Antimicrobial stewardship teams in hospitals are encouraging optimal use of antimicrobials. The goals of antimicrobial stewardship are to help practitioners pick the right drug at the right dose and duration of therapy while preventing misuse and minimizing the development of resistance. Stewardship may reduce the length of stay by an average of slightly over 1 day while not increasing the risk of death.

For isolates with a Vancomycin MIC , an alternative to Vancomycin should be used. The approach is to treat with at least one agent to which VISA/VRSA is known to be susceptible by "in vitro" testing. The agents that are used include daptomycin, linezolid, telavancin, ceftaroline, quinupristin–dalfopristin. For people with MRSA bacteremia in the setting of vancomycin failure the IDSA recommends high-dose daptomycin, if the isolate is susceptible, in combination with another agent (e.g. gentamicin, rifampin, linezolid, TMP-SMX, or a beta-lactam antibiotic).

Antibiotic stewardship programmes appear useful in reducing rates of antibiotic resistance.

Excessive antibiotic use has become one of the top contributors to the development of antibiotic resistance. Since the beginning of the antibiotic era, antibiotics have been used to treat a wide range of disease. Overuse of antibiotics has become the primary cause of rising levels of antibiotic resistance. The main problem is that doctors are willing to prescribe antibiotics to ill-informed individuals who believe that antibiotics can cure nearly all illnesses, including viral infections like the common cold. In an analysis of drug prescriptions, 36% of individuals with a cold or an upper respiratory infection (both viral in origin) were given prescriptions for antibiotics. These prescriptions accomplished nothing other than increasing the risk of further evolution of antibiotic resistant bacteria.

The chances of drug resistance can sometimes be minimized by using multiple drugs simultaneously. This works because individual mutations can be independent and may tackle only one drug at a time; if the individuals are still killed by the other drugs, then the mutations cannot persist. This was used successfully in tuberculosis. However, cross resistance where mutations confer resistance to two or more treatments can be problematic.

For antibiotic resistance, which represents a widespread problem nowadays, drugs designed to block the mechanisms of bacterial antibiotic resistance are used. For example, bacterial resistance against beta-lactam antibiotics (such as penicillins and cephalosporins) can be circumvented by using antibiotics such as nafcillin that are not susceptible to destruction by certain beta-lactamases (the group of enzymes responsible for breaking down beta-lactams). Beta-lactam bacterial resistance can also be dealt with by administering beta-lactam antibiotics with drugs that block beta-lactamases such as clavulanic acid so that the antibiotics can work without getting destroyed by the bacteria first. Recently, researchers have recognized the need for new drugs that inhibit bacterial efflux pumps, which cause resistance to multiple antibiotics such as beta-lactams, quinolones, chloramphenicol, and trimethoprim by sending molecules of those antibiotics out of the bacterial cell. Sometimes a combination of different classes of antibiotics may be used synergistically; that is, they work together to effectively fight bacteria that may be resistant to one of the antibiotics alone.

Destruction of the resistant bacteria can also be achieved by phage therapy, in which a specific bacteriophage (virus that kills bacteria) is used.

There is research being done using antimicrobial peptides. In the future, there is a possibility that they might replace novel antibiotics.

Cephalosporin use is a risk factor for colonization and infection by VRE, and restriction of cephalosporin usage has been associated with decreased VRE infection and transmission in hospitals. "Lactobacillus rhamnosus" GG (LGG), a strain of "L. rhamnosus", was used successfully for the first time to treat gastrointestinal carriage of VRE. In the US, linezolid is commonly used to treat VRE.

To limit the development of antimicrobial resistance, it has been suggested to:

- Use the appropriate antimicrobial for an infection; e.g. no antibiotics for viral infections

- Identify the causative organism whenever possible

- Select an antimicrobial which targets the specific organism, rather than relying on a broad-spectrum antimicrobial

- Complete an appropriate duration of antimicrobial treatment (not too short and not too long)

- Use the correct dose for eradication; subtherapeutic dosing is associated with resistance, as demonstrated in food animals.

The medical community relies on education of its prescribers, and self-regulation in the form of appeals to voluntary antimicrobial stewardship, which at hospitals may take the form of an antimicrobial stewardship program. It has been argued that depending on the cultural context government can aid in educating the public on the importance of restrictive use of antibiotics for human clinical use, but unlike narcotics, there is no regulation of its use anywhere in the world at this time. Antibiotic use has been restricted or regulated for treating animals raised for human consumption with success, in Denmark for example.

Infection prevention is the most efficient strategy of prevention of an infection with a MDR organism within a hospital, because there are few alternatives to antibiotics in the case of an extensively resistant or panresistant infection; if an infection is localized, removal or excision can be attempted (with MDR-TB the lung for example), but in the case of a systemic infection only generic measures like boosting the immune system with immunoglobulins may be possible. The use of bacteriophages (viruses which kill bacteria) has no clinical application at the present time.

It is necessary to develop new antibiotics over time since the selection of resistant bacteria cannot be prevented completely. This means with every application of a specific antibiotic, the survival of a few bacteria which already got a resistance gene against the substance is promoted, and the concerning bacterial population amplifies. Therefore, the resistance gene is farther distributed in the organism and the environment, and a higher percentage of bacteria does no longer respond to a therapy with this specific antibiotic.

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.

HIV is the prime example of MDR against antivirals, as it mutates rapidly under monotherapy.

Influenza virus has become increasingly MDR; first to amantadenes, then to neuraminidase inhibitors such as oseltamivir, (2008-2009: 98.5% of Influenza A tested resistant), also more commonly in people with weak immune systems. Cytomegalovirus can become resistant to ganciclovir and foscarnet under treatment, especially in immunosuppressed patients. Herpes simplex virus rarely becomes resistant to acyclovir preparations, mostly in the form of cross-resistance to famciclovir and valacyclovir, usually in immunosuppressed patients.

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.

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.

Screening for VRE can be accomplished in a number of ways. For inoculating peri-rectal/anal swabs or stool specimens directly, one method uses bile esculin azide agar plates containing 6 µg/ml of vancomycin. Black colonies should be identified as an enterococcus to species level and further confirmed as vancomycin resistant by an MIC method before reporting as VRE.

Vancomycin resistance can be determined for enterococcal colonies available in pure culture by inoculating a suspension of the organism onto a commercially available brain heart infusion agar (BHIA) plate containing 6 µg/ml vancomycin. The National Committee for Clinical Laboratory Standards (NCCLS) recommends performing a vancomycin MIC test and also motility and pigment production tests to distinguish species with acquired resistance (vanA and vanB) from those with vanC intrinsic resistance.

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.

A boil may clear up on its own without bursting, but more often it will need to be opened and drained. This will usually happen spontaneously within two weeks. Regular application of a warm moist compress, both before and after a boil opens, can help speed healing. The area must be kept clean, hands washed after touching it, and any dressings disposed of carefully, in order to avoid spreading the bacteria. A doctor may cut open or "lance" a boil to allow it to drain, but squeezing or cutting should not be attempted at home, as this may further spread the infection. Antibiotic therapy may be recommended for large or recurrent boils or those that occur in sensitive areas (such as the groin, breasts, armpits, around or in the nostrils, or in the ear). Antibiotics should not be used for longer than one month, with at least two months (preferably longer) between uses, otherwise it will lose its effectiveness. If the patient has chronic (more than two years) boils, removal by plastic surgery may be indicated.

Furuncles at risk of leading to serious complications should be incised and drained if antibiotics or steroid injections are not effective. These include furuncles that are unusually large, last longer than two weeks, or occur in the middle of the face or near the spine. Fever and chills are signs of sepsis and indicate immediate treatment is needed.

Staphylococcus aureus has the ability to acquire antimicrobial resistance easily, making treatment difficult. Knowledge of the antimicrobial resistance of "S. aureus" is important in the selection of antimicrobials for treatment.

Three classes of vancomycin-resistant "S. aureus" have emerged that differ in vancomycin susceptibilities: vancomycin-intermediate "S. aureus" (VISA), heterogeneous vancomycin-intermediate "S. aureus" (hVISA), and high-level vancomycin-resistant "S. aureus" (VRSA).

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)

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).

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.

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.

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.

Antibiotics improve outcomes in those with bacterial pneumonia. Antibiotic choice depends initially on the characteristics of the person affected, such as age, underlying health, and the location the infection was acquired. In the UK, treatment before culture results with amoxicillin is recommended as the first line for community-acquired pneumonia, with doxycycline or clarithromycin as alternatives. In North America, where the "atypical" forms of community-acquired pneumonia are more common, macrolides (such as azithromycin or erythromycin), and doxycycline have displaced amoxicillin as first-line outpatient treatment in adults. In children with mild or moderate symptoms, amoxicillin remains the first line. The use of fluoroquinolones in uncomplicated cases is discouraged due to concerns about side-effects and generating resistance in light of there being no greater clinical benefit.

For those who require hospitalization and caught their pneumonia in the community the use of a β-lactam such as cephazolin plus macrolide such as azithromycin or a fluoroquinolones is recommended. The addition of corticosteroids also appears to improve outcomes.

The duration of treatment has traditionally been seven to ten days, but increasing evidence suggests that shorter courses (three to five days) are similarly effective. Recommendations for hospital-acquired pneumonia include third- and fourth-generation cephalosporins, carbapenems, fluoroquinolones, aminoglycosides, and vancomycin. These antibiotics are often given intravenously and used in combination. In those treated in hospital, more than 90% improve with the initial antibiotics.

Neuraminidase inhibitors may be used to treat viral pneumonia caused by influenza viruses (influenza A and influenza B). No specific antiviral medications are recommended for other types of community acquired viral pneumonias including SARS coronavirus, adenovirus, hantavirus, and parainfluenza virus. Influenza A may be treated with rimantadine or amantadine, while influenza A or B may be treated with oseltamivir, zanamivir or peramivir. These are of most benefit if they are started within 48 hours of the onset of symptoms. Many strains of H5N1 influenza A, also known as avian influenza or "bird flu", have shown resistance to rimantadine and amantadine. The use of antibiotics in viral pneumonia is recommended by some experts, as it is impossible to rule out a complicating bacterial infection. The British Thoracic Society recommends that antibiotics be withheld in those with mild disease. The use of corticosteroids is controversial.

"Biological cost" or "metabolic price" is a measure of the increased energy metabolism required to achieve a function.

Drug resistance has a high metabolic price in pathogens for which this concept is relevant (bacteria, endoparasites, and tumor cells.) In viruses, an equivalent "cost" is genomic complexity.

High-dose antibiotics are administered by the intravenous route to maximize diffusion of antibiotic molecules into vegetation(s) from the blood filling the chambers of the heart. This is necessary because neither the heart valves nor the vegetations adherent to them are supplied by blood vessels. Antibiotics are typically continued for two to six weeks depending on the characteristics of the infection and the causative microorganisms.

In acute endocarditis, due to the fulminant inflammation empirical antibiotic therapy is started immediately after the blood has been drawn for culture. This usually includes vancomycin and ceftriaxone IV infusions until the microbial identification and susceptibility report with the minimum inhibitory concentration becomes available allowing for modification of the antimicrobial therapy to target the specific microorganism. It should be noted that the routine use of gentamicin to treat endocarditis has fallen out of favor due to the lack of evidence to support its use (except in infections caused by "Enterococcus" and nutritionally variant "streptococci") and the high rate of complications.

In subacute endocarditis, where patient's hemodynamic status is usually stable, antibiotic treatment can be delayed till the causative microorganism can be identified.

The most common organism responsible for infective endocarditis is "Staphylococcus aureus", which is resistant to penicillin in most cases. High rates of resistance to oxacillin are also seen, in which cases treatment with vancomycin is required.

Viridans group "streptococci" and "Streptococcus bovis" are usually highly susceptible to penicillin and can be treated with penicillin or ceftriaxone.

Relatively resistant strains of viridans group "streptococci" and "Streptococcus bovis" are treated with penicillin or ceftriaxone along with a shorter 2 week course of an aminoglycoside during the initial phase of treatment.

Highly penicillin resistant strains of viridans group "streptococci", nutritionally variant "streptococci" like "Granulicatella sp.", "Gemella sp." and "Abiotrophia defectiva", and "Enterococci" are usually treated with a combination therapy consisting of penicillin and an aminoglycoside for the entire duration of 4–6 weeks.

Selected patients may be treated with a relatively shorter course of treatment (2 weeks) with benzyl penicillin IV if infection is caused by viridans group "streptococci" or "Streptococcus bovis" as long as the following conditions are met:

- Endocarditis of a native valve, not of a prosthetic valve

- An MIC ≤ 0.12 mg/l

- Complication such as heart failure, arrhythmia, and pulmonary embolism occur

- No evidence of extracardiac complication like septic thromboembolism

- No vegetations > 5mm in diameter conduction defects

- Rapid clinical response and clearance of blood stream infection

Additionally oxacillin susceptible "Staphylococcus aureus" native valve endocarditis of the right side can also be treated with a short 2 week course of a beta-lactam antibiotic like nafcillin with or without aminoglycosides.

Surgical debridement of infected material and replacement of the valve with a mechanical or bioprosthetic artificial heart valve is necessary in certain situations:

- Patients with significant valve stenosis or regurgitation causing heart failure

- Evidence of hemodynamic compromise in the form of elevated end-diastolic left ventricular or left atrial pressure or moderate to severe pulmonary hypertension

- Presence of intracardiac complications like paravalvular abscess, conduction defects or destructive penetrating lesions

- Recurrent septic emboli despite appropriate antibiotic treatment

- Large vegetations (> 10 mm)

- Persistently positive blood cultures despite appropriate antibiotic treatment

- Prosthetic valve dehiscence

- Relapsing infection in the presence of a prosthetic valve

- Abscess formation

- Early closure of mitral valve

- Infection caused by fungi or resistant Gram negative bacteria.

The guidelines were recently updated by both the American College of Cardiology and the European Society of Cardiology. There was a recent meta-analysis published that showed surgical intervention at 7 days or less is associated with lower mortality .

Infective endocarditis is associated with 18% in-hospital mortality.

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.