The Gram Stain
In 1882, Dr. Hans Christian Gram discovered a stain which separated types of bacteria based on their morphology and characteristics. It separated bacteria into two groups:
- Gram-positive bacteria: which keep a violet stain after using a decolorizing agent
- Gram-negative bacteria: which lose the violet stain after the decolorizing agent
The differences between the two types of bacteria were based on their cell walls, which would be important later with the discovery of antibiotics, almost 50 years later. In 1928, a breach in laboratory protocol allowed a penicillin species of mold to contaminate a bacterial culture, demonstrating an antibiotic effect.
Bacteria are thus divided into Gram-positive and Gram-negative. Other classifications are also used to delineate them:
- Aerobic vs anaerobic (whether or not they thrive in air)
- Cocci (round) and rods (bacilli)
- Spore-formers and those that don’t form spores
- Pathologic and nonpathologic (with the understanding that a nonpathologic bacterium, if it becomes overgrown or grows in the wrong place, can become pathologic/infectious)
Antibiotics are medications that either kill bacteria directly (bactericidal) or stop them from multiplying (bacteriostatic). The biochemistry into what kills or stops the replication of bacteria makes use of the Gram stain, which identifies bacteria sensitive to different agents or those which are resistant.
As new antibiotics were discovered, an ingenuity of bacterial resistance arose due the sheer volume of organisms (millions are reproduced every hour), which makes mutations common. When exposure to antibiotics kills all of a particular bacterium except the ones with novel and coincidental mutations to resist, only the survivors carry on, containing the new genetics to pass on–as a new resistant species.
Types of Antibiotics
There have been many classes of bacteriostatic and bactericidal antibiotics developed over the years, including:
- Macrolides (erythromycin, including the later generations, azithromycin and clarithromycin)
- Sulfurs (currently in Bactrim, Septra, etc.)
- Beta-lactams (penicillins, including the next-generation ones: ampicillin and amoxicillin—2nd generation; carbenicillin and ticarcillin—3rd generation; and piperacillin—4th generation)
- Aminoglycosides (streptomycin, including the later generations, gentamicin and tobramycin)
- Cephalosporins (cephalexin, then cefoxitin)
- Quinolones (ciprofloxacin, levofloxacin)
- Glycopeptides (vancomycin)
Some antibiotics can be either bactericidal or bacteriostatic, depending on the concentration and/or susceptibility of the infection organism (nitrofurans, e.g., nitrofurantoin). Some antibiotics prescribed for a mixed infection of different organisms can be bactericidal to one species, bacteriostatic to another, or be ineffective to yet another (resistant) bacterium, all simultaneously.
From the discovery from natural sources of the first-generation antibiotics, second-, third-, and later-generation antibiotics have been developed specifically to increase the range of susceptible organisms as well as counter the resistances to the previous generation antibiotics.
What Tests Do I Need to Get Antibiotics?
Infections caused by bacteria are treated with antibiotics. There are two ways to use them:
- Rational choice of antibiotic(s) based on culture and sensitivity
- Empiric therapy, based on experience and a clinical educated guess in the absence of definitive information
While the culture and sensitivity is the mainstay of identifying and treating infections, the white blood count (WBC) with differential can list the types of WBCs that are elevated, possibly steering one to an empiric diagnosis. For example, eosinophils or basophils will be elevated in parasitic infections; the neutrophils are highly elevated in acute bacterial infections; and lymphocytes in viral illnesses or pertussis (whooping cough).
Culture and Sensitivity
Antibiotics can be chosen based on the exact bacteria causing the infection and the choice steered toward those for which the bacteria are not resistant.
- Culture: A sample from the infection, e.g., a throat swab of someone’s tonsils with tonsillitis, is retrieved and the sample deposited onto a culture medium to grow it.
- Sensitivity: Different antibiotics are applied to the culture and the results will demonstrate which ones kill the bacteria (bactericidal), which ones stop their growth or reproduction (bacteriostatic), and which ones don’t do anything at all (resistance).
Armed with this information, the physician can choose the best antibiotic based on the need for immediate action (e.g., sepsis), patient allergies, side effects (e.g., caution used in patient with kidney disease when using antibiotics cleared by or potentially toxic to the kidneys), expense, tolerability, oral vs intravenous/intramuscular, and length of therapy (some have a longer time for a full course, which can undermine patient compliance).
Empiric therapy is initiating an antibiotic based on a physician’s experience and knowledge of classical bacterial susceptibilities. It is used for two reasons:
- When the infection is so severe waiting the 2-3 days for the culture and sensitivity results could mean there is no patient alive to treat.
- When a physician is fairly certain that empiric therapy will give a 2-3 day head start that can be fine-tuned with a change in antibiotics should the culture and sensitivity so indicate.
Diagnosing an infection requires a sample of the infectious organism. While this may be simple with a ruptured skin abscess (a swab to the purulent exudate), Strep throat (a throat swab), or even sepsis (drawing blood), it may be more difficult with an infection in the lungs or abdomen. There are diagnostic procedures that can render such difficult retrievals:
- bronchoscopy (direct visualization of the lungs)
- “milking” of the prostate (rectal exam)
- amniocentesis (needle aspiration of amniotic fluid)
- arthrocentesis (needle aspiration of joint fluid)
- lumbar puncture (spinal tap to culture cerebrospinal fluid)
- paracentesis (abdominal tap via needle aspiration of abdominal fluid)
- thoracentesis/thoracocentesis (needle aspiration of the pleural cavity or lung abscess)
Management with Antibiotics
Empiric antibiotic therapy is begun when the infection is so severe that waiting the 2-3 days before the culture and sensitivity (C&S) results return could be life-threatening or life-altering:
- Sepsis: Blood infection from bacteria which can result in hypotension (shock) and hypoperfusion to the organs, threatening their failure or the patient’s death.
- Meningitis: Usually viral, but in such a threat to brain function, there is more risk than benefit in not beginning antibiotics based on the traditional bacteria known to cause it.
- Sexually transmitted infections (STIs): When signs and symptoms are classic for a particular STI, e.g., purulent urethral discharge in gonorrhea, beginning antibiotics as early as possible with one known to be particularly effective will begin treating a patient’s severe pain as well as may preserve fertility.
- Septic arthritis: Early treatment will begin limiting permanent joint damage sooner rather than later.
- Pyelonephritis: Kidney infection, more ominous than a simple bladder infection, can result in scarring with far-flung ramifications, such as renal dysfunction and hypertension, which can then further create risk for cardiovascular disease.
- High fevers: When a high temperature is the only sign in an otherwise mysterious infection, broad-spectrum antibiotics can be given empirically to cover for sepsis or prevent the rapid anemia that can develop from the fever while other diagnostics are implemented.
- Postoperative infections: Surgery in specific areas of the body can risk infections with certain types of bacteria, e.g., anaerobic bacteria in pelvic surgery. These are usually mixed infections in which a multi-drug regimen is used to cover all of the usual suspects until cultures return; if cultures cannot be obtained, the multi-drug regimen can be administered empirically while observing for clinical improvement.
Antibiotic Therapy Based on Culture and Sensitivity
When the C&S indicates the specific bacterium (bacteria) causing the infection and the sensitivity identifies the antibiotics to which the infectious organism(s) is (are) sensitive, a full course based on standard recommendations is begun and continues to completion unless the patient develops an allergic reaction or demonstrates worsening of the infection. As such, beginning antibiotic therapy requires close surveillance so that a mid-course correction can be made when necessary.
Prevention of Complications from Antibiotics
Antibiotics either are cleared by the kidney or detoxified by the liver for elimination by the kidney. Because of this, certain antibiotics should be used with caution in those with either kidney or liver disease, or both. To prevent too low a concentration or, more likely, too high a concentration of antibiotics which can lead to severe side effects, modifying the dosing regime is necessary in these individuals.
Prevention of Anaphylaxis
Those who have experienced an allergic reaction in the past to a specific antibiotic (which would intuitively include other members of its antibiotic family) should never be exposed to that antibiotic family again. Such re-exposure to an immune system “primed and ready” could lead to life-threatening anaphylactic shock. An exception to this is with penicillin therapy in pregnant patients with syphilis, in which the alternatives do not cross the placenta to treat the baby’s simultaneous infection; in these cases, a protocol of desensitization can be done by an allergist until which time penicillin can be given safely to treat both the baby and the mother.
Those with a history of rheumatic fever and/or valvular heart disease could suffer colonization of their valves if bacteria are seeded throughout the bloodstream via invasive procedures, such as surgery, dental work, or invasive testing (biopsies, etc.). These patients will have antibiotics begun before such procedures so that there will be a blood level on board when the theoretical seeding takes place.
Likewise, prophylactic antibiotics are used with indwelling catheters that have a high risk of infection over time, such as Foley bladder catheters, ports for peritoneal dialysis, or central lines.
Prior to placement of gastrostomy tubes or in surgeries that involve patients with a low white blood count or who are immunosuppressed, prophylactic antibiotics are indicated.
Surgeries that involve exposure of a “contaminated” environment to a “clean” environment should have antibiotic prophylaxis that covers the usual bacteria that normally reside in the unsterile areas. An example is a vaginal hysterectomy in which the sterile abdomen is breached to remove the uterus through the vagina. Another example is colon surgery that involves entering the lumen which can spill intestinal bacteria into the abdomen. Some feel that any surgery that involves a skin incision to enter the abdomen, thorax, or cranium, is such a “clean-contaminated” case.
Empiric antibiotic prophylaxis is appropriate in individualized situations specific to the patient. For example, if a man is treated for a sexually transmitted infection (STI), his sexual partner should be treated at the same time due to the likelihood of exposure, even if there are no symptoms. Prevention of recurrence of STIs is based on a culture and sensitivity after a full course of antibiotics, referred to as a “test of cure” (TOC).