question: If bacteriophages cause bacteria to lose antibiotic resistance in order to counter bacteriophage why have we relied on antibiotics for so long in the medical world instead of alternating?
comment: How does a doctor know what brands of bacteriophage to order? Is it even available? And how long do they keep before needing an update? It's pretty high science making bacteriophages on demand. Sure they're better in nearly every way except convenience. My doc can look at me for 5 minutes, determine its and infection of some sort and give me a scrip for antibiotics to be picked up down the block that will almost definitely cover it. Spend 15 minutes, bill 1hr. I lose half a day of work. If they were to use bacteriophages, they'd have to actually get a bit of infectious material, identify it, then wait for the targeted drug to arrive. Then the doc would have to administer it, watch my reaction to it, to make sure they ID'd the right bacteria AND drug. That's most of his day and mine for a simple infection. Spend 8+Hrs, bill 8++hrs, I lose the whole day and probably tomorrow IF the infection and treatment doesn't get complicated.
passages: Bacteriophages are very specific, targeting only one or a few strains of bacteria. Traditional antibiotics have more wide-ranging effect, killing both harmful bacteria and useful bacteria such as those facilitating food digestion. The species and strain specificity of bacteriophages makes it unlikely that harmless or useful bacteria will be killed when fighting an infection.
   Some disadvantages to the use of bacteriophages also exist, however. Bacteriophages may harbour virulence factors or toxic genes in their genomes and, prior to use, it may be prudent to identify genes with similarity to known virulence factors or toxins by genomic sequencing. In addition, the oral and IV administration of phages for the eradication of bacterial infections poses a much higher safety risk than topical application. Also, there is the additional concern of uncertain immune responses to these large antigenic cocktails. 
   Section::::Life cycle.
  
  Section::::Life cycle.:Adsorption and penetration.
   Section::::Lytic cycle.
   The use of phages has continued since the end of the Cold War in Georgia and elsewhere in Central and Eastern Europe. The first regulated, randomized, double-blind clinical trial was reported in the Journal of Wound Care in June 2009, which evaluated the safety and efficacy of a bacteriophage cocktail to treat infected venous ulcers of the leg in human patients. The FDA approved the study as a Phase I clinical trial. The study's results demonstrated the safety of therapeutic application of bacteriophages, but did not show efficacy. The authors explained that the use of certain chemicals that are part of standard wound care (e.g. lactoferrin or silver) may have interfered with bacteriophage viability. Shortly after that, another controlled clinical trial in Western Europe (treatment of ear infections caused by "Pseudomonas aeruginosa") was reported in the journal, Clinical Otolaryngology in August 2009. The study concludes that bacteriophage preparations were safe and effective for treatment of chronic ear infections in humans. Additionally, there have been numerous animal and other experimental clinical trials evaluating the efficacy of bacteriophages for various diseases, such as infected burns and wounds, and cystic fibrosis associated lung infections, among others. 
   Sometimes prophages may provide benefits to the host bacterium while they are dormant by adding new functions to the bacterial genome, in a phenomenon called lysogenic conversion. Examples are the conversion of harmless strains of "Corynebacterium diphtheriae" or "Vibrio cholerae" by bacteriophages, to highly virulent ones that cause diphtheria or cholera, respectively. Strategies to combat certain bacterial infections by targeting these toxin-encoding prophages have been proposed.
  
  Section::::Replication.:Attachment and penetration.
   In general, "B. fragilis" is susceptible to metronidazole, carbapenems, tigecycline, beta-lactam/beta-lactamase inhibitor combinations (e.g., Unasyn, Zosyn), and certain antimicrobials of the cephalosporin class, including cefoxitin. The bacteria have inherent high-level resistance to penicillin. Production of beta lactamase appears to be the main mechanism of antibiotic resistance in "B. fragilis". Clindamycin is no longer recommended as the first-line agent for "B. fragilis" due to emerging high-level resistance (30% in some reports).
  
  Section::::Environmental research.
  
  "B. fragilis" bacteriophages are commonly used as tracers of human faecal material.
  
  Section::::See also.
  
  BULLET::::- List of oncogenic bacteria
  
  BULLET::::- Infectious causes of cancer
  
  BULLET::::- Pathogenic bacteria
   Section::::T even phage genome.
   While it is more difficult to apply bacteriophages in a field setting, it is not impossible, and laboratory and greenhouse trials are showing bacteriophages to potentially be a very effective control mechanism. However, there are a few obstacles to surmount before field trials can begin. A large problem is that they are damaged by UV light, so applying the phage mixture during the evening will help promote its viability. Also, providing the phages with susceptible non-pathogenic bacteria to replicate with can ensure there is adequate persistence until the bacteriophages can spread to the targeted bacteria. The bacteriophages are unable to kill all the bacteria, because they need a dense population of bacteria in order to effectively infect and spread, so while the phages were able to decrease the number of diseased plants by up to 35%, around 2,000 Colony Forming Units per milliliter (an estimate of living bacteria cells) were able to survive the treatment. Lastly, the use of these bacteriophages places strong selection on the host bacteria, which causes a high probability of developing resistance to the attacking bacteriophage. Thus it is recommended that multiple strains of the bacteriophage be used in each application so the bacteria do not have a chance to develop resistance to any one strain.
   There are considerable regulatory hurdles that must be cleared for such therapies. Despite numerous challenges, the use of bacteriophages as a replacement for antimicrobial agents against MDR pathogens that no longer respond to conventional antibiotics, remains an attractive option.
  
  Section::::Research.:Phytochemicals.
   Host range analysis shows that not all mycobacteriophages from "M. smegmatis" infect other strains and only phages in Cluster K and in certain subclusters of Cluster A efficiently infect "M. tuberculosis" (Figure 1). However, mutants can be readily isolated from some phages that expand their host range to infect these other strains. However, the molecular basis of host range specificity is largely unknown.
  
  Section::::Genome architecture.
   Virulent bacteriophages multiply in their bacterial host immediately after entry. After the number of progeny phages reach a certain amount, they cause the host to lyse or break down, therefore they would be released and infect new host cells. The process of host lyses and release is called the lytic cycle. Lytic cycle is a cycle of viral reproduction that involves the destruction of the infected cell and its membrane. This cycle involves a virus that overtakes the host cell and its machinery to reproduce. Therefore, the virus must go through 5 stages in order to reproduce and infect the host cell. Such stages are Attachment, Penetration, Biosynthesis, Maturation, and then Release.
   Phage therapy is another method for treating antibiotic-resistant strains of bacteria. Phage therapy infects pathogenic bacteria with their own viruses. Bacteriophages and their host ranges are extremely specific for certain bacteria, thus, unlike antibiotics, they do not disturb the host organism and intestinal microflora. Bacteriophages, also known simply as phages, infect and can kill bacteria and affect bacterial growth primarily during lytic cycles. Phages insert their DNA into the bacterium, where it is transcribed and used to make new phages, after which the cell will lyse, releasing new phage that are able to infect and destroy further bacteria of the same strain. The high specificity of phage protects "good" bacteria from destruction. 
   Bacteriophages are much more specific than antibiotics. They are typically harmless not only to the host organism, but also to other beneficial bacteria, such as the gut flora, reducing the chances of opportunistic infections. They have a high therapeutic index, that is, phage therapy would be expected to give rise to few side effects. Because phages replicate "in vivo" (in cells of living organism), a smaller effective dose can be used.
   As of 2014 some bacteriocins had been studied in "in vitro" studies to see if they can stop viruss from replicating, namely staphylococcin 188 against Newcastle disease virus, influenza virus, and coliphage HSA virus; each of enterocin AAR-71 class IIa, enterocin AAR-74 class IIa, and erwiniocin NA4 against coliphage HSA virus; each of enterocin ST5Ha, enterocin NKR-5-3C, and subtilosine against HSV-1; each of enterocin ST4V and enterocin CRL35 class IIa against HSV-1 and HSV-2; labyrinthopeptin A1 against HIV-1 and HSV-1; and bacteriocin from "Lactobacillus delbrueckii" against influenza virus.
   In November, 2004, the CDC reported an increasing number of "A. baumannii" bloodstream infections in patients at military medical facilities in which service members injured in the Iraq/Kuwait region during Operation Iraqi Freedom and in Afghanistan during Operation Enduring Freedom were treated. Most of these were multidrug-resistant. Among one set of isolates from Walter Reed Army Medical Center, 13 (35%) were susceptible to imipenem only, and two (4%) were resistant to all drugs tested. One antimicrobial agent, colistin (polymyxin E), has been used to treat infections with multidrug-resistant "A. baumannii"; however, antimicrobial susceptibility testing for colistin was not performed on isolates described in this report. Because "A. baumannii" can survive on dry surfaces up to 20 days, they pose a high risk of spread and contamination in hospitals, potentially putting immunocompromised and other patients at risk for drug-resistant infections that are often fatal and, in general, expensive to treat.
   The distinction between bactericidal and bacteriostatic agents appears to be clear according to the basic/clinical definition, but this only applies under strict laboratory conditions and it is important to distinguish microbiological and clinical definitions. The distinction is more arbitrary when agents are categorized in clinical situations. The supposed superiority of bactericidal agents over bacteriostatic agents is of little relevance when treating the vast majority of infections with gram-positive bacteria, particularly in patients with uncomplicated infections and noncompromised immune systems. Bacteriostatic agents have been effectively used for treatment that are considered to require bactericidal activity. Furthermore, some broad classes of antibacterial agents considered bacteriostatic can exhibit bactericidal activity against some bacteria on the basis of in vitro determination of MBC/MIC values. At high concentrations, bacteriostatic agents are often bactericidal against some susceptible organisms. The ultimate guide to treatment of any infection must be clinical outcome.
   Mycobacteriophage genomes have been found to contain a subset of genes undergoing more rapid genetic flux than other elements of the genomes. These "rapid flux" genes are exchanged between mycobacteriophage more often and are 50 percent shorter in sequence than the average mycobacteriophage gene.
  
  Section::::Applications.
   Bacteriophage treatment offers a possible alternative to conventional antibiotic treatments for bacterial infection. It is conceivable that, although bacteria can develop resistance to phage, the resistance might be easier to overcome than resistance to antibiotics. Just as bacteria can evolve resistance, viruses can evolve to overcome resistance.
   Dairy industry - Bacteriophages present in the environment can cause fermentation failures of cheese starter cultures. In order to avoid this, mixed-strain starter cultures and culture rotation regimes can be used.
   Bacteriophages are thought to contribute extensively to horizontal gene transfer in natural environments, principally via transduction, but also via transformation. Metagenomics-based studies also have revealed that viromes from a variety of environments harbor antibiotic-resistance genes, including those that could confer multidrug resistance.
  
  Section::::Model bacteriophages.
  
  The following bacteriophages are extensively studied:
  
  BULLET::::- 186 phage
  
  BULLET::::- λ phage
  
  BULLET::::- Φ6 phage
  
  BULLET::::- Φ29 phage
  
  BULLET::::- ΦX174
  
  BULLET::::- G4 phage
  
  BULLET::::- M13 phage
  
  BULLET::::- MS2 phage (23–28 nm in size)
  
  BULLET::::- N4 phage
  
  BULLET::::- P1 phage
  
  BULLET::::- P2 phage
  
  BULLET::::- P4 phage
  
  BULLET::::- R17 phage
  
  BULLET::::- T2 phage
   Also, bacteriophages have been used in hydrological tracing and modelling in river systems, especially where surface water and groundwater interactions occur. The use of phages is preferred to the more conventional dye marker because they are significantly less absorbed when passing through ground waters and they are readily detected at very low concentrations. Non-polluted water may contain approximately 2×10 bacteriophages per mL.
   The emergence of strains of bacteria that are resistant to a broad range of antibiotics has become a problem in the treatment of bacterial infections. Only two new classes of antibiotics have been developed in the past 30 years, and novel ways of combating bacterial infections are being sought. Bacteriophages were first used to control bacteria in the 1920s, and a large clinical trial was conducted by Soviet scientists in 1963. This work was unknown outside the Soviet Union until the results of the trial were published in the West in 1989. The recent and escalating problems caused by antibiotic-resistant bacteria has stimulated a renewed interest in the use of bacteriophages and phage therapy.
   Therapeutic efficacy of a phage cocktail was evaluated in a mice model with nasal infection of multidrug-resistant (MDR) "A. baumannii". Mice treated with the phage cocktail showed a 2.3-fold higher survival rate than those untreated in seven days post infection. In 2017 a patient with a pancreas compromised by MDR "A. baumannii" was put on several antibiotics, despite this the patient’s health continued to deteriorate during a four-month period. Without effective antibiotics the patient was subjected to phage therapy using a phage cocktail containing nine different phages that had been demonstrated to be effective against MDR "A. baumannii". Once on this therapy the patient’s downward clinical trajectory reversed, and returned to health.
   Phages were discovered to be antibacterial agents and were used in the former Soviet Republic of Georgia (pioneered there by Giorgi Eliava with help from the co-discoverer of bacteriophages, Félix d'Herelle) during the 1920s and 1930s for treating bacterial infections. They had widespread use, including treatment of soldiers in the Red Army. However, they were abandoned for general use in the West for several reasons:
  
  BULLET::::- Antibiotics were discovered and marketed widely. They were easier to make, store, and to prescribe.
  
presuppositions: Bacteriophages are as easy to produce as antibiotics. It makes sense to alternate bacteriophage therapy with antibiotic therapy.
corrections: Bacteriophages are too inconvenient to produce on a mass scale. It is very complicated and time-consuming to make bacteriophages on demand.
raw_presuppositions: Bacteriophages are as easy to produce as antibiotics. It makes sense to alternate bacteriophage therapy with antibiotic therapy.
raw_corrections: Bacteriophages are too inconvenient to produce on a mass scale. It is very complicated and time-consuming to make bacteriophages on demand.