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Peggy Francis, DNP, RN, FNP, CUNP April 25, 2015

Treating Lower Urinary Tract Infections

GOALS: To provide cost-effective, quality care that is effective, efficient, & timely. Decreases mortality & morbidity Improves quality of life Effective and economical Easy and convenient to administer

Urologic Bacterial entry: 1. Periurethral – most common 2. Hematogenous spread (usually neonates & immunocompromised) 3. Lymphatogenous spread (rectal, colonic, periuterine- little scientific support) 4. Direct extension of bacteria from adjacent organs via abscesses or fistulas

IMPORTANT CONSIDERATIONS: ALLERGIES AGE (no TCN for children; dose adjustment for elderly) DRUG INTERACTIONS (OCPS w/ ABx; blood thinners) HEALTH STATUS (immunocompromised, pregnant, renal or hepatic dysfunction)

Urine Culture – gold standard for identification of UTI measured in CFU/mL (colony forming unit) 100,000 CFU/mL clinically significant,

Ideal practice is based on culture and sensitivity Empiric Tx may be too BROAD contributing to resistant strains and leading to toxicity Empiric Tx may be too NARROW – not covering the pathogen, increased mortality Dilemma requires CLINICAL JUDGEMENT

MIC – Mean Inhibitory Concentration (basis for culture susceptibility results) lowest concentration of ABx that prevents visible growth of bacteria after 18-24 hours S – susceptible – microbe eliminated with normal dose of drug – MIC easily achieved I – intermediate – microbe might be eliminated with maximum doses of drug R – resistant – microbe not likely to be eliminated even with max dose

MBC – Minimal Bactericidal Concentration – the concentration of drug that actually kills the bacteria (rather than the concentration that inhibits growth) Bactericidal drugs usually have MBC equal or very similar to MIC Bacteriostatic drugs usually have MBC significantly higher than MIC

DEFINITIONS: Bacteriuria – presence of bacteria in the urine Pyuria – presence of WBCs in the urine Uncomplicated UTI – patient has structurally and functionally normal urinary tract Complicated UTI – underlying anatomical or functional abnormality Isolated UTI – at least 6mo between infections Recurrent UTI - >2 infections in 6mo or 3 within 12 mo

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Peggy Francis, DNP, RN, FNP, CUNP April 25, 2015

ORGANISMS

GRAM + Enterococcus faecalis MRSA Staphylococcus sp Strep group A, B, C, G

GRAM – E coli (80%) Enterobacter H influenza Klebsiella M catarrhalis N gonorrhoeae Proteus mirabilis Pseudomonas Salmonella

ATYPICAL Chlamydia Legionella pneumonia Mycoplasma pneumonia

ANAEROBIC Actinomyces Bacterioides fragilis Clostridium

NEW ORGANISM (rare): Aerococcus urinae – gram+

A. urinae is susceptible to , , , , rifampin, and nitrofurantoin A. urinae is resistant to sulfonamides, trimethoprim, and netilmicin

Public Health Agency of Canada NIH – Journal of Microbiology

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Peggy Francis, DNP, RN, FNP, CUNP April 25, 2015

DEFINITIONS:

Pharmacology – science that studies biologically active chemical compounds in living cells/bodies

Pharmacy – manufacture, preparation, production, and dispensing of drugs

Drug – a substance used as a medicine to treat disease; any small chemical molecule that changes physiologic function through interaction at the chemical/molecular level

Supplement – (FDA definition) A dietary supplement is a product intended for ingestion that contains a "dietary ingredient" intended to add further nutritional value to (supplement) the diet. A "dietary ingredient" may be one, or any combination, of the following substances:

• a vitamin • a mineral • an herb or other botanical • an amino acid • a dietary substance for use by people to supplement the diet by increasing the total dietary intake • a concentrate, metabolite, constituent, or extract

Nutraceutical - The term "nutraceutical" has no meaning in US law. Term coined in 1989. Depending on its ingredients and the claims with which it is marketed, a product is regulated as a drug, dietary supplement, food ingredient, or food.

Pharmacotherapeutics – use of drugs to treat or prevent disease

Pharmacokinetics – what the body does to a specific drug

Pharmacodynamics – what the drug does to the body

Pharmacoeconomics – study of the costs of drugs and ultimately the cost of the disease (production, marketing)

Pharmagogeonomics – genetic influences

Resistance mechanisms: 1. enzymatic degradation of the drug 2. modification of the drug’s target 3. reduced permeability of the drug 4. active export of the drug

Tolerance – a form of resistance in which growth of the organism is inhibited but not eliminated

Unresolved infection – implies inadequate therapy caused by either resistance to treatment, infection by different organisms or rapid re-infection

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Peggy Francis, DNP, RN, FNP, CUNP April 25, 2015

Bactericidal – kills bacteria in absence of host defenses Beta-Lactams Aminoglycosides –Tobramycin, Gentamycin Quinolones – Cipro, Levaquin Bactrim/Septra DS Metronidazole Bacteriostatic – uses host’s immune system to prevent microbial growth Macrolides – azithromycin & clarithromycin Linesolid (Zyvox) Clindamycin Tetracycline – tetracycline, doxycycline, minocycline (some drugs can be both)

Concentration dependent drugs – increased concentration for more thorough and quick killing – maximize serum concentrations Quinolones, aminoglycosides, metronidazole, Time dependent drugs – optimal killing dependent upon duration of adequate exposure – maximize exposure of drug duration Beta Lactams, Vancomycin, Macrolides, Clindamycin, Tetracyclines

ANTIBIOTIC COMBINATIONS: 1. To treat serious infections prior to identification of organism 2. To achieve a synergistic inhibitory effect against certain organisms 3. To prevent the emergence of resistant organisms

Synergistic effect: the effect of the 2 drugs together is significantly greater than the sum the effects of each drug acting separately.

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Peggy Francis, DNP, RN, FNP, CUNP April 25, 2015

ANTIBIOTICS

Aminoglycosides – Gram –negative -bind to ribosome and inhibit protein synthesis resulting in cell death (Bactericidal) [many nosocomials – nephrotoxic & ototoxic] Amikacin (Amikin) Gentamicin (Garamycin) Kanamycin (Kantrex) Neomycin (Mycifradin) Paromomycin (Humatin) Streptomycin (Streptomycin) Tobramycin (Nebcin, Tobrex)

Antianaerobic Agents – gram +/- anaerobes - inhibit protein synthesis Clindamycin (Cleocin) - also used for aerobic gram + cocci Metronidazole (Flagyl) Tinidazole (Tindamax)

Beta-Lactam/Beta-Lactamase Inhibitor Combinations Amoxicillin & Clavulanate (Augmentin)

Carbapenems & (structurally related to B-lactam ABx) (Azactam) (Doribax) (INVanz) -cilastatin (Primaxin) (Merrem)

Cephalosporins First Generation: (Duricef) (Narrow Spectrum) (Ancef, Kefzol) Cephalexin (Keflex) Second Generation: (Ceclor (Intermediate Spec) (Zefazone) (Mefoxin) (Cefzil) (Ceftin, Kefurox, Zinacef) (Lorabid) Third Generation: Cefdinir (Omnicef) (Broad Spectrum) (Spectracef) Cefepime (Maxipeme) (Suprax) (Claforan) proxetil (Vantin) (Teflaro) (Fortaz, Tazidime) (Cedax) (Cefizox) (Rocephin) 5 | Page

Peggy Francis, DNP, RN, FNP, CUNP April 25, 2015

Fluoroquinolones & Quinolones – interfere with bacterial DNA gyrase, preventing bacterial replication [broad spectrum, but do not use in pregnancy & use carefully w/ children] Ciprofloxacin (Cipro) Gemifloxacin (Factive) Levofloxacin (Levaquin) Lomefloxacin (Maxaquin) Moxifloxacin (Avelox) Norfloxacin (Noroxin) Ofloxacin (Floxin)

Fosfomycin trometamol (Monurol)

Lincosamides (similar to Macrolides but more toxic) Clindamycin/ Lincomycin (Cleocin)

Nitrofurantoin nitrofurantoin (Macrobid) - inhibits bacterial enzymes & DNA activty [warning: pulmonary hypersensitivity reaction]

Macrolides Azithromycin (Zithromax) Clarithromycin (Biaxin) Erythromycin (Erythromycin)

Penicillin – Gram + ; inhibits bacterial growth by interference with synthesis [SE – low incidence, hypersensitivity (maculopapular rash and urticarial most common), GI, w/ several renal dysfunction & high dose – seizures and encephalopathy]

Amoxicillin (Amoxil) Amoxicillin/potassium clavulanate (Augmentin) – gram negative Ampicillin/ sodium (Unasyn) (Geocillin) Penicillin G Penicillin V (V-Cillin, PenVeeK) Piperacillin (Pipracil) Piperacillin/ sodium (Zosyn) (Ticar) Ticarcillin (clavulanate potassium (Timentin)

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Peggy Francis, DNP, RN, FNP, CUNP April 25, 2015

Sulfonamides - interferes with the bacterial metabolism of folate [adverse reaction in 6-8%; not in folate deficient, AIDS, or pregnant patients] General Purpose: Sulfadiazine Sulfixoxazole

Special Purpose: Mafenide (Sulfamylon) Silver Sulfadiazine (Silvadene) Sulfacetamide sodium Trimethoprim (Proloprim, Trimpex) Trimethoprim-sulfamethoxazole (co-trimoxazole, TMP-SMZ, Bactrim, Septra)

Tetracyclines Demeclocycline (Declomycin) Doxycycline (doxycycline, Vibramycin) Monocycline (Minocin) Tetracycline (Tetracycline) Tigecycline (Tygacil)

CLINICAL PEARLS

Elderly – when behavior or mood changes, think UTI suggest urology referral for chronic UTI or hematuria catheterized specimen best for SLOL when in doubt, check PVR

RESOURCES: Basic & Clinical Pharmacology, 12th Ed., McGraw Hill Medical, 2012 B. Katzung, S. Masters, & A. Trevor Drug Information Handbook for Advanced Practice Nursing, 15th Ed., Lexicomp, 2014 The Sanford Guide to Antimicrobial Therapy 2014, 44th Ed. Coverage drug cards, APEA (Advanced Practice Education Associates) www.apea.com

APPs: Epocrates Bugs & Drugs version 13.12 Guidelines-AT-A-Glance – American Urologic Association, 2014 AGS iGeriatrics – American Geriatrics Society, 2012

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