Cases & Commentaries

Staggered Sensitivity Results

Commentary By B. Joseph Guglielmo, PharmD

The Case

A 60-year-old woman with squamous cell carcinoma
of the glottis underwent laryngectomy, anterior neck dissection,
and pectoralis flap reconstruction of the anterior esophagus.
Postoperatively, she was started on clindamycin for surgical site
infection prophylaxis. On postoperative day three, increased
drainage from the surgical site was noted, which progressed and
required a return to the operating room for exploration on
postoperative day six. The site revealed purulent material with
involvement of the jugular sheath. Cultures of the wound were
taken, and the site was irrigated and re-closed.

Two days later, the wound cultures grew
Staphylococcus aureus. Per hospital protocol, the
microbiology laboratory called the nursing unit to report the
positive culture, and the patient's nurse informed the physician
team. Clindamycin was continued. Three days later, a final
sensitivity profile for the S. aureus isolate returned,
showing resistance to clindamycin. Hospital policy does not call
for notification to clinicians by the microbiology lab when a
"preliminary" culture result becomes "final" (when final
sensitivities become available). At this facility, physicians view
laboratory results in a scrolling text–based computer system,
which presents results in chronological order according to the time
of specimen collection. The final microbiology result and the
critical sensitivity results in this case remained in chronological
order (now 5 days prior). The physicians did not view the updated
culture results, and the patient remained on clindamycin.

The next day, the right internal jugular vein
ruptured, and the patient was taken emergently to the operating
room. A widespread infection of the surgical site with destruction
of the jugular sheath and erosion into the internal jugular vein
was noted. The internal jugular vein was ligated and sacrificed.
The patient died of sepsis and multiorgan system failure 3 days
later.

The Commentary

The case presented describes a 60-year-old woman
who developed a serious postoperative surgical wound infection
following laryngectomy, anterior neck dissection, and pectoralis
flap reconstruction. The scope of potentially preventable medical
errors ranges from inappropriate timing of surgical antibiotic
prophylaxis to inaccurate selection of empiric antibiotics. While
the procedures involved in reporting clinical microbiology
laboratory results can create opportunities for error, they likely
had little bearing on the outcome of this particular case, although
the issue warrants some discussion.

Timing and Clinical
Decision-Making

Importantly, the patient in this case did not
receive preoperative antibiotics prior to the surgical procedure.
The benefit of antibiotic prophylaxis in reducing surgical wound
infection after major, clean-contaminated otolaryngological tumor
resection is well-established.(1) The
most commonly implicated pathogens associated with postoperative
wound infection include normal oropharyngeal and nasal flora,
including anaerobes, but also streptococci and staphylococci. In
these elective procedures, clindamycin is active against these
pathogens and is an appropriate choice for prophylaxis.(2)
While clindamycin was an appropriate choice, prophylactic
antibiotics must be administered immediately prior to surgical
incision for maximal benefit
. In contrast, administering
postoperative antibiotics alone is no better than not using
perioperative antibiotics at all.(3)

In our case, antibiotics were administered only
after completion of the surgical procedure, a clear error. What
measures can improve the proper administration of antibiotic
prophylaxis? Obstacles to proper timing of surgical antibiotic
prophylaxis include the perception that timing of administration is
a "low priority," is inconvenient, and does not fit into the usual
preoperative workflow. In addition, insufficient organizational
communication and poor clarity of responsibility also have been
identified as barriers.(4) A
number of studies have identified mechanisms to improve the timing
of preoperative antibiotics.(5,6)
The most impressive results were seen from a multidisciplinary
computer-guided support system, which was associated with improved
timing of preoperative antibiotics and reduction in the rate of
clean wound infection.(6) In
this model, a multidisciplinary team reviewed published guidelines,
developed antibiotic recommendations, and shifted the
responsibility for administration from the preoperative nursing
staff to the anesthesiologist. Appropriate timing of antibiotic
administration improved from 51% to 98%, and clean wound infection
rate decreased from 2.7% to 1.4%.

Moving back to this case, increased drainage from
the surgical site was noted 3 days postoperatively while the
patient received clindamycin. On the sixth postoperative day, the
patient required re-exploration, still receiving empiric
clindamycin. Considering the apparent lack of response to 6 days of
clindamycin, an empiric broadening of antibiotic coverage to
include agents more predictably active against
methicillin-resistant Staphylococcus aureus (MRSA) and
aerobic gram-negative bacilli should have occurred. Ultimately, the
chosen empiric antibiotic did not match the susceptibility of the
bacterial pathogen. Potential mechanisms to improve the selection
of empiric antibiotics have centered upon computerized
decision support systems.(7-9)
In one study, a decision support system was found to reduce
antibiotic-susceptibility mismatches associated with empiric
antibiotics.(7)
Similarly, a computerized antimicrobial guidance program based upon
individual hospital clinical microbiology susceptibility data has
been demonstrated to significantly improve the correct choice of
empiric antibiotics associated with bacteremia.(8)

In this case, the initial clinical microbiology
laboratory reported the growth of S. aureus 2 days after
surgical re-exploration. Growth of S. aureus while the
patient was on clindamycin should have alerted the practitioner to
the possibility of clindamycin-resistant S. aureus and led
to a change to empiric vancomycin. Ultimately, 3 days later, the
susceptibility results were finalized, and the organism was
determined to be resistant to clindamycin. The chronological order
in which the susceptibility results were reported in this hospital
might have impacted their review by the surgical team. However,
considering that the rupture of the jugular vein and emergent
return to the operating room took place the day after the
susceptibility results were finalized, this staggered reporting
system likely had little impact on the unfortunate
outcome—particularly in comparison with the failure to
initiate antibiotics preoperatively or empirically broaden them
based on clinical response.

Staggered Reporting of Pathogens with
Sensitivity Results

While the reporting system here may not have
significantly influenced the outcome, a similar system may impact
care more dramatically in different circumstances. Standard
procedure calls for a clinical microbiology laboratory to provide
an early report identifying the isolated pathogen, pending
susceptibility results. The intent in providing early preliminary
microbiology reports is to streamline empirical therapy to that
consistent with the isolated pathogen. As mentioned previously,
early identification of S. aureus in the highlighted case
should have triggered a change in antibiotics, and such a change
may have favorably affected the outcome. From a systems standpoint,
standard practice also calls for the clinical laboratory to report
microbiological data chronologically based upon the time of the
sample, not at the time when the lab test was performed. One
systems change that might increase the likelihood of a clinician
viewing final susceptibility results from an earlier sampled
culture might be an additional, updated clinical microbiology entry
with finalized susceptibility results referring back to the
original sample. However, the impact of such a reporting mechanism
has not been confirmed in controlled studies, and two entries for
one culture could result in confusion and error. Potentially, the
best resolution to such reporting mismatch associated with a delay
between identification of the pathogen and final susceptibility
results might be the use of newer rapid susceptibility tests. In
the case of MRSA, commercially available latex agglutination
testing with associated identification of penicillin-binding
protein 2a can confirm the presence of MRSA within 24 hours. Using
this technology, the identification of the pathogen and
susceptibility results would have been reported at the same time,
eliminating the potential error associated with staggered
reporting.

Finally, the use of integrated pharmacy
systems—those with coordination between pharmacy and clinical
microbiology databases—represents a potential future solution
for pathogen-susceptibility mismatch. While some early commercial
systems are currently marketed, the success of such systems remains
to be proven. One system involves Therapeutic Antibiotic Monitoring
(TAM) alerts in which coordinated pharmacy and microbiology
databases notify the clinician of pathogen-antibacterial mismatch.
However, one particular challenge with such systems is the
identification of true mismatches as opposed to false positives
(e.g., colonizers vs. true pathogens). As per the recently released
Infectious Diseases Society of America and Society for Healthcare
Epidemiology of America guidelines, the combination of coordinated
pharmacy and microbiology databases along with an antibiotic
stewardship team may be the optimal solution toward appropriate
antibacterial use, including pathogen-antibacterial
mismatch.(10)

Take-Home Points

  • Appropriate timing of antibiotic
    prophylaxis and improved selection of empiric antibiotics are
    critical in the prevention of surgical site infections.
  • Institution-specific programs can
    improve the quality of timing for antibiotic prophylaxis through
    multidisciplinary teams and clear roles and responsibility for
    timing of the preoperative dose.
  • Systematic efforts to improve the
    selection of empiric antibiotics, through antimicrobial
    stewardship, include continuous summary, review, and dissemination
    of institutional susceptibility results with associated
    recommendations for therapy.
  • Rapid susceptibility testing will
    minimize errors associated with staggered reporting of preliminary
    culture and final susceptibility testing.

B. Joseph Guglielmo, PharmD
Professor and Thomas A. Oliver Chair in Clinical Pharmacy
School of Pharmacy, University of California, San Francisco

References

1. ASHP Therapeutic Guidelines on Antimicrobial
Prophylaxis in Surgery. Am J Health Sys Pharm. 1999;56:1839-1888.
[go to PubMed]

2. Johnson JT, Yu VL, Myers EN, Wagner RL. An
assessment of the need for gram-negative bacterial coverage in
antibiotic prophylaxis for oncological head and neck surgery. J
Infect Dis. 1987;155:331-333. [go to PubMed]

3. Classen DC, Evans RS, Pestotnick SL, Horn SD,
Menlove RL, Burke JP. The timing of prophylactic administration of
antibiotics and the risk of surgical-wound infection. N Engl J Med.
1992;326:281-286. [go to PubMed]

4. Tan JA, Naik VN, Lingard L. Exploring
obstacles to proper timing of prophylactic antibiotics for surgical
site infections. Qual Saf Health Care. 2006;15:32-38. [go to PubMed]

5. Burke JP. Maximizing appropriate antibiotic
prophylaxis for surgical patients: an update from LDS Hospital,
Salt Lake City. Clin Infect Dis. 2001;33(suppl 2):S78-S83. [go to PubMed]

6. Webb AL, Flagg RL, Fink AS. Reducing surgical
site infections through a multidisciplinary computerized process
for preoperative prophylactic antibiotic administration. Am J Surg.
2006;192:663-668. [go to PubMed]

7. Evans RS, Pestotnik SL, Classen DC, et al. A
computer-assisted management program for antibiotics and other
antiinfective agents. N Engl J Med. 1998;338:232-238. [go to PubMed]

8. Mullett CJ, Thomas JG, Smith CL, Sarwari AR,
Khakoo RA. Computerized antimicrobial decision support: an offline
evaluation of a database-driven empiric antimicrobial guidance
program in hospitalized patients with a bloodstream infection. Int
J Med Inform. 2004;73:455-460. [go to PubMed]

9. Davey P. The potential role of computerized
decision support systems to improve empirical antibiotic
prescribing. J Antimicrob Chemother. 2006;58:1105-1106. [go to PubMed]

10. Dellit TH, Owens RC, McGowan JE Jr, et al.
Infectious Diseases Society of America and the Society for
Healthcare Epidemiology of America guidelines for developing an
institutional program to enhance antimicrobial stewardship. Clin
Infect Dis. 2007;44:159-177. [go to PubMed]