Page 90 - JSOM Winter 2025

also noted that similar clones were being isolated at between penetrating extremity wounds and abdominal
other German hospitals at that time. This suggested that wounds in our recommendations. Recommendation
transmission events may have occurred before admis- against distinction here was also made on the premise
sion at the studied hospitals (e.g., local hospital trans- that expanding the spectrum of antibiotics beyond the
mission or during en-route care). This is comparable high-consequence pathogens above due to presumed
to the known Acinetobacter baumannii infections and perforation of abdominal viscera is unlikely to improve
colonization in military patients from the earlier Iraq survivability without surgical intervention and thus
and Afghanistan conflicts after transfer out of theater. 17 outside the spectrum of TCCC guidelines. The recom-
v. Based on this accumulated data, it is apparent that mended antimicrobial spectrum and duration remained
there is a difference in the pathogens isolated at or consistent with guideline-based antimicrobial regimens
near the point of injury (e.g., skin flora such as S. utilized for abdominal procedural prophylaxis. Further,
aureus, Streptococcus spp., including group A strep- excessive spectrum or duration of antimicrobials would
tococci (Streptococcus pyogenes), or environmen- drive resistance and eradicate non-pathogenic en-
tally-acquired agents such as Clostridium perfrin- teric commensals. Anaerobic (e.g., Bacteroides fragilis
gens) compared to nosocomial pathogens obtained group) and drug- resistant pathogen (e.g., Pseudomonas
from subsequent contact with medical care at var- aeruginosa, MRSA, carbapenem-resistant A. bauman-
ious points along the route to definitive care (such nii) coverage were weighted lower as these pathogens
as Enterobacterales, Pseudomonas aeruginosa, and are more likely to be encountered nosocomially or
Acinetobacter baumannii). The development of anti- contribute to morbidity and mortality after the scope
biotic resistance in these bacteria varies but seems less of TCCC. Also, their emergence may be increased via
likely to be inherent at the point of injury. It is unclear antibiotics given during the care rendered under TCCC
how much of this selective pressure occurs due to cur- protocols.
rent ertapenem use at the point of injury versus con- iii. A point that was frequently emphasized during panel
tinued broad-spectrum treatment and the logistical im- discussions was that the nature of future conflicts is
practicality of strict infection control protocols within less likely to guarantee the successful “Golden Hour”
a wartime environment. Regardless, a reasonable goal in transferring the wounded to a higher level of care,
in changing our antibiotic selection in TCCC would due to the potential location of future conflicts and
be to utilize a narrower-spectrum antibiotic to target projected lack of air and sea superiority with near-peer
known pathogens of high significance and attempt to adversaries. As such, the duration of action of the anti-
minimize collateral damage to the patient’s commensal biotics used was weighted higher.
and protective bacterial flora. Decisions must be made iv. The results of our matrix for oral antibiotic options
to either escalate antibiotic spectrum to cover for these resulted in a three-way tie for the lowest (best) score:
emerging drug-resistant pathogens, therefore introduc- cefadroxil, cephalexin, and linezolid at 37 points (see
ing more complex and potentially toxic antibiotics to Table 3). We considered these our first-tier options,
the wartime environment, or to target only high-yield with our second-tier options being dicloxacillin and
and broadly drug-susceptible pathogens such as strep- amoxicillin-clavulanate at 39 points. Cefadroxil, ceph-
tococci and staphylococci. alexin, and dicloxacillin have similar spectra of cover-
b. Update: age regarding excellent coverage for GAS and MSSA,
i. When looking for the “ideal antibiotic,” the panel less so for clostridia and B. fragilis, though these are
expanded upon a matrix weighing desirable charac- weighted less. Of these, cefadroxil has the advantage
teristics for the purposes of TCCC originally used by of once or twice daily dosing, compared to four times
Murray et al. in 2005. This weighed spectrum of cov- daily for the other two. One disadvantage of cefadroxil
18
erage, cost, half-life, tissue penetration, and adverse ef- compared to cephalexin is its slightly higher cost and
fects, among other factors. We also used two separate less reliable availability for partner nations who may
matrices, one for oral and one for parenteral antibi- base their recommendations on our guidelines, mak-
otics which considered additional factors such as sta- ing cephalexin an acceptable alternative. Linezolid is
bility, dosing form, and infusion time with parenteral similar in spectrum of coverage and adds MRSA cov-
antibiotics (see Tables 1 and 2). erage, which we had determined was not critical at the
ii. Regarding the spectrum of coverage for TCCC and point of injury. It also has the advantage of not being
point-of-injury pathogens, the main pathogens tar- a beta-lactam, which would be beneficial in avoiding
geted (and weighted higher) were GAS, methicillin- perceived complications of penicillin allergies, many of
susceptible S. aureus (MSSA), and Clostridium perfrin- which are not substantiated before battlefield encoun-
gens. These represent the pathogens known to be most ters nor safely testable in that environment (see further
likely inoculated from skin flora or the environment discussion on antibiotic allergies below). Linezolid
from penetrating combat wounds at the point of in- is also less tested in mass casualty/combat scenarios.
jury. They are also the pathogens most likely involved Lastly, amoxicillin-clavulanate provides additional
in necrotizing soft tissue infections that can lead to Gram-negative and anaerobic coverage, which is again
increased mortality in patients sustaining combat less useful at the point of injury, and slightly poorer
wounds, especially during the timeframe of TCCC, MSSA coverage. Notably, the previous recommen-
which may be further prolonged in future conflicts. dation of moxifloxacin scored a 42, reinforcing the
It was concluded that some Gram-negative coverage benefits of moving away from this prior recommen-
should still be included since they would be present dation based on the currently favored characteristics
in penetrating abdominal wounds. However, with sim- for our antibiotic choice. In addition, moxifloxacin is
plicity preferred in TCCC, we decided not to distinguish also more susceptible to potential supply chain issues

88 | JSOM Volume 25, Edition 4 / Winter 2025