Antibiotic Resistance: Drugs vs. Bugs

Bacteria Resist Antibiotics


Antibiotic resistance is serious.  The CDC estimates that each year 2 million people are infected with antibiotic-resistant bacteria, and at least 23,000 people die each year of infections caused by such bacteria.  However, antibiotic resistance is nothing new.  In 1940, a few years after the discovery of penicillin, scientists identified penicillinase in E. Coli.  Penicillinase is a beta-lactamase enzyme that breaks down (and thus resists) penicillin and other antibiotics.  In fact, the mechanisms that confer resistance to bacteria predate the development of antibiotics by eons; many antibiotics were derived from substances produced by mold and bacteria to inhibit the growth of rival microorganisms.  However, in recent years on account of the ubiquitous use and overuse of antibiotics,  the prevalence of bacteria resistance has skyrocketed with some bacteria emerging as resistant to multiple drugs.  Fortunately, measures can be taken to curb the spread of drug-resistant bacteria including patient and provider education.

Mechanisms of Antibiotic Resistance


When a physician prescribes antibiotics, these antibiotics usually end up killing most of the bacteria responsible for an infection.  But some bacteria are resistant to antibiotics, and not only survive but also proliferate and spread to other people.

Bacteria resists antibiotics using 4 mechanisms:

  • Production of enzymes like beta-lactamases which cleave the antibiotic.
  • Reduction in membrane permeability so that less antibiotic enters the bacteria and thus takes hold.
  • Synthesis of modified drug targets to which antibiotics have diminished effect.  In other words, bacteria alter the "lock" to an antibiotic's "key."
  • Export of foreign substances via a pump.  Such pumps confer resistance to many types of bacteria by exchanging antibiotics for protons.

Resistance can be either low level or high level.  Low-level resistance can be overcome by an increase in antibiotic dosage.  For example, modified drug targets confer low-level resistance because they invariably bind some drug albeit at decreased strength.  Whereas, enzymes like beta-lactamase confer high-level resistance and completely break down certain antibiotics regardless of dose.  

Most bacteria become resistant to antibiotics either through chromosome mutation or acquisition of genetic material like a plasmid or transposon.  .

Strains of Antibiotic-Resistant Bacteria


Let's briefly examine 4 strains of antibiotic-resistant bacteria.


Methicillin-resistant Staphylococcus aureus (MRSA) comes in two flavors: hospital acquired and community acquired.  But don't let their names fool you--community-acquired MRSA is becoming increasingly prevalent in hospitals and may soon overtake hospital-acquired strains as the main cause of MRSA in hospital settings.  MRSA produces a beta-lactamase that fends off drugs like penicillin and cefazolin.  In healthy individuals, MRSA can cause a pretty nasty skin infection including boils and abscesses which is usually treated with drugs like sulfamethoxazole/trimethoprim (Bactrim).  But in people who are already sick or immunocompromised (patients in the hospital), MRSA can cause much more serious infections of the heart (endocarditis), blood (bacteremia), lungs (pneumonia) and bone (osteomyelitis).  In hospital settings, MRSA is often treated with a heavy-hitting antibiotic like vancomycin.or daptomycin.

Vancomycin-resistant enterococci (VRE)

Vancomycin-resistant enterococci (VRE) are usually seen in hospital settings.  Enterococci is less dangerous than other types of bacteria but can cause a urinary tract infection (UTI) or bacteremia.  Treatment for VRE includes daptomycin or linezolid (Zyvox).

Extended-Spectrum Beta-Lactamases (ESBLs)

ESBLs are enzymes that cleave antibiotics like penicillins and cephalosporins and make them inactive.  Several different types of bacteria make ESBLs including Klebsiella pneumoniae, E. coli and Proteus mirabilis.  To date, there has been an increase in the prevalence of UTIs caused by bacteria with ESBLs.  ESBLs are treated with carbapenems.


In the United States, Klebsiella pneumoniae is the most common bacteria that produces carbapenamase.  Pneumonia caused by carbapenemase-producing Klebsiella is deadly and kills 40 to 50 percent of those infected.  Fortunately, carbapenamases currently pose limited risk to most of us and instead infect people who are sick with other disease or in the hospital for a long time (think a long stay in intensive care).  Treatment options for such bacteria is limited to polymixins or tigecycline.

Antibiotic Resistance: What Can We Do?


Experts recommend several interventions that could stem the spread of antibiotic resistance.  Some of these recommendations are for physicians and other health care providers who prescribe these drugs and include the following:

  • Proper dosing and monitoring of antibiotic use in patients.
  • Basing prescription patterns on antibiotic sensitivity data that's specific to a community.
  • More education regarding overuse and misuse of antibiotics.

As an individual, you can help curb the spread of antibiotic resistance, too. First, it's very important that you finish any course of antibiotics that you're prescribed.  You shouldn't stop taking antibiotics once you "feel better."  By taking antibiotics for only a couple days, you kill some but not all the bacteria.  The bacteria that's left over is much more likely to become resistant and spread to other people.  Second, you should recognize that antibiotics don't help with every type of sickness or infection and oftentimes there's no need for antibiotics at all.  For example, viruses cause flu or colds and shouldn't be treated with antibiotics.  On a final note, research shows that decreased use of antibiotics causes less antibiotic resistance.

Selected Sources


Levinson W. Chapter 11. Antimicrobial Drugs: Resistance. In: Levinson W. eds. Review of Medical Microbiology & Immunology, 12e. New York, NY: McGraw-Hill; 2012. . Accessed October 24, 2014.

Munoz-Price L. Chapter 186. Antibiotic Resistance. In: McKean SC, Ross JJ, Dressler DD, Brotman DJ, Ginsberg JS. eds. Principles and Practice of Hospital Medicine. New York, NY: McGraw-Hill; 2012.  Accessed October 24, 2014.

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