Why Ceftriaxone Rules Surgery Across East Africa: A Measurement Problem

Across the operating theatres of the East African Community, a single antibiotic has quietly become the default answer to a question it was never meant to address. Ceftriaxone, a third-generation cephalosporin classified by the World Health Organization as a Watch-group agent, now dominates surgical antibiotic prophylaxis from Kakamega to Kigali, despite international guidelines calling for a narrow-spectrum Access-group drug such as cefazolin, given as one pre-incision dose and stopped at wound closure. A new perspective article published in Frontiers in Antibiotics argues that this entrenched practice is not primarily a failure of prescriber knowledge or stewardship principles. It is a measurement problem: the exposure is named in every regional point-prevalence survey yet appears in no national indicator that governs procurement, and no instrument records the supply constraint that determines the agent or the resistance it selects.

The pharmacological objection to ceftriaxone rests on the biology of the molecule rather than a general preference for narrow spectra. Cefazolin has a half-life of roughly two hours, penetrates most surgical sites well, and covers the organisms responsible for the majority of clean and clean-contaminated procedures, which is precisely why WHO guidelines and international surgical societies recommend it as the preferred first-line prophylactic agent. Its effect on colonic flora is correspondingly limited. Ceftriaxone differs on both axes that determine selection pressure. Its long half-life sustains sub-inhibitory exposure well beyond the operative window, and a substantial fraction of each dose is excreted in bile directly into the gut lumen, acting on the densest reservoir of Enterobacterales in the human body. Exposure delivered straight to colonic flora is an efficient engine for selecting extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae, the organisms that subsequently cause resistant surgical-site and bloodstream infections.

What sustains the ceftriaxone default is a set of four interacting failure modes, each with a distinct measurable signal and each sitting with a different actor. The first is substitution: ceftriaxone is used where cefazolin is indicated, most often because cefazolin is unavailable. The mechanism has been documented in Ethiopia, where cefazolin is the first-line prophylactic agent in the national Standard Treatment Guideline and appears on the national Essential Medicines List, yet was unavailable for years and was removed from the government procurement list despite both recommendations. Stewardship teams there reverted to ceftriaxone once cefazolin went out of stock. The commercial logic generalises across the region: where no clear demand signal or supporting policy exists, suppliers favour broad-spectrum agents with multiple uses over a narrow agent with a single purpose, and thin margins on old injectable generics give manufacturers little reason to expand capacity.

The second mode is prolongation, the most consequential for selection. A single pre-incision dose becomes a multi-day postoperative course. At the University Teaching Hospital of Kigali and at Kakamega County Teaching and Referral Hospital in Kenya, prophylaxis exceeded one day in over 83 percent of surgical patients. Across three hospitals in north-eastern Tanzania, it continued beyond three days in 57 percent of cases, with ceftriaxone the commonest agent. In Uganda, only 4 percent of surgical patients at a regional referral hospital completed prophylaxis on the day of surgery, with a mean duration of 3.5 days and ceftriaxone plus metronidazole in 67.1 percent of prescriptions. At Kawempe National Referral Hospital in Kampala, a two-to-three-day postoperative course after caesarean section is hospital policy. The third mode is unnecessary combination: ceftriaxone is co-prescribed with metronidazole for caesarean and abdominal surgery, frequently without a documented anaerobic indication. In the Kawempe series, anaerobes were not among the organisms recovered. The fourth is empirical spillover, as ceftriaxone, the workhorse of undifferentiated sepsis on the wards, becomes the reflex in theatre. Ugandan surveys show ceftriaxone accounting for 37 percent of antibiotic prescriptions across 13 hospitals, with guideline compliance of just 30 percent, and in Tanzania 90 percent of surgical prophylaxis prescriptions carried no documented justification. These modes are layers, not alternatives: one caesarean episode can substitute ceftriaxone for cefazolin, combine it with metronidazole, and prolong it for five days.

Where indication-level prescribing data are absent, resistance data are increasingly available, and they paint a sobering picture. In post-caesarean surgical-site infections at Mulago Hospital in Kampala, all 11 E. coli isolates and 43 of 44 Klebsiella isolates were ceftriaxone-resistant. At Kawempe, the dominant gram-negatives were 94 to 100 percent resistant to third-generation cephalosporins, and carbapenem-resistant Acinetobacter accounted for 65.4 percent. At Kirehe District Hospital in Rwanda, 92.1 percent of post-caesarean isolates were ceftriaxone-intermediate or resistant. At Muhimbili National Hospital in Dar es Salaam, extended-spectrum beta-lactamase production was found in 79.3 percent of Enterobacteriaceae, rising to 92.3 percent among E. coli. A systematic review and meta-analysis of 59 studies across Central, Eastern, Southern, and Western Africa found resistance in E. coli above 40 percent for every antibiotic class except carbapenems, and in K. pneumoniae above 30 percent for every class except carbapenems. The review’s authors noted that third-generation cephalosporin resistance in E. coli exceeded what global burden estimates predicted and suggested this might reflect the proportion of surgical-site infections in the review and the use of ceftriaxone in surgical prophylaxis selecting out resistant isolates.

These series are heterogeneous, differing in case definition, specimen type, and setting; several are not confined to surgical-site infections, several rest on small denominators, and all come from referral centres where resistant organisms concentrate. The authors are careful about what the data can and cannot establish. Where most Enterobacterales causing surgical-site infection are already ceftriaxone-resistant, the effectiveness of ceftriaxone as prophylaxis against these organisms may be limited, but these data cannot determine whether prophylactic ceftriaxone exposure contributed to the observed resistance. They are drawn from infections that occurred, not from the flora of patients administered prophylaxis. What they do show is that prophylaxis and therapy draw on the same shrinking pool of susceptibility, and that resistance among surgical-site isolates is already high enough to threaten the value of prophylaxis itself.

The deeper puzzle is why surveillance cannot see the exposure that produced these isolates. National consumption reporting and the WHO GLASS-AMC platform aggregate ceftriaxone as a single line of defined daily doses procured or dispensed. Defined daily doses quantify volume, not indication, so the share generated by surgical prophylaxis cannot be recovered from them. Facility prevalence surveys do capture indication. One western Kenyan referral hospital identified ceftriaxone in 36.7 percent of prescriptions, much of it for prophylaxis of excessive duration, but these are episodic audits whose signal never reaches the national totals governing procurement. The AWaRe framework sets targets for reducing Watch consumption yet cannot reveal that a share of it is used needlessly in theatre. National Action Plans carry the same blindness: they commit to stewardship and surveillance, but none specifies an indication-stratified indicator for prophylaxis appropriateness. E. coli and K. pneumoniae are GLASS priority pathogens whose cephalosporin resistance is reported centrally, but that denominator is built from blood, urine, faeces, and genital swabs rather than from surgical-site or wound specimens, where resistance runs higher, and GLASS-AMR sits in a separate module from GLASS-AMC, linked to consumption only ecologically and never to indication.

The instruments in use, chiefly the Global Point Prevalence Survey, the ESAC protocols, and national quality-indicator sets, record duration, documented indication, and guideline concordance. Each was built to measure whether prophylaxis was administered correctly; none was built to measure what it cost. A system can report 95 percent compliance while ceftriaxone dominates the non-compliant remainder, and no established indicator would reveal it. Yet the gap is not uniformly one of absent instruments. For agent choice, the data are already collected: point-prevalence protocols record the molecule, the indication, and the duration in one record, and AWaRe-based quality indicators now cover surgical prophylaxis explicitly. What does not happen is transmission. Those figures live in episodic, facility-level surveys and never enter the national consumption totals that govern procurement. The authors propose four measures, one requiring routing rather than building and three genuinely absent. The first is agent share, the proportion of prophylactic episodes using a Watch-group agent rather than cefazolin, derivable today from point-prevalence data but reported facility by facility rather than nationally. The second is cefazolin stock-out days, recorded alongside prescribing, because a guideline recommending an agent that cannot be ordered is inert, and procurement is itself a stewardship intervention. The third is prophylaxis-attributable ceftriaxone consumption, identified from theatre and prescribing records and reconciled with national consumption totals, the central omission that prevents any stewardship intervention in theatre from demonstrating an effect on national consumption. The fourth is peri-operative carriage of cephalosporin-resistant Enterobacterales, measured through rectal-swab surveillance at sentinel sites, the only measure denominated in resistance rather than adherence or infection.

One caution should accompany these measures. High resistance among wound isolates must not be read as an argument against cefazolin. The same pooled data show resistance to first- and second-generation cephalosporins scarcely lower than to third-generation agents, and every gram-negative isolate in the Rwandan series was cefazolin-resistant. These figures describe organisms cultured from infections that occurred, the prophylactic failures, rather than the flora of patients in whom prophylaxis succeeded. Prophylaxis for clean and clean-contaminated surgery targets skin flora, principally staphylococci, for which cefazolin is selected rather than for gram-negative breadth. The live debate over broader cover in caesarean prophylaxis concerns adjunctive azithromycin, where a single dose added to cefazolin roughly halved the composite postoperative infection outcome in the C/SOAP trial, 6.1 percent versus 12.0 percent. That debate turns on what to add to the cephalosporin base, not which cephalosporin to use, and its base was cefazolin.

Reform is supported by existing quality-improvement experience rather than requiring entirely new infrastructure. At Thika Level 5 Hospital in Kenya, a locally developed policy advising preoperative prophylaxis and discouraging extended postoperative courses was audited with feedback to prescribers, and from near-exclusive postoperative use, adoption of preoperative prophylaxis was rapid. This example suggests that defined recommendations, local ownership, and feedback can improve prophylaxis practice. Comparability must be built in from the outset, since an infection recorded under five names with inconsistent case definitions cannot be pooled across borders. The evidence base assembled here rests substantially on Kenya, Uganda, Tanzania, and Rwanda; South Sudan contributes no surgical resistance data, Burundi and the Democratic Republic of the Congo contribute only uncultured incidence data, and Somalia contributes isolates not disaggregated by specimen source. The decision this argument calls for is administrative rather than clinical. Ministries of health, national AMR secretariats, and the Community’s regional machinery already collect prescribing, procurement, and consumption data. The main gap is the lack of a standardised system that links indication, agent selection, and consumption across facilities and countries. Establishing such measures would convert an ungoverned practice into a governable one, allowing ceftriaxone use for surgical prophylaxis to be quantified, compared across settings, and incorporated into stewardship and procurement decisions before the pool of susceptibility shrinks further.

Subject of Research: Ceftriaxone-by-default in surgical prophylaxis across the East African community: a measurement problem

Article Title: Ceftriaxone-by-default in surgical prophylaxis across the East African community: a measurement problem

Article References: Ceftriaxone-by-default in surgical prophylaxis across the East African community: a measurement problem. (n.d.). https://doi.org/10.3389/frabi.2026.1968363

Image Credits: AI Generated

DOI: 10.3389/frabi.2026.1968363

Keywords: Ceftriaxone-by-default, surgical, prophylaxis, across, East, African, community, measurement, problem, scientific research