Penicillins and Cephalosporins
Objectives
• Explain the mechanisms of action of antibacterial drugs.
• Differentiate between bacteria that are naturally resistant and those that have acquired resistance to an antibiotic.
• Summarize the three general adverse effects associated with antibacterial drugs.
• Differentiate between narrow-spectrum and broad-spectrum antibiotics.
• Compare the effects of the natural, broad-spectrum (extended), penicillinase-resistant, and antipseudomonal penicillins.
• Contrast the effects of first-, second-, third-, and fourth-generation cephalosporins.
• Apply the nursing process for patients receiving penicillins and cephalosporins.
Key Terms
acquired resistance, p. 402
antibacterials, p. 401
antimicrobials, p. 401
bactericidal, p. 401
bacteriostatic, p. 401
broad-spectrum antibiotics, p. 403
cross-resistance, p. 403
immunoglobulins, p. 402
inherent resistance, p. 402
microorganisms, p. 401
narrow-spectrum antibiotics, p. 403
nephrotoxicity, p. 409
nosocomial infections, p. 402
superinfection, p. 407
http://evolve.elsevier.com/KeeHayes/pharmacology/
This chapter discusses the antibacterials and their effects, which include mechanisms of antibacterial action, body defenses, resistance to antibacterials, use of antibacterial combinations, general adverse reactions to antibacterials, and narrow- and broad-spectrum antibiotics. This chapter also discusses two antibacterials in detail: penicillin and cephalosporin.
Pathophysiology
Bacteria, known as prokaryotes, are single-celled organisms lacking a true nucleus and nuclear membrane. Most bacteria have a rigid cell wall, and the structure of the cell wall determines the shape of the bacteria. One classification of bacteria involves the appearance or shape under a microscope. A bacillus is a rod-shaped organism. Cocci are spherical. When cocci appear in clusters, they are called staphylococci; when cocci are arranged in chains, they are called streptococci. Bacteria reproduce by cell division about every 20 minutes.
Another classification of bacteria involves staining properties of the cell. The Gram staining method was devised in 1882 by Hans Christian Gram, a Danish bacteriologist. Gram staining is determined by the ability of the bacterial cell wall to retain a purple stain by a basic dye. Crystal violet is normally used in the staining process but may be substituted with methylene blue. If bacteria retain a purple stain, they are classified as gram-positive microorganisms. Those bacteria not stained are known as gram-negative microorganisms. Examples of gram-positive bacteria include Staphylococcus aureus, Streptococcus pneumoniae, Group B streptococcus, and Clostridium perfringens. Examples of gram-negative bacteria include Neisseria meningitides, Escherichia coli, and Haemophilus influenzae.
Bacteria produce toxins that cause cell lysis (cell death). Many bacteria produce the enzyme beta-lactamase, which destroys beta-lactam antibiotics such as penicillins and cephalosporins.
Antibacterial Drugs
Antibacterials/Antibiotics
Although the terms antibacterial, antimicrobial, and antibiotic are frequently used interchangeably, there are some subtle differences in meaning. Antibacterials and antimicrobials are substances that inhibit bacterial growth or kill bacteria and other microorganisms (microscopic organisms including viruses, fungi, protozoa, and rickettsiae). Technically, the term antibiotic refers to chemicals produced by one kind of microorganism that inhibits the growth of or kills another. For practical purposes, however, these terms may be used interchangeably. Several drugs, including antiinfective and chemotherapeutic agents, have actions similar to those of antibacterial and antimicrobial agents. Antibacterial drugs do not act alone in destroying bacteria. Natural body defenses, surgical procedures to excise infected tissues, and dressing changes may be needed along with antibacterial drugs to eliminate the infecting bacteria.
Antibacterial drugs are either obtained from natural sources or manufactured. The use of moldy bread on wounds to fight infection dates back 3500 years. In 1928, a British bacteriologist named Alexander Fleming noted that “mold” was contaminating his bacterial cultures and inhibiting bacterial growth. The mold was called Penicillium notatum; thus Fleming called the substance penicillin. In 1939 Howard Florey expanded on Fleming's findings and purified the penicillin so it could be used commercially. Penicillin was used during World War II and marketed in 1945. Sulfonamide, a synthetic antibacterial, was introduced in 1935. Sulfonamides are discussed in greater detail in Chapter 31.
Bacteriostatic drugs inhibit the growth of bacteria, whereas bactericidal drugs kill bacteria. Some antibacterial drugs (tetracycline and sulfonamides) have a bacteriostatic effect, whereas other antibacterials (penicillins and cephalosporins) have a bactericidal effect. Depending on the drug dose and serum level, certain drugs can have both bacteriostatic and bactericidal effects.
For drugs with a narrow therapeutic index (e.g., aminoglycosides), peaks and troughs of serum antibiotic levels are monitored to determine if the drug is within the therapeutic range for its desired effect. If the serum peak level is too high, drug toxicity could occur. If the serum trough level (drawn minutes before administration of the next drug dose) is below the therapeutic range, the patient is not receiving an adequate antibiotic dose to kill the targeted microorganism.
Mechanisms of Antibacterial Action
Five mechanisms of antibacterial action are responsible for the inhibition of growth or destruction of microorganisms: (1) inhibition of bacterial cell-wall synthesis, (2) alteration of membrane permeability, (3) inhibition of protein synthesis, (4) inhibition of the synthesis of bacterial ribonucleic acid (RNA) and deoxyribonucleic acid (DNA), and (5) interference with metabolism within the cell (Table 29-1).
TABLE 29-1
MECHANISMS OF ACTIONS OF ANTIBACTERIAL DRUGS
| ACTION | EFFECT | DRUGS |
| Inhibition of cell wall synthesis | Bactericidal effect Enzyme breakdown of cell wall Inhibition of enzyme in synthesis of cell wall. |
penicillin cephalosporins bacitracin vancomycin |
| Alteration in membrane permeability | Bacteriostatic or bactericidal effect Increases membrane permeability. Loss of cellular substances causes lysis of the cell. |
amphotericin B nystatin polymyxin colistin |
| Inhibition of protein synthesis | Bacteriostatic or bactericidal effect Interferes with protein synthesis without affecting normal cell. Inhibits steps of protein synthesis. |
aminoglycosides tetracyclines erythromycin lincomycin |
| Inhibition of synthesis of bacterial RNA and DNA | Inhibits synthesis of RNA and DNA in bacteria. Binds to nucleic acid and enzymes needed for nucleic acid synthesis. | fluoroquinolones |
| Interference with cellular metabolism | Bacteriostatic effect Interferes with steps of metabolism within cells. |
sulfonamides trimethoprim isoniazid (INH) nalidixic acid rifampin |
Pharmacokinetics
Antibacterial drugs must not only penetrate the bacterial cell wall in sufficient concentration, but also must have an affinity (attraction) to the binding sites on the bacterial cell. The time the drug remains at the binding sites increases the effect of the antibacterial action. This time factor is controlled by the pharmacokinetics (distribution, half-life, and elimination) of the drug.
Antibacterials that have a longer half-life usually maintain a greater concentration at the binding site; therefore, frequent dosing is not required. Most antibacterials are not highly protein-bound, with a few exceptions (e.g., oxacillin, ceftriaxone, cefoperazone, cefprozil, cloxacillin, nafcillin, clindamycin). Protein binding does not have a major influence on the effectiveness of most antibacterial drugs. The steady state of the antibacterial drug occurs after the fourth to fifth half-lives, and the drug is eliminated from the body, mainly through urine, after the seventh half-life.
Pharmacodynamics
The drug concentration at the site or the exposure time for the drug plays an important role in bacterial eradication. Antibacterial drugs are used to achieve the minimum effective concentration (MEC) necessary to halt the growth of a microorganism. Many antibacterials have a bactericidal effect against the pathogen when the drug concentration remains constantly above the MEC during the dosing interval. Duration of time for use of the antibacterial varies according to the type of pathogen, site of infection, and immunocompetence of the host. With some severe infections, a continuous infusion regimen is more effective than intermittent dosing because of constant drug concentration and time exposure. Once-daily antibacterial dosing (e.g., aminoglycosides, macrolides, fluoroquinolones) has been effective in eradicating pathogens and has not caused severe adverse reactions (ototoxicity, nephrotoxicity) in most cases. The ease of compliance with once- or twice-daily drug dosing also increases the patient's adherence to the drug regimen.
Figure 29-1 illustrates the effect of three methods of drug dosing. The drug dose is effective when it remains above the MEC.
Body Defenses
Body defenses and antibacterial drugs work together to stop the infectious process. The effect that antibacterial drugs have on an infection depends not only on the drug but also on the host's defense mechanisms. Factors such as age, nutrition, immunoglobulins, white blood cells (WBCs), organ function, and circulation influence the body's ability to fight infection. Older adults and undernourished individuals have less resistance to infection than younger, well-nourished populations. If the host's natural body defense mechanisms are inadequate, drug therapy might not be as effective. As a result, drug therapy may need to be closely monitored or revised. When circulation is impeded, an antibacterial drug may not be distributed properly to the infected area. In addition, immunoglobulins (antibody proteins such as IgG and IgM) and other elements of the immune response system (WBCs) needed to combat infections may be depleted in individuals with poor nutritional status.
Resistance to Antibacterials
Bacteria may be sensitive or resistant to certain antibacterials. When bacteria are sensitive to a drug, the pathogen is inhibited or destroyed. If bacteria are resistant to an antibacterial, the pathogen continues to grow, despite administration of that antibacterial drug.
Bacterial resistance may result naturally (inherent resistance) or it may be acquired. A natural, or inherent, resistance occurs without previous exposure to the antibacterial drug. For example, the gram-negative (non–gram-staining) bacterium Pseudomonas aeruginosa is inherently resistant to penicillin G. An acquired resistance is caused by prior exposure to the antibacterial. Although Staphylococcus aureus was once sensitive to penicillin G, repeated exposures have caused this organism to evolve and become resistant to it. Penicillinase, an enzyme produced by the microorganism, is responsible for causing its penicillin resistance. Penicillinase metabolizes penicillin G, causing the drug to be ineffective. Penicillinase-resistant penicillins that are effective against S. aureus are available.
Antibiotic resistance is a major problem. In the early 1980s, pharmaceutical companies thought that enough antibiotics were on the market, so these companies concentrated on developing antiviral and antifungal drugs. As a result, fewer new antibiotics were developed during the 1980s. Now pharmaceutical companies have developed many new antibiotics, but antibiotic resistance continues to develop, especially when antibiotics are used frequently. As bacteria reproduce, some mutation occurs, and eventually the mutant bacteria survive the effects of the drug. One explanation is that the mutant bacteria strain may have grown a thicker cell wall.
In large health care institutions, there is a tendency toward drug resistance in bacteria. Mutant strains of organisms have developed, thus increasing their resistance to antibiotics that were once effective against them. Infections acquired while patients are hospitalized are called nosocomial infections. Many of these infections are caused by drug-resistant bacteria and can prolong hospitalization, which is costly to both the patient and third-party health care insurers.
Another problem related to antibiotic resistance is that bacteria can transfer their genetic instruction to another bacterial species. The other bacterial species becomes resistant to that antibiotic as well. Bacteria can pass along high resistance to a more virulent and aggressive bacterium (e.g., S. aureus, enterococci).
Methicillin (Staphcillin) was the first penicillinase-resistant penicillin developed in 1959 in response to a resistance of S. aureus. In 1968, strains of S. aureus were beginning to become resistant to methicillin. Highly resistant bacteria, known as methicillin-resistant Staphylococcus aureus (MRSA), became resistant not only to methicillin, but to all penicillins and cephalosporins as well. Resistance that was once found only in hospitals began to emerge in 1981 in the community as well. Methicillin is now off the market. The treatment of choice for MRSA is vancomycin (Vancocin). Other effective drugs used to treat MRSA include linezolid (Zyvox), daptomycin (Cubicin), trimethoprim/sulfamethoxazole (Bactrim), doxycycline (Vibramycin), and clindamycin (Cleocin). Telavancin (Vibativ), a glycopeptides antiinfective, was approved in September 2009 to treat gram-negative bacteria, including MRSA.
Many enterococcal strains are resistant to penicillin, ampicillin, gentamicin, streptomycin, and vancomycin. Another big resistance problem is vancomycin-resistant Enterococcus faecium (VREF), which can cause death in many persons with weakened immune systems. The incidence of VREF in hospitals has increased. A strain of MRSA has been reported to be resistant to vancomycin (vancomycin-resistant Staphylococcus aureus, or VRSA). Major medical problems result. One antibiotic after another is ineffective against new resistant strains of bacteria. As new drugs are developed, drug resistance will probably develop as well. Pharmaceutic companies and biotechnical firms are working on new classes of drugs to overcome the problem of bacterial resistance to antibiotics. A class of antibiotics, oxazolidinones, was discovered by a pharmaceutical company in 1988, but the company could not overcome toxicity problems in this class of drug. Another pharmaceutical company has taken the compound and made it less toxic. This antibiotic, linezolid, is effective against MRSA, VREF, and penicillin-resistant Streptococci. Quinupristin/dalfopristin (Synercid), which consists of two streptogramin antibacterials, is marketed in a combination of 30 : 70 for intravenous (IV) use against life-threatening infection caused by VREF and for treatment of bacteremia, S. aureus, and Streptococcus pyogenes.
Another way to attack antimicrobial resistance is to develop drugs that disable the antibiotic-resistant mechanism in the bacteria. Patients would take the antibiotic-resistance disabler along with the antibiotic already on the market, making the drug effective again. Developing a bacterial vaccine is another way to combat bacteria and lessen the need for antibiotics. The bacterial vaccine against pneumococcus has been effective in decreasing the occurrence of pneumonia and meningitis among various age groups.
Antibiotic misuse, a major problem today, increases antibiotic resistance. Studies reveal that 23% to 37.8% of patients in hospitals receive antibiotics and 50% of this population is receiving antibiotics inappropriately. When antibiotics are taken unnecessarily (e.g., for viral infections, when no infection is present) or incorrectly (e.g., skipping doses, not taking the full antibiotic regimen), one may develop resistance to antibacterials. Consumer education is important because many patients “demand” antibiotics for viral conditions. Antibiotics are ineffective against viruses. However, viral infections that persist could decrease the body's immune system, thus promoting a bacterial infection. The nurse should teach patients about the proper use of antibiotics to prevent situations that promote drug resistance to bacteria.
Cross-resistance can also occur between antibacterial drugs that have similar actions, such as the penicillins and cephalosporins. To ascertain the effect antibacterial drugs have on a specific microorganism, culture and sensitivity or antibiotic susceptibility laboratory testing is performed. A culture and sensitivity test (C&S) can detect the infective microorganism present in a sample (e.g., blood, sputum, swab) and what drug can kill it. The organism causing the infection is determined by culture, and the antibiotics the organism is sensitive to are determined by sensitivity. The susceptibility or resistance of one microorganism to several antibacterials can be determined by this method. Multiantibiotic therapy (daily use of several antibacterials) delays the development of microorganism resistance.
Use of Antibiotic Combinations
Combination antibiotics should not be routinely prescribed or administered except for specific uncontrollable infections. Usually a single antibiotic will successfully treat a bacterial infection. When there is a severe infection that persists and is of unknown origin or has been unsuccessfully treated with several single antibiotics, a combination of two or three antibiotics may be suggested. Before beginning antibiotic therapy, a culture or cultures should be taken to identify the bacteria.
When two antibiotics are combined, the result is additive, potentiative, or antagonistic. The additive effect is equal to the sum of the effects of two antibiotics. The potentiative effect occurs when one antibiotic potentiates the effect of the second antibiotic, increasing their effectiveness. The antagonistic result is a combination of a drug that is bactericidal, such as penicillin, and a drug that is bacteriostatic, such as tetracycline. When these two drugs are used together, the desired effect may be greatly reduced.
General Adverse Reactions to Antibacterials
Three major adverse reactions associated with the administration of antibacterial drugs are allergic (hypersensitivity) reactions, superinfection, and organ toxicity. Table 29-2 describes these adverse reactions, all of which require close monitoring of the patient.
TABLE 29-2
GENERAL ADVERSE REACTIONS TO ANTIBACTERIAL DRUGS
| TYPE | CONSIDERATIONS |
| Allergy or hypersensitivity | Allergic reactions to drugs may be mild or severe. Examples of mild reactions are rash, pruritus, and hives. An example of a severe response is anaphylactic shock. Anaphylaxis results in vascular collapse, laryngeal edema, bronchospasm, and cardiac arrest. Shortness of breath is frequently the first symptom of anaphylaxis. Severe allergic reaction generally occurs within 20 minutes. Mild allergic reaction is treated with an antihistamine; anaphylaxis requires treatment with epinephrine, bronchodilators, and antihistamines. |
| Superinfection | Superinfection is a secondary infection that occurs when the normal microbial flora of the body are disturbed during antibiotic therapy. Superinfections can occur in the mouth, respiratory tract, intestine, genitourinary tract, or skin. Fungal infections frequently result in superinfections, although bacterial organisms (e.g., Proteus, Pseudomonas, staphylococci) may be the offending microorganisms. Superinfections rarely develop when the drug is administered for less than 1 week. They occur more commonly with the use of broad-spectrum antibiotics. For fungal infection of the mouth, nystatin is frequently used. |
| Organ toxicity | The liver and kidneys are involved in drug metabolism and excretion. Antibacterials may result in damage to these organs. For example, aminoglycosides can be nephrotoxic (as well as ototoxic). |
Narrow-Spectrum and Broad-Spectrum Antibiotics
Antibacterial drugs are either narrow spectrum or broad spectrum. The narrow-spectrum antibiotics are primarily effective against one type of organism. For example, penicillin and erythromycin are used to treat infections caused by gram-positive bacteria. Certain broad-spectrum antibiotics (tetracycline and cephalosporins) can be effective against both gram-positive and gram-negative organisms. Because narrow-spectrum antibiotics are selective, they are more active against those single organisms than the broad-spectrum antibiotics. Broad-spectrum antibiotics are frequently used to treat infections when the offending microorganism has not been identified by C&S.
Penicillins and Cephalosporins
Penicillins
Penicillin, a natural antibacterial agent obtained from the mold genus Penicillium, was introduced to the military during World War II and is considered to have saved many soldiers' lives. It became widely used in 1945 and was labeled a “miracle” drug. With the advent of penicillin, many patients survived who would have normally died from wound and severe respiratory infections.
Penicillin's beta-lactam structure (beta-lactam ring) interferes with bacterial cell-wall synthesis by inhibiting the bacterial enzyme that is necessary for cell division and cellular synthesis. The bacteria die of cell lysis (cell breakdown). The penicillins can be both bacteriostatic and bactericidal, depending on the drug and dosage. Penicillin G is primarily bactericidal.
Penicillins are mainly referred to as beta-lactam antibiotics. Bacteria can produce a variety of enzymes, such as beta-lactamases, that can inactivate penicillin and other beta-lactam antibiotics such as the cephalosporins. The beta-lactamases, which attack penicillins, are called penicillinases.
Penicillin G was the first penicillin administered orally and by injection. With oral administration, only about one third of the dose is absorbed. Because of its poor absorption, penicillin G given by injection (intramuscular [IM] and intravenous [IV]) is more effective in achieving a therapeutic serum penicillin level. Aqueous penicillin G has a short duration of action, and the IM injection is very painful, because it is an aqueous drug solution. As a result, a longer-acting form of penicillin, procaine penicillin (milky color), was produced to extend the activity of the drug. Procaine in the penicillin decreases the pain related to injection.
Penicillin V was the next type of penicillin produced. Although two thirds of the oral dose is absorbed by the gastrointestinal (GI) tract, it is a less potent antibacterial drug than penicillin G. Penicillin V is effective against mild to moderate infections, including anthrax as a biologic weapon of bioterrorism.
Initially penicillin was overused. It was first introduced for the treatment of staphylococcal infections, but after a few years mutant strains of Staphylococcus developed that were resistant to penicillins G and V because of the bacterial enzyme penicillinase, which destroys penicillin. This led to the development of new broad-spectrum antibiotics with structures similar to penicillin to combat infections resistant to penicillins G and V.
Food in the stomach does not significantly alter absorption of penicillin V, so it should be taken after meals. Amoxicillins are penicillins that are unaffected by food.
Broad-Spectrum Penicillins (Aminopenicillins)
Broad-spectrum penicillins are used to treat both gram-positive and gram-negative bacteria. They are not, however, as “broadly” effective against all microorganisms as they were once considered to be. This group of drugs is costlier than penicillin and therefore should not be used when ordinary penicillins, such as penicillin G, are effective. The broad-spectrum penicillins are effective against some gram-negative organisms: Escherichia coli, Haemophilus influenzae, Shigella dysenteriae, Proteus mirabilis, and Salmonella. However, these drugs are not penicillinase resistant. They are readily inactivated by beta-lactamases, thus ineffective against S. aureus. Examples of this group are ampicillin (Omnipen), and amoxicillin (Amoxil) (Table 29-3). Amoxicillin is the most prescribed penicillin derivative for adults and children.
TABLE 29-3
| GENERIC (BRAND) | ROUTE AND DOSAGE | USES AND CONSIDERATIONS |
| Basic Penicillins | ||
| penicillin G procaine (Crysticillin, Wycillin) | A: IM: 600,000-1 million units/d in 1-2 divided doses C: IM: 300,000 units/d in 1-2 divided doses |
For moderately serious infections. Slow IM absorption with prolonged action. Solution is milky. Pregnancy category: B; PB: 60%;  : 0.5-1 h |
| penicillin G benzathine (Bicillin L-A) | A: IM: 1.2 million units as a single dose C >27 kg: IM: 900,000 units/dose C <27 kg: IM: 300,000-600,000 units/dose |
Long-acting penicillin when given by injection. Used as prophylaxis for rheumatic fever. Pregnancy category: B; PB: 60%;  : 0.5-1 h |
| penicillin G sodium/potassium (Pfizerpen) | A: IM/IV: 5-24 million units/d in divided doses q4-6 h; max: 80 million units/d C: IM/IV: 150,000-300,000 units/d in divided doses q4-6h; max: 24 million units/d Neonates: IM/IV: 50,000- 75,000 units/kg/d in divided doses q6-12h; max: 100,000/kg/d |
Treatment of lower respiratory infections. Monitor electrolyte levels with high doses. Injectable solution is clear. Pregnancy category: B; PB: 45%-68%;  : 20-30 min |
| penicillin V potassium (Veetids) | A/C >12 y: PO: 125-500 mg q6h | Treatment of upper respiratory infections. Acid-stable and less active than penicillin G against some bacteria. Not recommended in renal failure. Take drug after meals. Pregnancy category: B; PB: 75%-89%;  : 0.5 h |
| Broad-Spectrum Penicillins | ||
| amoxicillin (Amoxil) | See Prototype Drug Chart 29-1. | |
| amoxicillin-clavulanate (Augmentin) | A/C >40 kg: PO: 250-500/125 mg q8-12h for 10 d | Treatment of lower respiratory infections, otitis media, sinusitis, skin infections, and UTIs. Pregnancy category: B; PB: 17%-30%;  : 1-1.5 h |
| ampicillin (Principen) | A: PO/IM/IV: 250-500 mg q6h C: PO/IM/IV: 25-50 mg/kg/d in 4 divided doses |
Treatment of lower respiratory tract infections. First broad-spectrum penicillin. Effective against gram-negative and gram-positive bacteria. Individuals with penicillin allergies may also be allergic to ampicillin. Pregnancy category: B; PB: 15%-28%;  : 1-1.5 h |
| ampicillin-sulbactam (Unasyn) | A: IM/IV: 1.5-3 g q6h; max: 4 g sulbactam/d C: IV: 100-300 mg/kg/d, in divided doses q6h |
Same as ampicillin. Treatment of streptococcus pneumonia, nosocomial pneumonia, skin infections, and Neisseria gonorrhoeae. Sulbactam inhibits beta-lactamase thus extending the spectrum. Pregnancy category: B; PB; 28%-38%;  : 1-2 h |
| Penicillinase-Resistant Penicillins | ||
| dicloxacillin sodium (Dynapen) | See Prototype Drug Chart 29-1. | |
| nafcillin (Nallpen) | A: IM/IV: 500 mg-2 g q4-6h; max: 12 g/d | Highly effective against penicillin G–resistant Staphylococcus aureus. Not recommended orally due to instability in gastric juices. Pregnancy category: B; PB: 70%-90%;  : 0.5-1.5 h |
| oxacillin sodium | A/C >40 kg: IM/IV: 250 mg-1 g q4-6h; max: 6 g C <40 kg: IM/IV: 50-100 mg/kg/d in divided doses q4-6h; max: 6 g/d Neonates: IM/IV: 25 mg/kg/d in divided doses q6h |
For penicillin-resistant staphylococci in bone, joint, and skin infections. Pregnancy category: B; PB: 89%-94%;  : 0.5 h |
| Extended-Spectrum Penicillins | ||
| carbenicillin indanyl (Geocillin) | A: PO: 382-764 mg q6h | The first penicillin-like drug developed to treat infections caused by Pseudomonas aeruginosa and Proteus spp. Contains large amounts of sodium. Use with caution when administering to patients with hypertension or heart failure. Pregnancy category: B; PB: 30%-60%;  : 1 h |
| piperacillin-tazobactam (Zosyn) | A: IV: 3.375 g, q6h over 30 min, 7-10 d | To treat severe appendicitis, skin infections, pneumonia, and beta-lactamase–producing bacteria. Tazobactam is a beta-lactamase inhibitor. Pregnancy category: B; PB: 30%;  : 0.7-1.5 h |
| ticarcillin-clavulanate (Timentin) | A: IV: 3.1 g q6h C >3 mo: IV: 50 mg/kg/d in 4-6 divided doses |
Clavulanic acid protects ticarcillin from degradation by beta-lactamase enzymes. Effective for treating septicemia and lower respiratory tract, urinary tract, skin, bone, and joint infections. Pregnancy category: B; PB: 45%-65%;  : 1 h |
A, Adult; C, child; d, day; GI, gastrointestinal; h, hour; IM, intramuscular; IV, intravenous; max, maximum; NB, newborn; NSS, normal saline solution; PB, protein-binding; PO, by mouth; 
, half-life; UK, unknown; UTI, urinary tract infection; y, year; >, greater than; <, less than.
Penicillinase-Resistant Penicillins (Antistaphylococcal Penicillins)
Penicillinase-resistant penicillins (antistaphylococcal penicillins) are used to treat penicillinase-producing S. aureus. Dicloxacillin is an oral preparation of these antibiotics; nafcillin and oxacillin are IM and IV preparations. This group of drugs is not effective against gram-negative organisms and is less effective than penicillin G against gram-positive organisms. Prototype Drug Chart 29-1 compares the similarities and differences in the broad-spectrum penicillin amoxicillin and the penicillinase-resistant penicillin dicloxacillin.
Prototype Drug Chart 29-1
Amoxicillin and Dicloxacillin
| Drug Class | Dosage |
| amoxicillin: Broad-spectrum penicillin dicloxacillin: Penicillinase-resistant penicillin Trade Names: amoxicillin: Amoxil dicloxacillin: Dynapen Pregnancy Category: B | amoxicillin: A: PO: 250 q8h or 500 mg q12h C: PO: 20-40 mg/kg/d in 3 divided doses dicloxacillin: A: PO: 125-500 mg q6h C: PO: 12.5-25 mg/kg/d q6h |
| Contraindications | Drug-Lab-Food Interactions |
| amoxicillin/dicloxacillin: Allergic to penicillin, asthma, inflammatory bowel disease, pseudomembranous colitis, ulcerative colitis amoxicillin: mononucleosis Caution: amoxicillin/dicloxacillin: Hypersensitivity to cephalosporins amoxicillin: renal impairment | Drug: amoxicillin/dicloxacillin: Increase effect with aspirin, allopurinol, probenecid; increase bleeding with oral anticoagulants; increase effect of methotrexate; decrease effect with tetracycline, erythromycin Lab: Increase serum AST, ALT, BUN, and creatinine; increase PT, INR Food: Decrease effect with acidic fruits or juices |
| Pharmacokinetics | Pharmacodynamics |
| Absorption: PO: amoxicillin: >80% in GI tract dicloxacillin: 35%-76% in GI tract Distribution: PB: amoxicillin: 20% dicloxacillin: 95%-99% Metabolism:  :amoxicillin: 1-1.5 h dicloxacillin: 0.5-1 h Excretion: amoxicillin: 70% in urine; clavulanate: 30%-40% in urine dicloxacillin: Excreted in bile and urine | amoxicillin: PO: Onset: 0.5 h Peak: 1-2 h Duration: 6-8 h dicloxacillin: PO: Onset: 0.5 h Peak: 1 h Duration: 4-6 h |
| Therapeutic Effects/Uses | |
| amoxicillin: To treat respiratory tract infection, urinary tract infection, otitis media, and sinusitis dicloxacillin: To treat Staphylococcus aureus infection | |
| Mode of Action: amoxicillin/dicloxacillin: Inhibition of the enzyme in cell wall synthesis; bactericidal effect | |
| Side Effects | Adverse Reactions |
| amoxicillin/dicloxacillin: Nausea, vomiting, diarrhea, rash, stomatitis, seizures, pseudomembranous colitis amoxicillin: Edema, insomnia, dysphagia dicloxacillin: Abdominal pain, flatulence | amoxicillin/dicloxacillin: Superinfections (vaginitis) Life-threatening: amoxicillin/dicloxacillin: Blood dyscrasias, thrombocytopenia, neutropenia, hemolytic anemia, bone marrow depression, Stevens-Johnson syndrome amoxicillin: Respiratory distress dicloxacillin: Eosinophilia, agranulocytosis, angioedema, liver toxicity |
A, Adult; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; C, child; d, day; GI, gastrointestinal; h, hour; PB, protein-binding; PO, by mouth; 
, half-life; >, greater than.
Extended-Spectrum Penicillins (Antipseudomonal Penicillins)
The antipseudomonal penicillins are a group of broad-spectrum penicillins. This group of drugs is effective against Pseudomonas aeruginosa, a gram-negative bacillus that is difficult to eradicate. These drugs are also useful against many gram-negative organisms such as Proteus spp., Serratia spp., Klebsiella pneumoniae, Enterobacter spp., and Acinetobacter spp. The antipseudomonal penicillins are not penicillinase-resistant. Their pharmacologic action is similar to that of aminoglycosides, but they are less toxic.
Table 29-3 lists the drugs in the four categories of penicillin-type antibacterials. The administration route of various types of penicillins (oral, IM, IV), along with the cephalosporins, are available on the Evolve website.
Beta-Lactamase Inhibitors
When a broad-spectrum antibiotic (e.g., amoxicillin) is combined with a beta-lactamase (enzyme) inhibitor (e.g., clavulanic acid), the resulting antibiotic (e.g., amoxicillin-clavulanic acid [Augmentin]) inhibits the bacterial beta-lactamases, making the antibiotic effective and extending its antimicrobial effect. There are three beta-lactamase inhibitors: clavulanic acid, sulbactam, and tazobactam. These inhibitors are not given alone but combined with a penicillinase-sensitive penicillin such as amoxicillin, ampicillin, piperacillin, or ticarcillin. The combined drugs currently marketed include the following:
Pharmacokinetics
Amoxicillin is well absorbed from the GI tract, whereas dicloxacillin is only partially absorbed. Protein-binding power differs between the two drugs—amoxicillin is 20% protein-bound and dicloxacillin is highly protein-bound (95%). Drug toxicity may result when other highly protein-bound drugs are used with dicloxacillin. Both drugs have short half-lives. Sixty percent of amoxicillin is excreted in the urine; dicloxacillin is excreted in bile and urine.
Pharmacodynamics
Both amoxicillin and dicloxacillin are penicillin derivatives and are bactericidal. These drugs interfere with bacterial cell-wall synthesis, causing cell lysis. Amoxicillin may be produced with or without clavulanic acid, an agent that prevents the breakdown of amoxicillin by decreasing resistance to the antibacterial drug. The addition of clavulanic acid intensifies the effect of amoxicillin. The amoxicillin-clavulanic acid preparation (Augmentin) and amoxicillin trihydrate (Amoxil) have similar pharmacokinetics and pharmacodynamics, as well as similar side effects and adverse reactions. When probenecid is taken with amoxicillin or dicloxacillin, the serum antibacterial levels may be increased. The effects of amoxicillin are decreased when taken with erythromycin and tetracycline. The onset of action, serum peak concentration time, and duration of action for amoxicillin and dicloxacillin are very similar.
Geriatrics
Most beta-lactam antibiotics are excreted via the kidneys. With older adults, assessment of renal function is most important. Serum blood urea nitrogen (BUN) and serum creatinine should be monitored. With a decrease in renal function, the antibiotic dose should be decreased.
Side Effects and Adverse Reactions
Common adverse reactions to penicillin administration are hypersensitivity and superinfection (occurrence of a secondary infection when the flora of the body is disturbed) (see Table 29-2). Nausea, vomiting, and diarrhea are common GI disturbances. Rash is an indicator of a mild to moderate allergic reaction. Severe allergic reaction leads to anaphylactic shock. Clinical manifestations of a severe allergic reaction include laryngeal edema, severe bronchoconstriction with stridor, and hypotension. Allergic effects occur in 5% to 10% of persons receiving penicillin compounds; therefore close monitoring during the first dose and subsequent doses of penicillin is essential.
Drug Interactions
The broad-spectrum penicillins—amoxicillin and ampicillin—may decrease the effectiveness of oral contraceptives. Potassium supplements can increase serum potassium levels when taken with potassium penicillin G or V. When penicillin is mixed with an aminoglycoside in IV solution, the actions of both drugs are inactivated.
Cephalosporins
In 1948, a fungus called Cephalosporium acremonium was discovered in seawater at a sewer outlet off the coast of Sardinia. This fungus was found to be active against gram-positive and gram-negative bacteria and resistant to beta-lactamase (an enzyme that acts against the beta-lactam structure of penicillin). In the early 1960s, cephalosporins were used with clinical effectiveness. For cephalosporins to be effective against numerous organisms, their molecules were chemically altered, and semisynthetic cephalosporins were produced. Like penicillin, the cephalosporins have a beta-lactam structure and act by inhibiting the bacterial enzyme necessary for cell wall synthesis. Lysis to the cell occurs, and the bacterial cell dies.
First-, Second-, Third-, and Fourth-Generation Cephalosporins
Cephalosporins are a major antibiotic group used in hospitals and in health care offices. These drugs are bactericidal with actions similar to penicillin. For antibacterial activity, the beta-lactam ring of cephalosporins is necessary.
Nursing Process
Patient-Centered Collaborative Care
Antibacterials: Penicillins
Assessment
Assess for allergy to penicillin or cephalosporins. The patient who is hypersensitive to amoxicillin should not take any type of penicillin products. Severe allergic reaction could occur. A small percentage of patients who are allergic to penicillin could also be allergic to a cephalosporin product.
Evaluate laboratory results, especially liver enzymes. Report elevated alkaline phosphatase, alanine aminotransferase, or aspartate aminotransferase.
Record urine output. If amount is inadequate (<30 mL/h or <600 mL/d), drug or drug dosage may need to be changed.
Nursing Diagnoses
Planning
Nursing Interventions
Obtain sample (e.g., swab, blood, sputum) for laboratory culture and antibiotic sensitivity testing of infective organism (also known as C&S) before antibiotic therapy is started.
Monitor for signs and symptoms of superinfection, especially in patients taking high doses of an antibiotic for a prolonged time. Signs and symptoms include stomatitis (mouth ulcers), genital discharge (vaginitis), and anal or genital itching.
Examine patient for allergic reaction to the penicillin product, especially after the first and second doses. This may be a mild reaction, such as a rash, or a severe reaction, such as respiratory distress or anaphylaxis.
Have epinephrine available to counteract a severe allergic reaction.
Do not mix aminoglycosides with a high-dose or extended-spectrum penicillin G, because this combination may inactivate the aminoglycoside.
Assess patient for bleeding if high doses of penicillin are being given; a decrease in platelet aggregation (clotting) may result.
Monitor body temperature and infected area.
Dilute antibiotic for IV use in an appropriate amount of solution as indicated in the drug pamphlet.
Patient Teaching
General
Teach patient to take entire prescribed penicillin product, such as amoxicillin, until the bottle is empty. If only a portion of the penicillin is taken, drug resistance to that antibacterial agent may develop in the future.
Advise patient who is allergic to penicillin to wear a medical alert bracelet or necklace and carry a card that indicates the allergy. Patient should notify health care provider of any allergy to penicillin when reporting health history.
Keep drugs out of reach of small children. Request childproof containers.
Inform patient to report any side effects or adverse reaction that may occur while taking the drug.
Encourage patient to increase fluid intake; fluids aid in decreasing the body temperature and in excreting the drug.
Warn patient or child's parent that chewable tablets must be chewed or crushed before swallowing.
Advise female patients of childbearing years to use an additional form of birth control while taking penicillins.
Diet
Cultural Considerations
Recognize that patients and family members from various cultural backgrounds may have alternative practices for alleviating infections. Accept adjunctive alternative methods if not harmful to patient.
Request a translator to obtain a history of symptoms related to infection and any allergies to antibiotics if patient does not speak English.
Evaluation
Four groups of cephalosporins have been developed, identified as generations. Each generation is effective against a broader spectrum of bacteria (Table 29-4).
TABLE 29-4
ACTIVITY OF THE FOUR GENERATIONS OF CEPHALOSPORINS
| GENERATION | ACTIVITY |
| First | Effective against gram-positive bacteria (streptococci and most staphylococci). Effective against most gram-negative bacteria (Escherichia coli and species of Klebsiella, Proteus, Salmonella, and Shigella). |
| Second | Same effectiveness as first generation. Possess a broader spectrum against other gram-negative bacteria (Haemophilus influenzae, Neisseria gonorrhoeae, Neisseria meningitidis, Enterobacter spp., and several anaerobic organisms). |
| Third | Same effectiveness as first and second generations. Also effective against gram-negative bacteria (Pseudomonas aeruginosa, Serratia spp., and Acinetobacter spp). Less effective against gram-positive bacteria. |
| Fourth | Similar to third generation. Resistant to most beta-lactamase bacteria. Broader gram-positive coverage than third generation. Effective against E. coli, Klebsiella, Proteus, streptococci, certain staphylococci, and P. aeruginosa. |
Not all cephalosporins are affected by the beta-lactamases. First-generation cephalosporins are destroyed by beta-lactamases, but not all second-generation cephalosporins are affected by beta-lactamases. Third-generation cephalosporins are resistant to beta-lactamases. Most third- and fourth-generation cephalosporins (e.g., aztreonam, imipenem-cilastatin) are effective in treating sepsis and many strains of gram-negative bacilli. The cephalosporins ceftazidime and cefepime, along with aztreonam and imipenem-cilastatin, are effective against most strains of Pseudomonas aeruginosa. Table 29-5 lists the other unclassified beta-lactam antibiotics.
TABLE 29-5
| GENERIC (BRAND) | ROUTE AND DOSAGE | USES AND CONSIDERATIONS |
| aztreonam (Azactam) | Severe infections: A: IM/IV: 1.0-2.0 g q6-8h; max: 8 g/d C >9 mo: IV: 30 mg/kg q6-8h; max: 120 mg/kg/d |
For treatment of gram-negative infections of the lower respiratory tract, urinary tract, skin, and vagina. Not effective against gram-positive organisms. May be used in combination with other antibiotics. Pregnancy category: B; PB: 56%-60%;  : 1.7-2.1 h |
| imipenem-cilastatin (Primaxin) | A/C: IM: 500-750 mg q12h A: IV: 250 mg q6-8h; max 1 g/d C: IV: 15-25 mg/kg q6h |
For treatment of septicemia and severe infections of the lower respiratory tract, urinary tract, skin, bones, and joints. Effective against most gram-negative organisms, including Pseudomonas aeruginosa. Pregnancy category: C; PB: 20%-40%;  : 1 h |
| meropenem (Merrem) | A: IV: 1-2 g q8h C >3 mo: IV: 20-40 mg/kg q8h |
A carbapenem antibiotic, similar to cephalosporins. Effective against most strains of gram-negative organisms, including Pseudomonas aeruginosa, and effective for complicated appendicitis, peritonitis, meningitis, and soft-tissue infections. Pregnancy category: B; PB: 2%:  : 1.2 h |
A, Adult; C, child; d, day; h, hour; IM, intramuscular; IV, intravenous; max, maximum; min, minute; PB, protein-binding; PO, by mouth; 
, half-life; UK, unknown; y, year; >, greater than.
Approximately 10% of persons allergic to penicillin are also allergic to cephalosporins, because both groups of antibacterials have similar molecular structures. If a patient is allergic to penicillin and taking a cephalosporin, the nurse should watch for a possible allergic reaction to the cephalosporin, although the likelihood of a reaction is small.
Only a few cephalosporins are administered orally. These include cephalexin (Keflex), cefadroxil (Duricef), cefaclor (Ceclor), cefuroxime axetil (Ceftin), cefuroxime sodium (Zinacef), cefdinir (Omnicef), and cef-tibuten (Cedax). The rest of the cephalosporins are administered IM and IV. Prototype Drug Chart 29-2 describes the drug data related to ceftriaxone (Rocephin).
Prototype Drug Chart 29-2
Ceftriaxone
| Drug Class | Dosage |
| ceftriaxone: third-generation cephalosporin Trade Name: Rocephin Pregnancy Category: B | ceftriaxone: A: IM/IV: 1-2/d; max: 4 g/d C: IM/IV: 50-75 mg/kg/d in 2 divided doses; max: 100 mg/kg/d |
| Contraindications | Drug-Lab-Food Interactions |
| Hypersensitivity to cephalosporins, gallbladder disease, pseudomembranous colitis, bleeding, receiving calcium salts IV Caution: Hypersensitivity to penicillins; vitamin K deficiency, anticoagulants | Drug: increase nephrotoxicity with loop diuretics, aminoglycosides, calcium salts, vancomycin; increase bleeding with anticoagulants Lab: May increase AST, ALT, ALP, LDH. May increase PT and INR |
| Pharmacokinetics | Pharmacodynamics |
| Absorption: IM, IV Distribution: PB: 85%-95% Metabolism:  : 6-9 hExcretion: Urine | IM: Onset: UK Peak: 1.5-4 h Duration: UK IV: Onset: immediate Peak: 30 min Duration: UK |
| Therapeutic Effects/Uses | |
| For respiratory, urinary, bone, joint, and skin infections; otitis media; surgical infection prophylaxis, septicemia, gonorrhea, Klebsiella pneumoniae, E. coli, Streptococcus pneumoniae, and S. aureus | |
| Mode of Action: Inhibition of bacterial cell wall synthesis, causing cell death; bactericidal effect | |
| Side Effects | Adverse Reactions |
| Anorexia, nausea, vomiting, diarrhea, flatulence, rash, flushing, diaphoresis, dyspepsia, abdominal cramps, fever, pruritus, headaches, dizziness, vertigo, weakness, edema | Superinfections, bleeding, epistaxis, angioedema, palpitations, biliary obstruction, cholelithiasis, jaundice, hematuria Life-threatening: Seizures, anaphylaxis, agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, thrombocytopenia, neutropenia, pancytopenia, pseudomembranous colitis, Stevens-Johnson syndrome |
A, Adult; ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; C, child; d, day; h, hour; IM, intramuscular; IV, intravenous; LDH, lactic dehydrogenase; max, maximum; min, minute; PB, protein-binding; PO, by mouth; 
, half-life; UK, unknown.
Pharmacokinetics
Cefazolin is administered IM and IV, and cefaclor is given orally. The protein-binding power of cefazolin is greater than that of cefaclor. The half-life of each drug is short, and the drugs are excreted 60% to 80% unchanged in the urine.
Pharmacodynamics
Cefazolin and cefaclor inhibit bacterial cell-wall synthesis and produce a bactericidal action. For IM and IV use of cefazolin, the onset of action is almost immediate, and peak concentration time is 5 to 15 minutes for IV use. The peak concentration time for an oral dose of cefaclor is 30 to 60 minutes.
When probenecid is administered with either of these drugs, urine excretion of cefazolin or cefaclor is decreased, which increases the action of the drug. The effects of cefazolin and cefaclor can be decreased if the drug is given with tetracyclines or erythromycin. These drugs can cause false-positive laboratory results for proteinuria and glucosuria, especially when they are taken in large doses.
Table 29-6 lists the cephalosporins in their designated generation, dosages, and considerations.
TABLE 29-6
ANTIBACTERIALS: CEPHALOSPORINS
| GENERIC (BRAND) | ROUTE AND DOSAGE | USES AND CONSIDERATIONS |
| First-Generation | ||
| cefadroxil (Duricef) | A: PO: 1-2 g/d in 1-2 divided doses C: PO: 30 mg/kg/d in 2 divided doses |
For urinary tract infections, beta-hemolytic streptococcal infections, and staphylococcal skin infections. Well absorbed by GI tract and not affected by food. Pregnancy category: B; PB: 20%;  : 1-2 h |
| cefazolin sodium (Ancef) | A: IM/IV: 250 mg-1 g q6-8h; max: 12 g/d C: IM/IV: 25-100 mg/kg/d in 3 divided doses; max: 6 g/d |
For infections including otitis media, skin, bone, and respiratory or urinary tract. Pregnancy category: B; PB: 85%;  : 1.5-2.5 h |
| cephalexin (Keflex) | A: PO: 250-500 mg q6h; max: 4 g/d C: PO: 25-100 mg/kg/d in 4 divided doses |
First acid-stable cephalosporin sufficiently absorbed from the GI tract. For infections including otitis media, skin, bone, and respiratory or urinary tract. Pregnancy category: B; PB: 5%-15%;  : 1 h |
| Second-Generation | ||
| cefaclor (Ceclor, Raniclor) | See Prototype Drug Chart 29-2. | |
| cefotetan (Cefotan) | A: IM/IV: 500 mg-1 g q12h or 1-2 g q24h; max: 6 g/d | Effective against some gram-negative organisms, except Pseudomonas aeruginosa. Pregnancy category: B; PB: 75%-90%;  : 3-4.5 h |
| cefoxitin sodium (Mefoxin) | A: IM/IV: 1-2 g q6-8h; max: 12 g/d C: IM/IV: 80-100 mg/kg/d in divided doses q6-8h; max: 160 mg/kg/d |
For severe infections and septicemia. Pregnancy category: B; PB: 65%-95%;  : 45 min-1 h |
| cefprozil monohydrate (Cefzil) | A: PO: 250-500 mg/d or q12h × 10 d; max: 1 g/d C: PO: 7.5-15 mg/kg q12h × 10 d; max: 30 mg/kg/d |
Effective against gram-positive bacilli including Staphylococcus aureus. With impaired renal function, dose is usually decreased by 50%. Pregnancy category: B; PB: 36%;  : 1-1.3 h |
| cefuroxime (Ceftin, Zinacef) | A: PO: 250-500 mg q12h IM/IV: 750 mg-1.5 g q8h C: PO: 125-250 mg q12h IM/IV: 50-100 mg/kg/d in divided doses q6-8h |
Similar to cefamandole. Effective in treating meningitis and septicemia and for cardiothoracic procedures and surgical prophylaxis. Pregnancy category: B; PB: 33%-50%;  : 1.5 h |
| Third-Generation | ||
| cefdinir (Omnicef) | A/C >43 kg: PO: 300 mg q12h C <43 kg: PO: 7 mg/kg q12h |
New third-generation cephalosporin. For otitis media, acute sinusitis, chronic bronchitis, pharyngitis and tonsillitis, pneumonia, and skin infections. Active for Haemophilus influenzae, Streptococcus pyogenes, Neisseria gonorrhoeae, and many strains of enteric gram-negative bacilli. Pregnancy category: B; PB: 60%-70%;  : 1.7 h |
| cefixime (Suprax) | A/C >50 kg: PO: 400 mg/d in divided doses q12-24h C <50 kg: PO: 8 mg/kg/d in divided doses q12-24h |
For UTI, otitis media, and bronchitis. Effective against Streptococcus pyogenes, Streptococcus pneumonia, and gram-negative bacilli including Haemophilus influenzae and Neisseria gonorrhoeae. Pregnancy category: B; PB: 65%-70%;  : 3-4 h |
| cefoperazone (Cefobid) | A: IM/IV: 1-2 g q12h | To treat respiratory, urinary tract, and female genital tract infections. Most effective against Pseudomonas. Pregnancy category: B; PB: 80%-90%;  : 2 h |
| cefotaxime (Claforan) | A/C >50 kg: IM/IV: 1-2 g q8-12h; max: 12 g/d C <50 kg: IM/IV: 50-180 mg/kg/d in 4-6 divided doses; max: 12 g/d |
First of the third generation. Effective against P. aeruginosa. Also used in treating gram-negative meningitis. Pregnancy category: B; PB: 13%-38%;  : 1-2 h |
| cefpodoxime (Vantin) | A: PO: 200 mg q12h for 10 d C: 6 mo-12 y: PO: 10 mg/kg/d |
To treat otitis media and respiratory and urinary tract infections. Food enhances drug absorption. Pregnancy category: B; PB: 22%-33%;  : 3 h |
| ceftazidime (Fortaz) | A: IM/IV: 1-2 g q8-12h; max: 6 g/d C: IV: 30-50 mg/kg q8h; max: 150 mg/kg/d |
Most effective against Pseudomonas spp. Pregnancy category: B; PB: <10%;  : 1.5-2 h |
| ceftriaxone (Rocephin) | See Prototype Drug Chart 29-2. | |
| ceftizoxime sodium (Cefizox) | A: IM/IV: 500 mg-2 g q8-12h; max: 12 g/d C: IV: 50 mg/kg q6-8h; max: 200 mg/kg/d |
For respiratory, urinary tract, skin, bone, and joint infections. For surgical prophylaxis. Pregnancy category: B; PB: 30%;  : 1.7 h |
| ceftibuten (Cedax) | A: PO: 400 mg/d × 10 d C: 6 mo-12 y: PO: 9 mg/kg/d × 10 d; max: 400 mg/d |
For chronic bronchitis, pharyngitis, and tonsillitis. Active against gram-positive and gram-negative bacteria, H. influenzae, Streptococcus pneumoniae, and Streptococcus pyogenes. Poor activity against staphylococci and pneumococci. Pregnancy category: B; PB: 65%;  : 2-2.5 h |
| cefditoren pivoxil (Spectracef) | A/C: PO: 200-400 mg b.i.d. for 10 d; max: 800 mg/d | For chronic bronchitis, pharyngitis, tonsillitis, skin infections, and other mild to moderate bacterial infections. Pregnancy category: B; PB: 88%;  : 1.6 h |
| Fourth-Generation | ||
| cefepime (Maxipime) | Mild to moderate infection: A: IV: 0.5-2g q12h; max: 6 g/d C: IV: 50 mg/kg q12h; max: 50 mg/kg/dose |
Similar to third-generation cephalosporins. Resistant to most beta-lactamase bacteria. Effective against pneumonia, E. coli, Klebsiella, Proteus, streptococci, certain staphylococci, and P. aeruginosa. Has a broader gram-positive coverage than the third-generation cephalosporins. Pregnancy category: B; PB: 16%-19%;  : 2-2.3 h |
A, Adult; b.i.d., two times a day; C, child; d, day; GI, gastrointestinal; h, hour; IM, intramuscularly; IV, intravenously; max, maximum; mo, month; PB, protein-binding; PO, by mouth; 
, half-life; UK, unknown.
Side Effects and Adverse Reactions
The side effects and adverse reactions to cephalosporins include GI disturbances (nausea, vomiting, diarrhea), alteration in blood clotting time (increased bleeding) with administration of large doses, and nephrotoxicity (toxicity to the kidney) in individuals with a preexisting renal disorder.
Drug Interactions
Drug interactions can occur with certain cephalosporins and alcohol. For example, alcohol consumption may cause flushing, dizziness, headache, nausea, vomiting, and muscular cramps while taking cefamandole, or cefoperazone. Taking uricosuric drugs concurrently can decrease the excretion of cephalosporins, thereby greatly increasing serum levels. Uricosurics increase the excretion rate of uric acid by inhibiting its reabsorption.
Nursing Process
Patient-Centered Collaborative Care
Antibacterials: Cephalosporins
Assessment
Assess for allergy to cephalosporins or penicillins. If allergic to one type or class of cephalosporin, patient should not receive any other type of cephalosporin or penicillin.
Record vital signs and urine output. Report abnormal findings, which may include elevated temperature or decreased urine output.
Evaluate laboratory results, especially those that indicate renal and liver function (blood urea nitrogen, serum creatinine, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and bilirubin). Report abnormal findings. Use these laboratory results for baseline values.
Nursing Diagnoses
Planning
Nursing Interventions
Culture the infected area before cephalosporin therapy is started. The organism causing the infection can be determined by culture, and the antibiotics the organism is sensitive to are determined by sensitivity (C&S). (Antibiotic therapy may be started before culture result is reported. The antibiotic may need to be changed after C&S test results are received.)
Patient Teaching
General
Keep drugs out of reach of children. Request childproof containers.
Tell patient to report signs of superinfection, such as mouth ulcers or discharge from the anal or genital area.
Advise patient to ingest buttermilk, yogurt, or acidophilus supplement to prevent superinfection of the intestinal flora with long-term use of a cephalosporin.
Instruct patient to take the complete course of medication, even when symptoms of infection have ceased.
Infuse all IV cephalosporins over 30 minutes or as ordered to prevent pain and irritation.
Side Effects
Diet
Cultural Considerations
Allow adequate time for information processing for patient whose first language is not English. Failing to do so may result in an inaccurate response or no response.
Provide time for patients to respond to questions, especially when there is a language barrier.
Speak clearly and slowly, giving time for translation. Obtain an interpreter if necessary.
Evaluation
Key Websites
Information on oral ampicillin: www.nlm.nih.gov/medlineplus/druginfo/meds/a685015.html
Information on cephalosporins: www.emedexpert.com/compare/cephalosporins.shtml
Critical Thinking Case Study
SA, age 6 years, has otitis media. The health care provider ordered amoxicillin 250 mg every 8 hours. The nurse asks SA's parent if SA is allergic to any drugs, and the parent says that SA is allergic to penicillin.
The health care provider changed the amoxicillin order to cefaclor (Ceclor) 250 mg every 8 hours. The therapeutic dosage for children is 20 to 40 mg/kg/d in three divided doses. The child weighs 40 pounds.
3. What are the similarities and differences in amoxicillin and cefaclor? Explain your answer.
4. Is the prescribed cefaclor dosage for SA within safe parameters? Explain your answer.
5. Explain the significance of the nurse asking about allergies to antibiotics such as penicillin. What is the relationship of penicillin and cefaclor in regard to allergies?
6. What should the nurse include in patient teaching for SA and her parents?