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.

Tigecycline, a member of the glycylcyclines antibiotics, has proven to be an effective therapy against Enterobacteriaceae that typically display tetracycline resistance, because tigecycline has a higher binding affinity with ribosomal sites than tetracycline has. Tigecycline is capable of killing almost all of the ESBLs and multidrug-resistant (MDR) "E. coli" isolates and the large majority of ESBL and MDR isolates of "Klebsiella" species.

A 2008 review of 42 studies of "in vitro" susceptibility of bacteria to tigecycline showed that MDR "K. pneumoniae" and "E. coli", including those that were carbapenem resistant, were susceptible more than 90% of the time. A limited number of patients have been treated with tigecycline, but the FDA has approved it in certain cases with synergies of other drugs. The limited number of patients indicates that more trials are needed to determine the overall clinical effectiveness.

Although tigecycline is the one of the first lines of defense against carbapenemase-producing isolates, negative clinical outcomes with tigecycline have occurred. Both urinary tract and primary blood infections can make tigecycline ineffective, because it has limited penetration and rapid tissue diffusion after being intravenously infused, respectively.

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.

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.

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.

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).

Usually, multidrug-resistant tuberculosis can be cured with long treatments of second-line drugs, but these are more expensive than first-line drugs and have more adverse effects. The treatment and prognosis of MDR-TB are much more akin to those for cancer than to those for infection. MDR-TB has a mortality rate of up to 80%, which depends on a number of factors, including

1. How many drugs the organism is resistant to (the fewer the better)

2. How many drugs the patient is given (patients treated with five or more drugs do better)

3. Whether an injectable drug is given or not (it should be given for the first three months at least)

4. The expertise and experience of the physician responsible

5. How co-operative the patient is with treatment (treatment is arduous and long, and requires persistence and determination on the part of the patient)

6. Whether the patient is HIV positive or not (HIV co-infection is associated with an increased mortality).

The majority of patients suffering from multi-drug-resistant tuberculosis do not receive treatment, as they are found in underdeveloped countries or in poverty. Denial of treatment remains a difficult human rights issue, as the high cost of second-line medications often precludes those who cannot afford therapy.

A study of cost-effective strategies for tuberculosis control supported three major policies. First, the treatment of smear-positive cases in DOTS programs must be the foundation of any tuberculosis control approach, and should be a basic practice for all control programs. Second, there is a powerful economic case for treating smear-negative and extra-pulmonary cases in DOTS programs along with treating smear-negative and extra-pulmonary cases in DOTS programs as a new WHO “STOP TB” approach and the second global plan for tuberculosis control. Last, but not least, the study shows that significant scaling up of all interventions is needed in the next 10 years if the millennium development goal and related goals for tuberculosis control are to be achieved. If the case detection rate can be improved, this will guarantee that people who gain access to treatment facilities are covered and that coverage is widely distributed to people who do not now have access.

In general, treatment courses are measured in months to years; MDR-TB may require surgery, and death rates remain high despite optimal treatment. However, good outcomes for patients are still possible.

The treatment of MDR-TB must be undertaken by physicians experienced in the treatment of MDR-TB. Mortality and morbidity in patients treated in non-specialist centers are significantly higher to those of patients treated in specialist centers. Treatment of MDR-TB must be done on the basis of sensitivity testing: it is impossible to treat such patients without this information. When treating a patient with suspected MDR-TB, pending the result of laboratory sensitivity testing, the patient could be started on SHREZ (Streptomycin+ isonicotinyl Hydrazine+ Rifampicin+Ethambutol+ pyraZinamide) and moxifloxacin with cycloserine. There is evidence that previous therapy with a drug for more than a month is associated with diminished efficacy of that drug regardless of "in vitro" tests indicating susceptibility. Hence, a detailed knowledge of the treatment history of each patient is essential. In addition to the obvious risks (i.e., known exposure to a patient with MDR-TB), risk factors for MDR-TB include HIV infection, previous incarceration, failed TB treatment, failure to respond to standard TB treatment, and relapse following standard TB treatment.

A gene probe for "rpoB" is available in some countries. This serves as a useful marker for MDR-TB, because isolated RMP resistance is rare (except when patients have a history of being treated with rifampicin alone). If the results of a gene probe ("rpoB") are known to be positive, then it is reasonable to omit RMP and to use SHEZ+MXF+cycloserine. The reason for maintaining the patient on INH is that INH is so potent in treating TB that it is foolish to omit it until there is microbiological proof that it is ineffective (even though isoniazid resistance so commonly occurs with rifampicin resistance).

When sensitivities are known and the isolate is confirmed as resistant to both INH and RMP, five drugs should be chosen in the following order (based on known sensitivities):

- an aminoglycoside (e.g., amikacin, kanamycin) or polypeptide antibiotic (e.g., capreomycin)

- pyrazinamide

- ethambutol

- a fluoroquinolone (e.g., moxifloxacin (ciprofloxacin) should no longer be used);

- rifabutin

- cycloserine

- a thioamide: prothionamide or ethionamide

- PAS

- a macrolide: e.g., clarithromycin

- linezolid

- high-dose INH (if low-level resistance)

- interferon-γ

- thioridazine

- Ampicillin

"Note:" Drugs placed nearer the top of the list are more effective and less toxic; drugs placed nearer the bottom of the list are less effective or more toxic, or more difficult to obtain.

In general, resistance to one drug within a class means resistance to all drugs within that class, but a notable exception is rifabutin: Rifampicin-resistance does not always mean rifabutin-resistance, and the laboratory should be asked to test for it. It is possible to use only one drug within each drug class. If it is difficult finding five drugs to treat then the clinician can request that high-level INH-resistance be looked for. If the strain has only low-level INH-resistance (resistance at 0.2 mg/l INH, but sensitive at 1.0 mg/l INH), then high dose INH can be used as part of the regimen. When counting drugs, PZA and interferon count as zero; that is to say, when adding PZA to a four-drug regimen, another drug must be chosen to make five. It is not possible to use more than one injectable (STM, capreomycin or amikacin), because the toxic effect of these drugs is additive: If possible, the aminoglycoside should be given daily for a minimum of three months (and perhaps thrice weekly thereafter). Ciprofloxacin should not be used in the treatment of tuberculosis if other fluoroquinolones are available.

There is no intermittent regimen validated for use in MDR-TB, but clinical experience is that giving injectable drugs for five days a week (because there is no-one available to give the drug at weekends) does not seem to result in inferior results. Directly observed therapy helps to improve outcomes in MDR-TB and should be considered an integral part of the treatment of MDR-TB.

Response to treatment must be obtained by repeated sputum cultures (monthly if possible). Treatment for MDR-TB must be given for a minimum of 18 months and cannot be stopped until the patient has been culture-negative for a minimum of nine months. It is not unusual for patients with MDR-TB to be on treatment for two years or more.

Patients with MDR-TB should be isolated in negative-pressure rooms, if possible. Patients with MDR-TB should not be accommodated on the same ward as immunosuppressed patients (HIV-infected patients, or patients on immunosuppressive drugs). Careful monitoring of compliance with treatment is crucial to the management of MDR-TB (and some physicians insist on hospitalisation if only for this reason). Some physicians will insist that these patients remain isolated until their sputum is smear-negative, or even culture-negative (which may take many months, or even years). Keeping these patients in hospital for weeks (or months) on end may be a practical or physical impossibility, and the final decision depends on the clinical judgement of the physician treating that patient. The attending physician should make full use of therapeutic drug monitoring (in particular, of the aminoglycosides) both to monitor compliance and to avoid toxic effects.

Some supplements may be useful as adjuncts in the treatment of tuberculosis, but, for the purposes of counting drugs for MDR-TB, they count as zero (if four drugs are already in the regimen, it may be beneficial to add arginine or vitamin D or both, but another drug will be needed to make five).

- arginine (peanuts are a good source)

- vitamin D

- Dzherelo

- V5 Immunitor

The drugs listed below have been used in desperation, and it is uncertain as to whether they are effective at all. They are used when it is not possible to find five drugs from the list above.

- imipenem

- co-amoxiclav

- clofazimine

- prochlorperazine

- metronidazole

On December 28, 2012 the U.S. Food and Drug Administration (FDA) approved bedaquiline (marketed as Sirturo by Johnson & Johnson) to treat multi-drug resistant tuberculosis, the first new treatment in 40 years. Sirturo is to be used in a combination therapy for patients who have failed standard treatment and have no other options. Sirturo is an adenosine triphosphate synthase (ATP synthase) inhibitor.

The following drugs are experimental compounds that are not commercially available, but may be obtained from the manufacturer as part of a clinical trial or on a compassionate basis. Their efficacy and safety are unknown:

- pretomanid (manufactured by Novartis, developed in partnership with TB Alliance)

- delamanid

In cases of extremely resistant disease, surgery to remove infection portions of the lung is, in general, the final option. The center with the largest experience in this is the National Jewish Medical and Research Center in Denver, Colorado. In 17 years of experience, they have performed 180 operations; of these, 98 were lobectomies and 82 were pneumonectomies. There is a 3.3% operative mortality, with an additional 6.8% dying following the operation; 12% experienced significant morbidity (in particular, extreme breathlessness). Of 91 patients who were culture-positive before surgery, only 4 were culture-positive after surgery.

The resurgence of tuberculosis in the United States, the advent of HIV-related tuberculosis, and the development of strains of TB resistant to the first-line therapies developed in recent decades—serve to reinforce the thesis that Mycobacterium tuberculosis, the causative organism, makes its own preferential option for the poor. The simple truth is that almost all tuberculosis deaths result from a lack of access to existing effective therapy.

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.

The principles of treatment for MDR-TB and for XDR-TB are the same. Treatment requires extensive chemotherapy for up to two years. Second-line drugs are more toxic than the standard anti-TB regimen and can cause a range of serious side-effects including hepatitis, depression, hallucinations, and deafness. Patients are often hospitalized for long periods, in isolation. In addition, second-line drugs are extremely expensive compared with the cost of drugs for standard TB treatment.

XDR-TB is associated with a much higher mortality rate than MDR-TB, because of a reduced number of effective treatment options. Despite early fears that this strain of TB was untreatable, recent studies have shown that XDR-TB can be treated through the use of aggressive regimens. A study in the Tomsk oblast of Russia, reported that 14 out of 29 (48.3%) patients with XDR-TB successfully completed treatment. Nix-TB regimen, a combination pretomanid, bedaquiline, and linezolid, has shown promise in early clinical trials.

Successful outcomes depend on a number of factors including the extent of the drug resistance, the severity of the disease and whether the patient’s immune system is compromised. It also depends on access to laboratories that can provide early and accurate diagnosis so that effective treatment is provided as soon as possible. Effective treatment requires that all six classes of second-line drugs be available to clinicians who have special expertise in treating such cases.

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.

Antibiotics can cause severe reactions and add significantly to the cost of care. In the United States, antibiotics and anti-infectives are the leading cause of adverse effect from drugs. In a study of 32 States in 2011, antibiotics and anti-infectives accounted for nearly 24 percent of ADEs that were present on admission, and 28 percent of those that occurred during a hospital stay.

Prescribing by an infectious disease specialist compared with prescribing by a non-infectious disease specialist decreases antibiotic consumption and reduces costs.

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.

Common situations in which antibiotics are overused include the following:

- Apparent viral respiratory illness in children should not be treated with antibiotics. If there is a diagnosis of bacterial infection, then antibiotics may be used.

- When children with ear tubes get ear infections, they should have antibiotic eardrops put into their ears to go to the infection rather than having oral antibiotics which are more likely to have unwanted side effects.

- Swimmer's ear should be treated with antibiotic eardrops, not oral antibiotics.

- Sinusitis should not be treated with antibiotics because it is usually caused by a virus, and even when it is caused by a bacteria, antibiotics are not indicated except in atypical circumstances as it usually resolves without treatment.

- Viral conjunctivitis should not be treated with antibiotics. Antibiotics should only be used with confirmation that a patient has bacterial conjunctivitis.

- Older persons often have bacteria in their urine which is detected in routine urine tests, but unless the person has the symptoms of a urinary tract infection, antibiotics should not be used in response.

- Eczema should not be treated with oral antibiotics. Dry skin can be treated with lotions or other symptom treatments.

- The use of topical antibiotics to treat surgical wounds does not reduce infection rates in comparison with non-antibiotic ointment or no ointment at all.

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.

Tetracyclines are a class of antibiotics that inhibit protein synthesis by binding to the 30s ribosomal subunit of bacterial cells, keeping transcription of the bacterial genome from occurring. Tetracyclines are bacteriostatic, which means that the growth of the bacterium will be slowed. Tetracyclines are not often recommended for the treatment of "N. gonorrhoeae" because the treatment regimen requires many doses, which may affect compliance and contribute to resistance. Tetracycline is still used as treatment for this infection in developing countries because the cost for the drug is low

As with the penicillin resistance, the "penB" (porin formation) and "mtr" (efflux pump formation) mutations mediate chromosomal resistance. These adaptations will also affect the ability of the antibiotic to get into, or stay in the bacterial cell. High level resistance of "N. gonorrhoeae" to tetracyclines was first reported in 1986 with the discovering of the "tetM" determinant. The mechanism of resistance is still unknown.

Yersiniosis is usually self-limiting and does not require treatment. For severe infections (sepsis, focal infection) especially if associated with immunosuppression, the recommended regimen includes doxycycline in combination with an aminoglycoside. Other antibiotics active against "Y. enterocolitica" include trimethoprim-sulfamethoxasole, fluoroquinolones, ceftriaxone, and chloramphenicol. "Y. enterocolitica" is usually resistant to penicillin G, ampicillin, and cephalotin due to beta-lactamase production.

Countries aim to prevent XDR-TB by ensuring that the work of their national TB control programmes, and of all practitioners working with people with TB, is carried out according to the International Standards for TB Care. These emphasize providing proper diagnosis and treatment to all TB patients, including those with drug-resistant TB; assuring regular, timely supplies of all anti-TB drugs; proper management of anti-TB drugs and providing support to patients to maximize adherence to prescribed regimens; caring for XDR-TB cases in a centre with proper ventilation, and minimizing contact with other patients, particularly those with HIV, especially in the early stages before treatment has had a chance to reduce the infectiousness. Also an effective disease control infrastructure is necessary for the prevention of XDR tuberculosis. Increased funding for research, and strengthened laboratory facilities are much required. Immediate detection through drug susceptibility testing's are vital, when trying to stop the spread of XDR tuberculosis.

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.

The Gonorrhea bacterium Neisseria gonorrhoeae has developed antibiotic resistance to many antibiotics.

The bacteria was first identified in 1879, although some Biblical scholars believe that references to the disease can be found as early as Parshat Metzora of the Old Testament.

In the 1940s effective treatment with penicillin became available, but by the 1970s resistant strains predominated. Resistance to penicillin has developed through two mechanisms: chromasomally mediated resistance (CMRNG) and penicillinase-mediated resistance (PPNG). CMRNG involves step wise mutation of penA, which codes for the penicillin-binding protein (PBP-2); mtr, which encodes an efflux pump that removes penicillin from the cell; and penB, which encodes the bacterial cell wall porins. PPNG involves the acquisition of a plasmid-borne beta-lactamase. "N. gonorrheoea" has a high affinity for horizontal gene transfer, and as a result, the existence of any strain resistant to a given drug could spread easily across strains.

Fluoroquinolones were a useful next-line treatment until resistance was achieved through efflux pumps and mutations to the gyrA gene, which encodes DNA gyrase. Third-generation cephalosporins have been used to treat gonorrhoea since 2007, but resistant strains have emerged. As of 2010, the recommended treatment is a single 250 mg intramuscular injection of ceftriaxone, sometimes in combination with azithromycin or doxycycline. However, certain strains of "N. gonorrhoeae" can be resistant to antibiotics usually that are normally used to treat it. These include: cefixime (an oral cephalosporin), ceftriaxone (an injectable cephalosporin), azithromycin, aminoglycosides, and tetracycline.

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.

There are several ways that drug resistance to TB, and drug resistance in general, can be prevented:

1. Rapid diagnosis & treatment of TB: One of the greatest risk factors for drug resistant TB is problems in treatment and diagnosis, especially in developing countries. If TB is identified and treated soon, drug resistance can be avoided.

2. Completion of treatment: Previous treatment of TB is an indicator of MDR TB. If the patient does not complete his/her antibiotic treatment, or if the physician does not prescribe the proper antibiotic regimen, resistance can develop. Also, drugs that are of poor quality or less in quantity, especially in developing countries, contribute to MDR TB.

3. Patients with HIV/AIDS should be identified and diagnosed as soon as possible. They lack the immunity to fight the TB infection and are at great risk of developing drug resistance.

4. Identify contacts who could have contracted TB: i.e. family members, people in close contact, etc.

5. Research: Much research and funding is needed in the diagnosis, prevention and treatment of TB and MDR TB.

"Opponents of a universal tuberculosis treatment, reasoning from misguided notions of cost-effectiveness, fail to acknowledge that MDRTB is not a disease of poor people in distant places. The disease is infectious and airborne. Treating only one group of patients looks inexpensive in the short run, but will prove disastrous for all in the long run."- Paul Farmer

Antifungals are used for treatment with the specific type and dose depending on the patient's age, immune status, and specifics of the infection. For most adults, the initial treatment is an echinocandin class antifungal (caspofungin, micafungin, or anidulafungin) given intravenously. Fluconazole, amphotericin B, and other antifungals may also be used. Treatment normally continues for two weeks after resolution of signs and symptoms and "Candida" yeasts can no longer can be cultured from blood samples. Some forms of invasive candidiasis, such as infections in the bones, joints, heart, or central nervous system, usually need to be treated for a longer period. Retrospective observational studies suggest that prompt presumptive antifungal therapy (based on symptoms or biomarkers) is effective and can reduce mortality.

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)

"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.