DILEMMAS IN INFECTIOUS

DISEASE Paul D. Holtom, MD

Associate Professor of Medicine and Orthopaedics USC Keck School of Medicine

SEVERE CAP

What is the best antibiotic treatment

for severe CAP?

COMMON PATHOGENS IN CAP

CAP: Coinfection S.pneumoniae + “Atypicals”

•  Jokinen (CID 2001): 21% of Sp patients had coinfection: •  Mycoplasma, Chlamydia

•  Lieberman (Thorax, 1996): 148 S. pneumoniae patients

– Mycoplasma: 43 29% – Chlamydia: 34 23% – Legionella: 23 15% – TOTAL 67%

CAP: INPATIENT TREATMENT

•  Respiratory fluoroquinolone •  β-lactam PLUS a macrolide

Mandel et. al. CID 2007;44:S27-72

30-day CAP Mortality in Hospitalized Elderly Patients

0.00 0

Days from hospital admission

Adj

uste

d m

orta

lity

0.20

0.18

0.16

0.14

0.12

0.10

0.08

0.06

0.04

0.02

5 10 15 20 25 30

2nd gen. ceph + macrolide ↓29%*

Fluoroquinolone ↓36%*

*p < 0.05

n=12,945 inpatients β-Lactam/inhibitor + macrolide ↑77%*

CAP: INPATIENT TREATMENT (ICU)

•  β-lactam PLUS – Azithromycin OR – Fluoroquinolone

•  For CA-MRSA – add vancomycin or linezolid

Mandel et. al. CID 2007;44:S27-72

C. Difficile DIARRHEA

What antibiotic is best

and how long should I treat?

Epidemiology of CDAD

Scanning electron micrograph

DIAGNOSTIC CHALLENGES

•  EIA – Results in 2 hours – Sensitivity 60-95%; Specificity 75-100% – Repeat testing not warranted

•  Changes diagnosis in <1% of cases •  Increases rate of false positive test

Mohan SS et al. Am J Med 2006;119:356

STANDARD THERAPY •  Withdrawal of inducing agent •  Avoid drugs with antiperistaltic activity •  Oral metronidazole

– 250 mg qid or 500 mg tid x 10 d – First line therapy since 1980’s – CDC preferred therapy – New reports of failure rates of 16-38%

Bartlett, Ann Int Med 2006;145:758-764

STANDARD THERAPY •  Withdrawal of inducing agent •  Avoid drugs with antiperistaltic activity •  Oral metronidazole •  Oral vancomycin

– 125 mg-250 mg po qid x 10 d – Probably more effective, esp. in seriously

ill patients

Bartlett, Ann Int Med 2006;145:758-764

ESBL-PRODUCING GRAM NEGATIVES

What antibiotic would be effective?

Classification of Beta-Lactam Hydrolyzing Enzymes

Group 1 Group 2be Group 2d Group 3 Group 4

Class C

AmpC

Clav-R

Class A

TEM/SHV CTX-M ESBLs

Clav-S

Single point mutations in

TEM-1 create CTX-Ms

Class D

OXA

Clav-R/S

Chromosomal and plasmid

Class B

IMP/VIM

Clav-R EDTA-S

Plasmid-mediated transfer

Not well-characterized

Serine Serine acylation

Metallo(Zn) Zinc-facilitated

hydrolysis

Beta - Lactamases

Global Issues with ESBL-Producing Enterobacteriaceae

•  More frequent outside USA – Asia, 9-30% – Latin America and parts of Europe, ≤60%

•  In USA, ESBL-producing E.coli and K.pneumoniae have been 5% and 10% – Higher in Mid-Atlantic states (ESBL-

producing K.pneumoniae, ~20%) – Brooklyn, NY – 34% K.pneumoniae

produce ESBL •  ICUs have higher rates of ESBLs •  Rising incidence in LTCFs

Adverse Clinical Impact of ESBL-Producing Enterobacteriaceae

•  Inadequate initial antimicrobial therapy associated with higher mortality in non-urinary infections due to ESBL-producing Enterobacteriaceae (OR=2.28)1

•  Delay in time to institution of effective antimicrobial therapy was associated with increasing mortality1

•  The rate of treatment success for patients infected with ESBL-producing E. coli and Klebsiella spp. whose initial treatment involved non-carbapenems was lower than controls (39% vs 83%; P=0.013)2

1 Hyle EP et al. Arch Intern Med. 2005;163:1375-80. 2 Lee SY et al. Infect Cont Hosp Epidemiol. 2006;27:1226-32.

NECROTIZING SOFT-TISSUE INFECTIONS

What antibiotic would be effective?

NECROTIZING SOFT-TISSUE INFECTIONS

•  Delays in therapy are common •  Diagnosis requires a high index of

clinical suspicion

CLASSICAL TRIAD OF NECROTIZING

SOFT-TISSUE INFECTIONS

• Fever • Crepitance • Hypotension

SIGNS OF NECROTIZING SOFT-TISSUE INFECTIONS

•  Edema > erythema •  Skin vesicles or bullae •  Subcutaneous gas •  No lymphangitis or

lymphadenitis

DIAGNOSIS OF NECROTIZING STI

•  Clinical findings •  Laboratory testing

– Of little use – Lacks sensitivity and specificity

•  Ultrasound •  MRI scan •  SURGERY

CLASSIFICATION OF NECROTIZING FASCIITIS

•  Type I – Polymicrobial – Most common in diabetics,

immunocompromized

CLASSIFICATION OF NECROTIZING FASCIITIS

•  Type I •  Type II

– Group A Strep (Strep. pyogenes) – Most common type – 20% are nosocomial – 50% have no obvious portal of entry

CLASSIFICATION OF NECROTIZING FASCIITIS

•  Type I •  Type II •  Type III

– Marine vibrio – Acquired by puncture from fish or

ingestion of shellfish

NECROTIZING STI: THERAPY

• Prompt recognition • Urgent debridement • Broad-spectrum antibiotics

McHenry et al, Ann Surg 1995;221:558

NECROTIZING STI: ANTIMICROBIAL THERAPY

• Beta-lactam antibiotic • Streptococcal coverage

–  + Clindamycin • Gram negative coverage • Anaerobic coverage

CID 2005;41:1373-406

NECROTIZING STI: OTHER THERAPY

•  ? IVIG – Streptococcal necrotizing infections

• Study: 21 pts vs 32 historical controls • Improved 30 mortality rate

Kaul et al. CID 1999;28:800-7

NECROTIZING STI: OTHER THERAPY

•  ? IVIG •  ? Hyperbaric oxygen

– Post debridement – Several studies (observational, non-

randomized, suggest lower mortality)

THANK YOU