Antimicrobial Resistance

Antimicrobial resistance is the capacity of a pathogen to survive a drug that once controlled it. The evidence here comes from observational studies of bloodstream infections in African, Asian and Latin American hospitals, surveillance of Shigella and Candida, and genomic and survey data on drug-resistant tuberculosis.

Resistance matters clinically because the first antibiotic is usually chosen before the organism is known, so resistance turns into untreated infection. These studies show both how common resistance to first-line drugs already is in several settings and why resistance is often older or more widespread than surveillance assumes.

Claim ledger

What the evidence shows

Drawn from 9 studies in this library. Mix labels say which citation roles are present; they are not a strength score. Supports means evidence for a finding; Challenges means evidence against a stated position; Qualifies marks scope.

• ○ Limited citations

  When the empiric drug misses the bug, children die more often.

  In a prospective cohort of 1,787 febrile Tanzanian children, receiving an antibiotic that did not cover the bloodstream organism independently predicted death, alongside HIV and malnutrition; Gram-negative bloodstream infection carried 45.6% mortality, and only 20% of community-acquired Enterobacteriaceae were ampicillin-sensitive.

  1 study
  1. 1Does antibiotic resistance kill children with blood infections?

• ● Supporting studies only

  Last-line drugs are failing in first-line situations.

  Carbapenem resistance in Gram-negative bloodstream isolates is already common in several low- and middle-income hospital settings: 39.3% of Gram-negative isolates in a single-hospital adult oncology cohort of 414 bloodstream infections (rising each year), and 32.6% of Klebsiella pneumoniae and 71.4% of Acinetobacter isolates in the NeoOBS neonatal sepsis cohort.

  2 studies
  1. 1Which bacteria cause blood infections in cancer patients, and resist drugs?
  2. 2How are newborns with sepsis treated, and who is most likely to die?

  Study comparison

  Study	Role	Design	N	Population	Outcome
  Which bacteria cause blood infections in cancer patients, and resist drugs?2021	Supports	CohortRetrospective review of blood-culture surveillance and hospital records at one oncology hospital in Shiraz, Iran, with logistic regression for mortality and multidrug-resistance predictors.	N=414 · 414 adult patients with a positive bacterial blood culture (fungal, contaminant and polymicrobial results excluded).	Adults aged 18 or older with haematological malignancies or solid tumours admitted to a 100-bed oncology hospital who developed bacterial bloodstream infection.	Causative organisms, antibiotic susceptibility and resistance (ESBL, carbapenem resistance, multidrug resistance), mortality, and predictors of multidrug-resistant gram-negative infection.
  How are newborns with sepsis treated, and who is most likely to die?2023	Supports	CohortProspective observational cohort at 19 hospitals in 11 countries (2018-2020) with daily data on signs, antibiotics and microbiology; Cox models for 28-day mortality derived in a random 85% and validated in the remaining 15%.	N=3204 · 3,204 infants enrolled; 3,141 started empiric antibiotics; 3,195 had baseline blood cultures; score derivation used 2,726 infants and validation 478.	Hospitalised infants under 60 days old with clinical sepsis, mainly in low- and middle-income countries in Asia and Africa.	Empiric antibiotic regimens and switching, blood-culture pathogens and resistance, and 28-day mortality (plus performance of the NeoSep Severity and Recovery Scores).

• ○ Limited citations

  Broad empiric use is itself a driver of the resistance it responds to.

  Empiric prescribing often drifts to broad drugs and rarely steps back down. In NeoOBS, 3,204 infants received 206 different antibiotic combinations, only about a quarter got the WHO first-line Access regimen, 18.0% started on a carbapenem, 25.3% were escalated and only 5.9% de-escalated.

  1 study
  1. 1How are newborns with sepsis treated, and who is most likely to die?

• ● Supporting studies only

  Yesterday's antibiogram can mislead today's prescription.

  Resistance patterns shift over time as drug use changes. In southern Vietnamese children with shigellosis, S. sonnei replaced S. flexneri (29% to 78% of isolates) while resistance to nalidixic acid, ofloxacin and ceftriaxone rose stepwise (23% ceftriaxone-resistant in the last period) and resistance to ampicillin and chloramphenicol fell. Among candiduria isolates, fluconazole resistance rose from 6.8% in 2010-11 to 29.5% in 2012-13.

  2 studies
  1. 1How has childhood shigellosis in Vietnam changed over 14 years?
  2. 2Is fluconazole-resistant Candida hiding in urine?

  Study comparison

  Study	Role	Design	N	Population	Outcome
  How has childhood shigellosis in Vietnam changed over 14 years?2009	Supports	Cross-sectionalSerial comparison of three independent hospital studies (1995-96, 2000-02, 2006-08) with re-tested stored isolates and pooled clinical records	N=279 · 279 children with culture-confirmed shigellosis had clinical data (63, 113 and 103 across the three periods); 297 Shigella strains were analysed microbiologically	Children under 14 admitted with diarrhoea or dysentery to a tropical-diseases hospital in Ho Chi Minh City and a provincial hospital in southern Vietnam	Shigella species mix, antimicrobial susceptibility profiles, and clinical features of disease across the three periods
  Is fluconazole-resistant Candida hiding in urine?2023	Supports	Other12-year laboratory surveillance of Candida tropicalis isolates from candiduria vs invasive infection, plus ERG11 sequencing of fluconazole-resistant strains	N=519 · 519 unique C. tropicalis isolates from 485 patients (2010–2021); 363 urine (69.9%) and 156 invasive (30.1%)	Clinical C. tropicalis isolates from urine and invasive samples at a Beijing hospital laboratory	Fluconazole/voriconazole resistance rates over time and ERG11 mutations (especially Y132F / A395T/W)

• ● Supporting studies only

  Isoniazid resistance is common, comes first, and is invisible to a rifampicin-only test.

  Tuberculosis resistance arises repeatedly and in a consistent order. Genome dating of an extensively drug-resistant clone placed founding katG S315T resistance around 1957, and in that collection multidrug resistance emerged 56 separate times with isoniazid resistance preceding rifampicin resistance 46 times to 2. Global surveillance of 211,753 patients found isoniazid-resistant, rifampicin-susceptible TB in 7.4% of new and 11.4% of previously treated patients, with katG 315 mutations in 78.6% of isoniazid-resistant isolates.

  2 studies
  1. 1How old is KwaZulu-Natal’s XDR tuberculosis outbreak strain?
  2. 2How common is isoniazid-resistant TB, and which mutations cause it?

  Study comparison

  Study	Role	Design	N	Population	Outcome
  How old is KwaZulu-Natal’s XDR tuberculosis outbreak strain?2015	Supports	Computational / modellingWhole-genome sequencing, phylogenetic dating, and resistance-mutation ordering of KwaZulu-Natal M. tuberculosis isolates.	N=340 · 337 clinical isolates (2008–2013) plus 3 historical isolates (1994 pansusceptible/MDR; 2005 Tugela Ferry XDR).	Mycobacterium tuberculosis isolates from patients in KwaZulu-Natal, South Africa, including the LAM4 Tugela Ferry XDR lineage.	Timing and order of resistance-mutation acquisition, independent MDR/XDR emergences, and implications for rifampicin-only rapid tests.
  How common is isoniazid-resistant TB, and which mutations cause it?2020	Supports	Cross-sectionalPooled aggregated national drug-resistance surveillance and survey data reported to WHO (most recent year, 2002-2018) from 156 countries, weighted by notified cases; plus phenotypic testing and whole-genome or targeted sequencing of isolates from 7 high-burden countries.	N=211753 · 211,753 pulmonary TB patients with isoniazid results (aggregated country data); the molecular analysis used 4,559 patients with complete sequencing and phenotypic results, of whom 1,174 were isoniazid resistant.	New and previously treated pulmonary TB patients in national surveillance systems and drug-resistance surveys worldwide.	Prevalence of isoniazid-resistant, rifampicin-susceptible TB (Hr-TB), co-resistance to levofloxacin and pyrazinamide, and frequency of isoniazid-resistance mutations.

• ○ Limited citations

  A carbapenemase-only screen would have missed all of them.

  The mechanism of resistance is not always the one surveillance looks for. In a Brazilian matched case-control study, none of 20 carbapenem-resistant K. pneumoniae isolates produced a carbapenemase such as KPC; most combined a CTX-M-2 ESBL with disrupted porin genes, spread across seven clones.

  1 study
  1. 1Who gets carbapenem-resistant Klebsiella, and does it kill more?

Debates

Tensions and limits

Some items are genuine disagreements on the same question. Others mark different assays, populations, or outcomes.

Timeline

How understanding moved

Study years are when the paper was published. Evidence edits are dated changes to this page's claims. Explanations are when PaperFren added a Discovery — not a claim that the science happened that day.

Papers

9 studies in this library bear on Antimicrobial Resistance, ordered by citations.

• How old is KwaZulu-Natal’s XDR tuberculosis outbreak strain?

  WGS of 337 KZN isolates plus 3 historical genomes dated LAM4 XDR’s isoniazid/streptomycin mutations to ~1957 and found INH resistance evolved before rifampicin 46 times vs 2 the other way.

  PLoS medicine · 2015 · 226 citations

• How are newborns with sepsis treated, and who is most likely to die?

  Across 11 mostly low- and middle-income countries, newborns with sepsis received hundreds of different antibiotic combinations that often departed from WHO guidance, many infections resisted recommended drugs, and a simple bedside score picked out babies at high risk of death.

  PLoS medicine · 2023 · 156 citations

• Does antibiotic resistance kill children with blood infections?

  In a Tanzanian children's hospital, bloodstream infections that the standard antibiotics could not treat because of resistance independently predicted death.

  BMC infectious diseases · 2007 · 137 citations

• Which bacteria cause blood infections in cancer patients, and resist drugs?

  In one Iranian cancer hospital, most blood infections were caused by gram-negative bacteria, carbapenem resistance grew each year, and about one in five patients with these infections died.

  BMC infectious diseases · 2021 · 126 citations

• How common is isoniazid-resistant TB, and which mutations cause it?

  About 7.4% of new TB patients worldwide have TB resistant to isoniazid but not rifampicin, a form that current rifampicin-based rapid tests miss, and most cases are explained by a single katG mutation.

  PLoS medicine · 2020 · 112 citations

• How has childhood shigellosis in Vietnam changed over 14 years?

  Over 14 years the dominant cause of childhood dysentery in southern Vietnam switched from S. flexneri to S. sonnei, resistance to key drugs like ceftriaxone rose, and admitted children appeared more severely ill.

  BMC infectious diseases · 2009 · 102 citations

• Who gets carbapenem-resistant Klebsiella, and does it kill more?

  In one Brazilian hospital, longer use of a central venous catheter was the only independent risk factor for carbapenem-resistant Klebsiella infection, and resistance came from porin loss plus ESBL enzymes rather than a carbapenemase.

  BMC infectious diseases · 2013 · 90 citations

• What predicts bad outcomes in bacterial keratitis?

  In 283 UK eyes with suspected bacterial keratitis, almost all had a risk factor (OSD 47%, contact lenses 35%, immunosuppression 18%); age >50, infiltrate >3 mm, and poor presenting vision predicted worse vision and slow healing.

  Frontiers in medicine · 2021 · 66 citations

Questions

What is still open

1. Whether resistance itself raises mortality is design-dependent. The Tanzanian cohort found inadequate empiric cover independently predicted death, but the Brazilian case-control study (50% vs 27.5% mortality, p = 0.085, only 20 cases) and the oncology cohort (no factor significantly predicted death) could not show an independent effect, likely because of small samples and severely ill comparison groups.

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2. Whether resistant isolates represent disease or colonisation varies by site. Candiduria often reflects colonisation, so rising resistance in urine is not directly rising resistant disease, while culture-based series such as bacterial keratitis (only 45.2% culture-positive of 283 cases) draw organism-level conclusions from a minority of patients.

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