins including albumin, hold glucocorticoid unavailable for diffusion into the cell. Only glucocorticoid in excess of this binding capacity enters the cell and exerts a biologic effect.
Modifications of the basic glucocorticoid hormones have resulted in the development of numerous drug products available for either systemic or topical administration. The potency of these products is expressed as it relates to cortisol (Table 157-1). Importantly, the same metabolic effect can be attained by any of these glucocorticoid products when administered in a metabolically active form at equipotent dosages. The biologic half-life of systemically administered glucocorticoids is disparate from the plasma half-life. Because the biologic effects are largely due to alterations in genetic regulation of protein production, biologic effects are delayed and prolonged in comparison with plasma drug concentration. Glucocorticoid drugs are often divided into three groups based on duration of HPA suppression. Short-acting glucocorticoids typically suppress the HPA less than 12 hours; long-acting glucocorticoids more than 48 hours; and intermediate-acting products fall somewhere between.
Modifications of the basic glucocorticoid hormones have resulted in the development of numerous drug products available for either systemic or topical administration. The potency of these products is expressed as it relates to cortisol (Table 157-1). Importantly, the same metabolic effect can be attained by any of these glucocorticoid products when administered in a metabolically active form at equipotent dosages. The biologic half-life of systemically administered glucocorticoids is disparate from the plasma half-life. Because the biologic effects are largely due to alterations in genetic regulation of protein production, biologic effects are delayed and prolonged in comparison with plasma drug concentration. Glucocorticoid drugs are often divided into three groups based on duration of HPA suppression. Short-acting glucocorticoids typically suppress the HPA less than 12 hours; long-acting glucocorticoids more than 48 hours; and intermediate-acting products fall somewhere between.
Many glucocorticoid products are esterified in such a way as to alter water solubility of the compound and therefore affect rate of absorption of injectable preparations. Sodium phosphate, hemisuccinate, and sodium succinate esters are the most water soluble and allow for rapid absorption and action. The duration of action of these esterified compounds is equivalent to that of the base glucocorticoid. Acetate and diacetate esters are poorly water soluble, whereas pivalate, diproprionate, hexacetate, and acetonide are least soluble. Slow absorption from the site of injection prolongs the duration of action of any glucocorticoid base with which these esters are combined. For example, although the biologic duration of methylprednisolone is 12 to 36 hours, the duration of the repositol formulation methylprednisolone acetate is 3 to 6 weeks.
Many glucocorticoid products are esterified in such a way as to alter water solubility of the compound and therefore affect rate of absorption of injectable preparations. Sodium phosphate, hemisuccinate, and sodium succinate esters are the most water soluble and allow for rapid absorption and action. The duration of action of these esterified compounds is equivalent to that of the base glucocorticoid. Acetate and diacetate esters are poorly water soluble, whereas pivalate, diproprionate, hexacetate, and acetonide are least soluble. Slow absorption from the site of injection prolongs the duration of action of any glucocorticoid base with which these esters are combined. For example, although the biologic duration of methylprednisolone is 12 to 36 hours, the duration of the repositol formulation methylprednisolone acetate is 3 to 6 weeks.
Certain synthetic glucocorticoid compounds require conversion to an active metabolite. An example is prednisone, which requires hepatic conversion to prednisolone for activity; prednisone would therefore not be suitable for topical application. In the dog, hepatic conversion is rapid and thorough, allowing prednisone and prednisolone to be used interchangeably at equivalent dosages. In cats, however, prednisolone is preferred over prednisone. While it is unclear whether decreased gastrointestinal (GI) absorption or decreased hepatic conversion is to blame, pharmacokinetics of prednisone are inferior to those of prednisolone.4 Cats are also unique in that they have fewer, less sensitive, cellular glucocorticoid receptors than dogs.5 It has been suggested that cats may require twice the dose of glucocorticoid as dogs to achieve a similar effect, but the use of less available prednisone (vs. prednisolone) may have contributed somewhat to this clinical impression. Fortunately, cats seem to tolerate glucocorticoids with fewer “dog-common” adverse reactions, although when complications of glucocorticoid use arise in the cat, they can be serious (e.g., diabetes mellitus, congestive heart failure).6,7
Certain synthetic glucocorticoid compounds require conversion to an active metabolite. An example is prednisone, which requires hepatic conversion to prednisolone for activity; prednisone would therefore not be suitable for topical application. In the dog, hepatic conversion is rapid and thorough, allowing prednisone and prednisolone to be used interchangeably at equivalent dosages. In cats, however, prednisolone is preferred over prednisone. While it is unclear whether decreased gastrointestinal (GI) absorption or decreased hepatic conversion is to blame, pharmacokinetics of prednisone are inferior to those of prednisolone.4 Cats are also unique in that they have fewer, less sensitive, cellular glucocorticoid receptors than dogs.5 It has been suggested that cats may require twice the dose of glucocorticoid as dogs to achieve a similar effect, but the use of less available prednisone (vs. prednisolone) may have contributed somewhat to this clinical impression. Fortunately, cats seem to tolerate glucocorticoids with fewer “dog-common” adverse reactions, although when complications of glucocorticoid use arise in the cat, they can be serious (e.g., diabetes mellitus, congestive heart failure).6,7
Bacteriostatic antibiotics limit the growth of bacteria by interfering with bacterial protein production, DNA replication, or other aspects of bacterial cellular metabolism. They must work together with the immune system to remove the microorganisms from the body. However, there is not always a precise distinction between them and bactericidal antibiotics; high concentrations of some bacteriostatic agents are also bactericidal, whereas low concentrations of some bacteriocidal agents are bacteriostatic.
Bacteriostatic antibiotics limit the growth of bacteria by interfering with bacterial protein production, DNA replication, or other aspects of bacterial cellular metabolism. They must work together with the immune system to remove the microorganisms from the body. However, there is not always a precise distinction between them and bactericidal antibiotics; high concentrations of some bacteriostatic agents are also bactericidal, whereas low concentrations of some bacteriocidal agents are bacteriostatic.
This bacteriostatic group includes
Tetracyclines
Sulfonamides
Trimethoprim
Chloramphenicol
Macrolides
Clindamycin
This bacteriostatic group includes
Tetracyclines
Sulfonamides
Trimethoprim
Chloramphenicol
Macrolides
Clindamycin
Antibiotics that inhibit cell wall synthesis/bactericidal:
the Beta-lactam antibiotics (penicillin derivatives (penams), cephalosporins (cephems),
and vancomycin.
fluoroquinolones,
metronidazole,
Aminoglycosidic antibiotics are usually considered bactericidal, although they may be bacteriostatic with some organisms
Antibiotics that inhibit cell wall synthesis/bactericidal:
the Beta-lactam antibiotics (penicillin derivatives (penams), cephalosporins (cephems),
and vancomycin.
fluoroquinolones,
metronidazole,
Aminoglycosidic antibiotics are usually considered bactericidal, although they may be bacteriostatic with some organisms
Bactericidal antibiotics kill bacteria; bacteriostatic antibiotics slow their growth or reproduction.
Bactericidal antibiotics kill bacteria; bacteriostatic antibiotics slow their growth or reproduction.
Furthermore some broad classes of antibacterial agents considered bacteriostatic can exhibit bactericidal activity against some bacteria on the basis of in vitro determination of MBC/MIC values. At high concentrations, bacteriostatic agents are often bactericidal against some susceptible organisms The ultimate guide to treatment of any infection must be clinical outcome
Furthermore some broad classes of antibacterial agents considered bacteriostatic can exhibit bactericidal activity against some bacteria on the basis of in vitro determination of MBC/MIC values. At high concentrations, bacteriostatic agents are often bactericidal against some susceptible organisms The ultimate guide to treatment of any infection must be clinical outcome
