Surgical Infections(3): Guo Xueli ( )

Surgical Infections(3) Guo Xueli ( 郭学利 ) Dept. General Surgery, First Affiliated Hospital

Antibiotics One of the largest and most versatile classes of antibiotics---the beta-lactam group The beta-lactam group ---the penicillins the cephalosporins the carbapenems the monobactams

Penicillins Comment: prototype; hydrolyzed by all beta-lactamases Half-life: short Toxicity: low, but rarely allergic reaction may be life threatening Antibacterial spectrum: #Streptococcal species except enterococcus; #Neisseria species, except lactamase-producing gonococci

Recently, various penicillins---combined with one of the beta-lactamase inhibitors, clavulanic acid, sulbactam, or tazobactam These combination provide antibiotic compounds #retain their broad gram-negative activity #act against methicillin-sensitive staphylococci and anaerobes, facultative species, and aerobic bacteria

Cephalosporins #the largest and most frequently used group of antibiotics #be divided into three generation The first-generation ---have excellent activity against methicillinsusceptible staphylococci and all streptococcal species, but not against enterococci ---have modest activity against the easy enterobacteriaceae, such as E.coli, proteus mirabilis, and many Klebsiella species.

The second-generation ---have expanded gram-negative activity ---still lack activity against many gram-negative rods The most important distinction ---good activity against anaerobes(cefoxitin, cefotetan, and cefmetazole) and without important anaerobic activity (cefamandole, ceforanide, and cefonicid)

The third-generation ---have greatly expanded activity against gramnegative rods, including many resistant strains, and rival the aminoglycosides in their coverage while having a much more favorable safety profile ---have significantly less activity against staphylococci and streptococcal species than first- and secondgeneration The important distinction ---those with significant activity against Pseudomonas species (cefoperazone and ceftazidime) and those without (cefotaxime, ceftizoxime, and ceftriaxone)

Quinolones Nalidixic acid---useful only for urinary tract infection Recently, a large number of newer fluoroquinolone antibiotics---have been in development ---extremely broad activity against gram-negative rods, including Pseudomonas species ---relatively broad activity against gram-positive cocci, including some methicillin-resistant staphylococci ---excellent tissue penetration and comparable serum tissue levels with either intravenous or oral administration

Norfloxacin, ---useful in the urine Ciprofloxacin and ofloxacin ---effective against sensitive pathogens throughout the body

Aminoglycosides ---for the empiric treatment of serious gram-negative infection ---very broad activity against aerobic and facultative gram-negative rods ---relatively indifferent activity against gram-positive cocci

---the availability of third-generation cephalosporins, fluoroquinilones, and other has greatly reduced the instances when aminoglycosides must be used Difficult to use ---nephrotoxicity and eighth nerve damage, both auditory and vestibular Now reserve for specific therapy for known resistant organism or as part of a synergistic combination to treat serious enterococcal infections or certain gram-negative rod infections

Macrolides Erythromycin---a macrolide antibiotic ---widespread use ---as an oral agent used in combination with an aminoglycoside to reduce numbers of bacteria in the lumen of the bowel before operations on the colon. ---markedly suppresses anaerobic growth ---active against most gram-positive cocci and Neisseria species

---as an alternate agent for patients allergic to penicillins ---significant activity against mycoplasmas, Chlamydia, Legionella species, and Rickettsia. ---an effective antibiotic against Campylobacter jejuni Clarithromycin and azithromycin ---two more recent macrolides with expanded antimicrobial spectra

General principles The goal of therapy---is to achieve levels of antibiotics at the site of infection that exceed the minimum inhibitory concentration for the pathogens present For mild infections---oral antibiotics For severe surgical infections--intravenous antibiotics

Each patient with a serious infection ---should be evaluated daily or more frequently to assess response to treatment If obvious improvement is not seen within 2 to 3days You should notice the following

---the initial operative procedure was not adequate ---the initial procedure was adequate but a complication has occurred ---a superinfection has developed at a new site ---the drug choice is correct, but not enough is being given ---another or a different drug is needed

How to stop antibiotic therapy ---there is not a specific duration of antibiotics known to be ideal A good guideline--To continue antibiotics until the patient has shown an obvious clinical improvement based on clinical examination and has had a normal temperature for 48hours or more Signs of improvement include improved mental status, return of bowel function , and spontaneous diuresis

WBC count is normal --- the likelihood of further infectious problems is small WBC count is elevated ---further infections, which are not prevented by continuing antibiotics #To stop the existing drugs and observe the patient closely for subsequent developments #A new infection requires drainage or different antibiotics for a new, resistant pathogen in a different location

Superinfection a new infection that develops during antibiotic treatment for the original infection ---bacteria that remain are resistant to the antibiotics being used and become the pathogens in superinfection

Respiratory tract infections are common superinfection ---occur during the treatment of intra-abdominal infections ---superinfections in 2% to 10% of antibiotic-treated patients ---the best preventive actions: to limit the dose and duration of antibiotic treatment to what is obviously required and to be alert to the possibility of superinfections

Antibiotic-associated colitis is another significant superinfection ---occur in hospitalized patients with mild to serious illness ---caused by the enteric pathogen C.difficile ---has been reported after treatment with every antibiotic except vancomycin

C.difficile colitis can vary from a mild, selflimited disease to a rapidly progressive septic process culminating in death Diagnosis is by endoscopy ---revealing the typical mucosal changes with inflammation, ulceration, and plaque formation ---stool assay for the characteristic toxin ---stool culture to recover C.difficile

Treatment ---supportive with fluid and electrolytes, withdrawal of the offending antibiotic if possible ---oral metronidazole to treat the superinfection ---vancomycin should be reserved for metronidazole failure ---in rare instances, no respond to medical management---emergency colectomy