Carbapenem-resistant Acinetobacter baumannii in resource-limited ICUs: when ‘recommended therapy’ is not realistically deliverable

Carbapenem-resistant Acinetobacter baumannii (CRAB) remains a ‘critical’ priority pathogen in the WHO Bacterial Priority Pathogens List (BPPL) 2024, reflecting both its clinical impact and the paucity of reliably effective, safe and accessible therapies.¹ Contemporary reviews reiterate that CRAB disproportionately affects critically ill and ventilated patients, spreads efficiently within hospitals and is associated with substantial mortality, particularly in bloodstream infection.² In addition to the clinical burden, treatment options for CRAB have historically relied on ‘salvage’ agents, most notably colistin/polymyxin B, which are nephrotoxic and have other adverse effects, limiting tolerability and dosing in critically ill patients.

Our central argument is simple: in many low- and middle-income country (LMIC) settings, the choice of therapy for CRAB is often determined not by susceptibility results or guideline preference, but by drug availability, procurement time, infusion feasibility and the patient’s ability to pay. This fundamentally changes the clinical decision-making framework compared with high-income settings. Put plainly, the major barrier to improving outcomes in LMIC CRAB infections is increasingly not the absence of evidence, but the gap between recommended therapy and real-world deliverability.

This gap is particularly pronounced in low- and middle-income countries (LMICs), where CRAB is prevalent yet access to effective agents remains inconsistent. Indian Council of Medical Research - Antimicrobial Resistance Surveillance and Research Network (ICMR-AMRSN) 2024 report highlights A. baumannii as a major healthcare-associated pathogen, particularly in ventilator-associated pneumonia surveillance, and reports a very high carbapenem non-susceptibility rate of ∼86.1% among A. baumannii bloodstream isolates.^3,4 Beyond India, a recent modelling study estimated that across eight large LMICs (including India), only 103 647 treatment courses were procured for an estimated ∼1.5 million infections in 2019—implying that only 6.9% of patients were treated appropriately.⁵ Such data quantify what clinicians observe: the burden is high, but effective therapy is often absent or delayed.

Sulbactam remains central to contemporary CRAB strategies due to its intrinsic activity against A. baumannii; however, achieving effective exposure often requires high-dose, prolonged-infusion regimens.⁶ There is no universally accepted standard-of-care regimen for severe CRAB infection; available options are supported by variable-quality evidence and are often constrained by toxicity, pharmacokinetic and pharmacodynamic uncertainty and access. This uncertainty is reflected in European expert recommendations that propose individualized combination regimens rather than a single definitive standard of care for carbapenem-resistant A. baumannii infections.⁷ In practice, recommended regimens often require prolonged infusions, higher daily doses, combination partner drugs (e.g. minocycline/tigecycline) and close monitoring—each of which introduces cost and implementation barriers at the bedside in LMIC ICUs.⁸

Sulbactam–durlobactam represents a significant advance. In the Phase 3 ATTACK trial, sulbactam–durlobactam met non-inferiority to colistin for 28-day all-cause mortality and demonstrated a significantly lower nephrotoxicity signal, alongside favourable clinical and microbiological response trends.⁹ These data suggest that sulbactam–durlobactam may be an alternative to colistin-based therapy where available. Recent guidance continues to emphasize combination approaches in CRAB, typically ensuring that at least one agent is sulbactam based.⁶ The 2024 IDSA Antimicrobial Resistance (AMR) guidance recommends sulbactam–durlobactam (in combination with a carbapenem) as the preferred therapy for severe CRAB infections; however, this is not readily available at most centres. High-dose ampicillin–sulbactam combinations are alternatives when access to these medications is limited.¹⁰

However, in many Indian centres, access to sulbactam–durlobactam remains limited, and the agent is not routinely stocked; acquisition often depends on local procurement pathways. Although compassionate/named-patient import mechanisms exist in India for selected unapproved medicines, these pathways are often slow and operationally difficult for time-critical ICU infections. High-dose ampicillin–sulbactam combinations (often with a partner agent, such as minocycline), therefore, remain common ‘real-world’ alternatives, but may be unaffordable for self-paying families.¹⁰ Illustratively, based on listed retail prices in India, a 10-day course of high-dose ampicillin–sulbactam targeting ∼9 g sulbactam/day [≈9 vials/day of 3 g (2 g/1 g)] plus IV minocycline 100 mg q12h may cost ∼₹1.3–1.6 lakh (∼$1700) (drug acquisition only), roughly 5–12 months of household consumption expenditure for a 4–5-member family in India.¹¹ In our 10-bed mixed medical–surgical adult ICU in India, the issue is not the absence of evidence, but the gap between evidence and its deliverability. Delays due to procurement, inability to sustain prolonged infusions and out-of-pocket payment requirements commonly determine what is actually delivered at the bedside and may contribute to poorer outcomes.

Consequently, clinicians may be forced to use polymyxin-based salvage regimens (colistin/polymyxin B) and other susceptibility-guided combinations (e.g. high-dose sulbactam-containing regimens with tetracyclines, such as minocycline/tigecycline; cefiderocol, when available), acknowledging limited comparative data and variable feasibility across centres, with risk of toxicity and delayed effective therapy in severe infection.

What should change is also clear: CRAB guidance and evaluations should explicitly incorporate deliverability in LMIC contexts. In addition to microbiological endpoints, trials and real-world studies should report pragmatic access outcomes (e.g. including time to availability of the recommended agent, treatment discontinuation due to cost, course completion and the proportion of patients receiving guideline-concordant dosing/infusion strategies). Given limited therapeutic options, infection prevention and control (IPC) remain central to CRAB management in resource-limited ICUs; WHO guidance emphasizes that prevention and control of CRAB in healthcare facilities emphasize multimodal IPC programmes, hand hygiene, contact precautions, environmental cleaning and surveillance, integrated with antimicrobial stewardship.¹²

Finally, policy responses should match the urgency of CRAB: coordinated procurement and formulary pathways for evidence-based agents, tiered pricing and patient-assistance mechanisms and post-marketing effectiveness studies that include LMICs and measure access-related delays and interruptions. Without these measures, therapeutic advances risk remaining confined to well-resourced systems, while patients in resource-limited ICUs continue to experience excess mortality from a pathogen that global prioritization already recognizes as ‘critical.’

Funding

This correspondence received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. The work was performed as part of routine clinical practice.

Transparency declarations

None to declare.