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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.
"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.
Treatment can include topical steroids to diminish the inflammation. Antibiotics to diminish the proportion of aerobic bacteria is still a matter of debate. The use of local antibiotics, preferably local non-absorbed and broad spectrum, covering enteric gram-positive and gram-negative aerobes, can be an option. In some cases, systemic antibiotics can be helpful, such as amoxicillin/clavulanate or moxifloxacin. Vaginal rinsing with povidone iodine can provide relief of symptoms but does not provide long-term reduction of bacterial loads. Dequalinium chloride can also be an option for treatment.
Treatment is typically with the antibiotics metronidazole or clindamycin. They can be either given by mouth or applied inside the vagina. About 10% to 15% of people, however, do not improve with the first course of antibiotics and recurrence rates of up to 80% have been documented. Recurrence rates are increased with sexual activity with the same pre-/posttreatment partner and inconsistent condom use although estrogen-containing contraceptives decrease recurrence. When clindamycin is given to pregnant women symptomatic with BV before 22 weeks of gestation the risk of pre-term birth before 37 weeks of gestation is lower.
Other antibiotics that may work include macrolides, lincosamides, nitroimidazoles, and penicillins.
Bacterial vaginosis is not considered a sexually transmitted infection, and treatment of a male sexual partner of a woman with bacterial vaginosis is not recommended.
The cause of the infection determines the appropriate treatment. It may include oral or topical antibiotics and/or antifungal creams, antibacterial creams, or similar medications. A cream containing cortisone may also be used to relieve some of the irritation. If an allergic reaction is involved, an antihistamine may also be prescribed. For women who have irritation and inflammation caused by low levels of estrogen (postmenopausal), a topical estrogen cream might be prescribed.
The following are typical treatments for trichomoniasis, bacterial vaginosis, and yeast infections:
- Trichomoniasis: Single oral doses of either metronidazole, or tinidazole. "Sexual partner(s) should be treated simultaneously. Patients should be advised to avoid sexual intercourse for at least 1 week and until they and their partner(s) have completed treatment and follow-up."
- Bacterial vaginosis: The most commonly used antibiotics are metronidazole, available in both pill and gel form, and clindamycin available in both pill and cream form.
- Yeast infections: Local azole, in the form of ovula and cream. All agents appear to be equally effective. These anti-fungal medications, which are available in over the counter form, are generally used to treat yeast infections. Treatment may last anywhere between one, three, or seven days.
A 2009 Cochrane review found tentative but insufficient evidence for probiotics as a treatment for BV. A 2014 review reached the same conclusion. A 2013 review found some evidence supporting the use of probiotics during pregnancy. The preferred probiotics for BV are those containing high doses of lactobacilli (around 10 ) given in the vagina. Intravaginal administration is preferred to taking them by mouth. Prolonged repetitive courses of treatment appear to be more promising than short courses.
The affected areas are treated with iodine solutions. A common method to achieve this is to give the cattle sodium iodide orally on a regular treatment schedule. Antibiotics such as Tetracyclines are also used. These two treatment methods can be used alone or together; simultaneous use is considered more aggressive. Killing the bacteria that cause the infection is the ultimately purpose of these treatment methods. However, they are seldom effective unless treatment is started very early.
It is notable that surgery is not typically considered for treatment of cattle as it is in extreme human cases.
Nocardiosis requires at least 6 months of treatment, preferably with trimethoprim/sulfamethoxazole or high doses of sulfonamides. In patients who do not respond to sulfonamide treatment, other drugs, such as ampicillin, erythromycin, or minocycline, may be added.
Treatment also includes surgical drainage of abscesses and excision of necrotic tissue. The acute phase requires complete bed rest; as the patient improves, activity can increase.
A new combination drug therapy (sulfonamide, ceftriaxone, and amikacin) has also shown promise.
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)
Systemic candidiasis occurs when Candida yeast enters the bloodstream and may spread (becoming disseminated candidiasis) to other organs, including the central nervous system, kidneys, liver, bones, muscles, joints, spleen, or eyes. Treatment typically consists of oral or intravenous antifungal medications. In candidal infections of the blood, intravenous fluconazole or an echinocandin such as caspofungin may be used. Amphotericin B is another option.
As "Flavobacterium columnare" is Gram-negative, fish can be treated with a combination of the antibiotics furan-2 and kanamycin administered together. A medicated fish bath (using methylene blue or potassium permanganate and salt), is generally a first step, as well lowering the aquarium temperature to 75 °F (24 °C) is a must, since columnaris is much more virulent at higher temperatures, especially 85–90 °F.
Medicated food containing oxytetracycline is also an effective treatment for internal infections, but resistance is emerging. Potassium permanganate, copper sulfate, and hydrogen peroxide can also be applied externally to adult fish and fry, but can be toxic at high concentrations. Vaccines can also be given in the face of an outbreak or to prevent disease occurrence.
Treatment of AIT involves antibiotic treatment. Based on the offending organism found on microscopic examination of the stained fine needle aspirate, the appropriate antibiotic treatment is determined. In the case of a severe infection, systemic antibiotics are necessary. Empirical broad spectrum antimicrobial treatment provides preliminary coverage for a variety of bacteria, including "S. aureus" and "S. pyogenes." Antimicrobial options include penicillinase-resistant penicillins (ex: cloxacillin, dicloxacillin) or a combination of a penicillin and a beta-lactamase inhibitor. However, in patients with a penicillin allergy, clindamycin or a macrolide can be prescribed. The majority of anaerobic organisms involved with AIT are susceptible to penicillin. Certain Gram-negative bacilli (ex: "Prevotella", "Fusobacteria", and "Porphyromonas") are exhibiting an increased resistance based on the production of beta-lactamase. Patients who have undergone recent penicillin therapy have demonstrated an increase in beta-lactamase-producing (anaerobic and aerobic) bacteria. Clindamycin, or a combination of metronidazole and a macrolide, or a penicillin combined with a beta-lactamase inhibitor is recommended in these cases. Fungal thyroiditis can be treated with amphotericin B and fluconazole. Early treatment of AIT prevents further complications. However, if antibiotic treatment does not manage the infection, surgical drainage is required. Symptoms or indications requiring drainage include continued fever, high white blood cell count, and continuing signs of localized inflammation. The draining procedure is also based on clinical examination or ultrasound/CT scan results that indicate an abscess or gas formation. Another treatment of AIT involves surgically removing the fistula. This treatment is often the option recommended for children. However, in cases of an antibiotic resistant infection or necrotic tissue, a lobectomy is recommended. If diagnosis and/or treatment is delayed, the disease could prove fatal.
Candidiasis is treated with antifungal medications; these include clotrimazole, nystatin, fluconazole, voriconazole, amphotericin B, and echinocandins. Intravenous fluconazole or an intravenous echinocandin such as caspofungin are commonly used to treat immunocompromised or critically ill individuals.
The 2016 revision of the clinical practice guideline for the management of candidiasis lists a large number of specific treatment regimens for "Candida" infections that involve different "Candida" species, forms of antifungal drug resistance, immune statuses, and infection localization and severity. Gastrointestinal candidiasis in immunocompetent individuals is treated with 100–200 mg fluconazole per day for 2–3 weeks.
Treatment is not always easy and aims at correcting the three key changes encountered in aerobic vaginitis: the presence of atrophy, inflammation and abnormal flora. The treatment can include topical steroids to diminish the inflammation and topical estrogen to reduce the atrophy. The use and choice of antibiotics to diminish the load/proportion of aerobic bacteria is still a matter of debate. The use of local antibiotics, preferably local non-absorbed and broad spectrum, covering enteric gram-positive and gram-negative aerobes, like kanamycin can be an option. In some cases, systemic antibiotics can be helpful, such as amoxyclav or moxifloxacin. Vaginal rinsing with povidone iodine can provide rapid relief of symptoms but does not provide long-term reduction of bacterial loads. Dequalinium chloride can also be an option for treatment.
Treatments involve antibiotics that cover for "Pseudomonas aeruginosa". Antipseudomonal penicillins, aminoglycosides, fluoroquinolones, third generation cephalosporins or aztreonam can be given. Usually, the antibiotics are changed according to the culture and sensitivity result. In patients with very low white blood cell counts, Granulocyte-macrophage colony-stimulating factor may be given. Depending on the causal agents, antivirals or antifungals can be added.
Surgery will be needed if there is extensive necrosis not responding to medical treatments.
Condition predisposing to anaerobic infections include: exposure of a sterile body location to a high inoculum of indigenous bacteria of mucous membrane flora origin, inadequate blood supply and tissue necrosis which lower the oxidation and reduction potential which support the growth of anaerobes. Conditions which can lower the blood supply and can predispose to anaerobic infection are: trauma, foreign body, malignancy, surgery, edema, shock, colitis and vascular disease. Other predisposing conditions include splenectomy, neutropenia, immunosuppression, hypogammaglobinemia, leukemia, collagen vascular disease and cytotoxic drugs and diabetes mellitus. A preexisting infection caused by aerobic or facultative organisms can alter the local tissue conditions and make them more favorable for the growth of anaerobes. Impairment in defense mechanisms due to anaerobic conditions can also favor anaerobic infection. These include production of leukotoxins (by "Fusobacterium" spp.), phagocytosis intracellular killing impairments (often caused by encapsulated anaerobes and by succinic acid ( produced by "Bacteroides" spp.), chemotaxis inhibition (by "Fusobacterium, Prevotella" and "Porphyromonas" spp.), and proteases degradation of serum proteins (by Bacteroides spp.) and production of leukotoxins (by "Fusobacterium" spp.).
The hallmarks of anaerobic infection include suppuration, establishment of an abscess, thrombophlebitis and gangrenous destruction of tissue with gas generation. Anaerobic bacteria are very commonly recovered in chronic infections, and are often found following the failure of therapy with antimicrobials that are ineffective against them, such as trimethoprim–sulfamethoxazole (co-trimoxazole), aminoglycosides, and the earlier quinolones.
Some infections are more likely to be caused by anaerobic bacteria, and they should be suspected in most instances. These infections include brain abscess, oral or dental infections, human or animal bites, aspiration pneumonia and lung abscesses, amnionitis, endometritis, septic abortions, tubo-ovarian abscess, peritonitis and abdominal abscesses following viscus perforation, abscesses in and around the oral and rectal areas, pus-forming necrotizing infections of soft tissue or muscle and postsurgical infections that emerge following procedures on the oral or gastrointestinal tract or female pelvic area. Some solid malignant tumors, ( colonic, uterine and bronchogenic, and head and neck necrotic tumors, are more likely to become secondarily infected with anaerobes. The lack of oxygen within the tumor that are proximal to the endogenous adjacent mucosal flora can predispose such infections.
Treatment for TOA differs from PID in that some clinicians recommend patients with tubo-ovarian abscesses have at least 24 hours of inpatient parenteral treatment with antibiotics, and that they may require surgery. If surgery becomes necessary, pre-operative administration of broad-spectrum antibiotics is started and removal of the abscess, the affected ovary and fallopian tube is done. After discharge from the hospital, oral antibiotics are continued for the length of time prescribed by the physician.
Treatment is different if the TOA is discovered before it ruptures and can be treated with IV antibiotics. During this treatment, IV antibiotics are usually replaced with oral antibiotics on an outpatient basis. Patients are usually seen three days after hospital discharge and then again one to two weeks later to confirm that the infection has cleared. Ampicillin/sulbactam plus doxycycline is effective against C. trachomatis, N. gonorrhoeae, and anaerobes in women with tubo-ovarian abscess. Parenteral Regimens described by the Centers for Disease Control and prevention are Ampicillin/Sulbactam 3 g IV every 6 hours and Doxycycline 200 mg orally or IV every 24 hours, though other regiemes that are used for pelvic inflammatory disease have been effective.
There is no readily available evidence on the route of administration and duration of antibiotics in patients with pleural empyema. Experts agree that all patients should be hospitalized and treated with antibiotics intravenously. The specific antimicrobial agent should be chosen based on Gram stain and culture, or on local epidemiologic data when these are not available. Anaerobic coverage must be included in all adults, and in children if aspiration is likely. Good pleural fluid and empyema penetration has been reported in adults for penicillins, ceftriaxone, metronidazole, clindamycin, vancomycin, gentamycin and ciprofloxacin. Aminoglycosides should typically be avoided as they have poor penetration into the pleural space. There is no clear consensus on duration of intravenous and oral therapy. Switching to oral antibiotics can be considered upon clinical and objective improvement (adequate drainage and removal of chest tube, declining CRP, temperature normalization). Oral antibiotic treatment should then be continued for another 1–4 weeks, again based on clinical, biochemical and radiological response.
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.
The infection is frequently penicillin resistant. There are a number of antibiotics options including amoxicillin/clavulanate, clindamycin, or metronidazole in combination with benzylpenicillin (penicillin G) or penicillin V. Piperacillin/tazobactam may also be used.
Treatment is by removing the pus, antibiotics, sufficient fluids, and pain medication. Steroids may also be useful. Admission to hospital is generally not needed.
It is extremely difficult to successfully treat BPF, mainly because of the difficulty obtaining a proper diagnosis. Since the disease starts out with what seems to be a common case of conjunctivitis, "H. aegyptius" is not susceptible to the antibiotic eye drops that are being used to treat it. This treatment is ineffective because it treats only the local ocular infection, whereas if it progresses to BPF, systemic antibiotic treatment is required. Although BPF is susceptible to many commonly used antibiotics, including ampicillin, cefuroxime, cefotaxime, rifampin, and chloramphenicol, by the time it is diagnosed the disease has progressed too much to be effectively treated. However, with the fast rate of progression of BPF it is unlikely that it will be successfully treated. With antibiotic therapy, the mortality rate of BPF is around 70%.
If ear infections are treated in a reasonable amount of time, the antibiotics will usually cure the infection and prevent its spread. For this reason, mastoiditis is rare in developed countries. Most ear infections occur in infants as the eustachian tubes are not fully developed and don't drain readily.
In all developed countries with up-to-date modern healthcare the primary treatment for mastoiditis is administration of intravenous antibiotics. Initially, broad-spectrum antibiotics are given, such as ceftriaxone. As culture results become available, treatment can be switched to more specific antibiotics directed at the eradication of the recovered aerobic and anaerobic bacteria. Long-term antibiotics may be necessary to completely eradicate the infection. If the condition does not quickly improve with antibiotics, surgical procedures may be performed (while continuing the medication). The most common procedure is a myringotomy, a small incision in the tympanic membrane (eardrum), or the insertion of a tympanostomy tube into the eardrum. These serve to drain the pus from the middle ear, helping to treat the infection. The tube is extruded spontaneously after a few weeks to months, and the incision heals naturally. If there are complications, or the mastoiditis does not respond to the above treatments, it may be necessary to perform a mastoidectomy: a procedure in which a portion of the bone is removed and the infection drained.
Proven empyema (as defined by the "golden" criteria mentioned earlier) is an indication for prompt chest tube drainage. This has been shown to improve resolution of the infection and shorten hospital admission. Data from a meta-analysis has shown that a pleural fluid pH of <7.2 is the most powerful indicator to predict the need for chest tube drainage in patients with non-purulent, culture negative fluid. Other indications for drainage include poor clinical progress during treatment with antibiotics alone and patients with a loculated pleural collection.
Because of the viscous, lumpy nature of infected pleural fluid, in combination with possible septation and loculation, it has been proposed that intrapleural fibrinolytic or mucolytic therapy might improve drainage and therefore might have a positive effect on the clinical outcome. Intrapleural fibrinolysis with urokinase decreased the need for surgery but there is a trend to increased serious side effects.
Approximately 15 to 40 percent of people require surgical drainage of the infected pleural space because of inadequate drainage due to clogging of the chest tube or loculated empyema. Patients should thus be considered for surgery if they have ongoing signs of sepsis in association with a persistent pleural collection despite drainage and antibiotics. Video-assisted thoracoscopic surgery (VATS) is used as a first-line therapy in many hospitals, although open thoracic drainage remains a frequently used alternative technique.
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.