Bacterial infections are caused by many different micro-organisms. Many agents have been developed to treat bacterial infections, but resistance to them is a major problem. The pharmaceutical industry is working to develop new kinds of antibiotics. By staying one step ahead fewer people will die from infection.
Bacteria are microscopic organisms of many different types with a chemically distinctive cell wall. This membrane confers a particular shape on each type: spherical, rod-shaped or spiral. They multiply by cell division, a process that can occur every 20-30 minutes. A single bacterium entering the body and multiplying at this rate could give rise to over 30 billion new cells within 12 hours. Fortunately, most bacteria are harmless and some are even essential, such as those in the intestine which aid digestion.
But a minority, called pathogens, cause disease. These may be localised near the surface of the skin, as in acne, laryngitis, boils and abscesses, or invade internal organs and cause, for example, serious and life-threatening infections of the urinary tract (prostatitis), brain (meningitis) lung (pneumonia), heart (endocarditis), or bloodstream (septicaemia).
Everyone experiences bacterial infections from time to time, but most heal by themselves or are readily treated with antibiotics. However, resistance to antibiotics is a growing problem and infections that were treatable a decade ago are staging a comeback. For example, tuberculosis has staged a marked resurgence in various forms and is more often drug-resistant than before. Traditionally, methicillin-resistant Staphylococcus aureus (MRSA) infections occurred exclusively in hospitals and were limited to immunocompromised patients or individuals with predisposing risk factors. Recently, however, there have been alarming reports on community-associated MRSA strains, which cause severe infections that result in necrotizing fasciitis or even death in otherwise healthy adults outside of healthcare settings.
Another significant medical problem in hospitals, long-term care facilities and in the community has become Clostridium difficile-associated diarrhea (CDAD). CDAD results from infection of the inner lining of the colon by C. difficile bacteria, which produce toxins that cause inflammation of the colon, severe diarrhea and, in the most serious cases, death. Patients typically develop CDAD from the use of broad-spectrum antibiotics that disrupt normal gut flora, possibly allowing C. difficile bacteria to flourish. Approximately two-thirds of CDAD patients are 65 years of age or older.
People, whose immunity is depressed by illnesses such as cancer, or suppressed as in transplantation, are at greater risk of serious infection. As more patients are treated, hospital-acquired infections - after surgery, intensive care treatment or on prolonged catheterisation - are increasing. According to a report of the European Centre for Disease Prevention and Control (ECDC) from 2010, some 400,000 individuals develop infections with multi-drug resistant bacteria in the EU each year and about 25,000 of these die from the infection. Infections due to these selected multidrug-resistant bacteria in the EU result in extra healthcare costs and productivity losses of at least €1.5 billion. If septicaemia develops, it may lead to septic shock: a cascade of systemic inflammation, coagulation, and low blood pressure with a sometimes fatal outcome through multiple organ failure.
Many antibiotics have been discovered over the past 60 years, including the synthetic penicillins and cephalosporins, tetracyclines, macrolides, the aminoglycosides, i.e. the streptomycin group, and quinolones. The latter inhibit the bacterial enzyme gyrase and are another option to treat pneumonia and infections of the urogenital tract.
Despite this range of agents, the loss of efficacy in the face of resistant organisms such as MRSA, vancomycin-resistant enterococci (VRE) and highly resistant Gram-negative bacilli is creating widespread concern among clinicians. In an attempt to keep ahead of growing resistance, a variety of antibiotics have been introduced in recent years.
The combination of two compounds of the ‘streptogramin’ group contains two structurally different components that together kill a wide range of bacteria, including MRSA strains. Another avenue is an oxazolidinone derivative which is valuable in treating skin and soft tissue infections in hospitals where multiply resistant strains are likely to be present.
Novel broad-spectrum cephalosporin antibiotics have been developed to treat skin and skin structure infections. The ketolides are another new class of antibiotics. They are intended for the treatment of respiratory tract infections, including resistant strains of streptococcus pneumoniae. They may turn out to have useful activity against some less usual pathogens such as Chlamydia, mycobacteria, the protozoan Toxoplasma gondii, which causes opportunistic infections in HIV / AIDS patients, and Legionella pneumoniae, the cause of Legionnaires´ disease.
From 2000 on, new antibiotics belonging to a variety of different classes have been developed and are in clinical use now. The class of oxazolidinones were the first in a row of new molecules. In 2007, the first in the class of pleuromutilin antibiotics has been registered to treat skin and soft tissue infections. Another class of medicines which were introduced in 2005 for the therapy of complicated skin and skin structure infections are the lipoglycopeptides.
Also in 2005, the class of glycylcycline antibiotics was introduced. The compounds are related to the tetracyclines and show activity against a broad spectrum of bacterial strains, including those that are resistant to tetracyclines. Even tetracyclines which consist of four consecutively fused carbon rings, labelled A through D, have been studied. New D-ring variations have shown particular promise against resistant bacteria. New carbapenem antibiotics have been developed for treatment of community-acquired infections.
In 2010, a fifth generation cephalosporin with activity against both Gram-positive and Gram-negative microorganisms, was approved for the treatment of community-acquired bacterial pneumonia, including cases caused by Streptococcus pneumoniae bactaeremia, and acute bacterial skin and skin structure infection , including cases caused by methicillin-resistant Staphylococcus aureus (MRSA).
In 2011, both the U.S. Food and Drug Administration and the European Medicines Agency approved a macrolide antibacterial for the treatment of CDAD. To maintain the effectiveness of the compound, and to reduce the development of drug-resistant bacteria, the orally given medicine should be used only to treat infections that are proven or strongly suspected to be caused by C. difficile.
Antibiotic resistance has become an everyday occurrence and problem in hospitals across the world. Prudent use of antibiotics can prevent or at least diminish the emergence and selection of antibiotic-resistant bacteria. Decreasing antibiotic use has been shown to result in decreasing incidence of C. difficile infections. Strategies which include use of evidence-based hospital antibiotic guidelines and policies, consultations from infectious disease physicians, microbiologists and pharmacists have shown to result in better antibiotic prescribing practices.