Resistance isn't always futile

Optometric Management, Apr 2000 by Epstein, Arthur

Antibiotics aren't a sure cure anymore. Understanding resistant bacteria can help you prevent - or treat - infection.

Not long ago, antibiotic resistance was a problem limited to hospital settings. But in the past decade, overuse and misuse of antibiotics has catapulted this issue into a potential nightmare for everyone.

Recent data in the ophthalmic literature underscore increases in resistance to fluoroquinoloneclass antibiotics, especially among Staphylococcus aureus. Rising Pseudomonas resistance to fluoroquinolones has also been reported. Here, I'll look at the growing problem of antibiotic resistance, examine its causes and explore ways you can minimize and manage it.

The effects of resistance

Resistance to antibiotics is a normal part of a bacterium's defense system and survival strategy. Bacteria manifest resistance through several mechanisms:

* They induce enzymes that degrade or inactivate antibiotics.

* They alter or replace molecules to which the antibiotics bind.

* They alter membrane permeability or other cell characteristics, blocking antibiotic entry into bacterial cells.

* They create pumps that remove antibiotics from within the bacterial cell.

In each case, these mechanisms diminish or block the effectiveness of the antibiotic. Organisms with resistance traits flourish, while the antibiotic selects against and ultimately kills susceptible organisms, including harmless ones.

MDR bacteria

Until recently, multiple drug resistant (MDR) strains of bacteria were a problem of immune-compromised, hospitalized or institutionalized patients. For example, MDR tuberculosis primarily affects homeless people, prisoners and HIV infected patients. MDR Enterococcus infections are generally encountered in hospital settings. Recently, however, MDR bacterial strains have become a community-wide problem for all.

S. aureus is a common pathogen causing 50,000 blood stream infections, 500,000 cases of bacterial pneumonia, and 7 million cases of otitis media annually. Staphylococcus infections of the eye and surrounding structures aren't uncommon.

Throughout the 1960s, nearly all strains of S. aureus were susceptible to penicillin. Today, nearly 95 % are resistant to penicillin and more than 30% are resistant to all antibiotics but vancomycin. Recently, a strain of Staphylococcus has emerged that's resistant to vancomycin and all other known antibiotics. This strain has already been responsible for several deaths.

Where we went wrong

Several human actions have contributed to the problem of antibiotic resistance.

* Antibiotic overuse. Overuse is a factor in the emergence of resistant bacterial strains. Patients generally don't understand how antibiotics work, yet they demand them for illnesses where they're unnecessary or ineffective. Doctors succumb to these pressures. The Centers for Disease Control and Prevention (CDC) has estimated that 50 million of the 150 million annual prescriptions for antibiotics are unnecessary. Over-prescription also occurs in eye care, either through the unnecessary prescription of antibiotics or through prescription of antibiotic-steroid combination drugs when only an anti-inflammatory medication is necessary.

Rampant use of antibiotics, especially for systemic treatment, has several effects. Ideally, it kills the bacteria that cause infection. However, it may also kill beneficial bacteria. Without competition, resistant pathogenic bacteria will often fill the void.

* Improper dosing. Depending on the antibiotic used, effective treatment requires delivery of a lethal or inhibitory dose for a sufficient period. Once the bacterial population is reduced enough, the host's own immune system will typically finish the job. Subtherapeutic doses allow resistant organisms to proliferate by selecting against otherwise competing sensitive organisms. Differential (uneven) systemic absorption of an antibiotic may reduce effective doses reaching some tissues and can also lead to the development of resistance.

* Poor control over antibiotic distribution. Patients will frequently hoard antibiotics, not finishing their prescriptions or saving leftover drugs for later self-treatment. Shortened treatment times and subeffective doses select for resistant bacterial strains. Over-the-counter availability of antibiotics, including third-generation drugs, is a problem in some countries. In thirdworld countries, misuse of antibiotics is probable. Increased global travel also contributes to the problem by spreading resistant bacterial strains.

Agricultural use of antibiotics Agricultural use accounts for close to 50% of all antibiotics sold in the United States. About 80% of these antibiotics are used to help promote the growth of livestock. Such prolonged exposure to low doses of antibiotics creates a perfect environment for the development of resistance. Antibiotics are also used for aerial spraying of fruit orchards and in fish farming.

Otherwise obsolete antibiotics aren't only used in agriculture. Despite the risks, antibiotics like ciprofloxacin are routinely fed to cattle. Lobbying special interests has prompted the FDA to approve such use over the objections of the CDC and others.