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Antibiotic resistance

Some pathogens may have innate resistance to specific antibiotics.

Antimicrobial resistance is due to the ability of microbes to replicate rapidly and mutate.

Antibiotic resistance leads to an estimated 2.8 million infections and 35,000 deaths per year in the United States.

Antimicrobial resistance is escalating worldwide, particularly among common gram-negative pathogens that cause urinary tract infection and acute pyelonephritis.

Prescribing antibiotics inappropriately is an important modifiable risk factor for antibiotic resistance.

 

Antibiotic use in ambulatory settings represents the highest volume, 85%-95%, 3 and the majority of dollars spent on antibiotics.

 

Pediatricians have the lowest use of antibiotics, of all specialties.

 

Non-physician practitioners have the highest use of antibiotics.

Antibiotic resistance threatens the reversal of health gains.

Infections refractory to treatment resulting in more than 35,000 deaths in the US in 2019 have been reported.

It is estimated 700,000 global deaths are a result of drug resistant diseases.

Antibiotic-resistant bacteria cause at least 2 million infections and 23,000 deaths per year at an estimated cost of $55 billion.

About 35% of sexually transmitted diseases, infections of the urinary tract and respiratory system are resistant to currently used antibiotics.

80% of reported antibiotic resistance are for urinary tract infections, while 20% are bloodstream infections.
Healthcare-associated multi drug resistant organisms in the US is estimated at 622,390 cases among hospital patients annually.

Antimicrobial resistance has been linked to antibiotic use, and to mutations that occur even without the exposure to antibiotics.

Antibiotics use, and misuse, exacerbates resistance.

Antibiotic use is a predominant cause of resistance and interventions that limit over diagnosis and over treatment are required to minimize  antibiotic  resistance.

Patients infected with antibiotic resistant pathogens are more likely to have coexisting conditions, to be critically ill, and to be immune suppressed than those with infections caused by susceptible pathogens.

Each extended spectrum beta-lactamase producing E. coli or Klebsiella species infection and $16,500 and 9.7 days per hospital admission.

Nearly three-quarters of adults presenting for care in the United States with acute bronchitis, which is generally of viral origin, receive an unnecessary antibiotic.

Veterinary use represents about three-quarters of the antibiotic market in the United States, the majority of which is used for the promotion of animal growth.

Felt to be due to widespread use of antibiotics in agriculture and healthcare.

The number of resistance pathogen strains being created is at an unprecedented rate.

In the United States an estimated 23 000 deaths each year are associated with drug-resistant bacterial infections.

Estimated that it causes 700,000 deaths worldwide annually.

Overuse of antibiotics increases resistance, strains resources, places patients at risk for adverse effects.

The drug-resistant infections cost the US health care system an estimated $20 billion annually.

Drug-resistant infections cost the US an additional estimated $35 billion in lost productivity.

Compared with a patient with methicillin susceptible staphylococcal infection, a patient with MRSA has a higher all- cause mortality rate, bacteria associated mortality, longer hospital stay, and a 2 fold higher risk of being discharged to a skilled nursing facility.

Infections caused by carbapenum-resistant bacteria have 3-4 times higher mortality in patients with infections caused by carbapenum-susceptible bacterial strains.

Using narrow spectrum therapy, shorter durations of therapy, oral rather than parenteral therapy, as well as the development of new medicines and diagnostics to improve infection prevention are strategies for combating antimicrobial resistance.

The number of new antibiotics being developed and available is at an all time low.

Increasing incidence of antibiotic resistant gram-negative infections due to in discriminate antimicrobial use in humans and  animals coupled with increased global connectivity.

Exposure of susceptible bacteria populations to an antibiotic,  exerts selection pressure for genetic mutation, and subsequent resistant mutants soon outcompete the susceptible population.

Exposure to susceptible bacteria population also involves the sharing and spread of highly mobile genetic determinants  among bacteria of different species and genera.
Naked or damage DNA on hospital services can contribute to resistance in hospital acquired infection

Methicillin-resistant Staphylococcus aureus is found in approximately 50% of isolates in acute care hospitals in the United States.

Methicillin-resistant staphylococcal aureus (MRSA) and vancomycin resistant enterococcus (VRE) are associated with worse outcomes than those caused by antibiotics susceptible staff aureus and enterococcus.

Estimated cost of antibiotic resistance in the US is more than $4 billion per year.

An estimated 50% of antibiotic orders in the hospital are unnecessary (Dellit TH et al).

Many antibiotics accumulate in the gastrointestinal tract at levels sufficient to disrupt the gut microbiome, providing evolution, and propagation of antimicrobial resistance, and priming the microbiotome for opportunistic infectious, such as C. difficile.

Estimated 2 million individuals in the United States develop bacterial infections that are resistant to antibiotics, resulting in 23,000 deaths each year.

Only about 10% of adults with a sore throat have group A streptococcus infections and require antibiotics.

About 60% of adults receive a prescription for antibiotics for a sore throat.

Almost 3/4 of adults presenting with acute bronchitis receive an unnecessary antibiotic.

About three quarters of antibiotics used in United States are used by veterinarians.

May result from genetic mutations.

Bacteria may express enzymes which can inactivate or destroy antibiotics.

Occurs first among the most severely ill hospitalized patients, then spreads to less severely ill hospitalized individuals, and ultimately extends to the community.

Initially this occurs locally, then spreads regionally and eventually becomes a global process.

Hospital acquired antibiotic resistant infections resistance resistant estimated to cause 100,000 deaths per year in the US.

The pattern of spread of antimicrobial resistance noted above has been demonstrated by penicillin resistant Staphylococci, methicillin resistant Staphylococci and by extended spectrum Beta-lactamase (ESBL) producing Enterobacteriaceae.

ESKAPE pathogens refers to the 6 most important resistant pathogens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter species, Pseudomonas aeruginosa and Enterobacter species.

Bacteria may produce beta-lactamase enzyme which are generally resistant to penicillins, cephalosporins and related compounds.

Beta-lactamase is the most common mechanism of resistance of bacterial pathogens to β-lactam antibiotics.

New Delhi metallo- beta lactamase (NDM-1) enzyme confers a multi-drug-resistance by a certain gram-negative organisms.

In addition to β-lactam resistance gram-negative infections are often resistant to multiple drug classes commonly used to treat community onset infections.

Gram-negative resistant pathogens are typically associated with healthcare associated infections and/or disseminating into communities.

Non-enterobacteriaceae gram-negative bacilli such as Proteus aeruginosa and Acinetobacter baumannii are nosocomial pathogens found in the environment and on medical equipment that frequently possess multiple resistance mechanisms beyond β-lactamases.

Bacterial evolution may alter target of antibiotic.

Streptococci and staphylococci may alter DNA or ribosomal target sites of antibiotics.

Bacteria may alter porins (proteins which form a channel in bacterial cell membranes that facilitate water and small molecules in and out of the cell) to limit access of antibiotics to their target.

Bacteria such as enterobacteriaceae may expel antibiotics via efflux pumps.

Bacteria acquire resistance include genetic transformation, conjugation and transduction.

More than 70% of bacteria that cause hospital acquired infections are resistant to one or more commonly prescribed antibiotics.

Hospitals and particularly the ICU’s are important sites for such problems because of the frequent use of broad spectrum antibiotics, the crowding of acutely ill patients, reduced nursing staff coverage increasing the likelihood of person to person transmission of bacteria, and the presence of more acutely and chronically ill patients requiring prolonged hospitalizations and often harboring antibiotic resistant microorganisms.

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