3/17/19

1

Super Bugs Need Super Drugs, or Do They?George Dresden, MSN, ACNP, DNP

ObjectivesØDetermine which antibiotic to use based on

pharmacodynamic category: time dependent, concentration dependent, time dependent/concentration enhanced

ØImprove your prescribing of antibiotics for bacteria with resistance to beta lactams, including penicillin.

ØAssess for all gram negative and positive bacteria, as well as viral etiologies with secondary bacterial infections. Recognize, isolate, and treat the superbugs early.

ØIn immunocompromised patients test for fungal etiologies, and be prepared to treat them. Differentiate between opportunistic and non-opportunistic systemic infections.

Antibiotic/Antimicrobial Resistance Biggest Threats in 2013Urgent Threats

Ø Carbapenem-resistant Enterobacteriaeae (CRE)

Ø Drug-resistant Neisseria Gonorrhoeae

Ø Clostridiodes Difficile

Serious Threats

Ø Multidrug-resistant AcinetobacterØ Drug-resistant Campylobacter

Ø Fluconazole-resistant Candida

Ø Extended-spectrum Beta-lactamase producing Enterobacteriaceae

Ø Vancomycin-resistant Enterococcus (VRE)

Ø Multidrug-resistant Pseudomonas aerginosa

Ø Drug-resistant non-typhoidal Salmonella

Ø Drug-resistant Shigella

Ø Methicillin-resistant Staphyococcus aureus (MRSA)

Ø Drug-resistant Streptococcus pneumoniaeØ Drug-resistant Tuberculosis

Concerning Threats

Ø Vancomycin-resistant Staphylocccus aureus (VRSA)

Ø Erythromycin-Resistant Group A Streptococcus

Ø Clindamycin-resistant Group B Streptococcus

CDC is working toward releasing an updated Threats Report in the Fall of 2019.

3/17/19

2

World Health Organization’s Top 12 Priority PathogensPriority 1: CRITICAL

› Acintobacter baumannii, carbapenem-resistant

› Pseudomonas aeruginosa, carbapenem-resistant› Enterobacteriaceae, carbapenem-resistant, ESBL-

producing– Klebseilla pneumonia– Escherichia coli– Enterobacter spp.– Serratia spp.

– Proteus sp.– Providencia spp– Morganella spp.

Priority 2: HIGH

› Enterococcus faecium, vancomycin-resistant

› Staphylococcus, methicillin-resistant, vancomycim-intermediate and resistant

› Helicobacter pylori, clarithromycin-resistant

› Campylobacter spp., fluroquinolone-resistant

› Salmonellae, fluroquinolone-resistant› Neisseria gonorrhoeae, third generation

cephalosporin-resistant, fluroquinolone-resistant

Priority 3: MEDIUM

› Streptococus pneumoniae, penicillin-non-susceptible› Haemophilus influenzae, ampicillin-resistant

› Shigella spp., fluroquinolone-resistant

So, How Did We Get Here?Quick Terminology Review-Take a Nap if this is Old Hat for you› Bacteriostatic-inhibition of bacterial growth› Bactericidal-killing of bacteria› Minimum inhibitory concentration (MIC)-the lowest concentration

of antibiotic that completely inhibits growth of the specific organism being tested

› Minimum bactericidal concentration (MBC)- the lowest concentration of antibiotic at which bacteria are killed

Evidence supports killing when treating endocarditis, meningitis and osteomyelitis, otherwise, inhibition of growth is generally sufficient.

So How Did We Get Here?› Overuse or misuse of antibiotics, i.e. giving antibiotics for a

viral infection (#1 misuse)› Patients not completing courses of antibiotics when they start

feeling better, so they get re-infected› Saving antibiotics and sharing them with others or taking

them later for a different illness

3/17/19

3

Concentration vs Time-Dependent KillingFor an antibiotic to eradicate an organism:

– It must bind to its target site(s) in the bacterium

– It must occupy an adequate number of binding sites (concentration)

– To work effectively, it must remain there long enough for the metabolic processes of the bacteria to be sufficiently inhibited (Time-Dependent)

Pharmacokinetic/Pharmacodynamic Parameters Affecting Antibiotic Potency

Concentration vs Time-Dependent KillingAntibiotic Pharmacodynamic Categories

Time –Dependent(T> MIC)

No post-antibiotic effect(for gram-)

Concentration-DependentCmax/MIC or AUC/MIC

Strong post-antibiotic effect

Time-Dependent-Concentration Enhanced

AUC 24/MICModerate post-antibiotic effect

PenicillinsCephalosporinsErythromycin

AminoglycosidesFluroquinolonesMetronidazoleAmphotericin B

Macrolides (Azithromycin)ClindamycinVancomycinTetracyclinesAztreonamCarbapenemsAzole antifungals

>MIC for 40-50% of dosing interval-max killing seen when time above MIC is at least 70% of dosing interval.

AUC/MIC >125 for gram-

bacteria, > 25-50 for gram+ cocci Cmax/MIC >10.

DOUBLE COVERAGE

Based on the assumptions

Ø The combination provides a broad spectrum of coverage for empiric treatment before knowing the ID and susceptibility of offending pathogen

Ø The combination may provide additive or synergistic effects against the pathogen

Ø The combination of antibiotics may decrease or prevent the emergence of resistant bacteria

3/17/19

4

Beta Lactams

Development of Beta Lactam Resistance› Decreased penetration to the target site

– Permeability of the outer membrane no longer allows the antibiotic through such as with Pseudomonas aeruginosa

› Alteration of the target site– Penicillin binding proteins (PBPs) may be changed so that they no

longer have an affinity for the beta-lactam antibiotics so that the bacterial cell is no longer inhibited. Examples are pneumococci, methicillin resistance in staphylococci, and Haemophilus influenzae.

› Inactivation by a bacterial enzyme (ESBL)– Chromosomal beta-lactamases– Plasmid-mediated beta-lactamases

How to Use Beta Lactams EffectivelyNatural Penicillin › Pen V

– Gm+, less effective against gm -, narrow spectrum, PO, prone to ß-lactamase (tonsillitis, anthrax, rheumatic fever, streptococcal skin infections)

Amino-Penicillin› Ampicillin

– Gm+ & gm -, broad spectrum PO and IV, prone to ß-lactamase (ear infections, sinusitis, UTI, menigitis)

› Amoxicillin– Gm+ & gm -, broad spectrum PO and IV,

prone to ß-lactamase (skin infection, sinusitis, UTI, streptococcal pharyngitis)

Anti-Staphylococcal Penicillin › Methcillin

– Gm+, very narrow spectrum, should be given IV, may cause interstitial nephritis

› Oxacillin– Gm+, treatment for PCN-resistant Staphyloocus

aureus, very narrow spectrum, should be given IV

› Nafcillin– Gm+, treatment for staphylococcal infections, very

narrow spectrum, should be given IV

› Cloxacillin– Effective against staphylococci that produce ß-

lactamase, very narrow spectrum, should be given PO

› Dicloxacillin and Flucloxacillin– Gm+, and Staphyococci that produce ß-

lactamase, very narrow spectrum, should be given PO

3/17/19

5

How to Use Beta Lactams EffectivelyAnti-Pseudomonal Penicillin› Pipercillin

– Gm+ & Gm-, extended spectrum, should be given IV or IM if given with tazobactam a ß-lactamase inhibitor, further strengthens its effectiveness

› Carbenicillin– Gm- & limited Gm+, mainly useful for

UTI› Ticarcillin

– Mainly Gm-, particularly Pseudomonas aeruginosa, also stenotrophomonasmaltophilia infections

Cephalosporin› 1st generation predominantly active

against Gm+ bacteria, the 3 successive generations have increased activity against Gm- bacteria, reducing Gm+ activity.

› 1st generation: cefalothin, cefalexin, cefadroxil, & cefazolin

› 2nd generation: cefuroxime (PO), & cefotetan

› 3rd generation: cefotaxime, ceftriaxone, & ceftazidime› 4th generation: cefepime› 5th generation: ceftaroline

How to Use Beta Lactams EffectivelyCarbapenems› Broad spectrum beta-lactam

antibiotics. They are highly resistant to ß-lactamases.

› Imipenem– Aerobic and anaerobic, Gm+ and

Gm- (including ESBL-producing strains), and Pseudomonas, IV, can produce seizures at high doses

› Meropenem– Aerobic and anaerobic, Gm+ and

Gm-, ultra broad spectrum, IV

› Ertapenem– Gm+ and Gm-, broad spectrum, IV,

NOT effective against MRSA

Monobactam› Aztreonam

– Gm+ and Gm- & anaerobic bacteria, broad spectrum, IV, NOT active against MRSA

ß-lactamase Inhibitors› Resemble ß-lactam antibiotic

structure, so bind to the ß-lactamase and protect the antibiotic from destruction

› They are most successful when the binding is irreversible

› 3 Most Important: Clavulanic acid, Sulbactam, & Tazobactam

Beta-Lactamase Enzyme

3/17/19

6

Why Is It Important To Detect ESBL’s?› The presence of an ESBL-producing organism in a clinical infection

can result in treatment failure if the wrong antibiotic is used.› ESBL’s can be difficult to detect because they have varying levels of

activity against the cephalosporins. It is crucial to choose wisely which antibiotics to test against. For example, one enzyme may have a minimum inhibitory concentration (MIC) of 4 μg/ml on ceftazidime but have poor activity on cefotaxime with a MIC of 256 μg/ml.

› If an ESBL is detected, ALL PENICILLIN’S, CEPHALOSPORINS, AND AZTREONAM SHOULD BE REPORTED AS RESISTANT, even if in vitro test results indicate they have susceptibility.

Metallo Beta-Lacamase› Resistant against a broad spectrum of beta-lactam antibiotics.› This includes those in the carbapenem family.› This particular class is characterized by its ability to hydrolyze

carbapenems and by their resistance to available ß-lactamase inhibitors (tazobactam, sulbactam, clavulanic acid) but susceptibility by metal ion chelators (vitamin B12, ascorbic acid).

› The most common bacteria that are responsible for this enzyme are Gm- such as Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa.

Penicillin-under or over utilized?› Penicillin allergy is the most common, reported by up to 15%

of hospitalized patients› Clinically-can they be safely given structurally related

cephalosporins or carbapenems› Do they need allergy consultation first?

3/17/19

7

Approach to the Patient with a Past PCN Reaction Who Requires Antibiotics

The PenicillinsCategory Parenteral Agents Oral AgentsNatural Penicillins Penicillin G Penicillin VAntistaphylococcal penicillins Nafcillin, oxacillin DicloxacillinAminopenicillins Ampicillin Amoxacillin, ampicillinAminopenicillins+ß-lactamaseinhibitors

Ampicillin-Sulbactam Amoxicillin-clavulanate

Extended spectrum penicillins Pipercillin, ticarcillinExtended spectrum penicillins+ß-lactamase inhibitors

Pipercillin-tazobactam, ticarcillin-clavulanate

Knowledge AffirmationWhich of the following antibiotics is NOT a ß-lactam?

a. Ampicillinb. Meropenemc. Ceftriaxoned. Vancomycine. Aztreonam

3/17/19

8

Knowledge AffirmationWhich of the following antibiotics is NOT a ß-lactam?

a. Ampicillinb. Meropenemc. Ceftriaxoned. Vancomycine. Aztreonam

Treatment Options for Gram Positive Bacteria

Antimicrobial Agents for Treatment of Infections Caused by Staphylococcus AureusAntibiotic Class Antibiotic

Antistaphylococcal penicillins Nafcillin, oxacillin

1st generation cephalosporins Cefazolin

2nd generation cephalosporins Cefuroxime

3rd generation cephalosporins Ceftriaxone, cefotaxime

4th generation cephalosporins Cefepime

ß-lactam/ß-lactamase inhibitor combinations Ampcillin-sulbactam, pipercillin-tazobactam, ticarcillin-claculanate

Carbapenems Imipenem, meropenem, doripenem

Also sometimes active (not first choice, and only if susceptibilities are known

Clindamycin

Sulfa drugs Trimethoprim-sulfamethoxazole

Quinolones Ciprofloxacin, levofloxacin, moxifloxacin

Tetracyclines Minocycline, doxycycline

Macrolides Erythromycin, azithromycin

Rifamycins Rifampin

Aminoglycosides Gentamycin (synergistic dosing)

If MRSA

Glycopeptides and lipoglycopeptides Vancomycin, dalbavancin, ortavancin, telavancin

Oxazolidinones Linezolid, tedizolid

Streptogramins Quinupristin-dalfopristin

Daptomycin

Tetracycline-like Tigecycline

5th generation cephaosporins Ceftaroline

3/17/19

9

Treatment for Streptococcus pneumoniae in the Hospitalized Patient

Outpatient Treatment for Beta Lactam Susceptible Streptococcus pneumoniae

Antimicrobial Agents for Treatment of Infections Caused by Streptococcal Species Other than Streptococcal Pneumoniae

Antibiotic Class AntibioticNatural penicillins Penicillin GAminopenicillins AmpicillinAminoglycosides are sometimes added for synergy

Gentamycin

Clindamycin is added for severe invasive Streptococcus pyrogenes infectionsAlternatives1st generation cephalosporin CefazolinMacrolide AzithromycinIf PCN resistantGlycopeptide Vancomycin2nd generation cephalosporin Cefuroxime3rd generation cephalosporin Cefotaxime, ceftriaxone

3/17/19

10

IV Treatment for Susceptible Enterococcal Infections

Knowledge AffirmationEach of the following might be appropriate empiric monotherapy for cellulitis EXCEPT:a. Ceftazidime

b. Vancomycinc. Oxacillind. Cefazoline. Clindamycin

Knowledge AffirmationEach of the following might be appropriate empiric monotherapy for cellulitis EXCEPT:a. Ceftazidime

b. Vancomycinc. Oxacillind. Cefazoline. Clindamycin

3/17/19

11

Gram Negative Bacteria

Antimicrobial Agents for Treatment of Infections caused by Enterobacteriaceae

Antibiotic Class AntibioticEscherichia coli, Klebsiella spp., Proteus spp.Aminopenicillins (except Klepseilla spp. and Proteus vulgaris)

Ampicillin

1st generation cephalosporin (except for Proteus vulgaris)

Cefazolin

Sulfa drugs Trimethoprim-sulfamethoxazoleQuinolones Ciprofloxacin, levofloxacin, moxifloxacinIf resistant to the above antibiotics3rd, 4th and 5th generation cephalosporins Cefotaxime, ceftriaxone, cefipime, ceftarolineCephalosporin+ß-lactamase inhibitor Ceftazidime-avibactamMonobactam AztreonamExtended-spectrum penicillins+ß-lactamaseinhibitor

Pipercillin-tazobactam, ticarcillin-clavulanate

Carbapenems Imipenem, meropenem, doripenem, ertapenem+aminoglycoside in serious infections Gentamycin, tobramycin, amikacin

Antimicrobial Agents for Treatment of Infections caused by EnterobacteriaceaeAntibiotic Class AntibioticEnterobacter, Serratia, Citrobacter, Providencia, Morganella spp.Carbapenems Imipenem, meropenem, doripenem, ertapenem

Sulfa drugs Trimethoprim-sulfamethoxazoleQuinolones Ciprofloxacin, levofloxacin, moxifloxacin4th generation cephalosporins Cefepime

+aminoglycoside in serious infections Gentamycin, tobramycin, amikacinSalmonella enterica, shigella spp.Quinolones Ciprofloxacin, levofloxacin3rd generation cephalosporins Cefotaxime, ceftriaxone, cefiximeMacrolides Azithromycin

Sulfa drugs Trimethoprim-sulfamethoxazoleYersinia spp.Aminoglygosides Gentamycin, streptomycinTeracyclines Doxycycline

Quinolones (Yersenia enterocolitica) CiprofloxacinSulfa drugs (Yersenia enterocolitica) Trimethoprim-sulfamethoxazole

3/17/19

12

Antimicrobial Agents for Treatment of Infections Caused by Pseudomonas aeruginosaAntibiotic Class AntibioticExtended-spectrum penicillins Piperacillin3rd generation cephalosporins Ceftazidime4th generation cephalosporins CefepimeCephalosporin+ß-lactamase inhibitor Ceftolozane-tazobactamCarbapenems Imipenem, meropenem, doripenemMonobactams AztreonamQuinolones Ciprofloxacin, levofloxacinAminoglygosides Gentamycin, tobramycin, amikacinColistin

The Increasing Resistance of PseudomonasCriteria for defining MDR, XDR and PDR in Pseudomonas aeruginosa

› MDR: Non-susceptible to > 1 agent in > 3 antimicrobial categories

› XDR: Non-susceptible to > 1 agent in all but < 2 categories

› PDR: Non-susceptible to all antimicrobial agents listed.

MDR: multidrug-resistant; XDR: extensively drug resistant; PDR: pandrug-resistant

3/17/19

13

Treatment of Neisseria speciesNeisseria MeningitidisAntibiotic Class Antibiotic

Natural penicillins3rd generation cephalosporinsIntolerable to ß-lactam antibiotics

Penicillin GCeftriaxone, cefotaximeChloramphenicol (unavailable in US)

Postexposure prophylaxis QuinoloneRifamycin3rd generation cephalosporin

CiprofloxacinRifampinCeftriaxone

Neisseria gonorrhoeaeAntibiotic Class Antibiotic

3rd generation cephalosporin+macrolide Ceftriaxone+azithromycin

Campylobacter Jejuni Infection Treatment

Antibiotic Class AntibioticTreatment of ChoiceMacrolides Erythromycin, azithromycin, clarithromycinQuinolones Ciprofloxacin, leofloxacinAlternativesTetracyclines Tetracycline, doxycyclineAminoglycosides Gentamycin, tobramycin, amikacinAminopenicillin+ß-lactamase inhibitor Amoxicillin+clavulanic acidChloramphenicol

Treatment only indicated for a subset of patients –those with high fevers, bloody or profuse diarrhea, prolonged symptoms, or immunocompromised.

Antimicrobial Agents for Treatment of Infections Caused by Helicobacter pyloriAntibiotic Class AntibioticAminopenicillins AmoxicillinMacrolides ClarithromycinMetronidazoleTetracyclines TetracyclineBismuth subsalicylate (Pepto Bismol)Recommended Regimens *Duration of treatment is generally 2 weeksAmoxicillin+clarithromycin+PPIMetronidazole+clarithromycin+PPIBismuth subsalicylate+metronidazole+tetracycline+PPI

3/17/19

14

Antimicrobial Agents To Treat Infection from HaemophilusinfluenzaeAntibiotic Class AntibioticTreatment of ChoiceAminopenicillins+ß-lactamase inhibitor Amoxicillin+clavulanate, ampicillin+sulbactam2nd generation cephalosporins Cefuroxime3rd generation cephalosporins Ceftriaxone, cefotaximeAlso activeTetracyclines Tetracycline, doxycyclineMacrolide-like agents Azithromycin, telithromycinQuinolones Ciprofloxacin, levofloxacin, moxifloxacin,

GemifloxacinCarbapenems Imipenem, meropenem, doripenem, ertapenemSometimes activeSulfa drugs Trimethoprim-sulfamethoxazoleProphylaxis for serotype BRifamycins Rifampin

Antimicrobial Agents For Infection Due to Moraxella catarhalisAntibiotic Class AntibioticExtended-spectrum penicillins PiperacillinAminopenicillins+ß-lactamase inhibitor Amoxicillin+clavulanate, ampicillin+sulbactam2nd generation cephalosporins Cefuroxime3rd generation cephalosporins Ceftriaxone, cefotaximeMacrolides Azithromycin, clarithromycinAminoglycosides Gentamycin, tobramycin, amikacinSulfa drugs Trimethoprim-sulfamethoxazoleQuinolones Ciprofloxacin, levofloxacin, moxifloxacinTetracyclines Tetracycline, doxycycline

Acinetobacter species Infection Treatment

3/17/19

15

Knowledge AffirmationWhich of the following antibiotic regimens would be appropriate for a patient with a severe infection caused by Pseudomonas aerugnosa prior to knowledge of the isolate’s susceptibilities?a. Ceftazidime+tobramycinb. Ceftriaxone+gentamycinc. Pipercillin+rifampind. Ertapenem+amikacine. Ampicillin+tobramycin

Knowledge AffirmationWhich of the following antibiotic regimens would be appropriate for a patient with a severe infection caused by Pseudomonas aerugnosa prior to knowledge of the isolate’s susceptibilities?a. Ceftazidime+tobramycinb. Ceftriaxone+gentamycinc. Pipercillin+rifampind. Ertapenem+amikacine. Ampicillin+tobramycin

Anaerobic Bacteria

3/17/19

16

Antimicrobial Agents for Clostridioides (formerly Clostridium) spp. (NOT including C. difficile)

Antibiotic Class AntibioticTreatment of ChoiceNatural penicillins Penicillin GMetronidazole*For infections with Clostriodiodes perfingens add clindamycin to penicillin

Antibiotic Regimens for the Treatment of Clostridioides difficile Infection

Antimicrobial Agents that may Induce C. Difficile Diarrhea and Colitis

3/17/19

17

Anaerobic Gram-Negative BacilliTreatment for Infections Caused by Bacteroides, Prevotella, and Porphyromonas spp.

Antibiotic Class AntibioticFirst-line agentsß-lactam/ß-lactamase inhibitor combinations Ampicillin-sulbactam, piperacillin-tazobactam,

ticarcillin-clavulanateCarbapenems Imipenem, meropenem, doripenem, ertapenemMetronidazoleSecond-line agentsClindamycin2nd generation cephalosporins Cefotetan, cefoxitinExtended-spectrum penicillins PipercillinQuinolones MoxifloxacinTetracycline-like agents TigecyclineChloramphenicol

Knowledge AffirmationWhich of the following antibiotics has little activity against anaerobic bacteria?a. Imipenemb. Metronidazolec. Ceftriaxoned. Clindamycine. Amoxicillin+clavulanate

Knowledge AffirmationWhich of the following antibiotics has little activity against anaerobic bacteria?a. Imipenemb. Metronidazolec. Ceftriaxoned. Clindamycine. Amoxicillin+clavulanate

3/17/19

18

Atypical Bacteria

Treatment for Atypical Bacteria InfectionsMycoplasma pneumoniae

Antibiotic Class AntibioticMacrolide-like agents Azithromycin, Clarithromycin, erythromycin, telithromycinTetracyclines Tetraclycline, doxycyclineQuinolones Levofloxacin, moxifloxacin, gemifloxacin

Legionella speciesAntibiotic Class AntibioticFirst-line agentsMacrolides AzithromycinQuinolones Levofloxacin, moxifloxacinSecond-line agentsMacrolides Erythromycin, clarithromycinQuinolones Ciprofloxacin, gemifloxacinTetracyclines Doxycycline

Knowledge Affirmation› Which of the following

antibiotics does NOT have activity against Legionella pneumonphila?

a. Azithromycin

b. Levofloxacinc. Moxifloxacind. Erythromycine. Pipercillin+tazobactam

3/17/19

19

Knowledge Affirmation› Which of the following

antibiotics does NOT have activity against Legionella pneumonphila?

a. Azithromycin

b. Levofloxacinc. Moxifloxacind. Erythromycine. Pipercillin+tazobactam

Myobacteria

Antimicrobial Treatments for Infections Caused by Myobacterium species

Mycobacterium TuberculosisActive Disease(Isoniazid+rifampin+pyrazinamide+ethambutol) x 2 months, followed by (isoniazid+rifampin) x 4 monthsLatent InfectionIsoniazid x 9 months

Mycobacterium Avium ComplexAntibiotic Class AntibioticClarithromycin+ethambutol+rifabutinAlternative AgentsMacrolides AzithromycinQuinolones Ciprofloxacin, levofloxacinAminoglycosides Amikacin

3/17/19

20

Antimicrobial Treatment for Myobacterium leprae

Antibiotic Class AntibioticDapsone+rifampin+clofaximineAlternative AgentsTetracyclines MinocyclineQuinolones OfloxacinMacrolides Clarithromycin

Knowledge AffirmationAll of the following are used to treat patients with tuberculosis EXCEPT:a. Pyrazinamideb. Isoniazidc. Rifampind. Dapsonee. Ethambutol

Knowledge AffirmationAll of the following are used to treat patients with tuberculosis EXCEPT:a. Pyrazinamideb. Isoniazidc. Rifampind. Dapsonee. Ethambutol

3/17/19

21

Fungal Infections

Antifungal Agents for Candida speciesAntifungal Class AntifungalEchinocandins Caspofungin, anidulafungin, micafunginAzoles Fluconazole, voriconazole, posaconazole, itraconazole, isavuconazolePolyene Amphotericin B

• If your patient is not improving on standard antibacterial therapy, despite new negative cultures, look for an underlying fungal infection.

• At risk patients include: those with IV lines of catheters, bone marrow transplant recipients, ICU patients , patients with implanted joint prostheses, or who are immunosuppressed.

• Mortality of invasive candidiasis is 30%.

Opportunistic Infections-PJP

3/17/19

22

Antifungal Agents for Nonmeningeal Cryptococcal Infection

Treatment for AspergillosisAntifungal Class AntifungalInitial Therapy Voriconazole+ echinocandin (NOT fluconazole)If intolerant of voriconazole Amphotericin B or isavuconazoleSalvage Therapy

Echinocandin Caspofungin, micafungin, anidulafungin

+ Voriconazole, isavuconazole, OR liposomal amphotericin B

Duration of therapy at a minimum is 6-12 weeks. For most immunosuppressed patients it will continue for months to years.If the etiology was endocarditis, the patient should stay on a lifelong azole at a treatment dose.

Questions???? Headaches?

3/17/19

23

References• Antimicrobial fundamental concepts. Obtained from https://www.asp.mednet.ucla.edu/files/view/guidebook/AntimicrobialFundamentalConcepts.pdf

• Blumenthal, K. G., & Solensky, R. (2017). Choice of antibiotics in penicillin-allergic hospitalized patients. www.uptodate.com

• CDC. (2018). Antibiotic/antimicrobial resistance (AR/AMR). https://www.cdc.gov/drugresistance/biggest_threats.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fdrugresistance%2Fthreat-report-2013%2Findex.html

• Cox, G.M. & Perfect, J. R. (2017). Cryptococcus neoformans infection outside the central nervous system. www.uptodate.com

• Hauser, A. R. (2019). Anaerobic bacteria. In Antibiotic Basics for Clinicians, Wolters Kluwer: Philadelphia, PA.

• Hauser, A. R. (2019). Antibiotics that target the cell envelope. In Antibiotic Basics for Clinicians, Wolters Kluwer: Philadelphia, PA.

• Hauser, A. R. (2019). Atypical bacteria. In Antibiotic Basics for Clinicians, Wolters Kluwer: Philadelphia, PA

• Hauser, A. R. (2019). Gram negative bacteria. In Antibiotic Basics for Clinicians, Wolters Kluwer: Philadelphia, PA.

• Hauser, A. R. (2019). Gram positive bacteria. In Antibiotic Basics for Clinicians, Wolters Kluwer: Philadelphia, PA.

• Hauser, A. R. (2019). Mycobacteria. In Antibiotic Basics for Clinicians, Wolters Kluwer: Philadelphia, PA.

• Kanafani, Z. A. & Kanj, S. S. (2018). Acinetobacter infection: Treatment and prevention. www.uptodate.com.

• Kauffman, C. A. (2018). Management of candidemia and invasive candidiasis in adults. www.uptodate.com

• Kauffman, C. A. (2018). Treatment and prevention of invasive aspergillosis. www.uptodate.com

• Kelly, C. P. , Lamont, J. T. & Bakkan, J. S. (2019). Clostridioides (formerly Clostridium) difficile infection in adults: Treatment and prevention. www.uptodate.com

• Letourneau, A. R. (2017). Beta-lactam antibiotics: Mechanisms of action and resistance and adverse effects. www.uptodate.com

• Marrie, T. J., & Tuomanen, E. I. (2018). Pneumococcal pneumonia in adults. www.uptodate.com

• Melin, J. A., Kunins, L., Givens, J., & Sokol, H. N. (2019). What’s new in hospital medicine. www.uptodate.com

• Quindós-Andrés, G. (2016). Environmental Mycology in Public Health. https://doi.org/10.1016/B978-0-12-411471-5.00006-5

• Quintiliani, R. (2010). Pharmacodynamics of antimicrobial agents: Time-dependent vs. concentration dependent killing. www.antimicrobe.org.

• Sarma, S. C. (2015). Beta Lactam Antibiotics. Presentation. https://www.slideshare.net/saurav9119/beta-lactam-antibiotics-43630735