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Recovery from an anaerobic infection depends on adequate and rapid management. The main principles of managing anaerobic infections are neutralizing the toxins produced by anaerobic bacteria, preventing the local proliferation of these organisms by altering the environment and preventing their dissemination and spread to healthy tissues.
Toxin can be neutralized by specific antitoxins, mainly in infections caused by Clostridia (tetanus and botulism). Controlling the environment can be attained by draining the pus, surgical debriding of necrotic tissue, improving blood circulation, alleviating any obstruction and by improving tissue oxygenation. Therapy with hyperbaric oxygen (HBO) may also be useful. The main goal of antimicrobials is in restricting the local and systemic spread of the microorganisms.
The available parenteral antimicrobials for most infections are metronidazole, clindamycin, chloramphenicol, cefoxitin, a penicillin (i.e. ticarcillin, ampicillin, piperacillin) and a beta-lactamase inhibitor (i.e. clavulanic acid, sulbactam, tazobactam), and a carbapenem (imipenem, meropenem, doripenem, ertapenem). An antimicrobial effective against Gram-negative enteric bacilli (i.e. aminoglycoside) or an anti-pseudomonal cephalosporin (i.e. cefepime ) are generally added to metronidazole, and occasionally cefoxitin when treating intra-abdominal infections to provide coverage for these organisms. Clindamycin should not be used as a single agent as empiric therapy for abdominal infections. Penicillin can be added to metronidazole in treating of intracranial, pulmonary and dental infections to provide coverage against microaerophilic streptococci, and Actinomyces.
Oral agents adequate for polymicrobial oral infections include the combinations of amoxicillin plus clavulanate, clindamycin and metronidazole plus a macrolide. Penicillin can be added to metronidazole in the treating dental and intracranial infections to cover "Actinomyces" spp., microaerophilic streptococci, and "Arachnia" spp. A macrolide can be added to metronidazole in treating upper respiratory infections to cover "S. aureus" and aerobic streptococci. Penicillin can be added to clindamycin to supplement its coverage against "Peptostreptococcus" spp. and other Gram-positive anaerobic organisms.
Doxycycline is added to most regimens in the treatment of pelvic infections to cover chlamydia and mycoplasma. Penicillin is effective for bacteremia caused by non-beta lactamase producing bacteria. However, other agents should be used for the therapy of bacteremia caused by beta-lactamase producing bacteria.
Because the length of therapy for anaerobic infections is generally longer than for infections due to aerobic and facultative anaerobic bacteria, oral therapy is often substituted for parenteral treatment. The agents available for oral therapy are limited and include amoxacillin plus clavulanate, clindamycin, chloramphenicol and metronidazole.
In 2010 the American Surgical Society and American Society of Infectious Diseases have updated their guidelines for the treatment of abdominal infections.
The recommendations suggest the following:
For mild-to-moderate community-acquired infections in adults, the agents recommended for empiric regimens are: ticarcillin- clavulanate, cefoxitin, ertapenem, moxifloxacin, or tigecycline as single-agent therapy or combinations of metronidazole with cefazolin, cefuroxime, ceftriaxone, cefotaxime, levofloxacin, or ciprofloxacin. Agents no longer recommended are: cefotetan and clindamycin ( Bacteroides fragilis group resistance) and ampicillin-sulbactam (E. coli resistance) and ainoglycosides (toxicity).
For high risk community-acquired infections in adults, the agents recommended for empiric regimens are: meropenem, imipenem-cilastatin, doripenem, piperacillin-tazobactam, ciprofloxacin or levofloxacin in combination with metronidazole, or ceftazidime or cefepime in combination with metronidazole. Quinolones should not be used unless hospital surveys indicate >90% susceptibility of "E. coli" to quinolones.
Aztreonam plus metronidazole is an alternative, but addition of an agent effective against gram-positive cocci is recommended. The routine use of an aminoglycoside or another second agent effective against gram-negative facultative and aerobic bacilli is not recommended in the absence of evidence that the infection is caused by resistant organisms that require such therapy.
Empiric use of agents effective against enterococci is recommended and agents effective against methicillin-resistant "S. aureus" (MRSA) or yeast is not recommended in the absence of evidence of infection due to such organisms.
Empiric antibiotic therapy for health care-associated intra-abdominal should be driven by local microbiologic results. Empiric coverage of likely pathogens may require multidrug regimens that include agents with expanded spectra of activity against gram-negative aerobic and facultative bacilli. These include meropenem, imipenem-cilastatin, doripenem, piperacillin-tazobactam, or ceftazidime or cefepime in combination with metronidazole. Aminoglycosides or colistin may be required.
Antimicrobial regimens for children include an aminoglycoside-based regimen, a carbapenem (imipenem, meropenem, or ertapenem), a beta-lactam/beta-lactamase-inhibitor combination (piperacillin-tazobactam or ticarcillin-clavulanate), or an advanced-generation cephalosporin (cefotaxime, ceftriaxone, ceftazidime, or cefepime) with metronidazole.
Clinical judgment, personal experience, safety and patient compliance should direct the physician in the choice of the appropriate antimicrobial agents. The length of therapy generally ranges between 2 and 4 weeks, but should be individualized depending on the response. In some instances treatment may be required for as long as 6–8 weeks, but can often be shortened with proper surgical drainage.
The Infectious Disease Society of America (IDSA) recommends treating uncomplicated methicillin resistant staph aureus (MRSA) bacteremia with a 14-day course of intravenous vancomycin. Uncomplicated bacteremia is defined as having positive blood cultures for MRSA, but having no evidence of endocarditis, no implanted prostheses, negative blood cultures after 2–4 days of treatment, and signs of clinical improvement after 72 hrs.
The antibiotic treatment of choice for streptococcal and enteroccal infections differs by species. However, it is important to look at the antibiotic resistance pattern for each species from the blood culture to better treat infections caused by resistant organisms.
The presence of bacteria in the blood almost always requires treatment with antibiotics. This is because there are high mortality rates from progression to sepsis if antibiotics are delayed.
The treatment of bacteremia should begin with empiric antibiotic coverage. Any patient presenting with signs or symptoms of bacteremia or a positive blood culture should be started on intravenous antibiotics. The choice of antibiotic is determined by the most likely source of infection and by the characteristic organisms that typically cause that infection. Other important considerations include the patient's past history of antibiotic use, the severity of the presenting symptoms, and any allergies to antibiotics. Empiric antibiotics should be narrowed, preferably to a single antibiotic, once the blood culture returns with a particular bacteria that has been isolated.
Treatment of CAP in children depends on the child's age and the severity of illness. Children under five are not usually treated for atypical bacteria. If hospitalization is not required, a seven-day course of amoxicillin is often prescribed, with co-trimaxazole an alternative when there is allergy to penicillins. Further studies are needed to confirm the efficacy of newer antibiotics. With the increase in drug-resistant Streptococcus pneumoniae, antibiotics such as cefpodoxime may become more popular. Hospitalized children receive intravenous ampicillin, ceftriaxone or cefotaxime, and a recent study found that a three-day course of antibiotics seems sufficient for most mild-to-moderate CAP in children.
Most newborn infants with CAP are hospitalized, receiving IV ampicillin and gentamicin for at least ten days to treat the common causative agents "streptococcus agalactiae", "listeria monocytogenes" and "escherichia coli". To treat the herpes simplex virus, IV acyclovir is administered for 21 days.
Antibiotics are the treatment of choice for bacterial pneumonia, with ventilation (oxygen supplement) as supportive therapy. The antibiotic choice depends on the nature of the pneumonia, the microorganisms most commonly causing pneumonia in the geographical region, and the immune status and underlying health of the individual. In the United Kingdom, amoxicillin is used as first-line therapy in the vast majority of patients acquiring pneumonia in the community, sometimes with added clarithromycin. In North America, where the "atypical" forms of community-acquired pneumonia are becoming more common, clarithromycin, azithromycin, or fluoroquinolones as single therapy have displaced the amoxicillin as first-line therapy.
Local patterns of antibiotic-resistance always need to be considered when initiating pharmacotherapy. In hospitalized individuals or those with immune deficiencies, local guidelines determine the selection of antibiotics.
"Streptococcus pneumoniae" — amoxicillin (or erythromycin in patients allergic to penicillin); cefuroxime and erythromycin in severe cases.
"Staphylococcus aureus" — flucloxacillin (to counteract the organism's β-lactamase).
Among the categories of bacteria most known to infect patients are the category MRSA (resistant strain of "S. aureus"), member of gram-positive bacteria and "Acinetobacter" ("A. baumannii"), which is gram-negative. While antibiotic drugs to treat diseases caused by gram-positive MRSA are available, few effective drugs are available for "Acinetobacter". "Acinetobacter" bacteria are evolving and becoming immune to existing antibiotics, so in many cases, polymyxin-type antibacterials need to be used. "In many respects it’s far worse than MRSA," said a specialist at Case Western Reserve University.
Another growing disease, especially prevalent in New York City hospitals, is the drug-resistant, gram-negative "Klebsiella pneumoniae". An estimated more than 20% of the "Klebsiella" infections in Brooklyn hospitals "are now resistant to virtually all modern antibiotics, and those supergerms are now spreading worldwide."
The bacteria, classified as gram-negative because of their reaction to the Gram stain test, can cause severe pneumonia and infections of the urinary tract, bloodstream, and other parts of the body. Their cell structures make them more difficult to attack with antibiotics than gram-positive organisms like MRSA. In some cases, antibiotic resistance is spreading to gram-negative bacteria that can infect people outside the hospital. "For gram-positives we need better drugs; for gram-negatives we need any drugs," said Dr. Brad Spellberg, an infectious-disease specialist at Harbor-UCLA Medical Center, and the author of "Rising Plague", a book about drug-resistant pathogens.
One-third of nosocomial infections are considered preventable. The CDC estimates 2 million people in the United States are infected annually by hospital-acquired infections, resulting in 20,000 deaths. The most common nosocomial infections are of the urinary tract, surgical site and various pneumonias.
The mechanisms of the toxicity of fluoroquinolones have been attributed to their interactions with different receptor complexes, such as blockade of the GABAa receptor complex within the central nervous system, leading to excitotoxic type effects and oxidative stress.
Products containing multivalent cations, such as aluminium- or magnesium-containing antacids, and products containing calcium, iron or zinc invariably result in marked reduction of oral absorption of fluoroquinolones. Other drugs that interact with fluoroquinolones include sucralfate, probenecid, cimetidine, theophylline, warfarin, antiviral agents, phenytoin, cyclosporine, rifampin, pyrazinamide, and cycloserine.
Administration of quinolone antibiotics to a benzodiazepine dependent individual can precipitate acute benzodiazepine withdrawal symptoms due to quinolones displacing benzodiazepines from their binding site.
Fluoroquinolones have varying specificity for cytochrome P450, and so may have interactions with drugs cleared by those enzymes; the order from most P450-inhibitory to least, is enoxacin > ciprofloxacin > norfloxacin > ofloxacin, levofloxacin, trovafloxacin, gatifloxacin, moxifloxacin.
Usually initial therapy is empirical. If sufficient reason to suspect influenza, one might consider oseltamivir. In case of legionellosis, erythromycin or fluoroquinolone.
A third generation cephalosporin (ceftazidime) + carbapenems (imipenem) + beta lactam & beta lactamase inhibitors (piperacillin/tazobactam)
Two sets of blood cultures (aerobic and anaerobic) should be taken without delaying the initiation of antibitoics. Cultures from other sites such as respiratory secretions, urine, wounds, cerebrospinal fluid, and catheter insertion sites (in-situ more than 48 hours) can be taken if infections from these sites are suspected. In severe sepsis and septic shock, broad-spectrum antibiotics (usually two, a β-lactam antibiotic with broad coverage, or broad-spectrum carbapenem combined with fluoroquinolones, macrolides, or aminoglycosides) are recommended. However, combination of antibiotics is not recommended for the treatment of sepsis but without shock and immuno-compromised persons unless the combination is used to broaden the anti-bacterial activity. The choice of antibiotics is important in determining the survival of the person. Some recommend they be given within one hour of making the diagnosis, stating that for every hour of delay in the administration of antibiotics, there is an associated 6% rise in mortality. Others did not find a benefit with early administration.
Several factors determine the most appropriate choice for the initial antibiotic regimen. These factors include local patterns of bacterial sensitivity to antibiotics, whether the infection is thought to be a hospital or community-acquired infection, and which organ systems are thought to be infected. Antibiotic regimens should be reassessed daily and narrowed if appropriate. Treatment duration is typically 7–10 days with the type of antibiotic used directed by the results of cultures. In case the culture result is negative, antibiotics should be de-escalated according to person's clinical response or stopped altogether if infection is not present to decrease the chances that the person is infected with multiple drug resistance organisms. In case of people having high risk of being infected with multiple drug resistance organisms such as "Pseudomonas aeruginosa", "Acinetobacter baumannii", addition of antibiotic specific to gram-negative organism is recommended. For Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin and teicoplanin is recommanded. For Legionella infection, addition of macrolide or fluoroquinolone is chosen. If fungal infection is suspected, echinocandin (caspofungin and micafungin) is chosen for people with severe sepsis, followed by triazole (fluconazole and itraconazole) for less ill people. Prolonged antibiotic prophylaxis is not recommended in people who has SIRS without any infectious origion such as acute pancreatitis and burns unless sepsis is suspected.
Once daily dosing of aminoglycoside is sufficient to achieve peak plasma concentration for clinical response without kidney toxicity. Meanwhile, for antibiotics with low volume distribution (vancomycin, teicoplanin, colistin), loading dose is required to achieve adequate therapeutic level to fight infections. Frequent infusions of beta-lactam antibiotics without exceeding total daily dose would help to keep the antibiotics level above minimum inhibitory concentration (MIC), thus providing better clinical response. Giving beta-lactam antibiotics continuously may be better than giving them intermittently. Access to therapeutic drug monitoring is important to ensure adequate drug therapeutic level while at the same time preventing the drug from reaching toxic level.
General anaesthesia is recommended for people with sepsis who require surgical procedures to remove the infective source. Inhalational and intravenous anaesthetics are used. Requirements for anaesthetics may be reduced. Inhalational anaesthetics can reduce the level of proinflammatory cytokines, altering leukocyte adhesion and proliferation, inducing apoptosis (cell death) of the lymphocytes, possibly with a toxic effect on mitochondrial function. Although etomidate has a minimal effect on the cardiovascular system, it is often not recommended as a medication to help with intubation in this situation due to concerns it may lead to poor adrenal function and an increased risk of death. The small amount of evidence there is, however, has not found a change in the risk of death with etomidate.
It is recommended that the head of the bed be raised if possible to improve ventilation. Paralytic agents should be avoided unless ARDS is suspected.
Throughout history treatment relied primarily on β-lactam antibiotics. In the 1960s nearly all strains of "S. pneumoniae" were susceptible to penicillin, but more recently there has been an increasing prevalence of penicillin resistance especially in areas of high antibiotic use. A varying proportion of strains may also be resistant to cephalosporins, macrolides (such as erythromycin), tetracycline, clindamycin and the quinolones. Penicillin-resistant strains are more likely to be resistant to other antibiotics. Most isolates remain susceptible to vancomycin, though its use in a β-lactam-susceptible isolate is less desirable because of tissue distribution of the drug and concerns of development of vancomycin resistance. More advanced beta-lactam antibiotics (cephalosporins) are commonly used in combination with other drugs to treat meningitis and community-acquired pneumonia. In adults recently developed fluoroquinolones such as levofloxacin and moxifloxacin are often used to provide empiric coverage for patients with pneumonia, but in parts of the world where these drugs are used to treat tuberculosis resistance has been described.
Susceptibility testing should be routine with empiric antibiotic treatment guided by resistance patterns in the community in which the organism was acquired. There is currently debate as to how relevant the results of susceptibility testing are to clinical outcome. There is slight clinical evidence that penicillins may act synergistically with macrolides to improve outcomes.
Treatment consists of antibiotic therapy aimed at the typical bacterial pathogens in addition to supportive care for any complications which might result from the infection itself such as hypotension or respiratory failure. A typical regimen will include intravenous antibiotics such as from the penicillin-group which is active against "Staphylococcus aureus" and an aminoglycoside for activity against Gram-negative bacteria. For particularly invasive infections, antibiotics to cover anaerobic bacteria may be added (such as metronidazole). Treatment is typically for two weeks and often necessitates insertion of a central venous catheter or peripherally inserted central catheter.
As the infection is usually transmitted into humans through animal bites, antibiotics usually treat the infection, but medical attention should be sought if the wound is severely swelling. Pasteurellosis is usually treated with high-dose penicillin if severe. Either tetracycline or chloramphenicol provides an alternative in beta-lactam-intolerant patients. However, it is most important to treat the wound.
The methods used differ from country to country (definitions used, type of nosocomial infections covered, health units surveyed, inclusion or exclusion of imported infections, etc.), so the international comparisons of nosocomial infection rates should be made with the utmost care.
While antibiotics with activity specifically against "M. pneumoniae" are often used (e.g., erythromycin, doxycycline), it is unclear if these result in greater benefit than using antibiotics without specific activity against this organism in those with an infection acquired in the community.
The addition of a prokinetic drug to an antibiotic regime reduces the incidence of spontaneous bacterial peritonitis possibly via decreasing small intestinal bacterial overgrowth.
Symptomatic bacteriuria is typically treated as a urinary tract infection with antibiotics. Common choices include nitrofurantoin, and trimethoprim/sulfamethoxazole.
Alternatives to fosfomycin include nitrofurantoin, pivmecillinam, and co-amoxiclav in oral treatment of urinary-tract infections associated with extended-spectrum beta-lactamase.
In a separate study, CRE were treated with colistin, amikacin, and tigecycline, and emphasizes the importance of using gentamicin in patients undergoing chemotherapy or stem-cell therapy procedures.
While colistin had shown promising activity against carbapenemase-producing isolates, more recent data suggest a resistance to it is already emerging and it will soon become ineffective.
Using another antibiotic concomitantly with carbapenem can help prevent the development of carbapenem resistance. One specific study showed a higher rate of carbapenem resistance when using meropenem alone compared with combination therapy with moxifloxacin.
In addition, several drugs were tested to gauge their effectiveness against CRE infections. "In vitro" studies have shown that rifampin has synergistic activity against carbapenem-resistant "E. coli" and "K. pneumoniae". However, more data are needed to determine if rifampin is effective in a clinical setting.
Several new agents are in development. The main areas where scientists are focusing is new β-lactamase inhibitors with activity against carbapenemases. Some of these include MK-7655, NXL104, and 6-alkylidenepenam sulfones. The exact way they affect the carbapenemases is unknown. Another experimental agent with activity against CRE is eravacycline.
Patients with HCAP are more likely than those with community-acquired pneumonia to receive inappropriate antibiotics that do not target the bacteria causing their disease.
In 2002, an expert panel made recommendations about the evaluation and treatment of probable nursing home-acquired pneumonia. They defined probably pneumonia, emphasized expedite antibiotic treatment (which is known to improve survival) and drafted criteria for the hospitalization of willing patients.
For initial treatment in the nursing home, a fluoroquinolone antibiotic suitable for respiratory infections (moxifloxacin, for example), or amoxicillin with clavulanic acid plus a macrolide has been suggested. In a hospital setting, injected (parenteral) fluoroquinolones or a second- or third-generation cephalosporin plus a macrolide could be used. Other factors that need to be taken into account are recent antibiotic therapy (because of possible resistance caused by recent exposure), known carrier state or risk factors for resistant organisms (for example, known carrier of MRSA or presence of bronchiectasis predisposing to Pseudomonas aeruginosa), or suspicion of possible Legionella pneumophila infection (legionnaires disease).
In 2005, the American Thoracic Society and Infectious Diseases Society of America have published guidelines suggesting antibiotics specifically for HCAP. The guidelines recommend combination therapy with an agent from each of the following groups to cover for both "Pseudomonas aeruginosa" and MRSA. This is based on studies using sputum samples and intensive care patients, in whom these bacteria were commonly found.
- cefepime, ceftazidime, imipenem, meropenem or piperacillin–tazobactam; plus
- ciprofloxacin, levofloxacin, amikacin, gentamicin, or tobramycin; plus
- linezolid or vancomycin
In one observational study, empirical antibiotic treatment that was not according to international treatment guidelines was an independent predictor of worse outcome among HCAP patients.
Guidelines from Canada suggest that HCAP can be treated like community-acquired pneumonia with antibiotics targeting Streptococcus pneumoniae, based on studies using blood cultures in different settings which have not found high rates of MRSA or Pseudomonas.
Besides prompt antibiotic treatment, supportive measure for organ failure (such as cardiac decompensation) are also important. Another consideration goes to hospital referral; although more severe pneumonia requires admission to an acute care facility, this also predisposes to hazards of hospitalization such as delirium, urinary incontinence, depression, falls, restraint use, functional decline, adverse drug effects and hospital infections. Therefore, mild pneumonia might be better dealt with inside the long term care facility. In patients with a limited life expectancy (for example, those with advanced dementia), end-of-life pneumonia also requires recognition and appropriate, palliative care.
"Actinomyces" bacteria are generally sensitive to penicillin, which is frequently used to treat actinomycosis. In cases of penicillin allergy, doxycycline is used.
Sulfonamides such as sulfamethoxazole may be used as an alternative regimen at a total daily dosage of 2-4 grams. Response to therapy is slow and may take months.
Hyperbaric oxygen therapy may also be used as an adjunct to conventional therapy when the disease process is refractory to antibiotics and surgical treatment.
Antibiotic therapy has to overcome the blood/prostate barrier that prevents many antibiotics from reaching levels that are higher than minimum inhibitory concentration. A blood-prostate barrier restricts cell and molecular movement across the rat ventral prostate epithelium. Treatment requires prolonged courses (4–8 weeks) of antibiotics that penetrate the prostate well. The fluoroquinolones, tetracyclines and macrolides have the best penetration. There have been contradictory findings regarding the penetrability of nitrofurantoin , quinolones (ciprofloxacin, levofloxacin), sulfas (Bactrim, Septra), doxycycline and macrolides (erythromycin, clarithromycin). This is particularly true for gram-positive infections.
In a review of multiple studies, Levofloxacin (Levaquin) was found to reach prostatic fluid concentrations 5.5 times higher than Ciprofloxacin, indicating a greater ability to penetrate the prostate.
Persistent infections may be helped in 80% of patients by the use of alpha blockers (tamsulosin (Flomax), alfuzosin), or long term low dose antibiotic therapy. Recurrent infections may be caused by inefficient urination (benign prostatic hypertrophy, neurogenic bladder), prostatic stones or a structural abnormality that acts as a reservoir for infection.
In theory, the ability of some strains of bacteria to form biofilms might be one factor amongst others to facilitate development of chronic bacterial prostatitis.
Escherichia coli extract and cranberry have a potentially preventive effect on the development of chronic bacterial prostatitis, while combining antibiotics with saw palmetto, lactobacillus sporogens and arbutin may lead to better treatment outcomes.
Bacteriophages hold promise as another potential treatment for chronic bacterial prostatatis.
The addition of prostate massage to courses of antibiotics was previously proposed as being beneficial and prostate massage may mechanically break up the biofilm and enhance the drainage of the prostate gland. However, in more recent trials, this was not shown to improve outcome compared to antibiotics alone.
Cefotaxim s DOC. After confirmation of SBP, patients need hospital admission for intravenous antibiotics. They will often also receive intravenous albumin. A repeat paracentesis in 48 hours is sometimes performed to ensure control of infection. Once patients have recovered from SBP, they require regular prophylactic antibiotics as long as they still have ascites.