Download Antibiotic Use: The Fluoroquinolones

Antibiotic Use in the ED:
The Fluoroquinolones (FQ)
Hannah Allegretto
University of Pittsburgh School of Pharmacy
PharmD Candidate 2013
S
Objectives
S Identify the structure, mechanism of action, and significant
drug interactions of FQs
S List resistance mechanisms for the FQs
S Identify common infections seen in emergency departments
and provide treatment recommendations utilizing proper
use of the FQs
S Describe the role of nursing in enforcing CMS core
measures
FQ Background
S Synthetic broad spectrum antibacterial
activity
S Same skeleton as quinolones, but fluorine
atom attached at C6 or C7 position
S MOA: inhibit bacterial replication by
blocking their DNA replication pathway
S Concentration-dependent bacterial killing
S Should be reserved for severe infections
or when other regimens have failed
Generations
S First (quinolones)
S Rarely used
S Nalidixic acid
S Second
S Divided into Class I and Class II
Class I: Norfloxacin
S Class II: Ofloxacin, ciprofloxacin
S
S Third
S Levofloxacin
S Fourth
S Gatifloxacin, moxifloxacin, gemifloxacin
FQ Adverse Effects
S Gastrointestinal (2-20%)
S Nausea
S Anorexia and dyspepsia
S Diarrhea
S Musculoskeletal
S Central Nervous System (1-11%)
S Headaches
S Dizziness and drowsiness
S Restlessness/insomnia
S Convulsions/seizures
S Cardiovascular
S Dermatologic (0.5-3%)
S Phototoxicity
S
Ciprofloxacin > norfloxacin,
ofloxacin, levofloxacin >
moxifloxacin, gatifloxacn
S Arthropathy (1%)
S Tendonitis/Tendon Rupture
S QTc interval prolongation
S Tachycardia
Drug Interactions
S Antacids, Minerals, Sucralfate, Food
S Significant reduction of oral absorption of the FQ
S 98% decreased bioavailability of FQ when administered with sulcralfate
S When administered with food, peak concentration times delayed,
maximum plasma concentrations are decreased 8-16%
S
Deemed not clinically significant
S Recommend: Antacids/sucralfate should be taken at least 2 hours before or
4-6 hours after FQ
S Probenecid
S Inhibits renal tubular secretion of the FQ
S Recommend: Patients receiving renally eliminated FQ + probenecid should
be monitored for AEs.
Drug Interactions
S Theophylline/Caffeine
S Dependent on the affinity for FQ to CYP 1A2
S
ciprofloxacin > norfloxacin > ofloxacin > levo/gati/moxifloxacin
S Recommend: all patients receiving FQ + theophylline must be
monitored for theophylline toxicity
S Warfarin
FQ can inhibit hepatic CYP enzymes responsible for metabolizing
warfarin
S Recommend: when possible, avoid FQ. If not possible, monitor
INR more frequently, especially upon initiation and discontinuation
of FQ
S
Renal Dosing Adjustments
S FQ’s requiring renal dosage adjustments:
S Ciprofloxacin
S Levofloxacin
S Norfloxacin
S Ofloxacin
S Gemifloxacin
S Both decreased dosages and decreased dosing frequency
required
Resistance Mechanisms
S Increased use of FQ in 1990s led to doubling rate of resistance
to ciprofloxacin from gram-negative bacilli in hospitals
S Mechanisms:
S Mutations altering drug targets (DNA gyrase, topoisomerase IV)
S Mutations reducing drug accumulation
S Plasmids blocking quinolone effects qnr gene
FQ Indications in the ED
S Acute Uncomplicated Cystitis and Pyelonephritis
S Intra-abdominal Infections
S Community Acquired Pneumonia
Acute Uncomplicated Cystitis
S One of most common reasons for otherwise healthy women
to get prescribed antimicrobials
S Fluoroquinolones should only be considered after previous
recommended treatment regimens are ruled out
S Preferred agents: Nitrofurantoin, SMX/TMP, Fosfomycin
S Ofloxacin, ciprofloxacin, and levofloxacin highly effective in 3
day regimens, but “have a propensity for damage and should
be reserved”
Acute Pyelonephritis
S Non-hospitalized patients with prevalence of resistance of
community uropathogens <10%
S SMX/TMP 800/160mg PO BID x 14 days if uropathogen
known to be susceptible
S
If susceptibility not known, 1g ceftriaxone IV recommended
S Ciprofloxacin 500mg PO BID x 7 days
S
Optional loading dose of Ciprofloxacin 400mg IV
S Once daily FQ
S
Ciprofloxacin 1000mg ER PO QD x 7 days
S
Levofloxacin 750mg PO QD x 5 days
Intra-abdominal Infections
S Empiric treatment should be active against enteric gram-
negative aerobic and facultative bacilli and enteric grampositive streptococci
S Obligate anaerobic bacilli coverage recommended if distal
small bowel, appendiceal, and colon-derived infection present
S For high risk patients (APACHE II scores > 15), combination
therapies with metronidazole are recommended
S Quinolone-resistant E. coli common quinolones should be
avoided unless >90% susceptibility is known
Intra-abdominal Infections
Regimen
Mild-to-Moderate severity
High risk or severity
Single Agent
Cefoxitin, ertapenem, moxifloxacin,
tigecycline, ticarcillin-clavulanate acid
Imipenem-cilastin,
meropenem, doripenem,
piperacillin-tazobactam
Combination
Therapy
Metronidazole + one of the following
agents:
Cefazolin, cefuroxime, cefriaxone,
cefotaxime, ciprofloxacin/levofloxacin
Metronidazole + one of
the following agents:
Cefepime, ceftazidime,
ciprofloxain/levofloxacin
Community Acquired
Pneumonia (CAP)
S One of the leading causes of hospital admissions
S Streptococcus pneumoniae, Haemophilus influenzae, Moraxella
catarrhalis account for 85% CAP cases
S >$17 billion annual US costs due to CAP
CMS Core Measures: CAP
S Core Measures:
S Blood cultures performed within 24 hours prior to or 24 hours
after hospital arrival for patients transferred/admitted to the
ICU within 24 hours of hospital arrival
S Blood cultures performed in ED prior to initial antibiotic
received in hospital
S
Nursing plays role
S
Always DOCUMENT!
S Selection of most appropriate antibiotic based on patient
characteristics
Nursing Role
S Verify documentation of time when blood cultures taken
S Review recent antibiotic use through chart review/patient
interview
S Verify susceptibility of pathogen to antibiotic being
administered
S Ensure proper documentation of admission times, time to
culture, and time to antibiotic administration to comply with
CMS core values.
CAP Tx Recommendations
Non-ICU patients:
S Primary Regimen:
S Ampicillin/sulbactam IV PLUS azithromycin IV/PO
S Non-severe PCN allergy rxn
S Cefriaxone IV PLUS azithromycin IV/PO
S Severe PCN allergy rxn
S Moxifloxacin monotherapy
ICU Patients:
S Primary: Ampicillin/Sulbactam IV + Azithromycin IV
S Secondary: Azithromycin IV + Ceftriaxone IV
CAP Tx Recommendations
Non-ICU pts w/ Pseudomonal Risk
S Cefepime IV + tobramycin IV + azithromycin IV/PO
S Second Line: Cefepime IV + Ciprofloxacin IV/PO
S With SEVERE B-Lactam allergy: Aztreonam IV +
Moxifloxacin IV + Tobramycin IV
ICU pts w/ Pseudomonal Risk
S Cefepime IV + Tobramycin IV + azithromycin IV
S Second Line: Cefepime IV + Ciprofloxacin IV
CAP Tx Recommendations
S ICU Pts with SUSPECTED Francisella tularensis or Yersinia
pestis
S Doxycycline + ampicillin/sulbactam IV or cefepime IV
Summary
S The FQs exhibit powerful antimicrobial activity against
several organisms, but should be reserved in use due to high
risk of resistance
S Hospital nurses involvement imperative in ensuring the
CMS core measures for community acquired pneumonia
are being abided by in order to ensure reimbursement
References
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Solomkin JS, Mazuski JE, Bradley JS et al. diagnosis and management of complicated
intra-abdominal infection in audlts and children: The Guidelines by the Surgical Infection
Society and the Infectious Diseases Society of America. Clin Infect Dis. 2010;50:133-64.
References
Gupta K, Hooton TM, Naber KG et al. Internation clinical practice guidelines for the
treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010
updated by the Infectious Diseases Society of America and the European Society for
Microbiology and Infectious Diseases. Clin Infect Idis. 2011;52:e103-120.
File TM, Marrie TJ. Burden of community-acquired pneumonia in North American
adults. Postgrad Med. 2010; 122:130-41
Mandell LA, Wunderink RG, Anzueto A et al. Infectious Diseases Society of
America/American Thoracic Society consensus guidelines on the management of
community-acquired pneumonia in adults. Clin Infect Dis. 2007; 44:s27-72.