Bacteremia is most commonly diagnosed by blood culture, in which a sample of blood drawn from the vein by needle puncture is allowed to incubate with a medium that promotes bacterial growth. If bacteria are present in the bloodstream at the time the sample is obtained, the bacteria will multiply and can thereby be detected.

Any bacteria that incidentally find their way to the culture medium will also multiply. For example, if the skin is not adequately cleaned before needle puncture, contamination of the blood sample with normal bacteria that live on the surface of the skin can occur. For this reason, blood cultures must be drawn with great attention to sterile process. The presence of certain bacteria in the blood culture, such as S"taphylococcus aureus", "Streptococcus pneumoniae", and "Escherichia coli" almost never represent a contamination of the sample. On the other hand, contamination may be more highly suspected if organisms like "Staphylococcus epidermidis" or "Propionibacterium acnes" grow in the blood culture.

Two blood cultures drawn from separate sites of the body are often sufficient to diagnose bacteremia. Two out of two cultures growing the same type of bacteria usually represents a real bacteremia, particularly if the organism that grows is not a common contaminant. One out of two positive cultures will usually prompt a repeat set of blood cultures to be drawn to confirm whether a contaminant or a real bacteremia is present. The patient's skin is typically cleaned with an alcohol-based product prior to drawing blood to prevent contamination. Blood cultures may be repeated at intervals to determine if persistent — rather than transient — bacteremia is present.

Prior to drawing blood cultures, a thorough patient history should be taken with particular regard to presence of both fevers and chills, other focal signs of infection such as in the skin or soft tissue, a state of immunosuppression, or any recent invasive procedures.

Ultrasound of the heart is recommended in all those with bacteremia due to "Staphylococcus aureus" to rule out infectious endocarditis.

Patients with symptoms of CAP require evaluation. Diagnosis of pneumonia is made clinically, rather than on the basis of a particular test. Evaluation begins with a physical examination by a health provider, which may reveal fever, an increased respiratory rate (tachypnea), low blood pressure (hypotension), a fast heart rate (tachycardia) and changes in the amount of oxygen in the blood. Palpating the chest as it expands and tapping the chest wall (percussion) to identify dull, non-resonant areas can identify stiffness and fluid, signs of CAP. Listening to the lungs with a stethoscope (auscultation) can also reveal signs associated with CAP. A lack of normal breath sounds or the presence of crackles can indicate fluid consolidation. Increased vibration of the chest when speaking, known as tactile fremitus, and increased volume of whispered speech during auscultation can also indicate fluid.

When signs of pneumonia are discovered during evaluation, chest X-rays, are performed to support a diagnosis of CAP, and examination of the blood and sputum for infectious microorganisms and blood tests may be used to support a diagnosis of CAP. Diagnostic tools depend on the severity of illness, local practices and concern about complications of the infection. All patients with CAP should have their blood oxygen monitored with pulse oximetry. In some cases, arterial blood gas analysis may be required to determine the amount of oxygen in the blood. A complete blood count (CBC) may reveal extra white blood cells, indicating infection.

Chest X-rays and X-ray computed tomography (CT) can reveal areas of opacity (seen as white), indicating consolidation. CAP does not always appear on x-rays, because the disease is in its initial stages or involves a part of the lung an x-ray does not see well. In some cases, chest CT can reveal pneumonia not seen on x-rays. However, congestive heart failure or other types of lung damage can mimic CAP on x-rays.

Several tests can identify the cause of CAP. Blood cultures can isolate bacteria or fungi in the bloodstream. Sputum Gram staining and culture can also reveal the causative microorganism. In severe cases, bronchoscopy can collect fluid for culture. Special tests can be performed if an uncommon microorganism is suspected, such as urinalysis for Legionella antigen in Legionnaires' disease.

In hospitalised patients who develop respiratory symptoms and fever, one should consider the diagnosis. The likelihood increases when upon investigation symptoms are found of respiratory insufficiency, purulent secretions, newly developed infiltrate on the chest X-Ray, and increasing leucocyte count. If pneumonia is suspected material from sputum or tracheal aspirates are sent to the microbiology department for cultures. In case of pleural effusion thoracentesis is performed for examination of pleural fluid. In suspected ventilator-associated pneumonia it has been suggested that bronchoscopy(BAL) is necessary because of the known risks surrounding clinical diagnoses.

In terms of the diagnosis of Klebsiella pneumonia the following can be done to determine if the individual has this infection, including "susceptibility testing" for (ESBL) "Extended Spectrum β-Lactamase", as well as:

- CBC

- Sputum(culture]

- Radiography(chest)

- CT scan

In addition to hand washing, gloves play an important role in reducing the risks of transmission of microorganisms. Gloves are worn for three important reasons in hospitals. First, they are worn to provide a protective barrier for personnel, preventing large scale contamination of the hands when touching blood, body fluids, secretions, excretions, mucous membranes, and non-intact skin. In the United States, the Occupational Safety and Health Administration has mandated wearing gloves to reduce the risk of bloodborne pathogen infections. Second, gloves are worn to reduce the likelihood that microorganisms present on the hands of personnel will be transmitted to patients during invasive or other patient-care procedures that involve touching a patient's mucous membranes and nonintact skin. Third, they are worn to reduce the likelihood that the hands of personnel contaminated with micro-organisms from a patient or a fomite can transmit those micro-organisms to another patient. In this situation, gloves must be changed between patient contacts, and hands should be washed after gloves are removed.

Wearing gloves does not replace the need for handwashing, because gloves may have small, undtectable defects or may be torn during use, and hands can become contaminated during removal of gloves. Failure to change gloves between patient contacts is an infection control hazard.

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.

CAP is treated with an antibiotic that kills the offending microorganism and by managing complications. If the causative microorganism is unidentified (often the case), the laboratory identifies the most-effective antibiotic; this may take several days.

Health professionals consider a person's risk factors for various organisms when choosing an initial antibiotic. Additional consideration is given to the treatment setting; most patients are cured by oral medication, while others must be hospitalized for intravenous therapy or intensive care.

Therapy for older children and adults generally includes treatment for atypical bacteria: typically a macrolide antibiotic (such as azithromycin or clarithromycin) or a quinolone, such as levofloxacin. Doxycycline is the antibiotic of choice in the UK for atypical bacteria, due to increased clostridium difficile colitis in hospital patients linked to the increased use of clarithromycin.

PCR-based screening methodologies are in the process of development. Although they speed up detection immensely, they are costly and the reliability of the tests is questionable due to false positives. Nested arbitrary PCR (ARB-PCR) was used during a 2007 CRE outbreak at the University of Virginia Medical Center to identify the specific "bla" KPC plasmid involved in the transmission of the infection, and researchers suggest that ARB-PCR may also be used to identify other methods of CRE spread.

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 presence of bacteria in the blood almost always requires treatment with antibiotics. This is because there are high mortality rates from progression to sepsis if antibiotics are delayed.

The treatment of bacteremia should begin with empiric antibiotic coverage. Any patient presenting with signs or symptoms of bacteremia or a positive blood culture should be started on intravenous antibiotics. The choice of antibiotic is determined by the most likely source of infection and by the characteristic organisms that typically cause that infection. Other important considerations include the patient's past history of antibiotic use, the severity of the presenting symptoms, and any allergies to antibiotics. Empiric antibiotics should be narrowed, preferably to a single antibiotic, once the blood culture returns with a particular bacteria that has been isolated.

Treatment for "Klebsiella" pneumonia is by antibiotics such as aminoglycosides and cephalosporins, the choice depending upon the person’s health condition, medical history and severity of the disease.

"Klebsiella" possesses beta-lactamase giving it resistance to ampicillin, many strains have acquired an extended-spectrum beta-lactamase with additional resistance to carbenicillin, amoxicillin, and ceftazidime. The bacteria remain susceptible to aminoglycosides and cephalosporins, varying degrees of inhibition of the beta-lactamase with clavulanic acid have been reported. Infections due to multidrug-resistant gram-negative pathogens in the ICU have invoked the re-emergence of colistin. However, colistin-resistant strains of "K. pneumoniae" have been reported in ICUs. In 2009, strains of "K. pneumoniae" with gene called New Delhi metallo-beta-lactamase ( NDM-1) that even gives resistance against intravenous antibiotic carbapenem, were discovered in India and Pakistan."Klebsiella" cases in Taiwan have shown abnormal toxicity, causing liver abscesses in people with diabetes mellitus (DM), treatment consists of third generation cephalosporins.

The disc diffusion method can be used by hospital laboratories to screen for CRE. In this technique, antibiotic discs are placed onto plates of Mueller Hinton agar that have already been inoculated with the sample strain. The plates are then incubated overnight at 37 °C. Following incubation, the zones of inhibition surrounding the various antibiotic discs are measured and compared with Clinical and Laboratory Standard Institute guidelines. Identification of KPCs, MBLs and OXAs can be achieved by demonstrating synergistic inhibition with phenyl boronic acid, EDTA or neither, respectively.

In a Thailand-based study of CRE in hospital settings, carbapenem resistance was defined as any strain that shows resistance to at least one of three carbapenem antibiotics tested.

Clinical prediction rules have been developed to more objectively predict outcomes of pneumonia. These rules are often used in deciding whether or not to hospitalize the person.

- Pneumonia severity index (or "PSI Score")

- CURB-65 score, which takes into account the severity of symptoms, any underlying diseases, and age

In pneumonia, a collection of fluid may form in the space that surrounds the lung. Occasionally, microorganisms will infect this fluid, causing an empyema. To distinguish an empyema from the more common simple parapneumonic effusion, the fluid may be collected with a needle (thoracentesis), and examined. If this shows evidence of empyema, complete drainage of the fluid is necessary, often requiring a drainage catheter. In severe cases of empyema, surgery may be needed. If the infected fluid is not drained, the infection may persist, because antibiotics do not penetrate well into the pleural cavity. If the fluid is sterile, it must be drained only if it is causing symptoms or remains unresolved.

In rare circumstances, bacteria in the lung will form a pocket of infected fluid called a lung abscess. Lung abscesses can usually be seen with a chest X-ray but frequently require a chest CT scan to confirm the diagnosis. Abscesses typically occur in aspiration pneumonia, and often contain several types of bacteria. Long-term antibiotics are usually adequate to treat a lung abscess, but sometimes the abscess must be drained by a surgeon or radiologist.

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.

The diagnosis can be confirmed by the characteristic appearance of the chest x-ray, which shows widespread pulmonary infiltrates, and an arterial oxygen level (PaO) that is strikingly lower than would be expected from symptoms. Gallium 67 scans are also useful in the diagnosis. They are abnormal in approximately 90% of cases and are often positive before the chest x-ray becomes abnormal. The diagnosis can be definitively confirmed by histological identification of the causative organism in sputum or bronchio-alveolar lavage (lung rinse). Staining with toluidine blue, silver stain, periodic-acid schiff stain, or an immunofluorescence assay will show the characteristic cysts. The cysts resemble crushed ping-pong balls and are present in aggregates of 2 to 8 (and not to be confused with "Histoplasma" or "Cryptococcus", which typically do not form aggregates of spores or cells). A lung biopsy would show thickened alveolar septa with fluffy eosinophilic exudate in the alveoli. Both the thickened septa and the fluffy exudate contribute to dysfunctional diffusion capacity which is characteristic of this pneumonia.

"Pneumocystis" infection can also be diagnosed by immunofluorescent or histochemical staining of the specimen, and more recently by molecular analysis of polymerase chain reaction products comparing DNA samples. Notably, simple molecular detection of "Pneumocystis jirovecii" in lung fluids does not mean that a person has "Pneumocystis" pneumonia or infection by HIV. The fungus appears to be present in healthy individuals in the general population.

People who have difficulty breathing due to pneumonia may require extra oxygen. An extremely sick individual may require artificial ventilation and intensive care as life-saving measures while his or her immune system fights off the infectious cause with the help of antibiotics and other drugs.

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 diagnosis of actinomycosis can be a difficult one to make. In addition to microbiological examinations, magnetic resonance imaging and immunoassays may be helpful.

The prime example for MDR against antiparasitic drugs is malaria. "Plasmodium vivax" has become chloroquine and sulfadoxine-pyrimethamine resistant a few decades ago, and as of 2012 artemisinin-resistant Plasmodium falciparum has emerged in western Cambodia and western Thailand.

"Toxoplasma gondii" can also become resistant to artemisinin, as well as atovaquone and sulfadiazine, but is not usually MDR

Antihelminthic resistance is mainly reported in the veterinary literature, for example in connection with the practice of livestock drenching and has been recent focus of FDA regulation.

As the infection is usually transmitted into humans through animal bites, antibiotics usually treat the infection, but medical attention should be sought if the wound is severely swelling. Pasteurellosis is usually treated with high-dose penicillin if severe. Either tetracycline or chloramphenicol provides an alternative in beta-lactam-intolerant patients. However, it is most important to treat the wound.

Diagnosis is made with isolation of "Pasteurella multocida" in a normally sterile site (blood, pus, or cerebrospinal fluid).

Patients with ascites underwent routine paracentesis, the incidence of active SBP ranged from 10% to 27% at the time of hospital admission.

Biochemical tests used in the identification of infectious agents include the detection of metabolic or enzymatic products characteristic of a particular infectious agent. Since bacteria ferment carbohydrates in patterns characteristic of their genus and species, the detection of fermentation products is commonly used in bacterial identification. Acids, alcohols and gases are usually detected in these tests when bacteria are grown in selective liquid or solid media.

The isolation of enzymes from infected tissue can also provide the basis of a biochemical diagnosis of an infectious disease. For example, humans can make neither RNA replicases nor reverse transcriptase, and the presence of these enzymes are characteristic of specific types of viral infections. The ability of the viral protein hemagglutinin to bind red blood cells together into a detectable matrix may also be characterized as a biochemical test for viral infection, although strictly speaking hemagglutinin is not an "enzyme" and has no metabolic function.

Serological methods are highly sensitive, specific and often extremely rapid tests used to identify microorganisms. These tests are based upon the ability of an antibody to bind specifically to an antigen. The antigen, usually a protein or carbohydrate made by an infectious agent, is bound by the antibody. This binding then sets off a chain of events that can be visibly obvious in various ways, dependent upon the test. For example, "Strep throat" is often diagnosed within minutes, and is based on the appearance of antigens made by the causative agent, "S. pyogenes", that is retrieved from a patients throat with a cotton swab. Serological tests, if available, are usually the preferred route of identification, however the tests are costly to develop and the reagents used in the test often require refrigeration. Some serological methods are extremely costly, although when commonly used, such as with the "strep test", they can be inexpensive.

Complex serological techniques have been developed into what are known as Immunoassays. Immunoassays can use the basic antibody – antigen binding as the basis to produce an electro-magnetic or particle radiation signal, which can be detected by some form of instrumentation. Signal of unknowns can be compared to that of standards allowing quantitation of the target antigen. To aid in the diagnosis of infectious diseases, immunoassays can detect or measure antigens from either infectious agents or proteins generated by an infected organism in response to a foreign agent. For example, immunoassay A may detect the presence of a surface protein from a virus particle. Immunoassay B on the other hand may detect or measure antibodies produced by an organism's immune system that are made to neutralize and allow the destruction of the virus.

Instrumentation can be used to read extremely small signals created by secondary reactions linked to the antibody – antigen binding. Instrumentation can control sampling, reagent use, reaction times, signal detection, calculation of results, and data management to yield a cost effective automated process for diagnosis of infectious disease.

Diagnosis is made by paracentesis (needle aspiration of the ascitic fluid). SBP is diagnosed if the fluid contains neutrophils (a type of white blood cell) at greater than 250 cells per mm (equals a cell count of 250 x10/L) fluid in the absence of another reason for this (such as inflammation of one of the internal organs or a perforation). The fluid is also cultured to identify bacteria. If the sample is sent in a plain sterile container 40% of samples will identify an organism, while if the sample is sent in a bottle with culture medium the sensitivity increases to 72–90%.