Staphylococcal infections

The simplest pyrimidine antibiotic is bacimethrin, 5-hydroxymethyl-2-methoxypyrimidin-4-amine (985), which was isolated in 1961 from Bacillus megatherium and is active against several yeasts and bacteria in vitro as well as against staphylococcal infections in vivo it has some anticarcinoma activity in mice (69MI21301). It may be synthesized by LAH reduction of ethyl 4-amino-2-methoxypyrimidine-5-carboxylate (984) which may be made by primary synthesis in poor yield, or better, from the sulfone (983) (B-68MI21304). 

Employed as a sodium salt, fusidic acid (Fig. 5.14B) is achve against many types of Gram-positive bacteria, especially staphylococci, although streptococci are relatively resistant. It is employed in the treatment of staphylococcal infections, including strains resistant to other antibiotics. However, bacterial resistance may occur in vitro and in vivo. 

Broad intravenous antibiotic coverage for the encapsulated organisms can include ceftriaxone or cefotaxime. For patients with true cephalosporin allergy, clindamycin may be used. If staphylococcal infection is suspected owing to previous history or the patient appears acutely ill, vancomycin should be initiated. Macrolide antibiotics, such as erythromycin and azithromycin, may be initiated if Mycoplasma pneumonia is suspected. While the patient is receiving broad-spectrum antibiotics, their regular use of penicillin for prophylaxis can be suspended. Fever should be controlled with acetaminophen or ibuprofen. Because of the risk of dehydration during infection with fever, increased fluid may be needed.6,27... 

Lorenz E, Mira JP, Cornish KL, Arbour NC, Schwartz DA. A novel polymorphism in the toll-like receptor 2 gene and its potential association with staphylococcal infection. Infect Immunol 2000 68(11] 6398—6401. 

Kapusnik JE, Parenti F, Sande MA The use of rifampicin in staphylococcal infections - A review. J Antimicrob Chemother 1984 13(suppl C) 61-66. 

Sodium chloride 0.9% is safe and effective in relieving rhinorrhoea. It is safer to use in children than topical nasal decongestants (xylometazoline), which are to be avoided in children under 6 years as the latter are more likely are cause side-effects (such as effects on sleep or hallucinations). Budesonide spray is used for allergic conditions and is not normally used in paediatric patients. Benzydamine spray is a throat spray intended to relieve pain in the throat. Mupirocin is indicated for staphylococcal infections. 

Euruncles boil, staphylococcal infection of a gland or hair follicle... 

Penicillinase-resistant penicillins The percentage of staphylococcal isolates resistant to penicillin G outside the hospital is increasing, approximating the high percentage found in the hospital. Therefore, use a penicillinase-resistant penicillin as initial therapy for any suspected staphylococcal infection until culture and sensitivity results are known. 

Duration - Duration of therapy varies with the type and severity of infection as well as the overall condition of the patient therefore, determine duration by the clinical and bacteriological response of the patient. In severe staphylococcal infections, continue nafcillin therapy for at least 14 days. Continue therapy for at least 48 hours after the patient has become afebrile and asymptomatic and cultures are negative. The treatment of endocarditis and osteomyelitis may require a longer duration of therapy. 

Staphylococcal infections Moderately severe infections of the skin and soft tissue... 

Staphylococcal infections Mild infections of skin 250 to 500 mg orally and soft tissue every 6 to 8 h... 

Note Do not use tetracyclines for streptococcal disease unless organism has been shown to be susceptible. Tetracyclines are not the drugs of choice in treatment of any type of staphylococcal infection. 

Severe staphylococcal Infections - Severe staphylococcal infections (including methicillin-resistant staphylococci) in patients who cannot receive or who have failed to respond to penicillins and cephalosporins, or who have infections with resistant staphylococci. Infections may include endocarditis, bone infections, lower respiratory tract infections, septicemia, and skin and skin structure infections. 

The glycopeptides include vancomycin and teico-planin. They are bactericidal antibiotics. Their mechanism of action is based on inhibition of bacterial cell-wall synthesis by blocking the polymerization of glycopeptides. They do not act from within the peptidoglycan layer, as the beta-lactam antibiotics do, but intracellularly. The indications are mainly restricted to the management of severe or resistant staphylococcal infections, especially those caused by coagulase negative staphylococcal species such as S. epidermidis. 

Fusidic acid is a product of, among others, the fungus Fusidium coccineum. It has a steroidal structure and has mainly bacteriostatic activity. Its mechanism of action is based on inhibition of bacterial protein synthesis. Its indications are limited to the treatment of severe staphylococcal infections, usually in combination with another antistaphylococcal agent to prevent the emergence of resistance. 

For parenteral therapy, nafciUin and oxacillin offer comparable efficacy and antimicrobial spectra of activity. Although both drugs undergo hepatic metabolism, only nafcillin requires dose adjustment in patients with combined hepatic and renal insufficiency. Other pharmacokinetic data for nafcillin and oxacillin appear in Table 45.1. Indications for nafcillin or oxacillin include severe staphylococcal infections like cellulitis, empyema, endocarditis, osteomyelitis, pneumonia, septic arthritis, and toxic shock syndrome. 

For oral therapy, cloxaciUin and dicloxacillin are comparable alternatives. Both undergo hepatic metabolism, and neither drug requires dose adjustment in patients with hepatic insufficiency. Additional pharmacokinetic data are in Table 45.1. Indications for cloxacillin or dicloxacillin include clinically mild staphylococcal infections like impetigo. 

Teicoplanin, although not available in the United States, has been used to treat a wide range of gram-positive infections, including endocarditis and peritonitis. It is not as effective as the (3-lactams, but its actions are similar to those of vancomycin against staphylococcal infections. 

Rifampin is a first-line antitubercular drug used in the treatment of all forms of pulmonary and extrapul-monary tuberculosis. Rifampin is an alternative to isoniazid in the treatment of latent tuberculosis infection. Rifampin also may be combined with an antileprosy agent for the treatment of leprosy and to protect those in close contact with patients having H. influenza type b and N. meningitidis infection rifampin is also used in methicillin-resistant staphylococcal infections, such as osteomyelitis and prosthetic valve endocarditis. 

Streptococcal infections Pharyngitis, rheumatic fever, otitis media and even for subacute bacterial endocarditis. Staphylococcal infections Penicillinase resistant penicillin can be used. Meningococcal infections Meningitis other infections caused by meningococci. 

It is indicated in serious life threatening staphylococcal infections resistant to other antibiotics, in severe staphylococcal infections in patients who are allergic to penicillin and cephalosporin. 

An isoxazolyl penicillin such as oxacillin, cloxacillin, or dicloxacillin, 0.25-0.5 g orally every 4-6 hours (15-25 mg/kg/d for children), is suitable for treatment of mild to moderate localized staphylococcal infections. All are relatively acid-stable and have reasonable bioavailability. However, food interferes with absorption, and the drugs should be administered 1 hour before or after meals. 

For serious systemic staphylococcal infections, oxacillin or nafcillin, 8-12 g/d, is given by intermittent intravenous infusion of 1-2 g every 4-6 hours (50-100 mg/kg/d for children). 

Rifampin combined with a second agent is used to eradicate staphylococcal carriage. Rifampin combination therapy is also indicated for treatment of serious staphylococcal infections such as osteomyelitis and prosthetic valve endocarditis. 

Erythromycin is a macrolide antibiotic produced by Streptomyces erythreus. It is considered the most active macrolide for treatment of staphylococcal infections in cases of penicillin resistance. It is used parenterally at a dosage of 3-5 mg/kg bw, in intramammary form at 300 mg/quarter, and orally at 20-50 mg/kg bw. For treatment of mycoplasmal infections in poultry, an oral medication... 

Oleandomycin is a macrolide antibiotic produced by Streptomyces antibi-oticus. Oleandomycin and its triacetylated form, troleandomycin, are less effective than erythromycin against staphylococcal infections. They are usually administered orally or intravenously intramuscular administration is avoided because of the pain and tissue irritation it induces. Oleandomycin is also used in intramammary treatments and as a feed additive for growth promotion purposes. 

Lincomydn is an antibiotic produced by Streptomyces lincolnensis. It is used in monopreparations or in combination with other antibiotics such as spectinomycin, sulfamethazine, and gentamicin, for the initial treatment of mild to moderate staphylococcal infections in a variety of animal species. It can be administered orally to poultry at dosages equivalent to up to 50 mg/kg hw/day for up to 7 days, and to swine at dosages equivalent to up to 10 mg/kg bw/day for up to 21 days. In calves, sheep, goats, and swine, it can be administered intramuscularly at dosages of up to 15 mg/kg bw/day for up to 4-7 days. It is also added in feeds for growth-promoting purposes. 

Novobiocin (Fig. 3.9) is a narrow-spectrum antibiotic with antibacterial activity against many gram-positive pathogens. It is frequently used, in combination with penicillin, for treatment of bovine mastitis by intramammary infusion of 200 mg/ quarter in two quarters, and to control fowl cholera and staphylococcal infections in chickens and turkeys at a level of 200-350 g/ton in feed. 

---