Infectious Diseases II

Ceftolozane is a novel fifth-generation cephalosporin.

ii.

Spectrum of activity: Gram-negative organisms, including P. aeruginosa. Activity includes

coverage against ESBL and AmpC β-lactamase–producing organisms. Limited gram-

positive and anaerobic coverage. Among multidrug-resistant and extended drug–resistant

Pseudomonas, ceftolozane/tazobactam retains good activity, with its MIC90 still below the

MIC breakpoint for resistant, as determined by the FDA.

iii.

FDA approved for the treatment of complicated intra-abdominal infection, complicated UTI,

and hospital-acquired and ventilator-associated pneumonia. However, clinically, its coverage

will most likely be reserved for resistant pseudomonal infections. A recent study concluded

that high-dose ceftolozane/tazobactam (3 g every 8 hours) was noninferior to meropenem in

the treatment of nosocomial pneumonia. Twenty-eight day mortality, clinical response, and

adverse reactions were similar between groups.

CLSI aminoglycoside breakpoint revisions

ii.

Recommend tobramycin 7 mg/kg every 24 hours if expanding coverage for Pseudomonas.

MRSA

MRSA is a significant cause of both community- and hospital-acquired infections.

Skin and soft tissue infections

Community-acquired MRSA often presents as a skin and soft tissue infection.

ii.

Cutaneous infections and abscesses are best treated with adequate drainage.

iii.

Antibiotics are usually not necessary unless the patient does not respond to drainage, has

extensive disease, or has signs and symptoms of systemic infection.

iv.

Antibiotic treatment choices for community-acquired MRSA cutaneous and skin infections

include trimethoprim/sulfamethoxazole, clindamycin, and tetracycline.

MRSA bacteremia and endocarditis

Can be treated with either vancomycin or daptomycin

ii.

In a study of patients with right-sided endocarditis, daptomycin was noninferior to vancomycin.

Of interest, treatment response was poor with both therapies, with only about 40% in each

group meeting the primary outcome of treatment success 42 days after the end of therapy.

Daptomycin was dosed at 6 mg/kg in this study.

iii.

Some experts recommend giving higher daptomycin doses (8–10 mg/kg) to optimize the PD

target attainment for daptomycin. Daptomycin resistance in S. aureus has been reported.

A correlation appears to exist between intermediate sensitivity to vancomycin, thought to

be caused by a thickened cell wall–limiting penetration, and decreased susceptibility to

daptomycin. Currently, the daptomycin breakpoint MIC for MRSA is 1 mcg/mL or less.

iv.

Several investigations have also evaluated daptomycin compared with vancomycin for

MRSA bacteremia when the vancomycin MIC was greater than 1 mcg/mL. Although these

investigations showed outcome benefit associated with daptomycin use, the studies have

several limitations, which may limit their applicability.

diseases consultation, which may have other treatment implications.

vancomycin MIC is greater than 1 mcg/mL cannot be recommended.