infectious disease ppt

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


Gram +/-

Anaerobes

Zosyn: only one to cover pseudomonas

MRSA

Gram +/-

Anaerobes

MRSA


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


CefazolinCephalexinCefadroxil

Enterococcus MRSAAnaerobes

Cefaclor Cefotetan Cefoxitin Cefprozil Cefuroxime

Pseudomonas

Cefpodoxime Ceftazidime Ceftibuten Ceftizoxime Ceftriaxone

Cefdinir Cefixime Cefotaxime


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


Cefepime GPC, GNR, including strep, staph, enterobacter, pseudomonas

Anaerobes


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


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



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 -


infectious disease ppt

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