Health and Me

Rachel V Thomas

98 Years After Penicillin, Are We Running Out Of Effective Antibiotics?

On September 3, 1928, Scottish scientist <span>Alexander Fleming</span> returned to his laboratory after a holiday. He famously noticed the antibacterial effect of mold contaminating a <span>Staphylococcus</span> culture. 

Fleming identified the mold as belonging to the Penicillium genus and found that it produced a substance capable of inhibiting bacterial growth, which he named <span>penicillin</span>.

However, Fleming’s discovery was only the beginning. Penicillin proved difficult to isolate, purify and mass-produce. During World War II, scientists Howard Florey and Ernst Chain built on Fleming’s work to develop large-scale production methods, converting penicillin into a life-saving medicine and ushering in the modern antibiotic era.

<h2>How Did Penicillin Resistance Develop?</h2>

As penicillin came into widespread medical use in the 1940s, resistance to the drug also emerged.

“Penicillin acts through a beta-lactam ring, which targets the bacteria, but then the organisms started producing an enzyme known as beta-lactamase,” Dr NK Ganguly, former Director General of the Indian Council of Medical Research (ICMR) told <strong>HealthandMe.</strong>

“This beta-lactamase broke the ring, so various derivative varieties of penicillins were synthesized,” he explained.

But as new penicillin derivatives were developed, bacteria also evolved or acquired mechanisms, including different beta-lactamases, that could break down these drugs.

As a result, penicillin became less effective against many bacteria. However, it remains effective against certain organisms and infections, including:

<ul><li>Syphilis</li><li>Group A beta-haemolytic Streptococcus</li><li>Streptococcus pneumoniae (pneumococcus)</li></ul>

“Penicillin remains the gold standard for certain infections and indications, including neonatal sepsis, childhood pneumonia, rheumatic heart disease prophylaxis and resurging cases of syphilis,” Dr Ganguly said.

<h2>The Growing Threat Of Resistance </h2>

The story of penicillin resistance is an early example of a much broader problem the world is grappling with today: antimicrobial resistance (<span>AMR</span>), which threatens the effectiveness of modern healthcare.

Decades after <span>antibiotics</span> transformed medicine, the bacteria these drugs were designed to target have evolved significant resistance. This threat has been further compounded by the misuse and overuse of antibiotics across sectors.

According to the World Health Organization (WHO), approximately 1 in 6 laboratory-confirmed bacterial infections worldwide were resistant to antibiotic treatments in 2023.

Low- and middle-income countries bear the heaviest burden of infectious disease but face severe shortages of specialized antibiotics.

A global study covering 82 countries, led by the Murdoch Children’s Research Institute (MCRI), found that antibiotic resistance increased across every region between 2004 and 2022. As a result, critical treatments for routine childhood infections are becoming increasingly ineffective.

“The discovery of antibiotics is perhaps the most significant, life-changing breakthrough in the history of medicine,” Dr. Rajeev Jayadevan, Ex-President of IMA Cochin and Convener of the Research Cell, Kerala, told <strong><em>HealthandMe</em></strong>. 

“However, bacteria possess natural evolutionary mechanisms to resist antibiotics as part of their survival machinery. Unfortunately, overuse in human healthcare, veterinary medicine and agriculture has allowed bacteria to continuously adapt and evade treatment,” he added.

<h2>Major Drivers Of Antimicrobial Resistance</h2>

Antimicrobial resistance is driven by a combination of clinical, agricultural, industrial and environmental factors:

<ol><li>Inappropriate syndromic and empirical prescribing<ul><li>Viral infections</li><li>Unnecessary STD treatment</li></ul></li><li>Self-medication and suboptimal adherence</li><li>Informal healthcare providers</li><li>Substandard and falsified medicines</li><li>Agricultural and veterinary misuse<ul><li>Growth promoters in animal feed</li><li>Use of human-critical antibiotics in livestock</li></ul></li><li>Industrial and environmental contamination<ul><li>Manufacturing effluents</li><li>Fermentation and industrial waste</li><li>Effluents and sewage</li></ul></li><li>Lack of public awareness</li></ol>

So, are we running out of effective antibiotics? Not entirely, yet "the development of newer antibiotics has not kept pace with bacterial evolution" Dr Rajeev said.

Resistance is also making some infections increasingly difficult to treat. To counter, stronger national policies are needed the unnecessary antibiotic prescribing while ensuring that patients who genuinely need specialized antibiotics can access them.

Improving access will require coordinated action at both local and national levels. This includes:

<ul><li>Ensuring quality-assured antibiotics are available and affordable in frontline healthcare settings</li><li>Procuring the right antibiotics in adequate quantities</li><li>Strengthening surveillance of antibiotic use</li><li>Setting country-specific prescribing targets based on local disease burden and public health needs.</li></ul>

“Beyond discovering new drugs, the long-term solution lies in regulating antibiotic use globally—because antimicrobial resistance knows no boundaries. A resistant organism originating in one region can rapidly spread worldwide,” Dr Rajeev said.

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On September 3, 1928, Scottish scientist Alexander Fleming returned to his laboratory after a holiday. He famously noticed the antibacterial effect of mold contaminating a Staphylococcus culture. Fleming identified the mold as belonging to the Penicillium genus and found that it produced a substance capable of inhibiting bacterial growth, which he named penicillin.However, Fleming’s discovery was only the beginning. Penicillin proved difficult to isolate, purify and mass-produce. During World War II, scientists Howard Florey and Ernst Chain built on Fleming’s work to develop large-scale production methods, converting penicillin into a life-saving medicine and ushering in the modern antibiotic era.How Did Penicillin Resistance Develop?As penicillin came into widespread medical use in the 1940s, resistance to the drug also emerged.“Penicillin acts through a beta-lactam ring, which targets the bacteria, but then the organisms started producing an enzyme known as beta-lactamase,” Dr NK Ganguly, former Director General of the Indian Council of Medical Research (ICMR) told HealthandMe.“This beta-lactamase broke the ring, so various derivative varieties of penicillins were synthesized,” he explained.But as new penicillin derivatives were developed, bacteria also evolved or acquired mechanisms, including different beta-lactamases, that could break down these drugs.As a result, penicillin became less effective against many bacteria. However, it remains effective against certain organisms and infections, including:SyphilisGroup A beta-haemolytic StreptococcusStreptococcus pneumoniae (pneumococcus)“Penicillin remains the gold standard for certain infections and indications, including neonatal sepsis, childhood pneumonia, rheumatic heart disease prophylaxis and resurging cases of syphilis,” Dr Ganguly said.The Growing Threat Of Resistance The story of penicillin resistance is an early example of a much broader problem the world is grappling with today: antimicrobial resistance (AMR), which threatens the effectiveness of modern healthcare.Decades after antibiotics transformed medicine, the bacteria these drugs were designed to target have evolved significant resistance. This threat has been further compounded by the misuse and overuse of antibiotics across sectors.According to the World Health Organization (WHO), approximately 1 in 6 laboratory-confirmed bacterial infections worldwide were resistant to antibiotic treatments in 2023.Low- and middle-income countries bear the heaviest burden of infectious disease but face severe shortages of specialized antibiotics.A global study covering 82 countries, led by the Murdoch Children’s Research Institute (MCRI), found that antibiotic resistance increased across every region between 2004 and 2022. As a result, critical treatments for routine childhood infections are becoming increasingly ineffective.“The discovery of antibiotics is perhaps the most significant, life-changing breakthrough in the history of medicine,” Dr. Rajeev Jayadevan, Ex-President of IMA Cochin and Convener of the Research Cell, Kerala, told HealthandMe. “However, bacteria possess natural evolutionary mechanisms to resist antibiotics as part of their survival machinery. Unfortunately, overuse in human healthcare, veterinary medicine and agriculture has allowed bacteria to continuously adapt and evade treatment,” he added.Major Drivers Of Antimicrobial ResistanceAntimicrobial resistance is driven by a combination of clinical, agricultural, industrial and environmental factors:Inappropriate syndromic and empirical prescribingViral infectionsUnnecessary STD treatmentSelf-medication and suboptimal adherenceInformal healthcare providersSubstandard and falsified medicinesAgricultural and veterinary misuseGrowth promoters in animal feedUse of human-critical antibiotics in livestockIndustrial and environmental contaminationManufacturing effluentsFermentation and industrial wasteEffluents and sewageLack of public awarenessWhat Can Be Done?So, are we running out of effective antibiotics? Not entirely, yet "the development of newer antibiotics has not kept pace with bacterial evolution" Dr Rajeev said.Resistance is also making some infections increasingly difficult to treat. To counter, stronger national policies are needed the unnecessary antibiotic prescribing while ensuring that patients who genuinely need specialized antibiotics can access them.Improving access will require coordinated action at both local and national levels. This includes:Ensuring quality-assured antibiotics are available and affordable in frontline healthcare settingsProcuring the right antibiotics in adequate quantitiesStrengthening surveillance of antibiotic useSetting country-specific prescribing targets based on local disease burden and public health needs.“Beyond discovering new drugs, the long-term solution lies in regulating antibiotic use globally—because antimicrobial resistance knows no boundaries. A resistant organism originating in one region can rapidly spread worldwide,” Dr Rajeev said.

98 years after penicillin, are we running out of effective antibiotics?

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