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INFECTIOUS DISEASE REVIEW
April 23, 2009Ginny Schaffer
CSP ID Case Review
Objectives Define the three types of institution-acquired
pneumonia
Discuss strategies used to diagnose HAP, VAP, and HCAP
Determine how to develop an empiric antimicrobial regimen
Review classes and coverage of antimicrobial agents
Pneumonia Definitions
Hospital-acquired pneumonia (HAP) Pneumonia that
occurs 48 hours or more after admission
Infection not incubating at the time of admission
Healthcare-associated pneumonia (HCAP)
Any patient admitted to an acute care facility for 2 or more days within 90 days of infection
Facilities include nursing homes and skilled nursing facilities
Any patient who has received IV antibiotic therapy, chemotherapy, hemodialysis, or wound care within 30 days of infection
Ventilator-associated pneumonia (VAP) Arises 48-72 hours
after endotracheal intubation
Epidemiology
HAP is the second most common nosocomial infection in the United States
Incidence of HAP is 5-15 cases per 1,000 admissions
Incidence increases 6-20 fold in mechanically ventilated patients (VAP)
Risk of VAP is highest early in the hospital stay 3% per day during first 5 days of ventilation 2% per day for days 5-10 1% per day after day 10
Epidemiology HAP is responsible for 25% of all ICU
infections and for 50% of antibiotics prescribed
Early-onset HAP and VAP carry a better prognosis and are likely caused by antibiotic-sensitive organisms
Late-onset HAP and VAP are likely caused by MDR organisms
Etiology Caused by wide spectrum of bacterial
pathogens Gram negative
Gram positive Can be polymicrobial in adult respiratory
distress syndrome (ARDS) Pathogens are hospital/unit specific Anaerobic organisms rare; higher following
aspiration Rarely due to viral or fungal pathogens in
immunocompetent patients
Etiology Gram-negative bacilli
Pseudomonas aeruginosa Klebsiella pneumoniae Acinetobacter species Enterobacter species Proteus species Serratia marcescens Escherichia coli
Gram-positive cocci Staphylococcus aureus (mostly MRSA)
Etiology
Specific MDR pathogens Frequency varies by hospital, patient
population, antibiotic exposure, type of ICU patient
More common in specific patient types Severe, chronic underlying disease Risk factors for HCAP Late-onset HAP or VAP
Anaerobic pathogens are very rare
UNC Data Pathogen HAP (%) VAP (%) P-Value
Gram positive organisms
All Gram positive 42.5 32.0 0.0054
S. aureus 33.7 27.0 0.070
S. pneumoniae 5.56 2.00 0.017
Gram negative organisms
All Gram negative 39.63 59.0 <0.001
K. pneumoniae 4.81 2.00 0.045
Non-Enterobacteriaceae 19.63 40.75 <0.001
P. aeruginosa 9.26 17.5 0.003
Acinetobacter 3.33 7.75 0.020
Other
Flora 7.41 3.75 0.050
Viruses 1.85 0 0.010Weber, DJ. Infect Control Hosp Epidemiol, 2007
Pathogenesis Sources of Infection
Healthcare devices Environment (air, water, equipment) Transfer of organisms from staff to
patient
Routes of bacterial entry Aspiration of oropharyngeal contents Leakage of secretions around
endotracheal tube
Risk Factors
Non-modifiable
Male gender Pre-existing
pulmonary disease Multiple organ system
failure
Modifiable
Intubation Body position Interruption Strict glycemic
control Stress ulcer
prophylaxis Modulation of
colonization
Mechanical Ventilation Should be avoided if possible
Noninvasive ventilation whenever possible
Reduced duration may prevent VAP and can be achieved by using sedation protocols
Maintaining adequate ICU staff can reduce length of stay, improve infection control, and reduce duration of mechanical ventilation
Modifiable Risk Factors Body position
Patients should be kept in the semirecumbent position (35-45º) rather than supine to prevent aspiration
Three fold decrease in incidence of HAP
Interruption Interrupting or lightening sedation
allows cough reflex to work
Modifiable Risk Factors
Stress ulcer prophylaxis Reduced incidence of VAP but slightly
higher incidence of GI bleed when sucralfate used
Weigh risks and benefits between sucralfate and H2 blockers/PPI
Modifiable Risk Factors
Strict glycemic control Intensive insulin therapy recommended Blood glucose: 80-110 mg/dl Reduces nosocomial bloodstream infections,
ICU stay, morbidity, and mortality
Modulation of colonization Prophylaxis of HAP with oral antibiotics can
reduce incidence but increases the risk of MDR pathogens
Not recommended for routine use
CASE OF TM
TM is a 79 y/o WM who was admitted from his nursing home for increased SOB, DOE, fever and tachycardia. He recently received a 10-day course of amoxicillin/clavulanate 875 mg Q12h for an URI. He initially improved however began to sleep more than usual and today was found minimally responsive. Pertinent laboratory tests include Scr of 1.8, WBC of 17.9, BP of 87/48, HR of 116 and temperature of 39.1. His CXR was significant for LLL infiltrates and was diagnosed with pneumonia.
Clinical Signs of Infection
Fever WBC Chest X-Ray showed LLL infiltrates Tachycardia
Which type of pneumonia does TM likely have?
Healthcare Associated Pneumonia (HCAP)
TM is admitted to the medicine floor to receive IV antibiotics and NS at 150 ml/hr. TM’s BP medications are currently being held secondary to hypotension. Unfortunately, TM was transferred to the MICU due to respiratory failure and required ventilation. The patient’s BG has been ranging from 65-105 mg/dL. He was put on lansoprazole NG. He was placed in a recumbent position.
Diagnostic Testing
PMH and PE Chest radiograph Arterial oxygen
saturations Blood cultures Lower respiratory
tract secretions
Purpose of Diagnostic Testing
¨ Define whether a patient has pneumonia as a reason for new signs and symptoms
¨ Determine pathogen when pneumonia present
¨ Determine course of therapy once the organism is identified
Diagnostic Testing
How do we get samples of lower respiratory tract secretions? Endotracheal
aspirate Bronchoalveolar
lavage (BAL) Protected specimen
brush (PSB) Can gather these
specimens with or without a bronchoscope
Goals of Diagnostic Strategies
Pulmonary vs. extrapulmonary infection
Ensure collection of appropriate cultures
Aid in selecting initial empiric therapy
Allow for therapy de-escalation when results are obtained
Clinical Strategy
Presence of pneumonia defined by new lung infiltrate plus clinical evidence that infiltrate is infectious
Cause of pneumonia determined by lower respiratory tract cultures
Need two of three clinical features Fever greater than 38 degrees C Leukocytosis or leukopenia Purulent secretions
Clinical Strategy
PROS
Emphasizes prompt empiric therapy for all patients suspected of having HAP
Use of broad spectrum empiric therapy regimen can reduce incidence of inappropriate initial therapy
CONS
Leads to more antibiotic therapy
Overly sensitive May not separate
colonizers from true pathogens
May result in more or broader spectrum therapy
Bacteriologic Strategy Uses quantitative cultures of lower
respiratory secretions to define presence of pneumonia and the pathogen responsible
Growth above a threshold concentration is required for diagnosis of HAP/VAP and to determine the causative pathogen
Used to guide decisions on whether to start antibiotics, which pathogens are responsible, which antibiotics to use, and whether to continue therapy
Bacteriologic Strategy
PROS Avoids overtreatment
with antibiotics Patient may receive a
more narrow spectrum of therapy
Shown to reduce 14-day mortality as compared to a clinical strategy
CONS
False negative culture can lead to a failure to treat
Results are not always consistent or reproducible
Absence of a gold standard with which diagnostic results can be compared
Culture results not available immediately
Recommended Strategy
Initiating Antibiotic Therapy
Broad-spectrum empiric therapy based on: Risk factors for MDR pathogens Time of onset of the disease
Therapy should be deescalated once clinical and microbiological data is available
Initiating Antibiotic Therapy
HCAP patients should be treated as having MDR pathogens if they were recently hospitalized or came from a healthcare facility, such as a nursing home
HAP/VAP patients that have been hospitalized for >5 days are at greater risk for MDR pathogens
Delays in starting empiric therapy in patients with VAP have led to excess mortality
Choice of antibiotics should take into account which therapies patients have received within the past 14 days
Empiric Therapy for HAP
Empiric Antibiotic Therapy for HAP
HAP, VAP, HCAP Suspected
Late Onset (>5 days) or Risk Factors forMDR Pathogens
Yes
Broad Spectrum Antibiotic Therapy
(Table 2)
No
Limited SpectrumAntibiotic Therapy
(Table 1)
Antibiotic SelectionTable 1. Patients with no risk of MDR pathogens
Potential Pathogen Recommended Antibiotic
Streptococcus pneumoniae Ceftriaxone
Or
Levofloxacin, moxifloxacin, or ciprofloxacin
Or
Ampicillin/sulbactam
Or
Ertapenem
Haemophilus influenzae
Methicillin-sensitive Staphylococcus aureus
Antibiotic-sensitive enteric gram-negative bacilli
Escherichia coli
Klebsiella pneumoniae
Enterobacter species
Proteus species
Serratia marcescens
Antibiotic Selection
Potential Pathogen Recommended AntibioticPathogens listed in previous table
PLUS MDR pathogens
Antipseudomonal cephalosporin (cefepime, ceftazidime)
OrAntipseudomonal carbapenem
OrBeta lactam/beta lactamase inhibitor
(piperacillin/tazobactam)PLUS
Antipseudomonal fluoroquinolone (levofloxacin or ciprofloxacin)
OrAminoglycoside (amikacin, gentamicin, tobramycin)
PLUS
Vancomycin
Pseudomonas aeruginosa
Klebsiella pneumoniae (ESBL)
Acinetobacter species
Methicillin-resistant Staphylococcus aureus (MRSA)
Table 2. Patients at risk for MDR organisms
Dosing for Late Onset or MDRAntibiotic Dosage
Antipseudomonal cephalsporin Cefepime Ceftazidime
1 -2 g q8-12 hours2 g q8 hours
Carbapenems Imipenem Meropenem
500 mg q6h or 1 g q8h1 g q8h
Beta-lactam/Beta-lactamase inhibitor Piperacillin/tazobactam 4.5 g q6h
Aminoglycosides* Gentamicin Tobramycin Amikacin
7 mg/kg/day7 mg/kg/day20 mg/kg/day
Antipseudomonal quinolones Levofloxacin Ciprofloxacin
750 mg daily400 mg q8h
Vancomycin* 15 mg/kg q12h
Linezolid 600 mg q12h
*Dose based on levels (Vancomycin trough should be 15-20 mcg/mL)
Duration of Therapy Longer duration for MDR Pathogens
Pseudomonas and Acinetobacter 14-21 days MRSA 10-14 days
Shorten duration of therapy to 7 days if: Any other pathogen Clinical response and a resolution of clinical
features of the infection is present
Methicillin-resistant S. aureus
Vancomycin is standard >40% failure at standard dose of 1 g q12h Inappropriate dosing
Linezolid associated with clinical cure & lower mortality Higher penetration into epithelial lining
fluid Should be used in renal insufficiency over
vancomycin
ESBL Enterobacteriaceae
Extended-spectrum beta lactamase (ESBL)
K. pneumoniae & E. coli
Degrade penicillin and cephalosporin ring structure
May have cross resistance to aminoglycosides, fluoroquinolones, tetracyclines, etc.
Combination therapy uncertain due to resistance to fluoroquinolones and aminoglycosides
Carbapenem is the drug of choice
Tigecycline may have role in ESBL infections
Once intubated, TM’s respiratory acidosis improved. TM was afebrile. SCr decreased from 1.8 to 1.2. WBC decreased from 17.9 to 9.9. Pressor agents were discontinued on Day 2. On Day 4, TM started to become hypotensive. WBC was 14.7. His tracheal aspirate secretions have turned from clear to thick and yellowish-brown. He was currently Day 7 of levofloxacin for his admitting pneumonia.
TM’s tracheal aspirate revealed 4+ Gram negative rods, 3+ Gram positive cocci and 2+ yeast. The Gram negative rods was identified as K. pneumoniae. The Gram positive cocci was identified ORSA. The yeast was identified as Candida albicans. The organisms are susceptible to the following anti-infectives:
K. pneumoniae ORSA C. albicansCefepime Vancomycin FluconazoleTobramycin Linezolid Amphotericin BPiperacillin/ TMP/SMX tazobactam
Which agents would you choose with this new susceptibility information?
Piperacillin/tazobactam FluconazoleVancomycin
Resolution of Disease
Clinical improvement starts between 48-72 hours after antimicrobial therapy is initiated
Respiratory tract cultures are used to define resolution from a microbiology standpoint
WBC count, measures of oxygenation, & core temperature are used to define resolution from a clinical standpoint
Why Therapy Does Not Work Responsible pathogen is not being
treated effectively
Illness is not pneumonia CHF PE with infarction Lung contusion Chemical pneumonitis from aspiration Pulmonary hemorrhage in ventilated patients
Host has condition that increases mortality Prolonged mechanical ventilation Respiratory failure Old age Bilateral radiographic infiltrates Prior antibiotic therapy Prior pneumonia Chronic lung disease
Why Therapy Does Not Work
Pathogen is resistant to therapy or has acquired resistance throughout therapy
P. aeruginosa Acinetobacter species
Some pathogens are associated with poor outcomes
Gram-negative bacilli, polymicrobial flora, or bacteria that have acquired resistance
Development of a lung abscess or empyema
Other sources of fever Sinusitis Vascular catheter-related infection Pseudomembranous enterocolitis Urinary tract infection
The Non-Responding Patient
Broaden antimicrobial coverage while awaiting culture results
Once culture is obtained, modify therapy appropriately
If current therapy is sufficient, think about noninfectious pneumonia mimic or a complication
ANTIBIOTIC COVERAGE REVIEW
Antibiotic Review
Class Drug(s) Coverage Indications Not Covered
PenicillinsNatural
Penicillin GPenicillin V
Some gram + generally not Staphylococcus aureus; some gram - (Neisseria gonorrhoeae), and some anaerobes and spirochetes
Pen G: sepsis, pneumonia, pericarditis, endocarditis, meningitis, anthraxPen V: RTI, otitis media, sinusitis, skin, and UTI; prophylaxis in rheumatic fever
Staphylococcus aureas, most GNR
PenicillinsPenicillinase-resistant
Cloxacillin Dicloxacillin Nafcillin Oxacillin
Pneumonia, skin/soft tissue infections, and osteomyelitis caused by penicillinase-producing staphylococci
Monobactam Aztreonam UTI, LRTI, septicemia, skin/skin structure infections, intra-abdominal infections, and gynecological infections
Gram +, anaerobes
Sanford Guide, Lexicomp, Facts and Comparisons 4.0
Gram negative
Anaerobes
Gram +, good for Staph/Strep, OSSA
Gram neg (including Pseudomonas)
Antibiotic ReviewClass Drug(s) Coverage Indications Not
Covered
PenicillinsExtended Spectrum
Piperacillin Pip/TazoTicarcillin Tic/Clav K
Zosyn: better lung coverage
LRTI, CAP, HAP, UTI, uncomplicated and complicated skin/skin structures; gynecologic (endometritis, PID); bone/joint infections; intra-abdominal infections and septicemia
Tazobactam expands activity of piperacillin to include beta-lactamase producing strains of S. aureus, H. influenzae, Bacteroides, and other Gram - bacteria
PenicillinsAmino-Pen
AmoxicillinAmpicillinAmox/ClavAmpicillin/sulbactam
Unasyn: better GI coverage
Otitis media, sinusitis, LRTI, skin/skin structure, UTI, additional coverage of beta-lactamase producing B. catarrhalis, H. influenzae, N. gonorrhoeae, and S. aureus
Sanford Guide, Lexicomp, Facts and Comparisons 4.0
Gram +/-
Anaerobes
Zosyn: only one to cover pseudomonas
MRSA
Gram +/-
Anaerobes
MRSA
Antibiotic ReviewClass Drug(s) Coverage Indications Not
Covered
Cephalosporins 1st Generation
Gram + CocciLimited GNR(E. coli, Klebsiella, Proteus)
URI, UTI, uncomplicated skin, soft-tissue infections, bone infections, septicemia
Cephalosporins2nd Generation
Gram + cocci*, better GNR, anaerobes (including Bacteroides fragilis)*less against Staph/Strep
Intra-abdominal, URI, skin, bone/joint, UTI, septicemia
Cephalosporins3rd Generation
Greater GNR, poorer GPC, limited anaerobic
Some have better pseudomonas coverage: cefotaxime, ceftazidime
Lower RTI, otitis media, skin/skin structure infections, bone/joint infections, intra-abdominal and UTI, PID, uncomplicated gonorrhea, bacterial septicemia, and meningitis
Legionella, Bacteroides
Sanford Guide, Lexicomp, Facts and Comparisons 4.0
CefazolinCephalexinCefadroxil
Enterococcus MRSAAnaerobes
Cefaclor Cefotetan Cefoxitin Cefprozil Cefuroxime
Pseudomonas
Cefpodoxime Ceftazidime Ceftibuten Ceftizoxime Ceftriaxone
Cefdinir Cefixime Cefotaxime
Antibiotic ReviewClass Drug(s) Coverage Indications Not
Covered
Cephalosporins4th Generation
UTI, monotherapy for febrile neutropenia; uncomp skin/skin structure infections caused by Streptococcus pyogenes; moderate-to-severe pneumonia caused by pneumococcus, Pseudomonas aeruginosa, comp. intra-abdominal infections, methicillin-susceptible staphylococci, Enterobacter
Misc. Trimethoprim/sulfamethoxazole
Most Gram +,Gram - except Pseudomonas and Proteus
UTI, acute otitis media in children; acute exacerbations of chronic bronchitis in adults due to susceptible strains of H. influenzae or S. pneumoniae; treatment and prophylaxis of PCP; traveler's diarrhea due to enterotoxigenic E. coli; treatment of enteritis caused by Shigella flexneri or Shigella sonnei
Enterococcus faecium, Pseudomonas,Proteus
Sanford Guide, Lexicomp, Facts and Comparisons 4.0
Cefepime GPC, GNR, including strep, staph, enterobacter, pseudomonas
Anaerobes
Antibiotic ReviewClass Drug(s) Coverage Indications Not
Covered
Carbapenems Ertapenem Imipenem and Cilastatin MeropenemDoripenem
Gram +/-, anaerobes
Resistanace is high
Complicated intra-abdominal infections, complicated skin/skin structure infections (including diabetic foot infections without osteomyelitis), complicated UTI (including pyelonephritis), acute pelvic infections (including postpartum endomyometritis, septic abortion, post surgical gynecologic infections), and CAP
ORSA, pen-resistant
enterococcus, MRSA
Fluoro-quinolones
Ciprofloxacin Gatifloxacin Gemifloxacin Levofloxacin Lomefloxacin Moxifloxacin Nalidixic Acid Norfloxacin Ofloxacin
Gram +/-, anaerobes,
atypical bacteria (Legionella
pneumophilia, Mycoplasma pneumoniae, Chlamydia
pneumoniae)
CAP, including multidrug resistant strains of S. pneumoniae (MDRSP);
HAP; chronic bronchitis acute bacterial sinusitis; prostatitis,
urinary tract infection (uncomplicated or complicated); acute pyelonephritis; skin or skin
structure infections (uncomplicated or complicated); reduce incidence or disease progression of inhalational
anthrax (post exposure)Cipro: better pseudomonas
Levaquin: better GPC including OSSA, enterococcus, strept pneumo
Bacteroides fragilis
Sanford Guide, Lexicomp, Facts and Comparisons 4.0
Class Drug(s) Coverage Indications Not Covered
Macrolides Azithromycin Clarithromycin Erythromycin
Gram +, some gram - and anaerobes (except Bacteroides)
Otitis media due to H. influenzae, M. catarrhalis, or S. pneumoniae; pharyngitis/tonsillitis due to S. pyogenes; U/LRTI, skin/skin structure, CAP, PID, genital ulcer disease (chancroid) due to susceptible strains of Chlamydophila pneumoniae, C. trachomatis, M. catarrhalis, H. influenzae, S. aureus, S. pneumoniae, Mycoplasma pneumoniae, and C. psittaci; acute bacterial exacerbations of chronic obstructive pulmonary disease (COPD); acute bacterial sinusitis
Tetracyclines DoxycyclineMinocyclineTetracycline
Gram + including Listeria,Limited gram negative Anaerobes
Infections caused by susceptible Rickettsia, Chlamydia, Mycoplasma, and a variety of uncommon gram-negative and gram-positive bacteriaRarely used for the treatment of infections caused by common gram-negative or gram-positive bacteria
Enterococcus, Enterobacter, Serratia, Pseudomonas, Proteus, Acinetobacter
Amino-glycosides
AmikacinGentamicinTobramycin
Amikacin may cover Acinetobacter
Gram - including PseudomonasLimited Gram + (Covers Staph and has synergism with penicillins for Enterococcus)
Treatment of susceptible bacterial infections, usually gram-negative organisms and gram-positive StaphylococcusTreatment of bone infections, respiratory tract infections, skin and soft tissue infections, as well as abdominal and urinary tract infections, and septicemia
Neisseria meningiditis, anaerobes
Sanford Guide 2008, Lexicomp, Facts and Comparisons 4.0
Antibiotic Review
Antibiotic ReviewClass Drugs(s) Coverage Indications Not
Covered
Tetra-cyclines Tigecycline
Gram+/- including MRSA, Anaerobes
Complicated skin and skin structure infectionsComplicated intra-abdominal infection
Pseudomonas, ESBL+ org, Actinomyces
Misc.
Vancomycin Gram +
Infections caused by staphylococcal species and streptococcal species; used orally for staphylococcal enterocolitis or for antibiotic-associated pseudomembranous colitis produced by C. difficile
Gram neg bacilli, mycobacteria, or fungi
Linezolid
Gram +, limited gram– (Pasteurella multocida)
Treatment of vancomycin-resistant Enterococcus faecium (VRE) infections, HAP caused by Staphylococcus aureus including MRSA or Streptococcus pneumoniae (including multidrug-resistant strains [MDRSP]), complicated and uncomplicated skin/skin structure infections (including diabetic foot infections w/o concomitant osteomyelitis), and CAP
Most gram -, anaerobes
DaptomycinGram +, including MRSA
Treatment of complicated skin and skin structure infections caused by susceptible aerobic gram-positive organisms; Staphylococcus aureus bacteremia
Gram -, anaerobes
Sanford Guide, Lexicomp, Facts and Comparisons 4.0
Antibiotic ReviewClass Drug(s) Coverage Indications Not
CoveredMisc. Quinupristin/
dalfopristin combination
Gram + including MRSA, limited Gram -
Serious or life-threatening infections due to vancomycin-resistant Entercoccus (VRE) and MRSA
AnaerobesSome gram - (Proteus, pseudomonas, Acinetobacter)
Misc. Metronidazole Anaerobes, protozoal parasites
Amebiasis, symptomatic and asymptomatic trichomoniasis; skin/skin structure infections; CNS infections; intra-abdominal infections (as part of combination regimen); antibiotic-associated pseudomembranous colitis (AAPC), bacterial vaginosis; as part of a multidrug regimen for H. pylori eradication
Gram +/-
Clindamycin Gram + cocci, anaerobes
Bacterial vaginosis (vaginal cream, vaginal suppository); PID (I.V.); topically in treatment of severe acne; vaginally for Gardnerella vaginalis, bone/joint infections, septicemia, intra abdominal, LRTI
Gram -
Sanford Guide, Lexicomp, Facts and Comparisons 4.0
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