What is the purpose of culture and sensitivity when administering antibiotic therapy?

Antimicrobial Therapy

No randomized controlled trials have evaluated the efficacy of different antimicrobial agents in the treatment of bacterial brain abscess. The antimicrobial agents used to treat bacterial brain abscess should be able to penetrate into the abscess cavity and should have in vitro activity against the pathogens isolated.1,2 The few studies that have addressed the penetration of antimicrobial agents into brain abscess fluid have included limited numbers of patients. Concentrations of penicillin G have been measured in brain abscess pus but were detected consistently only if the daily dosage in adults exceeded 24 million units; in some cases, penicillin G may be inactivated in pus, with the result that bacteria can still be cultured despite adequate penicillin concentrations. Limited data are available on the penetration of the semisynthetic penicillins (e.g., nafcillin, oxacillin) into brain abscesses, although some studies suggest that concentrations of these drugs in brain abscess fluid are variable.

Metronidazole has excellent in vitro activity against strict anaerobes, making it an important agent for the treatment of patients with brain abscess.165 Its excellent pharmacokinetic profile (i.e., good oral absorption and penetration into brain abscess cavities) has made metronidazole a more attractive antianaerobic agent than chloramphenicol for therapy of brain abscess. However, metronidazole must always be used in combination with an antimicrobial agent effective against streptococci because polymicrobial infections are common in patients with brain abscesses. Vancomycin has also been shown to have excellent concentrations in brain abscess fluid after prolonged therapy. In one study, simultaneous measurement of vancomycin concentrations in serum and brain abscess fluid was obtained 1 hour after a 500-mg dose166; vancomycin concentrations obtained before and during operative removal of the brain abscess were 15 µg/mL and 18 µg/mL, respectively, with a simultaneous serum vancomycin concentration of 21 µg/mL.

The third-generation cephalosporins are attractive agents for the treatment of brain abscess because of their good CNS penetration and excellent in vitro activity against many of the pathogens isolated from bacterial brain abscesses. When cefotaxime was given in higher doses than usually recommended (3 g every 8 hours), brain abscess concentrations of cefotaxime and its active metabolite, desacetylcefotaxime, were greater than the minimal inhibitory concentrations of most gram-positive and gram-negative organisms against which cefotaxime is used systemically. When combined with metronidazole and used in conjunction with surgical excision, high doses of cefotaxime also have been effective clinically in the treatment of brain abscess.172 Ceftriaxone and ceftazidime have been used in the treatment of brain abscess,173,174 although only a few patients have been studied. Ampicillin-sulbactam has also been shown to successfully treat brain abscesses175; intracavitary concentrations were variable but adequate in most cases.

Antibiotic Therapy

Antibiotic therapy should be initiated as soon as pyothorax is suspected (based on historical and clinical signs, as well as purulent material from thoracocentesis) or diagnosed. Studies in people suggest that early intervention with antibiotics decreases morbidity and mortality, and recommendations are to provide broad spectrum antibiotic therapy within 1 hour of diagnosis of sepsis.9 Initial therapy is usually empirical and should be based on cytology of the effusion. The initial antimicrobials empirically selected should be effective against obligate and facultative anaerobes and bacteria generally associated with the oropharyngeal flora. Therapy should then be adjusted after C&S testing results are finalized. Antibiotics should be administered IV at the early stages of treatment to ensure therapeutic serum concentrations. Oral antibiotics can be initiated after the patient is stable, has begun to show signs of response to therapy, and is ideally eating and drinking well. Table 81-1 provides recommended IV antibiotic therapy for cats with pyothorax.10 The use of intrapleural antibiotics is controversial and is thought to offer no additional benefit to IV antibiotics.11 Oral antibiotics should be initiated when appropriate, and antibiotic therapy should be maintained for at least 4 to 6 weeks.10

Antimicrobial Therapy

Antimicrobial therapy historically has been the centerpiece of bronchiectasis care. However, there is no clear consensus on the major questions in this area, including whether treatment should be given on a routine, periodic schedule (rotating) or an as-needed basis for clinical exacerbations. In a meta-analysis of the use of prolonged oral antibiotics for purulent bronchiectasis, sputum volume/purulence was shown to decrease, but there were no significant beneficial effects in regard to rates of exacerbations, lung function, or death.231 There are also limited data on the empirical selection of an antimicrobial agent or treatment guided by species identification and in vitro susceptibility testing. For patients unresponsive to empirical antibiotics or who experience frequent exacerbations, it appears prudent to obtain comprehensive microbiologic cultures, including for NTM and fungal organisms, and to tailor antibiotics based on the type of organism identified and drug susceptibility profile.

Aerosolized antibiotics also appear promising in treating or preventing exacerbations. Given the role of chronicP. aeruginosa in the pathogenesis and prognosis of bronchiectasis, there is ongoing research to develop strategies for acute and chronic treatment of this infection.

The success of inhalational antibiotics targeted towardP. aeruginosa in CF lung disease has prompted extensive evaluation of this strategy in non-CF bronchiectasis. In the earliest studies, addition of inhaled tobramycin to oral ciprofloxacin forPseudomonas-associated exacerbation of non-CF bronchiectasis showed improved microbiologic outcome; however, there was no additional clinical benefit over ciprofloxacin alone, perhaps due to approximately threefold greater incidence of bronchospasm in the tobramycin arm.232 In patients with CF, inhaled tobramycin twice daily given in alternating months decreased the frequency of exacerbations due toP. aeruginosa.233 Even in patients without CF, inhaled tobramycin was found to be efficacious.234 In a randomized study of nebulized gentamicin (twice daily for 12 months) versus saline for 65 patients with non-CF bronchiectasis, the gentamicin-treated subjects had reduced microbial burden, airway neutrophils, and sputum purulence.235 Improved exercise capacity, decreased exacerbation frequency, and better health-related QOL measure were also seen in the gentamicin arm, with the caveat that patients were not blinded to the treatment.236 Compared to nebulized saline, nebulized gentamicin given prophylactically for 12 months also showed significant reduction in markers of inflammation in both the airways and circulation.237

Inhaled ciprofloxacin has been studied for its efficacy in preventing exacerbations fromPseudomonas and several other chronic infections associated with frequent exacerbations. In companion Phase III studies (RESPIRE 1 and 2), the effect of ciprofloxacin in varied on-off cycles was examined in reducing time to next exacerbation.238,239 Given the inconsistent results on the primary end point, inhaled ciprofloxacin was not approved. In a separate trial of aerosolized liposomal ciprofloxacin (150 mg liposome encapsulated plus 60 mg of free ciprofloxacin) in 582 subjects, there was no significant difference in the time to first exacerbation between the ciprofloxacin and placebo arms, although the ciprofloxacin arm had a significant reduction in the annualized exacerbation frequency.240

Antibiotic Therapy

Antibiotic therapy should be governed by culture and sensitivity findings; however, therapy should be instigated as soon as practical after diagnosis, and, further, sensitivity results for anaerobic bacteria are not routinely available (another consideration is that samples should be collected anaerobically). The bacteria most commonly responsible for pyothorax are anaerobes, typical of oral flora; the most commonly isolated aerobes, Pasteurella spp., have been recognized in 12.5% to 20% of cases, in many cases in addition to anaerobes.7,74,130 Empiric therapy with penicillin-based antibiotics (including aminopenicillins or potentiated penicillins), therefore, should be effective against these bacteria. It is important to use parenteral antibiotics initially because affected cats are debilitated and unlikely to be eating. Most intravenous antibiotics require dosing at 6- to 8-hour intervals; in some cases antibiotics can be added to the intravenous fluids and provided as constant-rate infusion. Antibiotic therapy should be continued for an extended duration, typically 6 to 8 weeks.7,25 Amoxicillin–clavulanate at 15-20 mg/kg twice daily is an appropriate empiric antibiotic choice in most cases; cefovecin has an appropriate in vitro spectrum,116 and the author has successfully used this antibiotic in cases when the owner has had difficulty administering oral antibiotics; however, the revisits for repeat injections at 10- to 14-day intervals are vital, and the owner should be reminded of appointments in the preceding days.

Antimicrobial Therapy

The initial empirical antimicrobial therapy is based on knowledge of likely bacterial pathogens at various ages, the results of the Gram stain of aspirated material, and additional considerations. In neonates, an antistaphylococcal penicillin, such as nafcillin or oxacillin (150-200 mg/kg/24 hr divided q6h IV), and a broad-spectrum cephalosporin, such as cefepime (100 to 150 mg/kg/24 hr divided q12h IV), provide coverage for the methicillin-susceptibleS. aureus, group B streptococcus, and Gram-negative bacilli. If methicillin-resistantStaphylococcus is suspected, vancomycin is substituted for nafcillin. If the neonate is a small premature infant or has a central vascular catheter, the possibility of nosocomial bacteria (Gram-negative enteric,Pseudomonas, orS. aureus) or fungi(Candida spp.) should be considered. In older infants and children, the principal pathogens areS. aureus, K. kingae, and group A streptococcus.

Cefazolin (150 mg/kg/24 hr divided q6h IV) or nafcillin (150-200 mg/kg/24 hr divided q6h) is the agent of choice for parenteral treatment of osteomyelitis caused by methicillin-susceptibleS. aureus and is the backbone of empirical treatment for acute hematogenous osteomyelitis. A major factor influencing the selection of empirical therapy is the rate of methicillin resistance among communityS. aureus isolates. Vancomycin (60 mg/kg/24 hr divided q6h IV) is the “gold standard” agent for treating invasive MRSA infections. In areas with a high local prevalence of CA-MRSA infection, the addition of vancomycin to a beta-lactam should be considered, especially if the child is critically ill. Because β-lactams are superior to vancomycin for the treatment of MSSA, dual drug therapy in critically ill children should be continued until the causative organism is identified and susceptibilities are known. Rapid molecular diagnostic tests which can accurately differentiate MRSA from MSSA within hours of blood culture positivity can help to avoid prolonged exposure to multiple agents. Clindamycin (40 mg/kg/24 hr divided q6h IV) is the best studied alternative therapy for susceptible isolates of MRSA and for MSSA when a β-lactam cannot otherwise be used. Clindamycin can also be considered for empirical treatment when the rate of clindamycin resistance is low among communityS. aureus isolates, the child is not severely ill, and bacteremia is not a concern or blood cultures are known to be negative. Penicillin is first line therapy for treating osteomyelitis caused by susceptible strains ofS. pneumoniae, as well as all group A streptococci. Cefotaxime or ceftriaxone is recommended for pneumococcal isolates with resistance to penicillin and for mostSalmonella spp.

Special situations dictate deviations from the usual empirical antibiotic selection. In patients with sickle cell disease with osteomyelitis, Gram-negative enteric bacteria(Salmonella) are common pathogens, as well asS. aureus, so a broad-spectrum cephalosporin such as cefepime (150 mg/kg/24 hr q8h IV) is used in addition to vancomycin or clindamycin. Clindamycin (40 mg/kg/24 hr divided q6h IV) is a useful alternative drug for patients allergic to β-lactam drugs. In addition to good antistaphylococcal activity, clindamycin has broad activity against anaerobes and is useful for treating infections secondary to penetrating injuries or compound fractures. For immunocompromised patients, combination therapy is usually initiated, such as with vancomycin and ceftazidime, cefepime, or piperacillin-tazobactam, with or without an aminoglycoside.K. kingae responds to β-lactam antibiotics, including penicillin and cephalosporins, but some isolates produce a β-lactamase. Thus a first-generation cephalosporin (cefazolin) is a reasonable component of empirical therapy in children younger than 4 yr of age. Although the efficacy of treating osteomyelitis caused byB. henselae is uncertain, azithromycin plus rifampin may be considered.

Principles of Therapy

Antibiotic therapy for horses has always been challenging because of their poor oral absorption, the large volumes required for administration, and the high cost of some drugs. The risk of some adverse drug reactions that affect the gastrointestinal (GI) tract is a greater concern in horses than in other animals. Despite these drawbacks, it is essential that horses with serious infections receive appropriate therapy to prevent a chronic or life-threatening condition. Drug-resistant bacterial infections are an emerging problem, and the use of highly active drugs has become more important than ever before. Foals, in particular, need highly active drugs because they may be immunocompromised at the time of treatment. Drug treatment for foals has additional challenges because of differences in drug disposition in foals versus adults. Differences in oral absorption, volumes of distribution, metabolism, and clearance between foals and adults must be considered when selecting antibacterial dosage regimens.

To assist veterinarians in prescribing effective antibiotics for their equine patients, pharmacokinetic-pharmacodynamic relationships have been used to provide guidelines for effective use. The selection of the most appropriate drug has been facilitated by new approaches to bacterial identification and susceptibility testing. This chapter reviews some of these concepts that guide antibiotic therapy for equine patients and provide important strategies for effective dosing.

Postoperative care and assessment

Antimicrobial Treatment

Appropriate antibiotic therapy must be immediately instituted based on clinical suspicion, and before diagnostic tests confirm infection. Inappropriate or delayed antibiotic therapy may increase morbidity and mortality.17,46 Some antimicrobial drugs such as trimethoprim sulfonamides may actually worsen disease progression in human patients.46 Doxycycline is the treatment of choice (Table 30-2). It effectively eliminates infection and is active against A. phagocytophilum, Ehrlichia spp., and B. burgdorferi, which may be present in co-infections or cause disease that resembles RMSF. Seven days of treatment is adequate in most cases. Treatment a few days past defervescence is recommended. A longer course of treatment is recommended for dogs that are co-infected with Ehrlichia spp. or B. burgdorferi. Chloramphenicol was effective in experimentally infected dogs.76 However, it may be less effective than doxycycline for treating RMSF in people and has less activity in vitro against Ehrlichia chaffeensis and A. phagocytophilum.46 Enrofloxacin was effective for treatment of RMSF in experimentally infected dogs.76 However, enrofloxacin is not effective for treatment of E. canis infections.77 Use of parenteral antimicrobial drugs may be necessary in severely debilitated or vomiting patients.

Causes

I.

Antibiotic therapy may be a predisposing factor.

Other predisposing causes in dogs include the following (Matuosek and Campbell, 2002):

Diseases of keratinization: primary seborrhea

Immunosuppression: secretory IgA defects

Endocrine diseases: hypothyroidism (especially Labrador retrievers), hyperadrenocorticism

Possibly atopic dermatitis: role controversial

Generalized Malassezia spp. dermatitis in cats is usually associated with a systemic disease (e.g., metabolic disease, neoplasia) and is considered a serious finding.

It is more common in the spring and summer, as well as in any months with high humidity.

Treatment

Aggressive antibiotic therapy, wound fenestration, aggressive surgical debridement over the entire affected area, and supportive care are the hallmarks of successful treatment.115 High doses of intravenous potassium penicillin are recommended every 2 to 4 hours until the horse is stable (1 to 5 days), combined or followed by oral metronidazole. Supportive fluid therapy and antiinflammatory agents for control of pain and swelling are recommended. Short-acting corticosteroids such as prednisolone or hydrocortisone may be used for initial therapy of systemic/toxic shock, but continued use is contraindicated in the face of overwhelming infection. Extensive skin sloughing over the affected area is common in surviving horses.