Rising Threat of Drug-Resistant Sepsis in Southeast Asian Infants: A Critical Look at Indonesia’s Crisis

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Newborn deaths account for 47% of deaths among children under the age of 5 globally, resulting in 2.4 million lives lost each year. about one third of newborn deaths occur on the day of birth and close to three quarters occur within the first week of life.

This study closes important gaps in understanding the burden of antimicrobial resistance (AMR) in neonatal sepsis in areas with high prevalence. By examining the causes of neonatal sepsis and the level of appropriateness of antibiotics commonly used in 10 hospitals in five South and Southeast Asian countries, this study found that gram-negative bacteria dominated as a cause of neonatal sepsis, with a worrying level of resistance to the recommended empirical antibiotics.

These results are in line with observational research in Asia and Africa, which also shows that gram-negative bacteria are the main cause of neonatal sepsis in health facilities with limited resources. Klebsiella spp.,Acinetobacter spp., and E. coli most often found, while contribution Enterobacter spp. higher than reports from othre regions. High cases Klebsiella and Acinetobacter – which is frequently enough associated with hospital infection – shows the possibility of bacterial transmission from an early age in health facilities. Conversely, gram-positive bacteria only contribute around 13.2 percent of cases, with Staphylococcus aureus as a major pathogen, although the proportion is lower than the previous multinational study.

The main pathogens that cause sepsis indicate a high level of resistance to the first-line antibiotics recommended by the World Health Organization (WHO), such as a combination of benzylpenicillin/ampicillin with gentamicin, as well as third-generation cephalosporins. This low level of sensitivity confirms that WHO’s standard empirical therapy is no longer adequate in South and Southeast Asian urban hospitals. Therefore, new empirical therapy guidelines that are tailored to the high burden of drug resistance infections are very urgent to protect babies, support local antibiotic control programs, and harmonize global practices.

Sadly, even alternative antibiotics such as amikacin and carbapenem also show low effectiveness against Enterobacterales and non-fermenter gram-negative bacteria. This highlights the urgent need for better access to new antibiotics that are able to overcome infections caused by multidrug-resistant (MDR) bacteria.

Interestingly, this study also found 8 percent of cases of neonatal sepsis caused by invasive fungal infections, especially candida parapsilosis and Candida albicans. This finding confirms the importance of increasing the diagnostic capacity of mycology and a system of monitoring fungal infections in low- and middle-income countries. Even though antifungal resistance in south and Southeast Asia is still low, but the emergence of cases Candida auris which is multidrug-resistant in other regions become a serious warning.

Though, this study has limitations. Data was taken mainly from large referral hospitals in urban areas,so it might not represent national conditions. In addition, blood culture data is collected retrospectively, so that it cannot be analyzed further in relation to clinical risk factors or patient outcome. Limited laboratory capacity in several locations also affects the completeness of data.

Even so, this finding provides strong evidence that neonatal sepsis in South and Southeast Asia is dominated by gram-negative bacteria that are resistant to many drugs. This strengthens the call to update empirical therapy guidelines, conduct clinical trials to evaluate alternative regimens, and develop new antibiotics.

In addition, further research on how resistant bacteria spread in hospitals is critically important to develop more targeted interventions.

What public health interventions could effectively reduce antibiotic consumption in Indonesia, considering both human and animal agriculture sectors?

The Growing Challenge of Neonatal Sepsis

Neonatal sepsis, an infection occurring in the frist 28 days of life, remains a leading cause of infant mortality globally, notably in low- and middle-income countries. Southeast Asia is experiencing a particularly alarming surge in cases,compounded by the escalating crisis of antimicrobial resistance (AMR). This resistance renders common antibiotics ineffective, turning treatable infections into life-threatening emergencies.Indonesia, with its large population and complex healthcare landscape, is at the epicenter of this growing public health threat.Understanding neonatal sepsis causes, sepsis symptoms in babies, and the factors driving AMR is crucial for effective intervention.

Indonesia’s Unique vulnerabilities

Several factors contribute to Indonesia’s heightened vulnerability to drug-resistant neonatal sepsis:

* High Antibiotic Consumption: Over-the-counter availability of antibiotics and widespread use in animal agriculture contribute to selective pressure favoring resistant bacteria.

* Limited Access to Healthcare: Uneven distribution of healthcare facilities,particularly in rural areas,delays diagnosis and treatment. This leads to more severe infections and increased antibiotic use.

* Inadequate Infection Control: Poor hygiene practices in healthcare settings and limited resources for infection prevention and control (IPC) facilitate the spread of resistant organisms.

* Nutritional Deficiencies: Malnutrition weakens the immune system, making infants more susceptible to infection and increasing the risk of mortality.

* Environmental Factors: Poor sanitation and limited access to clean water contribute to the spread of infectious diseases.

Key Pathogens and Resistance Patterns

The most common pathogens causing neonatal sepsis in Indonesia include:

* Staphylococcus aureus (including Methicillin-resistant Staphylococcus aureus – MRSA)

* Escherichia coli (often exhibiting resistance to multiple antibiotics)

* Klebsiella pneumoniae (increasingly resistant to carbapenems – a last-resort antibiotic class)

* Acinetobacter baumannii (known for its extensive drug resistance)

Recent studies demonstrate a significant rise in carbapenem-resistant Enterobacterales (CRE), posing a critical threat. Resistance mechanisms include the production of extended-spectrum beta-lactamases (ESBLs) and carbapenemases. Monitoring antibiotic susceptibility patterns is vital for guiding empirical therapy.

Clinical Manifestations and Diagnostic Challenges

Recognizing early sepsis signs is paramount. Symptoms in infants can be subtle and non-specific, making diagnosis challenging. Common signs include:

* Fever or hypothermia (low body temperature)

* Lethargy or irritability

* Poor feeding

* Rapid breathing or difficulty breathing

* Skin rashes or discoloration

* Jaundice

Diagnostic tools, such as blood cultures, are often slow and may have limited sensitivity. Procalcitonin (PCT) levels are increasingly used as a biomarker to aid in early diagnosis and guide antibiotic stewardship, but interpretation requires careful consideration. Point-of-care diagnostics are needed to improve access to rapid and accurate testing.

Impact of Drug Resistance on Treatment Outcomes

Drug-resistant sepsis significantly increases the risk of:

* treatment failure

* Prolonged hospital stays

* Increased healthcare costs

* Higher mortality rates

In Indonesia, mortality rates associated with drug-resistant neonatal sepsis are alarmingly high, exceeding those observed in developed countries. The lack of effective treatment options leaves clinicians with limited recourse, often resorting to toxic and expensive alternatives with uncertain efficacy.

Public Health Interventions and Strategies

addressing this crisis requires a multi-faceted approach:

1. Antibiotic Stewardship Programs: Implementing strict guidelines for antibiotic use in hospitals and communities. This includes promoting rational prescribing practices, restricting access to certain antibiotics, and educating healthcare professionals.
2. Strengthening Infection Prevention and Control: Improving hygiene practices in healthcare facilities, ensuring adequate sterilization of equipment, and promoting hand hygiene.
3. Improving Access to Healthcare: Expanding healthcare coverage, particularly in rural areas, and ensuring timely access to diagnostic and treatment services.
4. Enhancing Surveillance: Establishing robust surveillance systems to monitor antibiotic resistance patterns and track the spread of resistant organisms. The Indonesia National Antimicrobial Resistance Surveillance System (INARSS) plays a crucial role.
5. Promoting Vaccination: Increasing vaccination coverage against preventable infections,reducing the need for antibiotic use.
6. Improving Sanitation and Hygiene: Investing in water and sanitation infrastructure to reduce the spread of infectious diseases.
7. Research and Growth: Supporting research to develop new antibiotics and option therapies. exploring phage therapy and immunomodulatory strategies are promising avenues.

Case Study: A Regional Hospital in East Java

A recent audit at a regional hospital in East Java revealed a 40% increase in carbapenem-resistant Klebsiella pneumoniae infections among neonates over the past two years. The hospital implemented a comprehensive antibiotic stewardship program, including mandatory antibiotic review by an infectious disease specialist and enhanced IPC measures. preliminary data suggest a stabilization of resistance rates, highlighting the potential impact of targeted interventions.

Benefits of Proactive Measures

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