Antibiotic Awareness: a round-up of Cochrane evidence

Page last updated 05 October 2023.

In 2017, Professor Dame Sally Davies, England’s Chief Medical Officer at the time, warned that the world could face a “post-antibiotic apocalypse.” She urged that, unless action is taken to halt the practices that have allowed antibiotic resistance to spread and ways are found to develop new types of antibiotics, we could return to the days when simple wounds, infections or routine operations, are life-threatening.

We created this page in 2017 to mark World Antibiotic Awareness Week and we keep it up-to-date. In 2023, the threat of antibiotic resistance – and the need for responsible antibiotic use – are as great as ever.

Below, you can find summaries of Cochrane Reviews which have investigated the benefits and harms of antibiotics for a wide range of health problems. This evidence supports decision-making in the appropriate use of antibiotics. You can scroll through this page or click on any of the links below to jump to the relevant section.


1

Dental care

What are the benefits are harms of antibiotics for irreversible pulpitis (severe tissue damage within a tooth, which causes severe tooth ache)?

In people with irreversible pulpitis (when the tissue inside the tooth is damaged beyond repair, causing severe toothache), it is uncertain whether antibiotics reduce pain or the need for painkillers compared with placebo (low-certainty evidence). EVIDENCE GAP. There is not enough information about possible adverse effects of antibiotics. Cochrane Review (published May 2019); one study with 40 adults with irreversible pulpitis, comparing painkillers plus antibiotics with painkillers plus placebo.


2

Labour and birth

What are the benefits and harms of prophylactic antibiotics for women undergoing operative vaginal delivery? 

Compared with placebo or no treatment, prophylactic antibiotics reduce serious infectious complications and deep and superficial perineal wound infection (high‐certainty evidence), and probably reduce wound breakdown (moderate‐certainty evidence). Effects on organ or space perineal wound infection, maternal length of stay or endometritis are uncertain (low-certainty evidence). The studies did not report on maternal fever or urinary tract infection. It is uncertain whether prophylactic antibiotics have any impact on maternal adverse reactions (low-certainty evidence). The studies did not report on neonatal adverse reactions. Cochrane Review (published March 2020); two studies with 3813 women undergoing either vacuum or forceps deliveries. One study (3420 women) compared intravenous amoxicillin and clavulanic acid with placebo. The other study (393 women) compared intravenous cefotetan after cord clamping with no treatment.


What are the benefits and harms of routine antibiotic prophylaxis after normal (uncomplicated) vaginal birth?

Routinely giving antibiotics to women after uncomplicated vaginal birth, compared with placebo or no antibiotics, may reduce mothers’ risk of endometritis but may make little or no difference to mothers’ length of hospital stay or risk of wound infection. However these effects are very uncertain (all very low-certainty evidence). Routine antibiotics may make little or no difference to mothers’ risk of urinary tract infection (low-certainty evidence). None of the studies reported information about severe maternal infections. Routine antibiotics may have little or no impact on mothers’ risk of skin rash, but this effect is very uncertain (very low-certainty evidence). None of the studies reported information about antimicrobial resistance. Cochrane Review (published November 2017); three studies with 1779 women. The studies compared routine use of antibiotics with placebo or no treatment after normal (uncomplicated) vaginal birth.


What are the benefits and harms of routine antibiotics for women undergoing episiotomy repair after a normal (uncomplicated) vaginal birth?

The effects of routine antibiotic prophylaxis for episiotomy repair after normal birth are uncertain (very low-certainty evidence or no information reported). EVIDENCE GAP. There is not enough information about the possible harms of routine antibiotic prophylaxis. Cochrane Review (published November 2017); one study with 73 women in a hospital in Brazil, comparing oral chloramphenicol with no treatment.


4

Meningococcal disease

What are the benefits and harms of giving antibiotics prior to admission to hospital for suspected meningococcal disease?

There is probably little or no difference between single IM injections of ceftriaxone and long-acting chloramphenicol in reducing deaths or failure to respond to treatment (both moderate-certainty evidence) and there may be little or no difference in the incidence of neurological disabilities (low-certainty evidence). No adverse events were reported with either intervention. Cochrane Review (published June 2017); 1 study with 510 people during an epidemic in Niger, comparing single dose intramuscular (IM) ceftriaxone with IM long-acting chloramphenicol. No studies were found comparing pre-admission antibiotics with no antibiotics or placebo.


3

Prescribing practices and choosing appropriate antibiotic treatment

NICE antimicrobial prescribing guidelines

There are 21 NICE antimicrobial prescribing guidelines for common conditions, most of which cite Cochrane Reviews. Some also have accompanying Cochrane Clinical Answers. Each NICE guideline also has a visual summary of the recommendations, including tables to support prescribing decisions. You can find these in this references pdf.

Does delaying antibiotic prescription compared to immediate prescription or no antibiotics decrease the number of antibiotics taken for people with respiratory tract infections including sore throat, middle ear infection, cough (bronchitis) and the common cold?

One strategy to reduce unnecessary antibiotic use is to provide an antibiotic prescription, but with advice to delay filling the prescription. The person prescribing the antibiotics assesses that antibiotics are not immediately required, expecting that symptoms will resolve without antibiotics. Alternatively, they may not prescribe antibiotics at all. The authors of the Cochrane Review Immediate versus delayed versus no antibiotics for respiratory infections (published October 2023) explored how these different approaches compare. They included 12 studies with data from 3750 people (children and adults).

They found that:

  • Antibiotic use was greatest in the immediate antibiotic group (93%), followed by delayed antibiotics (29%) and no antibiotics (13%).
  • Patient satisfaction was probably similar for people who had delayed antibiotics (88% satisfied) compared to immediate antibiotics (90% satisfied), but was greater than no antibiotics (86% versus 81% satisfied).
  • For many symptoms including fever, pain, feeling unwell, cough and runny nose, there are probably no differences between immediatedelayed and no antibiotics. The only differences were small and favoured immediate antibiotics for relieving pain, fever and runny nose for sore throat; and pain and feeling unwell for middle ear infections.
  • Compared to no antibiotics, delayed antibiotics probably lead to a small reduction in how long pain, fever and cough persist in people with colds.
  • There may be little difference in antibiotic adverse effects, or complications.
  • None of the studies evaluated antibiotic resistance.

Overall the findings suggest that delayed antibiotics for respiratory infections is a strategy that reduces antibiotic use compared to immediate antibiotics, maintains similar patient satisfaction, and may not result in greater numbers of complications.

Can tests for inflammation help doctors decide whether to use antibiotics for airway infections?

The authors of the updated Cochrane Review Biomarkers as point‐of‐care tests to guide prescription of antibiotics in people with acute respiratory infections in primary care (published October 2022) conclude that “The use of C‐reactive protein point‐of‐care tests as an adjunct to standard care likely reduces the number of participants given an antibiotic prescription in primary care patients who present with symptoms of acute respiratory infection. The use of C‐reactive protein point‐of‐care tests likely does not affect recovery rates.” Also that “The use of C‐reactive protein point‐of‐care tests may not increase mortality within 28 days follow‐up, but there were very few events. Studies that recorded deaths and hospital admissions were performed in children from low‐ and middle‐income countries and older adults with comorbidities.”

Improving how physicians working in hospital settings prescribe antibiotics

Interventions aimed at physicians to improve antibiotic prescribing practices for hospital inpatients lead to more patients receiving appropriate treatment and shorten the duration of antibiotic treatment compared with usual care (high-certainty evidence). Interventions to improve antibiotic prescribing probably also reduce the length of hospital stay, without increasing patient deaths (moderate-certainty evidence). Restrictive interventions (which apply rules to make physicians prescribe properly) may lead to delays in treatment and negative professional culture because of breakdown in communication and trust between infection specialists and clinical teams (low-certainty evidence). Cochrane Review (published February 2017); 221 studies, including high-certainty evidence from 29 studies with 23,394 hospital inpatients (adults or children undergoing antibiotic prophylaxis or treatment). Most studies compared the effect of enabling interventions (which provide advice or feedback to help physicians prescribe properly) or restrictive interventions with usual care on antibiotic prescribing decisions.

Can rapid point‐of‐care tests help reduce antibiotic use in people with acute sore throat in primary care?

Rapid testing probably reduces antibiotic prescription rates by 25% (absolute risk difference) (moderate-certainty evidence) but may have little or no effect on rates of antibiotic dispensing (low-certainty evidence). The impact on the number of people who develop complications from the initial infection, or who need to have another consultation, is uncertain (very low- and low-certainty evidence). There was no information about adverse events attributed to the rapid tests. Cochrane Review (published June 2020); 5 studies with 2545 adults and children in primary care settings, comparing the use of rapid tests (alone or with a clinical scoring system) with clinical grounds (with or without a scoring system) to guide antibiotic prescriptions for sore throat.

Deciding when to start and stop antibiotics in adults with acute respiratory infections: can testing blood procalcitonin levels help?

Using procalcitonin tests to decide when to start and stop antibiotic treatment in adults with acute respiratory infection reduces antibiotic consumption and makes little or no difference to mortality rates compared with usual care (high-certainty evidence). Procalcitonin-guided treatment probably has little or no impact on rates of treatment failure (moderate-certainty evidence). Using procalcitonin to guide antibiotic treatment probably reduces antibiotic-related side effects (moderate-certainty evidence). Cochrane Review (published October 2017); 26 studies with 6708 adults with acute respiratory infections such as pneumonia, bronchitis, exacerbation of chronic obstructive pulmonary disease, and others. Studies took place in different settings (primary care, emergency departments, intensive care units) and compared antibiotic treatment based on a procalcitonin test with usual care.

5

Respiratory infections, illnesses and conditions

Are antibiotics an effective treatment for COVID-19 and do they cause unwanted effects?

Recently, antibiotics have been studied as a potential treatment for COVID-19. This is because some laboratory studies have suggested that some antibiotics slow the reproduction of certain viruses, including SARS-CoV-2, the virus that causes COVID-19. There has been particular interest in one antibiotic, azithromycin, as some laboratory studies have indicated it may reduce inflammation and viral activity. However, we need good evidence before using antibiotics for COVID-19. This is because overuse and/or misuse of antibiotics can lead to ‘antimicrobial resistance’ where, ultimately, antibiotics stop working.

The authors of the review Antibiotics for the treatment of COVID‐19 (published October 2021) found 11 studies with 11,281 people. The studies only investigated one antibiotic, azithromycin, so we do not know the effects of other antibiotics for treating COVID-19.

Only nine of the studies reported data that could be analysed. These studies (with 10,807 people) compared azithromycin to no treatment, placebo or usual care alone.

Main results

For inpatients with moderate-to-severe COVID-19:

  • Azithromycin does not lead to more or fewer deaths in the 28 days after treatment
  • Azithromycin probably does not:
    • worsen or improve patients’ condition
    • increase or decrease serious unwanted events, or heart rhythm problems
  • Azithromycin may increase non-serious unwanted effects slightly

No studies looked at quality of life.

Read more: For adults hospitalized with moderate to severe COVID‐19, what are the effects of azithromycin?

People with mild COVID-19:

For people with mild COVID-19 (or with no symptoms), treated as outpatients, azithromycin may have little to no benefit. The evidence about possible serious unwanted effects is uncertain. No studies reported on non-serious unwanted events, heart rhythm problems, or quality of life.

Read more: For adults with asymptomatic or mild COVID‐19, what are the effects of azithromycin?

The review authors found 19 ongoing studies that are investigating antibiotics for COVID-19 and will update this review soon.

However, given the current evidence and the threat of antimicrobial resistance, the authors say that “antibiotics should not be used for treatment of COVID-19 outside well-designed randomized controlled trials”.


In children aged 2-59 months with severe pneumonia, what are the benefits and harms of a short course of intravenous antibiotics compared with a long course? 

For children aged 2-59 months with severe pneumonia, it is unclear whether there are any differences in treatment outcomes between short- (two to three days) and long-course (five days) intravenous antibiotics (alone or combined with oral antibiotics). EVIDENCE GAP. It is uncertain how short- and long-course intravenous antibiotics compare in terms of safety and adverse effects. Cochrane Review (published October 2017); no eligible studies found.


Which antibiotic regimen is safer and more effective in treating neonates (newborns) and children with hospital‐acquired pneumonia?

The evidence is very uncertain about the potential benefits and harms of different antibiotic regimens for treating newborns and children with hospital-acquired pneumonia. EVIDENCE GAP. Cochrane Review (published November 2021): four studies with 84 children (aged 0-18 years) with hospital‐acquired pneumonia. The studies compared different antibiotic regimens: cefepime versus ceftazidime; linezolid versus vancomycin; meropenem versus cefotaxime; and ceftobiprole versus cephalosporin.

What are the benefits and harms of antibiotics for treating cough or wheeze after acute bronchiolitis in children?

Giving antibiotics to children with persistent cough or wheeze within six months of having acute bronchiolitis may make little or no difference to symptoms or to the likelihood of going back into hospital, compared with giving a placebo (all low-certainty evidence). There was not enough information about possible harms. Cochrane Review (published August 2017); 2 studies with 249 children aged 24 months and under, with wheeze or cough more than 14 days after hospital treatment for bronchiolitis, comparing antibiotics with placebo (something that appears the same as the antibiotic preparation but without the active ingredient).


Long term antibiotics taken at regular intervals by people with bronchiectasis

Bronchiectasis is a common condition arising from a cycle of repeated chest infections that damage the airways, increasing the risk of further infection. Patients may be offered long term antibiotics with the aim of breaking this cycle of reinfection. However, it’s important that this is balanced against increased risk of developing resistance to antibiotics. To reduce this risk, antibiotics may be taken at intervals – but little is known about the length of intervals that may work best.

A Cochrane Review Intermittent prophylactic antibiotics for bronchiectasis (published January 2022) explored the benefits and harms of taking antibiotics at regular intervals – particularly at the length of the intervals.

The authors found eight studies with 2180 adults. The studies either looked at antibiotics given at intervals of: 28 days on followed by 28 days off; or 14 days on then 14 days off; or compared 14‐ and 28‐day intervals, for up to 48 weeks.

Key findings

  • Long‐term antibiotics given at 14‐day on/off intervals probably slightly reduce the frequency of chest infections compared to no antibiotics
  • These benefits were not observed with intervals of 28 days on/off antibiotics, but study participants had fewer severe chest infections.
  • Antibiotic resistance was over twice as common in people receiving antibiotics, whatever the interval between doses.
  • There was little to no impact on deaths or hospitalisations, other aspects of lung functioning, or health‐related quality of life.
  • None of the studies included children, so the benefits and safety of this type of treatment in children are unknown.

In patients with bronchiectasis, how do oral antibiotics compare with inhaled antibiotics?

There is no high quality evidence on the comparative effectiveness and safety of oral versus inhaled antibiotics for treating people with bronchiectasis. EVIDENCE GAP. Cochrane Review (published March 2018); no eligible studies found. The review aimed to compare the effectiveness and safety of oral versus inhaled antibiotics for treating adults and children with bronchiectasis.


In patients with bronchiectasis, how do continuous antibiotics compare with intermittent antibiotics? 

The risks and benefits of continuous antibiotic therapy compared with intermittent antibiotic therapy for adults and children with bronchiectasis remain uncertain. EVIDENCE GAP. Cochrane Review (published June 2018); no eligible studies found. The review aimed to compare the safety and effectiveness of continuous versus intermittent antibiotics for adults and children with bronchiectasis.


Antibiotics for treatment of sore throat in children and adults

A Cochrane Review (updated in December 2021), explored whether antibiotics are effective in treating the symptoms, and reducing potential complications of, sore throat. The review included 29 studies with 15,337 cases of sore throat, mostly in adults.

Symptoms:

Compared with placebo or no treatment, antibiotics reduce the number of people who still have a headache or sore throat on the third day of illness, or sore throat after one week. However, antibiotics make little or no difference to the number of people who still have a fever on the third day of illness.

Importantly, sore throats typically resolve by themselves, without treatment (and often quickly, within three or four days). Just over 8 in every 10 people (82%) who receive placebo or no treatment are symptom-free after one week.

Complications of sore throat:

Not many people in the studies went on to have complications. Nonetheless, the evidence suggests that antibiotics reduce the number of people who get:

  • infection of the middle ear (acute otitis media) within 14 days
  • infection of the tonsils (quinsy) within two months

Antibiotics probably also reduce the number of people who get acute rheumatic fever within two months.

However, antibiotics make little or no difference to the number of people who get infected sinuses (acute sinusitis) within 14 days. It is unclear whether antibiotics offer protection against acute glomerulonephritis – a rare type of kidney problem sometimes associated with sore throat.

Harms 

The studies did not provide clear information about harms of antibiotics. However, it is known that antibiotics can have harms such as diarrhoea and rash – as well as antimicrobial resistance.

Overall, the authors conclude that while antibiotics provide modest symptom reduction, it’s important to carefully weigh up whether this is worthwhile, given the potential hazards of antimicrobial resistance. It’s also important to carefully determine that the sore throat is likely to be caused by a bacterial infection, rather than a viral infection (given that antibiotics can reduce infections caused by bacteria, but not those caused by viruses).

It’s also important to note that the majority of included studies were conducted in the 1950s – it’s unclear whether changes in bacterial resistance more recently may make antibiotics less effective today.


6

Surgical procedures

Are antibiotics safe and effective for preventing infection in women with stress urinary incontinence who are undergoing continence surgery?

Stress urinary incontinence (SUI) is uncontrolled leakage of urine when the pressure inside the abdomen increases suddenly, such as during coughing, sneezing or laughing. Continence surgery is one treatment for SUI. The Cochrane Review Prophylactic antibiotics for preventing infection after continence surgery in women with stress urinary incontinence (published March 2022) explored the potential benefits and harms of prophylactic antibiotics (where women are given antibiotics either before or during surgery in order to try to prevent postoperative wound infection).

However, the authors only identified three studies with 390 women. They concluded that “there is insufficient evidence” about the potential effects of using prophylactic antibiotics in this way, and no data about potential harms.

In women undergoing a cervical excision to reduce the risk of developing cervical cancer, what are the benefits and harms of antibiotics?

In woman undergoing cervical excision, prophylactic antibiotics (taken before the surgical procedure to prevent infection) may make little or no difference to lower abdominal pain, prolonged vaginal discharge or the need for unscheduled medical consultation compared with placebo or no treatment (low-certainty evidence). Prophylactic antibiotics may also make little or no difference to severe vaginal bleeding after the procedure, the risk of having a fever, or the need for additional self‐medication but the evidence is very uncertain (very low-certainty evidence). EVIDENCE GAP. The evidence is very uncertain about antibiotic‐related adverse effects (very low-certainty evidence). Cochrane Review (published January 2017); three studies with 708 women with pre‐cancerous cervical lesions undergoing excisional treatment to the cervix to reduce the risk of developing cervical cancer in the future. Two of the studies tested an antimicrobial vaginal pessary versus no treatment; the other tested oral antibiotics compared with placebo.


7

Transplants

Can antibiotics given around the time of transplant surgery prevent surgical site infections in organ transplant recipients? 

Can antibiotics given around the time of transplant surgery prevent surgical site infections in organ transplant recipients? In people undergoing organ transplant surgery, it is uncertain whether antibiotics reduce the incidence of surgical site infections compared with no antibiotics. It is also uncertain how an extended course of antibiotics compares with a shorter course of antibiotics. The effect on other outcomes including deaths, graft loss and other infections is uncertain (all very low-certainty evidence). None of the studies reported on adverse effects. Cochrane Review (published August 2020); eight studies with 718 organ transplant recipients, assessing whether antibiotics given around the time of transplant surgery prevent surgical site infections. The studies compared antibiotics with no antibiotics, or compared a short duration of antibiotics with an extended duration of antibiotics.

What are the benefits and harms of antibiotics in kidney transplant recipients who have bacterial infection in the urine but no symptoms? 

Compared with no treatment, the effects of giving antibiotics to kidney transplant recipients with asymptomatic bacteriuria on the incidence of symptomatic urinary tract infection (UTI), on hospitalization for UTI, and on antimicrobial resistance, graft loss, graft function, acute graft rejection and all-cause mortality are uncertain (all low-certainty evidence). EVIDENCE GAP. There was not enough information about harms. Cochrane Review (published February 2018); 2 studies with 212 adult kidney transplant recipients with asymptomatic bacteriuria, comparing antibiotic treatment with no treatment. 3 ongoing studies were also identified.


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Further reading:

In April 2022, NICE announced their evaluation of two new antimicrobial drugs, cefiderocol and ceftazidime-avibactam, as part of a new model designed to try and encourage the development of new antimicrobials. These will only be used to treat patients with severe drug-resistant infections who would otherwise have limited or no other treatment options. This represents an important milestone in the UK’s efforts to tackle antimicrobial resistance.

References (pdf)



Antibiotic Awareness: a round-up of Cochrane evidence by Selena Ryan-Vig

is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International

2 Comments on this post

  1. It’s quite frightening in a way how little we actually do know about such a ubiquitous treatment.

    Roger Harrison / Reply

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