Infections caused by Methicillin-resistant Staphylococcus aureus (MRSA) have emerged as one of the most pressing global public health challenges. In concert with global rise of antimicrobial resistance at alarming rate, there is an urgent need for alternative strategies to combat MRSA. Here, the high throughput screening indicated that the Alisol A 24-acetate (AA) effectively inhibits the mevalonate (MVA) synthesis in MRSA. The mechanistic analysis revealed that AA competitively inhibits the 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGR) protein to blockade the MVA pathway, thereby disrupting the bacterial membrane integrity and functions. Further investigations showed that this disruption consequently restores the β-lactam susceptibility in MRSA by retarding the expression of PBP2a protein and dampens the virulence of MRSA by reducing the exotoxins secretion. In addition to the effect on MRSA, AA has been found to exert host-acting activity to reduce the MRSA-induced inflammation. The promising anti-MRSA activity of AA was further confirmed in vivo. Collectively, the current study highlighted the potential of AA as a proposing drug for combating MRSA and emphasize the MVA pathway as an ideal therapeutic target for MRSA treatment.

Antimicrobial resistance (AMR) represents a major threat to global health. Infection caused by Methicillin-resistant Staphylococcus aureus (MRSA) is one of the well-recognized global public health problem globally. In some regions, as many as 90% of S. aureus infections are reported to be MRSA, which cannot be treated with standard antibiotics. WHO reports indicated that MRSA is circulating in every province worldwide, significantly increasing the risk of death by 64% compared to drug-sensitive forms of the infection which is attributed to its antibiotic resistance. The emergence and spread of antibiotic-resistant MRSA strains have contributed to its increased prevalence in both healthcare and community settings. The resistance of S. aureus to methicillin is due to expression of penicillin-binding protein 2a (PBP2a), which renders it impervious to the action of β-lactam antibiotics including methicillin. The other is through the production of beta-lactamases. Although the treatment options for MRSA are limited, there are promising alternatives to antibiotics to combat the infections. Innovative therapeutic strategies with wide range of activity and modes of action are yet to be explored. The review highlights the global challenges posed by MRSA, elucidates the mechanisms underlying its resistance development, and explores mitigation strategies. Furthermore, it focuses on alternative therapies such as bacteriophages, immunotherapy, nanobiotics, and antimicrobial peptides, emphasizing their synergistic effects and efficacy against MRSA. By examining these alternative approaches, this review provides insights into the potential strategies for tackling MRSA infections and combatting the escalating threat of AMR. Ultimately, a multifaceted approach encompassing both conventional and novel interventions is imperative to mitigate the impact of MRSA and ensure a sustainable future for global healthcare.

Although neonatal Staphylococcus aureus pneumonia is common and usually curable, it can also be refractory and life-threatening. Herein, we report a case of severe neonatal community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) necrotizing pneumonia with bilateral recurrent pyopneumothorax, respiratory failure, heart failure, and cardiac arrest. We hope our report will add to the understanding of this disease.

An 18-d-old boy presented with cough for five days, fever for three days, and dyspnea for two days. Preadmission chest radiograph revealed high-density shadows in both lungs. On admission, his oxygen saturation fluctuated around 90% under synchronized intermittent mandatory ventilation. He was unconscious, with dyspnea, weak heart sounds and hepatomegaly. Moist crackles were present throughout his left lung, while the breath sounds in the right lung were decreased. After high-frequency oscillatory ventilation, empiric antimicrobials (meropenem and vancomycin), improved circulation, and right pleural cavity drainage for right pneumothorax (approximately 90% compression), his oxygen saturation level stayed above 95%, and recruitment of the right lung was observed. His condition did not deteriorate until the 5th day of hospitalization (DOH 5). On the morning of DOH 5, his oxygen saturation decreased. Subsequent chest radiograph showed bilateral pneumothorax with nearly 100% compression of the left lung. Desaturation was not relieved after urgent left pleural cavity drainage, and cardiac arrest occurred soon thereafter. Although his spontaneous heartbeat returned through emergency resuscitation and salvage antibacterial therapy (linezolid and levofloxacin) was administered given the detection and antimicrobial susceptibility of MRSA, he showed no improvement, with recurrent pyopneumothorax and continued drainage of purulent fluid and necrotic lung tissue fragments from the pleural cavity. Eventually, his parents refused extracorporeal membrane oxygenation (ECMO) and gave up all the treatments, and the newborn passed away soon after withdrawal on DOH 13.

Neonatal MRSA pneumonia can be refractory and lethal, especially in cases where necrotizing pneumonia leads to extensive lung necrosis and recurrent pneumothorax. Despite treatment with linezolid and other medical measures, it may still be ineffective. Currently, ECMO has been a remedial therapy, but if the lung tissue is too severely eroded to be repaired, it may be useless unless the infection can be controlled and lung transplantation can be performed. Regardless of whether ECMO is initiated, the key to successful treatment is to achieve control over the pneumonia caused by MRSA as soon as possible and to reverse lung injury as much as possible.