NAPLEX - Antimicrobial Regimen Selection McGraw Hill

A patient with a health care-associated pneumonia infection is found to have a multidrug-resistant organism (this was found by the culture and susceptibility and the pathogen Pseudomonas aeruginosa exhibits a high MIC to all antibiotics). Since the pathogen exhibits a high-level resistance, modifications to the dose or interval will be required to achieve successful outcomes. Currently the patient is receiving the β-lactam piperacillin/tazobactam 4.5 g intravenously every 6 hours infused over 30 minutes. Select the factor that may be done to piperacillin/tazobactam that could optimize the pharmacodynamic (PD) property. A Increase the infusion time B Increase the dose C Add combination therapy with another β-lactam D Decrease the dose to 3.375 mg

A Β-Lactam antimicrobials are often administered intravenously as 30-minute infusions. An example is piperacillin/tazobactam (Zosyn) 4.5 g intravenously every 6 hours infused over 30 minutes. In efforts to optimize the time-dependent activity of β-lactams, extending the infusion interval is being clinically utilized (piperacillin/tazobactam 3.375 g intravenously every 8 hours *infused over 4 hours*). Extending the infusion interval allows for the concentration to remain above the minimal inhibitory concentration for longer periods of time (time-dependent activity). Answer b is incorrect. Increasing the dose would optimize the PD property for concentration-dependent agents, not time-dependent agents. Answer c is incorrect. A common subject of debate involves the utilization of combination anti-infective therapy. Proponents state that double coverage may be synergistic, prevent the emergence of resistance, and improve outcomes. However, there are few clinical examples in the literature to support these assertions. Double antimicrobial coverage may be beneficial for selected infections associated with high bacterial loads or for initial empirical coverage of critically ill patients in whom antimicrobial-resistant organisms are suspected. Monotherapy usually is satisfactory once antimicrobial susceptibilities are known. In the case application question above, the combination of the two anti-infectives would not be ideal because they are of the same mechanism of action (β-lactams). When the clinical situation calls for combination therapy, utilization of drugs with different mechanisms of action is preferred. Answer d is incorrect. Decreasing the dose would not assist in optimizing the pharmacokinetic / pharmacodynamic (PK/PD) property of piperacillin/tazobactam. Note: some providers may decrease the dose when they increase the infusion time.

Select the infectious disease state that requires excellent tissue penetration (distribution). Select all that apply. A Meningitis B Acute cystitis C Bronchitis D Cellulitis

A, B Meningitis infections require anti-infective distribution within the cerebrospinal fluid (CSF). Anti-infectives that do not reach significant concentrations in the CSF should be avoided or instilled directly. Anti-infectives with moderate to good penetration within the CSF will still require higher doses. For example, the dose/interval for IV ceftriaxone in meningitis is 2 g every 12 hours, compared to 1 g every 24 hours for community-acquired pneumonia. Sites of infections that require specific distribution properties of the anti-infectives include CSF, urine, synovial fluid, and peritoneal fluid. Apart from these areas, more attention should be paid to clinical efficacy, antimicrobial spectrum, adverse effects, and cost than to comparative data on penetration.

Select the antibiotics that may be clinically utilized to treat an Enterococcus faecalis urinary tract infection (UTI). Select all that apply. A Amoxicillin B Fosfomycin C Nitrofurantoin D Fluconazole

A, B, C .Amoxicillin, fosfomycin, and nitrofurantoin are commonly used in the management of UTIs and may be prescribed for E. faecalis UTIs.

Select the correct dose of cefepime (Maxipime) for a patient with normal renal function and empirically treated for an infection (at this time the site or source of infection has not been identified). Select all that apply. A 1 g IV every 12 hours B 2 g IV every 12 hours C 2 g IV every 8 hours D 4.5 g every 6 hours

A, B, C .Cefepime 1 g every 12 hours may be utilized for patients with community-acquired pneumonia and urinary tract infection (UTIs). Answer b is correct.Cefepime *2 g every 12 hours may be utilized for patients with intra-abdominal infections, skin and skin structure infections, and UTIs.* Answer c is correct.Cefepime *2 g every 8 hours may be utilized for patients with febrile neutropenia and suspected-resistant pathogens (ie, Pseudomonas aeruginosa infections)* All of the above doses of cefepime may be utilized, depending upon the site of infection and the potential for bacterial resistance. High doses of cefepime are often utilized empirically, especially when the site or source of infection has not been identified, as is the situation with our current case application question. Since this patient has been diagnosed with an infection and cefepime is going to be utilized, high doses would likely be the best option until the site or source has been identified. Once the site and/or source has been identified the dose or anti-infective may be required to be changed. Also, if a patient were suspected to have a multidrug-resistant organism, other methods of dosing may be utilized (eg, extended infusion β-lactam therapy). Please note this case application question was about dosing of anti-infectives, not selection of anti-infectives, with cefepime serving as an example. Answer d is incorrect. 4.5 g every 6 hours is the dose/interval for piperacillin/tazobactam.

Select the anti-infective(s) that is associated with the adverse reaction of antibiotic- associated diarrhea (C. difficile). Select all that apply. A Augmentin B Levaquin C Cleocin D Vancocin

A, B, C .Vancomycin (Vancocin) is not associated with the adverse reaction of antibiotic-associated diarrhea (C. difficile). Oral vancomycin is used to treat C. diff infections.

Select the oral anti-infective(s) that displays good bioavailability. Select all that apply. A Fluconazole B Linezolid C Levofloxacin D Vancomycin

A, B, C Oral fluconazole displays good bioavailability (>90%). Other azole antifungals (itraconazole and ketoconazole) have critical bioavailability concerns. They must be administered and absorbed in an acidic gastrointestinal pH. Major drug interactions with ketoconazole and itraconazole are acid-suppressing agents (H-2 blockers and proton pump inhibitors).

Select the potential cause of a fever. Select all that apply. A Infection B Piperacillin C Trauma D Cancer

A, B, C, D Infections may cause a fever. However, patients with infections may also present with hypothermia (eg, patients with overwhelming infection, sepsis). Elderly patients may be afebrile, as well as patients with localized infection (eg, uncomplicated urinary tract infections). Answer b is correct. Medications may cause a fever. Examples of mediations that have been associated with a drug fever are anticonvulsants, minocycline, penicillins, cephalosporins, allopurinol, and heparin.

Select the drug interaction(s) with aminoglycosides. Select all that apply. A Amphotericin B B Vancomycin C Furosemide D Cisplatin

A, B, C, D nephrotox Other drug interactions with the aminoglycoside antimicrobials are neuromuscular blocking agents, cyclosporine, nonsteroidal anti-inflammatory drugs, and radio contrast. The clinical management for the aminoglycoside drug interactions is to monitor aminoglycoside serum drug concentrations and renal function (except when combined with neuromuscular blocking agents, it is best to avoid utilization of aminoglycosides and neuromuscular blocking agents).

Select the host factor(s) that may impact antimicrobial therapy. Select all that apply. A Age B Pregnancy C Metabolic abnormalities D Organ dysfunction E All of the above

A, B, C, D, E Age is an important factor in determining causative pathogens for certain infections (ie, meningitis) and pharmacokinetic (PK) factors (renal dysfunction). Answer b is correct. Antimicrobial agents must be used with caution in pregnant and nursing women. Some agents are known or likely to be teratogenic (eg, metronidazole), and others pose potential threats to the fetus or infant (eg, quinolones, tetracyclines, and sulfonamides). PK variables also are altered during pregnancy. Both the clearance and volume of distribution are increased during pregnancy. As a result, increased dosages and/or more frequent administration of certain drugs may be required to achieve adequate concentrations. Answer c is correct. Inherited or acquired metabolic abnormalities influence infectious diseases therapy. Patients with peripheral vascular disease may not absorb drugs given by intramuscular injection. Other examples include patients who are phenotypically slow acetylators of isoniazid are at greater risk for peripheral neuropathy; patients with glucose-6-phosphate dehydrogenase deficiency can develop hemolysis when exposed to sulfonamides and dapsone. Answer d is correct. Patients with renal or hepatic dysfunction will accumulate certain drugs unless the dosage is adjusted.

RL is a patient with a past medical history of iron deficiency anemia. He is being treated with ferrous sulfate. Select the antimicrobial(s) that would have a decreased bioavailability when combined with ferrous sulfate. Select all that apply. A Moxifloxacin B Tetracycline C Azithromycin D Doxycycline

A, B, D .Moxifloxacin (and other fluoroquinolones) have decreased absorption when combined with multivalent cations (antacids, iron, sucralfate, zinc, vitamins, dairy, and citric acid). The clinical management for this interaction is to separate administration of the two agents by at least 2 hours. Answers b and d are correct.Tetracycline and doxycycline have decreased absorption when combined with iron, antacids, calcium, and sucralfate. The clinical management for this interaction is to separate administration of the two agents by at least 2 hours. Answer c is incorrect.Azithromycin and the macrolide antimicrobials are not affected by concurrent administration of multivalent cations.

Select the risk factor(s) for the acquisition of exogenous pathogens. Select all that apply. A Nursing home admission B Pregnancy C Recent antimicrobial use D Hospital admission for 7 days

A, C, D Nursing home and hospital admission may expose the patient to different types of bacteria and change the patient's normal flora. This change in normal flora may necessitate a change in empiric treatment of infections. Answer c is correct. Patients with a history of recent antimicrobial use may have altered normal flora (acquisition of exogenous pathogen). Answer b is incorrect. Pregnancy would not change the normal (endogenous) flora. Pregnancy may change pharmacokinetic parameters such as volume of distribution.

Select the pathogen(s) that is part of the normal (endogenous) flora of the large intestine. Select all that apply. A Escherichia coli B Viridans streptococci C Neisseria meningitidis D Enterococcus species

A, D .E. coli and Enterococcus species reside within the normal flora of the large intestine. Other organisms that reside with the large intestine include Enterobacteriaceae, E. species, and Anaerobes. E. coli also resides in the small intestine. Answer b is incorrect. *Viridans streptococci reside within the normal flora of the mouth and are a potential cause of endocarditis.* Answer c is incorrect.N. meningitidis reside within the normal flora of the upper respiratory tract and may cause meningitis.

Select the antimicrobial that may cause collateral damage by selecting for a nontargeted organism (ie, Clostridioides difficile) leading to a colitis infection. Select all that apply. A Clindamycin B Levofloxacin C Ciprofloxacin D Ceftriaxone

ALL Clostridia are anaerobic, spore-forming rods (bacillus). C. difficile is the most serious cause of antibiotic-associated diarrhea (AAD) and can lead to pseudomembranous colitis, a severe infection of the colon, often resulting from eradication of the normal gut flora by antibiotics. The C. difficile bacteria, which naturally reside in the body, become overpopulated. The overpopulation is harmful because the bacterium releases toxins that can cause bloating, constipation, and diarrhea with abdominal pain, which may become severe. Discontinuation of causative antibiotic treatment is often curative. In more serious cases, oral administration of metronidazole or vancomycin is the treatment of choice. Relapses of C. difficile AAD have been reported in up to 20% of cases.

Select the antimicrobial pharmacokinetic (PK) property that impacts the dose and/or interval. Select all that apply. A Bioavailability B Volume of distribution C Metabolism D Elimination

ALL Patients who may have altered Vd include ascites, edema, pregnant, burn, obese, thin, loss of extremities (ie, above the knee amputation), and dehydrated patients. Elimination is a key PK property in describing antimicrobial properties. Understanding renal and/or hepatic function are important factors in determining anti-infective dose and/or interval. Renally eliminated anti-infectives are usually dose-based upon results from the approximation of the glomerular filtration rate (GFR) via calculation of the creatinine clearance (Cockroft-Gault or modification of diet in renal disease [MDRD] equations). Anti-infectives eliminated via the hepatic system may be dosed upon a Child-Pugh score, although recommendations for dosing anti-infectives in patients with liver dysfunction are not as formalized as guidelines for patients with renal dysfunction.

Select the anti-infective that exhibits the pharmacodynamic (PD) property of time-dependent activity. A Levofloxacin B Doripenem C Amikacin D Metronidazole

B .Doripenem (other carbapenems, penicillins, cephalosporins) exhibit time-dependent activity. The PD property of time-dependent activity is maximized when the free concentration (nonprotein bound) exceeds the minimum inhibitory concentration (MIC) for a certain period of time. For the cell wall agents to exhibit bactericidal time-dependent activity, the following parameters must be met: Carbapenems require that the concentration be above the MIC for 40% of the dosing interval. Cephalosporins require that the concentration be above the MIC for 60% to 70% of the dosing interval. Penicillins require that the concentration be above the MIC for 50% of the dosing interval. For the cell wall agents to exhibit bacteriostatic time-dependent activity, the following parameters must be met: Carbapenems require that the concentration be above the MIC for 20% of the dosing interval. Cephalosporins require that the concentration be above the MIC for 35% to 40% of the dosing interval. Penicillins require that the concentration be above the MIC for 30% of the dosing interval.

Select the factor that may affect the bioavailability of an oral anti-infective. A A medication that is a substrate of the CYP-450 system. B Dosage formulation of the anti-infective. C A patient who has peripheral vascular disease. D A patient who has renal dysfunction.

B The dosage formulation of the anti-infective may have significant effects on the bioavailability. A classic example is vancomycin. Vancomycin is available as oral and parenteral formulations. Oral vancomycin is not absorbed and reserved for treatment of C. difficile infections (antibiotic-associated diarrhea). Intravenous vancomycin has a bioavailability of 100% (F=1) and is used for treatment of systemic gram-positive infections (ie, methicillin resistant Staphylococcus aureus). Parenteral formulations of an anti-infective may also have various degrees of bioavailability. Examples include a potential difference in bioavailability of β-lactams when administered via IV versus intramuscular routes. Answer a is incorrect. Anti-infective CYP-450 activity (substrates, inhibitors, inducers) will not affect the bioavailability. P-450 activity will affect the *metabolism and elimination, but not absorption*. Anti-infectives administered orally that are circulated through the liver may be affected by the first-pass effect. The first-pass effect will eliminate some of the anti-infective and would indirectly affect the amount of medication able to be absorbed. The first-pass effect is a phenomenon of drug metabolism whereby the concentration of a drug is reduced before it reaches the systemic circulation. It is the fraction of lost drug during the process of absorption which is generally related to the liver and gut wall. Notable drugs that experience a significant first-pass effect are imipramine, propranolol, and lidocaine. Answer c is incorrect. A patient with peripheral vascular disease would not be expected to have different bioavailability. However, comorbidities (like peripheral vascular disease) may impact other PK properties of anti-infectives like distribution and elimination. Answer d is incorrect. Renal dysfunction would not have an impact on bioavailability. Renal dysfunction would affect the elimination of the anti-infective.

Select the anti-infective that exhibits the pharmacodynamic property of concentration dependent activity. A Ceftriaxone B Amoxicillin C Ciprofloxacin D Meropenem

C .Ciprofloxacin exhibits the pharmacodynamic (PD) property of concentration-dependent activity. Other anti-infectives that exhibit concentration-dependent activity include: *aminoglycosides, metronidazole, and other fluoroquinolones*. Concentration-dependent activity is maximized when the peak concentration (Cmax) to minimum inhibitory concentration (MIC) ratio is greater than or equal to 10:1 for aminoglycosides. Quinolone pharmacodynamic properties are maximized according to the area under the curve (AUC) to MIC ratio. For gram-positive bacteria, the ideal AUC:MIC ratio is greater than or equal to 30:1. For gram-negative bacteria, the ideal AUC:MIC ratio is greater than or equal to 125:1.

Select the pathogen(s) that is classified as an atypical organism. A Escherichia coli B Klebsiella pneumoniae C Mycoplasma pneumoniae D Streptococcus pneumoniae

C M. pneumoniae is an aerobic gram-negative bacteria, but it retains the gram stain poorly and thus cannot be reliably seen on routine gram stain, and therefore referred to as an atypical pathogen. Other atypical organisms are Legionella pneumophila and Chlamydia pneumoniae. Answer a is incorrect.E. coli is an aerobic lactose-positive fermenting gram-negative rod. Escherichia coli belongs to the Enterobacteriaceae (Enteric) family. Answer b is incorrect.Klebsiella species are aerobic lactose-positive fermenting gram-negative rods. Klebsiella species belong to the Enterobacteriaceae (Enteric) family. Answer d is incorrect.S. pneumoniae is an aerobic gram-positive organism.

Select the information that is revealed by a gram stain. A Minimum inhibitory concentration B Genre and species of the bacteria C Morphologic characteristics of the bacteria D Antibiotic susceptibility

C Minimum inhibitory concentration (MIC) and antibiotic susceptibility are revealed by the culture and susceptibility test. Answer b is incorrect. The genre and species of the bacteria are revealed by the culture and susceptibility test.

JG is a patient with an immediate-allergic reaction to ticarcillin/clavulanate (Timentin). Select the antimicrobial that JG may take in relation to his allergy. A Piperacillin/tazobactam B Amoxicillin/clavulanate C Cephalexin D Aztreonam

D

Select the anti-infective that is associated with the adverse effects of nephrotoxicity and ototoxicity. A Amoxicillin/Clavulanate B Cefpodoxime C Moxifloxacin D Gentamicin

D

Central nervous system (CNS) side effects (seizures and mental status changes) are associated with β-lactam and quinolone anti-infectives. A risk factor for development of the CNS reactions is: A Duration of therapy B Infusion interval C Bioavailability D Renal dysfunction

D Antibiotic-associated CNS toxicities may be common effects for penicillin, cephalosporin, carbapenem, and quinolone anti-infectives, especially if the dose or interval is not adjusted for renal dysfunction. Answer a is incorrect. Duration of therapy would not be a factor in CNS side effects of β-lactams or quinolones, unless the patient was accumulating (not eliminating) the anti-infective. Answer b is incorrect. The infusion interval would not impact the CNS side effect. Answer c is incorrect. Bioavailability would not impact the CNS side effect.

Select the factor that would usually necessitate a patient to be given IV anti-infectives. A Fever of 101.9°F B Severe cough C Glucose-6-phosphate dehydrogenase (G6PD) deficiency D Blood pressure of 91/52 mm Hg with signs of hypoperfusion (baseline blood pressure for patient is 129/86 mm Hg)

D Hyper or hypothermia would not necessitate a patient to be given IV anti-infectives. Patients diagnosed with sepsis (overwhelming infection) would be recommended to receive IV anti-infectives. Septic patients will most likely present with hyper or hypothermia, but they must have other signs and symptoms to be classified as sepsis. Fever is one of the factors that is utilized in the recommendation of switching from IV to oral anti-infectives. The factors that are involved in streamlining patients from IV to oral anti-infectives are: (1) display of clinical improvement, (2) lack of fever for 8 to 24 hours, (3) decreased white blood cell count, and (4) functioning gastrointestinal tract.

Select the pathogen that represents an exogenous bacteria flora (ie, acquired from the hospital). Characteristics of this pathogen are nonlactose fermenting gram-negative bacilli. A Neisseria meningitidis B Enterobacter cloacae C Streptococcus pneumoniae D Pseudomonas aeruginosa

D P. aeruginosa is a nonlactose fermenting gram-negative bacilli. Other nonlactose fermenting gram-negative bacilli include Proteus, Serratia, Morganella, Stenotrophomonas, and Acinetobacter. Answer a is incorrect.N. meningitidis is a gram-negative cocci. Answer b is incorrect.E.r cloacae is a lactose-fermenting gram-negative bacilli. Answer c is incorrect.S. pneumoniae is a gram-positive cocci (diplococcic).

Select the best answer that represents part of the normal (endogenous) flora of the lower respiratory tract. A Enterobacteriaceae B Streptococcus pneumoniae C Enterococcus species D Normally sterile

D The lower respiratory tract is normally sterile. Other areas that are normally sterile include the cerebrospinal fluid and urine. Answer a is incorrect. Enterobacteriaceae reside as part of the normal flora in the small and large intestine. Answer b is incorrect.*S. pneumoniae reside as part of the normal flora in the upper respiratory tract.* Answer c is incorrect.Enterococcus species reside as part of the normal flora in the small and large intestine.

Select the penicillin antimicrobial that is broad-spectrum and has coverage against nonlactose negative (oxidase-positive) gram-negative bacilli. A Amoxicillin B Nafcillin C Cefepime D Doripenem E Piperacillin/tazobactam

E .Piperacillin/tazobactam is a broad-spectrum penicillin antimicrobial that has activity against the nonlactose negative (oxidase-positive) gram-negative bacilli (P. aeruginosa). Answer a is incorrect.Amoxicillin is a narrow-spectrum antimicrobial and it does not have activity against the nonlactose negative (oxidase-positive) gram-negative bacilli (P. aeruginosa) Answer b is incorrect.Nafcillin is a narrow-spectrum gram-positive antimicrobial and it does not have activity against the nonlactose negative (oxidase-positive) gram-negative bacilli (P. aeruginosa) or any gram negative. Answer c is incorrect.Cefepime is broad-spectrum and it does have coverage against nonlactose negative (oxidase-positive) gram-negative bacilli (P. aeruginosa); however, it is a cephalosporin. Answer d is incorrect.Doripenem is broad-spectrum and it does have coverage against nonlactose negative (oxidase-positive) gram-negative bacilli (P. aeruginosa); however, it is a carbapenem.