During pregnancy, the body undergoes significant changes in the immune system and metabolism [1], which can increase the risk of bacterial infections, including bacterial sepsis [2]. Globally, there are approximately 48.9 million cases of maternal sepsis each year, 17 million of which were reported in Africa [3]. Annually, 5.7 million women develop severe sepsis during pregnancy, childbirth, post-abortion, or the postpartum period. According to the WHO, the magnitude of deaths from sepsis is greater in Sub-Saharan Africa and southern Asia, accounting for 253,000 (87%) maternal sepsis-related deaths [4]. Identifying and diagnosing maternal sepsis early can be difficult, as maternal sepsis is often similar to other serious obstetric conditions, according to previous studies [4, 5]. Thus, most sepsis-infected mothers experience severe morbidity when they arrive at health facilities [6]. Maternal sepsis is responsible for 11% of maternal mortality. On the other hand, mothers can also contract sepsis through bacterial contamination at health facilities. Up to 50% of sepsis survivors may experience lasting disabilities, including myopathy, neuropathy, chronic pelvic pain, infertility, and psychological distress [7, 8].
Emerging carbapenemase- and ESBL-producing K. pneumoniae strains threaten maternal and neonatal health despite progress in treating and managing sepsis and bacteria [9, 10]. These strains can survive in various environments, such as water, soil, and the gastrointestinal tract [9–11]. Its ubiquitous nature leads to spontaneous mutations and acquired antimicrobial resistance genes that undergo gene transfer by mobile genetic elements (MGEs). Once they acquire resistance genes, they can transfer them horizontally and vertically within and between species [9–12]. This bacterium has acquired antimicrobial resistance genes (ARGs) (blaLAP-2, blaTEM-1B, and blaSHV-106) from the ecosystem [13] and the primary source genes blaKPC-2, NDM-1, and KPC-2 [14–15]. As a result, they were shown to be non-susceptible to carbapenem, colistin, carbapenem, polymyxin, fluoroquinolone, aminopenicillin, third-generation cephalosporin, and tigecycline [13–18]. K. pneumoniaeis estimated to cause 124,000 deaths annually, accounting for 20% of AMR-related fatalities and 18% of AMR-related deaths, resulting in healthcare costs of $9 billion per year [2, 18, 19].
K. pneumoniae strains that produce carbapenemase/ESBL are known to possess antimicrobial resistance and virulence genes. In this regard, some of virulence genes include fepA, ent (enterobactin), iutA (aerobactin), fyuA, irp1, irp2 (yersiniabactin), irp1, fyuA, iutA, peg 344, ST29, PAI, ehxA, toxB, eae, sfa, pai, fim H, aggR, hly, pap, hyl A, traT pai, cnf-1, afaandrmpA/A. Similarly, antimicrobial resistance genes such as blaKPC, blaCTX, blaTEM, blaOXA, blaSHV, strA/B, aac(3)-IIa, aac(6)Ib-cr, qnrB1, oqxAB, sul2, dfrA14,and catB3 are common in K.pneumoniae strains. These genes serve as the foundation for developing and spreading highly infectious MDR-, XDR-, and PDR-K. pneumoniae strains[13–15, 20–22].Therefore, K. pneumoniae causes urinary tract infections, skin infections, respiratory tract infections, sepsis, meningitis, and pyogenic liver abscesses [20, 22]. This superbug infection is common in pregnant women, immune-compromised patients, and elderly adults. It can be contracted in hospitals and in the community. Many studies indicate that K. pneumoniae possesses various virulence factors, such as capsules, adhesions, fimbriae, type II secretion systems, siderophores, endotoxin-mediated factors, lipopolysaccharides, biofilms, and inner membranes [15, 18, 23, 24]. These factors can activate macrophages and apoptosis-inducing ligands, which lead to the overproduction of pro-inflammatory cytokines and interleukins, causing sepsis [25]. As a result of the release of these factors, complex immunological responses can be activated that can devastate both the maternal and fetal health; these responses include fetal neurological defects, premature birth, stillbirth, and intrauterine growth restriction. Furthermore, long-term cognitive impairments and multiorgan dysfunction can occur, eventually leading to death [25, 26].
Maternal sepsis can be worsened by various factors such as socioeconomic status, stress, lack of education, poverty, poor sanitation, family responsibilities, limited financial resources, and an unhealthy diet [27–28]. Many studies have shown that various contributing factors include a medical history of chronic diseases such as gestational hypertension, diabetes, cancer, hospitalization, ventilator use, catheterization, kidney or lung disease, preeclampsia, abortion, and a history of antibiotic use during gestation [29]. Habits, such as smoking, alcoholism, and drug abuse, can also play a role in the development of these bacterial infections[30]. Educational level and intravenous drug administration can also be contributing factors [28, 30]. Additionally, when maternal sepsis patients arrive at tertiary hospitals, they are given immediately antibiotics such as trimethoprim-sulfamethoxazole, ampicillin, ciprofloxacin, cefepime, aztreonam, ceftriaxone, amoxicillin, gentamicin, clindamycin, vancomycin, piperacillin-tazobactam, and tigecycline. In cases of severe maternal sepsis, physicians often use a combination of two or three cephalosporins, carbapenems, aminoglycosides, and polymyxins[31–33]. If these antimicrobial agents fail, the recommended treatment for maternal sepsis is tigecycline combination therapy with avibactam/ceftazidime, or imipenem/meropenem caused by MDR-/XDR-/PDR-K. pneumoniae [34–37].
Multidrug-resistant K. pneumoniae strains have compromised the effectiveness of antibiotics for treating maternal sepsis. Carbapenem-resistant Klebsiella pneumoniae (CRKP) constitute a significant concern, and urgent attention is needed to reduce maternal and neonatal sepsis [35, 38]. Recent studies indicate that Klebsiella is responsible for 65.7% of antibiotic-resistant bacteria that cause healthcare-associated infections [39, 40]. Among these bacteria, half are ESBL-producing K. pneumoniae isolates. The primary source of these infections was multiple sites, for a prevalence rate of 76.8%. MDR K. pneumoniae was the most common type of bloodstream infection, with a prevalence rate of 62.9%. The rate of MDR infections was greater for hospital-acquired infections (72.1%) than for hospital- or community-acquired infections [19, 27, 33, 37, 41].
Carbapenemase- and ESBL-producing K. pneumoniae are the most severe global public health threats identified on the WHO priority pathogen list due to their ability to transfer antimicrobial resistance genes [2, 4, 16, 42].However, the impact of K. pneumoniae on maternal and neonatal health in developing countries, including Ethiopia, has not yet been well established [43]. Overall, maternal sepsis has a disproportionate effect on neonates and pregnant women, suggesting that research on maternal sepsis caused by ESBL-producing K. pneumoniae and CRKP is essential [3, 6, 9, 38, 44, 46]. This research will help establish a baseline, measure interventions, and ensure that patients receive the most effective care. We performed a nationwide study to generate evidence-based data and comprehensive information on the burden, risk factors, diagnosis, and treatment of maternal sepsis to develop better strategies to combat carbapenem-resistant strains and improve the quality of maternal care.