Is My Patient Getting Better? What to Expect Regarding Time Frame for Improvement in Skin/Soft
Tissue Infections and Pneumonia
Infectious Diseases Section, VA Greater Los Angeles Healthcare System
March 2013
Skin/soft tissue infection
 General principles
 Clinical course of SSTI: what the literature suggests
Pneumonia
 General principles
 Clinical course of community-acquired pneumonia: what the literature suggests
References
Skin/Soft Tissue Infection:
General principles:
 Due to the inherent variability in its presentation, improvement of skin/soft tissue infections
(SSTIs) with antimicrobial therapy can be difficult to gauge.
 Even with appropriately-directed antimicrobial therapy, some presentations of SSTI may appear
worse in the initial 24-48 hours of antimicrobial treatment.
 Therapy directed against Gram-negative pathogens is typically not necessary in most SSTI but
should be considered if:
o
A deep surgical site infection or moderate to severe diabetic foot infection is present,
OR
o
There is concern for polymicrobial necrotizing fasciitis (which can be associated with
surgical procedures involving the bowel or penetrating abdominal trauma, infections
originating in the perineum, or from sites of injection in injection drug users).
 Worsening of skin/soft tissue infections where the above two diagnostic entities are not present
should prompt consideration of surgical consultation rather than broadening of therapy to
include Gram-negative pathogens, per se.
[TOP]
Clinical course of SSTI: What the literature suggests:
One study of intravenous antimicrobial treatment for cellulitis at home versus in the hospital
determined a mean time of 1.5 days to achieve no advancement of cellulitis. Approximately 90% of
patients achieved no advancement of cellulitis by treatment day 3.
Two recent randomized trials of ceftaroline vs. vancomycin plus aztreonam for the treatment of
complicated SSTI were conducted in which patients were included only if the infection required
hospitalization and involved deeper soft tissue or required significant surgical intervention (apart from
bedside I&D) OR consisted of cellulitis or lower extremity abscess in patients with diabetes mellitus or
peripheral vascular disease. Diabetic foot infections with underlying osteomyelitis, human or animal bite
wounds, necrotizing fasciitis, gangrene, and prosthesis-associated infections were excluded. By end of
treatment (typically 14 days), approximately 90% of all patients enrolled achieved clinical cure, defined
as resolution of all signs and symptoms of SSTI to the extent that further antimicrobial therapy was not
necessary. Early clinical response was defined as cessation of spread of the lesion from baseline and
absence of fever at day 3; this was seen in approximately 70% of patients. Only 50-60% of analyzed
patients had a 20% decrease in lesion size by day 3.
Another randomized trial comparing the new oxazolidinone tedizolid to linezolid in the treatment
of acute SSTI enrolled patients who had cellulitis, major cutaneous abscess, or wound infection
surrounded by erythema with a minimum total lesion surface area of 65 cm2 accompanied by at least 1
local and regional (lymphadenopathy) or 1 systemic sign of infection, and a Gram-positive pathogen was
suspected or documented. At 48-72h approximately 90% had early clinical treatment response, and
approximately 75% of analyzed patients had a 20% decrease in lesion size. Overall, these are higher
early response rates than that observed in the ceftaroline studies, potentially due to lower acuity of
underlying disease (fever on presentation was less common and median lesion areas were smaller in the
tedizolid study).
In summary, it seems reasonable to expect resolution of fever and, at minimum, cessation of
spread of lesion at 72h in the large majority of cases of SSTI that require hospitalization and are
appropriately treated. However, lack of early response does not necessarily imply later clinical failure.
[TOP]
Pneumonia:
General principles:
 Due to competing clinical morbidities in our patient population (e.g. congestive heart failure,
COPD), discerning clinical improvement of pneumonia may be more difficult than in other
populations with less comorbid conditions.
 While the appearance of new infiltrates on chest radiograph in ventilated patients is a sensitive
(78-100%) marker for ventilator-associated pneumonia, it is not particularly specific (33-75%),
particularly when there is little else to support the diagnosis.
 Improvement and/or resolution of infiltrates due to pneumonia on chest radiograph often lags
other markers of clinical improvement with appropriate antimicrobial therapy.
 Encouragement of early mobilization and early switch to oral antimicrobial therapy has been
associated with decreased length of stay without decreasing subsequent readmission or
mortality.
[TOP]
Clinical course of community-acquired pneumonia: What the literature suggests:
Two recent randomized trials of ceftaroline vs. ceftriaxone for the treatment of communityacquired pneumonia were conducted in which patients with acute onset of illness (≤ 7 days) that
required initial dosing with an intravenous agent and hospitalization were enrolled. By day 4 of therapy,
roughly 60-70% of patients for whom data was available experienced clinical stability (i.e. no fever,
stable vital signs, baseline mental status, and improvement in either cough, dyspnea, pleuritic chest
pain, and sputum production). Clinical cure was defined as total resolution of all signs and symptoms of
pneumonia or improvement to such an extent that further antimicrobial therapy was not necessary (i.e.
absence of fever for at least 24h and a substantial improvement in signs and symptoms of pneumonia).
By end of therapy at 5-7 days, over 80% of patients experienced clinical cure.
Patients admitted to the general medical ward for community-acquired pneumonia may be able
to be converted to oral antimicrobial therapy and discharged fairly quickly. A recent analysis of
implementation of a 3-step critical pathway that encouraged early mobilization and use of objective
criteria for switching to oral antimicrobial therapy and for deciding on hospital discharge or usual care
for community-acquired pneumonia enrolled 401 immunocompetent patients admitted to general
medicine wards at a single medical center in Spain. The median length of stay was 3.9 days in the group
receiving the 3-step intervention, compared to 6.0 days in the usual care group. The median duration of
intravenous antimicrobial therapy was 2.0 days in the 3-step group and 4.0 days in the usual care group.
No significant differences were found with regard to subsequent readmission, 30-day mortality, or
patient satisfaction with care.
[TOP]
References:
1. Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of
skin and soft-tissue infections. Clinical Infectious Diseases 2005;41:1373-406.
2. Corwin P, Toop L, McGeoch G, et al. Randomised controlled trial of intravenous antibiotic treatment
for cellulitis at home compared with hospital. BMJ 2005;330:129-35.
3. Corey GR, Wilcox M, Talbot GH, et al. Integrated analysis of CANVAS 1 and 2: Phase 3, multicenter,
randomized, double-blind studies to evaluate the safety and efficacy of ceftaroline versus
vancomycin plus aztreonam in complicated skin and skin-structure infection. Clinical Infectious
Diseases 2010; 51(6):641–650.
4. Prokocimer P, De Anda C, Fang E, Mehra P, Das A. Tedizolid phosphate vs linezolid for treatment of
acute bacterial skin and skin structure infections: the ESTABLISH-1 randomized trial. JAMA
2013;309(6):559-69.
5. File TM, Low DE, Eckburg PB, et al. Integrated Analysis of FOCUS 1 and FOCUS 2: Randomized, DoubleBlinded, Multicenter Phase 3 Trials of the Effiicacy and Safety of Ceftaroline Fosamil vs.
Ceftriaxone in Patients with Community-Acquired Pneumonia. Clinical Infectious Diseases
2010;51(12):1395-1405.
6. Carratala J, Garcia-Vidal C, Ortega L, et al. Effect of a 3-step critical pathway to reduce duration of
intravenous antibiotic therapy and length of stay in community-acquired pneumonia: a
randomized controlled trial. Arch Int Med 2012; 172(12):922-8.
[TOP]