What factors should be known before administering antimicrobial therapy to a patient?

Cited by (0)

β-Lactam Antibiotics

β-Lactam antibiotics, such as penicillins, potentiated amino­penicillins, and cephalosporins, are slowly bactericidal. Their concentration should be kept above the MIC throughout most of the dosing interval (long T > MIC) for the optimal bactericidal effect.24 In general, the goal is to maintain plasma concentrations above the MIC for at least 50% of the dosing interval. For gram-negative organisms, however, no postantibiotic effect (PAE) exists for β-lactam antibiotics, and reduced efficacy of cephalosporin antimicrobial therapy has been reported when T greater than MIC is less than 80% of the dosing interval.24,38 In neutropenic patients, maintaining concentrations greater than the MIC for 90% to 100% of the dosing interval is required for maximal bactericidal action against gram-negative organisms and streptococci.24 For the treatment of some gram-negative bacteria, some regimens for penicillins and cephalosporins require administration three to four times per day to meet this target. Some of the third-generation cephalosporins have longer half-lives, and less frequent dosing intervals have been used for these drugs (e.g., cefotaxime, ceftiofur). Because the MICs are lower for gram-positive bacteria and antibacterial effects occur at concentrations below the MIC (PAE), longer dose intervals may be possible for infections caused by gram-positive compared with gram-negative bacteria.

Antimicrobial Therapy

Antimicrobial therapy may be indicated in trauma cases depending on the organ that is traumatized and the extent of injury to the skin, subcutaneous tissue, and muscles. If a penetrating injury has occurred, antimicrobials should be initiated; all wounds should be cultured and broad-spectrum antimicrobials administered pending the results of the susceptibility. For cases of bowel perforation and pyothorax, antimicrobial therapy should be started immediately with broad-spectrum drugs that also have anaerobic coverage (see Antimicrobial Therapy section, Chapters 175 to 182Chapter 175Chapter 176Chapter 177Chapter 178Chapter 179Chapter 180Chapter 181Chapter 182).29

Internal Infection

Antimicrobial therapy is indicated for the treatment of horses with systemic infection caused by C. pseudotuberculosis.13 The median duration of antimicrobial therapy in a recent study was 36 days and ranged from 7 to 97 days. A variety of antimicrobials to which C. pseudotuberculosis is susceptible were used to treat these internal infections (Table 45-2). Rifampin was used in combination with another antimicrobial in the majority of horses. Rifampin alone was used for continued treatment in horses after initial treatment with a combination of rifampin and another antimicrobial.22 Thoracic and abdominal ultrasound are useful to monitor response to therapy. Ultrasound findings, in addition to clinicopathologic data, aid in the decision-making process for continued antimicrobial therapy in these cases (see Fig. 45-10).

The overall mortality associated with internal infections is reported to be 30% to 40%,13,15 but horses that did not receive antimicrobial therapy had a 100% fatality rate.13 Antimicrobial therapy for treatment of internal abscesses and ulcerative lymphangitis must be continued for 1 to 6 months. Resolution of infection is determined based on clinical signs, normal clinical pathologic values, and decline in immunoglobulin concentrations. Some horses with very high SHI titers remain seropositive for up to 1 year because of the lengthy half-life of IgG (21 days) and for other reasons that are unknown. Under such situations the clinician should monitor a steady decline in serum SHI titers to C. pseudotuberculosis. Purpura hemorrhagica or vasculitis has been reported in horses with systemic infection requiring concurrent therapy with antimicrobials and corticosteroids.13

Pyelonephritis

Antimicrobial therapy must be based on urine culture and sensitivity results. When urine culture and sensitivity is negative despite evidence of bacteria on urinalysis, several possible explanations exist (see Box 32-4). It may be necessary to harvest the urine specimen directly from the renal pelvis using ultrasound guidance to obtain a representative sample.

Antimicrobial therapy should continue for 3 to 5 weeks for the initial episode and for 5 to 8 weeks should re-infection or relapse occur. Urine may be cultured during therapy to verify antimicrobial efficacy and should be repeated 1 week after the end of treatment to ensure that infection has been eradicated.

Antimicrobial Therapy

Antimicrobial therapy is indicated for treatment of horses with ulcerative lymphangitis or internal abscesses. The use of antimicrobials for external abscesses is not necessary in many horses and may prolong the time to resolution. Antimicrobial therapy may be justified when signs of systemic illness (e.g., fever, depression, or anorexia) or extensive cellulitis are present, or for horses with severe or recurrent infections. Horses with deep intramuscular abscesses that are lanced and draining through healthy tissue may also benefit from antimicrobial therapy.

Corynebacterium pseudotuberculosis has in vitro susceptibility to many of the antimicrobials that are commonly used in horses, including penicillin G, macrolides, tetracyclines, cephalosporins, chloramphenicol, fluoroquinolones, and rifampin, but some isolates may be resistant to aminoglycosides. Several factors should be considered when choosing an antimicrobial: the intracellular location of the organism, the presence of exudate and a thick abscess capsule, anticipated duration of therapy, cost of the drug, and convenience of administration. Despite in vitro susceptibility, the nature of the bacteria and the copious exudate render certain antimicrobials ineffective in some instances. Trimethoprim-sulfamethoxazole (5 mg/kg based on the trimethoprim fraction, twice daily, orally) and procaine penicillin G (20,000 U/kg, twice daily, intramuscularly) are effective for treatment of external abscesses, especially on the ventral midline.

Antibiotics

Antimicrobial therapy is not indicated in the early stages of aspiration pneumonitis. Antibiotics are appropriate for aspiration pneumonia, and selection should be based on culture and sensitivity results from samples obtained by TW or BAL. This will not be possible in all cases and results will not be immediately available. Cytologic analysis of airway washes, including Gram stain, can be used to guide antimicrobial choices while culture results are pending. In general, broad spectrum antimicrobial agents should be chosen with consideration of local resistance profiles. Anaerobic coverage is unlikely to be necessary.36 Antimicrobial therapy should be reevaluated frequently on the basis of clinical response and culture results. The pharmacokinetics of antimicrobial agents should also be considered. Polar drugs such as the cephalosporins and penicillins penetrate poorly, although they may achieve higher levels in inflamed tissues. Lipophilic molecules such as the fluoroquinolones penetrate natural body barriers readily and will reach therapeutic levels in bronchial secretions (see Chapter 22, Pneumonia).

Antimicrobial Therapy

Antimicrobial therapy

Antimicrobial therapy is not indicated in the early stages of aspiration pneumonitis management. Early use of antimicrobials after aspiration may be more appropriate in patients with additional risk factors for pneumonia such as concurrent proton pump inhibitor use or gastrointestinal obstruction. Antimicrobials are, however, a vital part of treatment for patients with aspiration pneumonia. Antimicrobial selection should be based on culture and susceptibility testing results from samples obtained by TW or BAL. Cultures will not be possible in all cases and, regardless, results will not be available immediately. Cytologic analysis of airway washes, including Gram stain, should be used to guide antimicrobial choices while culture and susceptibility testing results are pending. The polymicrobial nature of many aspiration pneumonia infections supports the use of broad-spectrum antimicrobials or the use of several agents with overlapping spectra. Anaerobic coverage is unlikely to be necessary.3,51 Empirical antimicrobial therapy should be chosen with consideration of local resistance profiles and should be deescalated or withdrawn if bacterial cultures are negative. Regardless of whether therapy is empirical or based on culture, it must be reevaluated based on clinical response; if patients are worsening, alternative therapy and repeated airway sampling and culture should be considered. In patients with worsening respiratory signs or failure, research suggests that the bacterial isolates may have different resistance profiles from those infecting patients with less severe disease.51 The pharmacokinetics of antimicrobial agents should be considered during product selection (see Chapter 175). Polar drugs such as the cephalosporins and penicillins penetrate poorly, although they may achieve higher levels in inflamed tissues. Lipophilic molecules such as the fluoroquinolones penetrate natural body barriers readily and will reach therapeutic levels in bronchial secretions. Commonly used antimicrobials include β-lactamases in combination with fluoroquinolones.2,3 Due consideration for prudent use of antimicrobials should be given before use of second- or third-line drugs.52

Antimicrobial Therapy

Antimicrobial therapy is the definitive therapy for treatment of septic foals. Initially, broad-spectrum bactericidal antibiotics must be used with specific choices based on previous experiences and cost. Antimicrobial therapy should begin immediately in any foal in which sepsis is suspected and should not be delayed pending blood culture results, as sensitivity data typically require 3 to 4 days. Therapy can be altered if necessary when these data become available. A minimum therapeutic course of 2 weeks is recommended for bacteremic foals without localizing clinical signs. If localizing signs, such as pneumonia or septic arthritis, are present, a minimum course of 4 weeks is recommended.27 Recommended dosages for commonly used antimicrobials are listed in Table 6-2.

Few published veterinary reports discuss antimicrobial sensitivity of organisms isolated from septic neonatal foals. Geographic variability is evident, and a summary of selected antimicrobial susceptibility profiles published since 2000 are listed in Table 6-3. In some reports, a slightly lower percentage of gram-negative isolates are sensitive to gentamicin relative to amikacin.2,8,45,50 In 1994, it was reported that 95% and 91% of gram-negative isolates were sensitive to amikacin and cefotaxime, respectively, while sensitivity to gentamicin and trimethoprim-sulfa was much lower.2 Some organisms, such as Enterobacter, Acinetobacter, Enterococcus, and coagulase-positive Staphylococcus spp. have demonstrated substantial resistance.8 Few studies have evaluated developing antimicrobial resistance. But a Florida study revealed that no group of organisms became more resistant to any drug or drug class over time between the 1980s and 2007.10

Thus, based on available data, a recommended initial therapeutic approach involves combining amikacin or gentamicin with penicillin or ampicillin. Alternatively, ceftiofur can be used alone or in combination with an aminoglycoside. If a foal is severely hypovolemic and azotemic, amikacin should be avoided; a safer initial choice would likely involve a third-generation cephalosporin. If amikacin is used, therapeutic drug monitoring is recommended to ensure appropriate individual dosing. An additional recommendation includes serial creatinine monitoring every 2 to 3 days and/or serial urinalyses, including sediment examination to monitor for potential renal adverse effects. Cefotaxime is a good choice for foals with gram-negative meningitis51 or those with unresponsive pneumonia.

Unfortunately, the range of oral antibiotics is limited in horses. Because of significant resistance, trimethoprim/sulfamethoxazole combinations should not be used in septic foals without documented sensitivity and then only as a long-term option following initial parenteral therapy. Several aminobenzyl penicillins (amoxicillin and ampicillin) and first-generation cephalosporins (cefadroxil and cephradine) have good bioavailability in young foals (in contrast to older foals and adult horses) but have a limited gram-positive spectrum of activity.52-55 Cefpodoxime proxetil, a third-generation cephalosporin available for oral administration, was recently shown to be effective against 90% of Klebsiella spp., Pasteurella spp., and β-hemolytic streptococci.56 An increase in the frequency of administration would likely increase the effectiveness of this drug against E. coli. Fluoroquinolones, such as enrofloxacin, have an excellent spectrum of activity against gram-negative and some gram-positive organisms but have been associated with arthropathy in foals.57,58 Thus use of this agent should be reserved for those cases with documented resistance to other antimicrobial agents and informed owner consent.

Antimicrobials

Antimicrobial therapy is commonly used to treat animals diagnosed with infectious diseases. In reptile medicine there are additional challenges associated with the lack of pharmacokinetic studies for most drugs, extra label use, small patient size, cost, ease of administration, frequency of administration, and safety. Use and selection of antimicrobial agents must be done judiciously, taking into account a number of clinical considerations. First, select drugs that have been used safely in the lizard species being treated and that will cause no harm to the animal. Second, choose an appropriate drug based on the spectrum of coverage, tissue distribution, and results of culture and sensitivity testing. The best antimicrobial agents will be effective against a number of organisms and are classified as broad-spectrum antibiotics. Broad-spectrum antibiotics may show effectiveness against Gram-positive and Gram-negative organisms as well as aerobes and anaerobes. Not all drugs are considered broad spectrum, and a combination of drugs may be needed to cover all four treatment areas. In addition to the four areas just listed, also consider if the drug is cidal or static. Cidal drugs will kill the organism, whereas static drugs will inhibit or slow its growth. The method of action of the antimicrobial product must also be considered especially when choosing penicillin. Table 8-1 shows some of the major drug groups available, with examples of specific drugs, coverage spectrum, and method of action.

Other limitations associated with the use of antimicrobial agents in lizards are related to the ease and frequency of administration. In fractious animals, it may be more challenging to give a drug by mouth, especially when multiple treatments are required over a 24-hour period. Therefore, try to select a product that has a low frequency of administration and one that the patient will tolerate. A final point about antimicrobial therapy and prevention of antimicrobial resistance involves the dosing and length of treatment. Always select and calculate appropriate dosages for the patient. This may require finding multiple references for comparison of recommended doses. Once a dosage is calculated, it must be administered for the correct period of time and not discontinued before the end of the treatment period. Some people follow the practice of giving one injection of an antimicrobial agent and discharging the patient with no additional treatments. Not only will this promote antimicrobial resistance, but it will not effectively treat the patient's condition. Antimicrobial treatment should only be discontinued 7 to 10 days after resolution of clinical signs.

It is the responsibility of the veterinarian to choose the appropriate drugs to avoid the perpetuation of antimicrobial resistance. Unfortunately, many veterinary practitioners have formulated the habit of using a single antibiotic (e.g., enrofloxacin) as a sole source of therapy for all infectious diseases, even in cases in which a bacterial infection is questionable. Although fluoroquinolones are very good broad-spectrum antimicrobials with good tissue distribution, other antimicrobials may be equally effective. This is one reason why culture and antibiotic sensitivity testing is important. The same principles also apply to the use of topical antimicrobials. The indiscriminate use of topical antimicrobial products can also lead to antimicrobial resistance. When appropriate, bacterial cultures and sensitivity testing should always be offered as part of the diagnostic plan of lizards. It is imperative that the veterinarian inform the pet owner of the benefits of appropriate antimicrobial selection and the prevention of drug resistance.