Hospital-Acquired Infections

  • Author: Haidee T Custodio, MD; Chief Editor: Russell W Steele, MD  more...
Updated: Sep 16, 2014

Practice Essentials

Hospital-acquired infections are caused by viral, bacterial, and fungal pathogens; the most common types are bloodstream infection (BSI), pneumonia (eg, ventilator-associated pneumonia [VAP]), urinary tract infection (UTI), and surgical site infection (SSI).

Essential update: Study reports falling VAP and BSI rates in critically ill children

The incidence of central line-associated BSI and VAP declined significantly between 2007 and 2012 in critically ill pediatric patients, according to a national cohort study of patients admitted to 173 neonatal intensive care units (NICUs) and 64 pediatric intensive care units (PICUs).[1, 2] No change was observed, however, in the rate of catheter-associated UTI.

In the NICUs, the rate of central line-associated BSI decreased from 4.9 to 1.5 per 1000 central-line days during the study period; in the PICUs, the rate fell from 4.7 to 1.0 per 1000 central-line days.[2] The rate of VAP decreased from 1.6 to 0.6 per 1000 ventilator days in the NICUs and from 1.9 to 0.7 per 1000 ventilator days in the PICUs.

Signs and symptoms

Risk factors for catheter-associated BSI in neonates include the following[3] :

  • Catheter hub or exit-site colonization
  • Catheter insertion after the first week of life
  • Duration of parenteral nutrition
  • Extremely low birth weight (< 1000 g) at catheter insertion
  • Disruption of catheter dressings [4]
  • Pediatric ICU: Neutropenia, prolonged catheter dwell time (>7 days), percutaneously placed central venous lines, frequent manipulation of lines [5]

Risk factors for candidemia in neonates include the following[6] :

  • Gestational age of less than 32 weeks
  • 5-minute Apgar scores below 5
  • Shock, disseminated intravascular coagulation
  • Prior intralipid use
  • Parenteral nutrition, central venous line placement
  • H2 blocker administration
  • Intubation
  • Hospital stay longer than 7 days

Risk factors for VAP in pediatric patients include the following[7, 8] :

  • Reintubation
  • Genetic syndromes
  • Immunodeficiency, immunosuppression
  • Prior BSI [9]

Risk factors for hospital-acquired UTI in pediatric patients include the following[10] :

  • Bladder catheterization
  • Prior antibiotic therapy
  • Cerebral palsy

The source of infection may be suggested by the instrumentation, as follows:

  • Endotracheal tube: Sinusitis, tracheitis, pneumonia
  • Intravascular catheter: Phlebitis, line infection
  • Foley catheter: UTI

Patients with pneumonia may have the following:

  • Fever, cough, purulent sputum
  • Abnormal chest auscultatory findings (eg, decreased breath sounds, crackles, wheezes)

Patients with UTI may have the following:

  • Fever or normal temperature
  • Tenderness, suprapubic (cystitis) or costovertebral (pyelonephritis)
  • Cloudy, foul-smelling urine

See Clinical Presentation for more detail.


Because not all bacterial or fungal growth on a culture is pathogenic and because such growth may reflect simple microbial colonization, interpretation of cultures should take into account the following:

  • Clinical presentation of the patient
  • Reason for obtaining the test
  • Process by which the specimen was obtained
  • Presence or absence of other supporting evidence of infection

Methods used to diagnose and characterize BSIs include the following:

  • Suspected catheter-associated BSI: Differential time to positivity of paired blood cultures (simplest) [11] ; quantitative culture of blood obtained from the catheter and peripheral vein; quantitative culture of catheter segment
  • Suspected fungal infection: Fungal cultures
  • Possible thrombosis or vegetations: Imaging studies such as echocardiography
  • Immunocompromised patients: Occasional special studies (eg, cultures for Nocardia, atypical mycobacteria, cytomegalovirus [CMV], and CMV antigenemia)

Tests used to identify pneumonia include the following:

  • Acute-phase reactants
  • Oxygen saturation and hemodynamic studies
  • Chest radiography
  • Sputum Gram stain and culture (if necessary, samples can also be obtained through bronchoalveolar lavage or thoracocentesis)
  • Rapid diagnostic tests, in specific cases

Urinalysis and urine culture, along with clinical findings, are essential for differentiating between asymptomatic bacteriuria, cystitis, and pyelonephritis. The following factors should be kept in mind in the interpretation of urine cultures:

  • Number of colonies and species isolated
  • Method of sample collection
  • Time from collection to laboratory processing
  • Sex of the patient
  • Previous antibiotic use

Although imaging studies are controversial, they are recommended by most experts in evaluating children with first-time UTI.

See Workup for more detail.


Medical care includes symptomatic treatment of shock, hypoventilation, and other complications, along with empiric broad-spectrum antimicrobial therapy.

Management of BSI may include the following:

  • Line removal as appropriate [11]
  • Antibiotic therapy covering gram-positive and gram-negative organisms, started empirically and then tailored according to specific susceptibility patterns
  • Antifungal therapy as appropriate
  • Antiviral therapy as appropriate
  • Prevention through use of catheter disinfection caps

Management of pneumonia includes the following:

  • Initial empiric broad-spectrum antibiotic therapy, later streamlined on the basis of identified organisms and susceptibilities, with attention to the risk of multidrug-resistant (MDR) pathogens
  • Antiviral medications against influenza for symptomatic patients and patients with immunodeficiency or chronic lung diseases to limit morbidity and mortality

Management of UTI includes the following:

  • Removal of indwelling catheters if possible
  • Empiric antibiotic and antifungal therapy

Management of SSI includes the following:

  • Surgical debridement
  • Antibiotic therapy

See Treatment and Medication for more detail.



Healthcare-associated infections (HAI) are defined as infections not present and without evidence of incubation at the time of admission to a healthcare setting. As a better reflection of the diverse healthcare settings currently available to patients, the term healthcare-associated infections replaced old ones such as nosocomial, hospital-acquired or hospital-onset infections.[12] Within hours after admission, a patient's flora begins to acquire characteristics of the surrounding bacterial pool. Most infections that become clinically evident after 48 hours of hospitalization are considered hospital-acquired. Infections that occur after the patient is discharged from the hospital can be considered healthcare-associated if the organisms were acquired during the hospital stay.

Hospital-based programs of surveillance, prevention and control of healthcare-associated infections have been in place since the 1950s.[13] The Study on the Efficacy of Nosocomial Infection Control Project (SENIC) from the 1970s showed nosocomial rates could be reduced by 32% if infection surveillance were coupled with appropriate infection control programs.[14] In 2005, the National Healthcare Safety Network (NHSN) was established with the purpose of integrating and succeeding previous surveillance systems at the Centers for Disease Control and Prevention (CDC): National Nosocomial Infections Surveillance (NNIS), Dialysis Surveillance Network (DSN) and National Surveillance System for Healthcare Workers (NaSH).[15]

Continued surveillance, along with sound infection control programs, not only lead to decreased healthcare-associated infections but also better prioritization of resources and efforts to improving medical care.

Healthcare-associated infections are of important wide-ranging concern in the medical field. They can be localized or systemic, can involve any system of the body, be associated with medical devices or blood product transfusions. This article focuses on the 3 major sites of healthcare-associated infections (ie, bloodstream infection, pneumonia, and urinary tract infection) with focus on the pediatric population.



Infectious agents causing healthcare-associated infections may come from endogenous or exogenous sources.

Endogenous sources include body sites normally inhabited by microorganisms. Examples include the nasopharynx, GI, or genitourinary tracts. Exogenous sources include those that are not part of the patient. Examples include visitors, medical personnel, equipment and the healthcare environment.

Patient-related risk factors for invasion of colonizing pathogen include severity of illness, underlying immunocompromised state and/or the length of in-patient stay.



United States

Healthcare-associated infections are estimated to occur in 5% of all hospitalizations in the United States.[16] In 1999, national point-prevalence surveys in pediatric intensive care units (PICU) and neonatal intensive care units (NICU) showed 11.9% of 512 patients had PICU-acquired infections, whereas 11.4% of 827 patients had NICU-acquired infections.[17, 18]

In 2014, the Centers for Disease Control and Prevention (CDC) released a pair of reports on healthcare-associated infections, with one indicating that significant progress has been made in their prevention.[19, 20]

In the National and State Healthcare-associated Infections Progress Report, the CDC notes a 44% reduction in central line–associated bloodstream infections and a 20% decrease in infections related to 10 surgical procedures, between the years 2008 and 2012. Other decreases were much smaller, with a 4% reduction in hospital-onset methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections and a 2% decrease in hospital-onset Clostridium difficile infections, occurring between 2011 and 2012. Catheter-associated urinary tract infections (UTIs) increased by 3% between 2009 and 2012.

In the second report, a survey of 11,282 patients from 183 acute care hospitals, Magill and colleagues found that 452 patients (4.0%) had at least 1 healthcare-associated infection (504 total infections). Device-associated infections, such as catheter-associated UTIs, were responsible for 25.6% of these. Surgical-site infections and pneumonia each accounted for 21.8%, and gastrointestinal infections accounted for approximately 17.1%. C difficile was the most common pathogen, causing 12.1% of healthcare-associated infections. The researchers estimated that nationwide, 648,000 patients had at least 1 healthcare-associated infection in 2011, with the total number of such infections coming to an estimated 721,800.


Both developed and resource-poor countries are faced with the burden of healthcare-associated infections. In a World Health Organization (WHO) cooperative study (55 hospitals in 14 countries from four WHO regions), about 8.7% of hospitalized patients had nosocomial infections.[21]

A 6-year surveillance study from 2002-2007 involving intensive care units (ICUs) in Latin America, Asia, Africa, and Europe, using CDC's NNIS definitions, revealed higher rates of central-line associated blood stream infections (BSI), ventilator associated pneumonias (VAP), and catheter-associated urinary tract infections than those of comparable United States ICUs.[22] The survey also reported higher frequencies of methicillin-resistant Staphylococcus aureus (MRSA), Enterobacter species resistance to ceftriaxone, and Pseudomonas aeruginosa resistance to fluoroquinolones.

A study of bacteremia in African children found distinct differences in the microbiological causes of nosocomial bacteremia compared with community-acquired bacteremia. Nosocomical bacteremia resulted in a higher rate of morbidity and mortality and longer hospital stay. Because it is largely unrecognized in low-income countries, nosocomial infections are likely to become public health priorities as their occurrence increases.[23]

With increasing recognition of burden from healthcare-associated infections, national surveillance systems have been developed in various countries; these have shown that nationwide healthcare-associated infection surveillance systems are effective in reducing healthcare-associated infections.[24]



Healthcare-associated infections result in excess length of stay, mortality and healthcare costs. In 2002, an estimated 1.7 million healthcare-associated infections occurred in the United States, resulting in 99,000 deaths.[25] In March 2009, the CDC released a report estimating overall annual direct medical costs of healthcare-associated infections that ranged from $28-45 billion.[26]

A report from the CDC showed that among the intensive care units in the United States, the year 2009 had 25,000 fewer central line-associated bloodstream infections (CLABSI) than in 2001, representing a 58% reduction. Between 2001 and 2009, an estimated 27,000 lives were saved and potential $1.8 billion cumulative excess health-care costs were prevented. Coordinated efforts from state and federal agencies, professional societies, and healthcare personnel in implementing best practices for insertion of central lines were thought to play a role in this achievement.[27]


Healthcare-associated infections do not have a discernible sex predilection.


Healthcare-associated infections occur in both adult and pediatric patients. Bloodstream infections, followed by pneumonia and urinary tract infections are the most common healthcare-associated infections in children; urinary tract infections are the most common healthcare-associated infections in adults.[28] Among pediatric patients, children younger than 1 year, babies with extremely low birth weight (≤1000 g) and children in either the PICU or NICU have higher rates of healthcare-associated infections.[12, 17, 18, 28]

Contributor Information and Disclosures

Haidee T Custodio, MD Assistant Professor, Department of Pediatrics, Division of Pediatric Infectious Diseases, University of South Alabama College of Medicine

Haidee T Custodio, MD is a member of the following medical societies: American Academy of Pediatrics, Infectious Diseases Society of America, Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Joseph Domachowske, MD Professor of Pediatrics, Microbiology and Immunology, Department of Pediatrics, Division of Infectious Diseases, State University of New York Upstate Medical University

Joseph Domachowske, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa

Disclosure: Received research grant from: Pfizer;GlaxoSmithKline;AstraZeneca;Merck;American Academy of Pediatrics<br/>Received income in an amount equal to or greater than $250 from: Sanofi Pasteur;Astra Zeneca;Novartis<br/>Consulting fees for: Sanofi Pasteur; Novartis; Merck; Astra Zeneca.

Chief Editor

Russell W Steele, MD Clinical Professor, Tulane University School of Medicine; Staff Physician, Ochsner Clinic Foundation

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, Southern Medical Association

Disclosure: Nothing to disclose.


The authors and editors of Medscape Drugs & Diseases gratefully acknowledge the contributions of previous author Ayesha Mirza, MD, to the development and writing of this article.

  1. Barclay L. Healthcare-acquired infections fall in critically ill kids. Medscape Medical News. September 8, 2014. [Full Text].

  2. Patrick S, Kawai A, Kleinman K, et al. Health care-associated infections among critically ill children in the US, 2007–2012. Pediatrics. 2014 Sep 8. [Epub ahead of print]:

  3. Mahieu LM, De Muynck AO, Ieven MM, De Dooy JJ, Goossens HJ, Van Reempts PJ. Risk factors for central vascular catheter-associated bloodstream infections among patients in a neonatal intensive care unit. J Hosp Infect. 2001 Jun. 48(2):108-16. [Medline].

  4. Timsit JF, Bouadma L, Ruckly S, Schwebel C, Garrouste-Orgeas M, Bronchard R, et al. Dressing disruption is a major risk factor for catheter-related infections*. Crit Care Med. 2012 Jun. 40(6):1707-1714. [Medline].

  5. Newman CD. Catheter-related bloodstream infections in the pediatric intensive care unit. Semin Pediatr Infect Dis. 2006 Jan. 17(1):20-4. [Medline].

  6. Saiman L, Ludington E, Pfaller M, et al. Risk factors for candidemia in Neonatal Intensive Care Unit patients. The National Epidemiology of Mycosis Survey study group. Pediatr Infect Dis J. 2000 Apr. 19(4):319-24. [Medline].

  7. Elward AM, Warren DK, Fraser VJ. Ventilator-associated pneumonia in pediatric intensive care unit patients: risk factors and outcomes. Pediatrics. 2002 May. 109(5):758-64. [Medline].

  8. Fayon MJ, Tucci M, Lacroix J, et al. Nosocomial pneumonia and tracheitis in a pediatric intensive care unit: a prospective study. Am J Respir Crit Care Med. 1997 Jan. 155(1):162-9. [Medline].

  9. Apisarnthanarak A, Holzmann-Pazgal G, Hamvas A, Olsen MA, Fraser VJ. Ventilator-associated pneumonia in extremely preterm neonates in a neonatal intensive care unit: characteristics, risk factors, and outcomes. Pediatrics. 2003 Dec. 112(6 Pt 1):1283-9. [Medline].

  10. Moulin F, Quintart A, Sauvestre C, Mensah K, Bergeret M, Raymond J. [Nosocomial urinary tract infections: retrospective study in a pediatric hospital]. Arch Pediatr. 1998. 5 Suppl 3:274S-278S. [Medline].

  11. Zaoutis TE, Coffin SE. Clinical Syndromes of Device-Associated Infections. Long SS, Pickering LK, Prober CG. Principles and Practice of Pediatric Infectious Diseases. 3rd ed. Churchill Livingstone; 2008. chap 102.

  12. Coffin SE, Zaoutis TE. Healthcare-Associated Infections. Long SS, Pickering LK, Prober CG. Principles and Practice of Pediatric Infectious Diseases. 3rd ed. Churchill Livingstone; 2008. chap 101.

  13. Hospital Infections Program, National Center for Infectious Diseases, CDC. Public Health Focus: surveillance, prevention, and control of nosocomial infections. MMWR. October 1992. 41(42):783-787.

  14. Hughes JM. Study on the efficacy of nosocomial infection control (SENIC Project): results and implications for the future. Chemotherapy. 1988. 34(6):553-61. [Medline].

  15. Edwards JR, Peterson KD, Andrus ML, Dudeck MA, Pollock DA, Horan TC. National Healthcare Safety Network (NHSN) Report, data summary for 2006 through 2007, issued November 2008. Am J Infect Control. 2008 Nov. 36(9):609-26. [Medline].

  16. Wenzel RP, Edmond MB. The impact of hospital-acquired bloodstream infections. Emerg Infect Dis. 2001 Mar-Apr. 7(2):174-7. [Medline]. [Full Text].

  17. Grohskopf LA, Sinkowitz-Cochran RL, Garrett DO, et al. A national point-prevalence survey of pediatric intensive care unit-acquired infections in the United States. J Pediatr. 2002 Apr. 140(4):432-8. [Medline].

  18. Sohn AH, Garrett DO, Sinkowitz-Cochran RL, Grohskopf LA, Levine GL, Stover BH. Prevalence of nosocomial infections in neonatal intensive care unit patients: Results from the first national point-prevalence survey. J Pediatr. 2001 Dec. 139(6):821-7. [Medline].

  19. CDC. National and State Healthcare-associated Infections Progress Report. Mar 2014. Available at

  20. Magill SS, Edwards JR, Bamberg W, et al. Multistate point-prevalence survey of health care-associated infections. N Engl J Med. 2014 Mar 27. 370(13):1198-208. [Medline].

  21. Tikhomirov E. WHO programme for the control of hospital infections. Chemioterapia. June 1987. 6(3):148-51.

  22. Rosenthal VD, Maki DG, Mehta A, Alvarez-Moreno C, Leblebicioglu H, Higuera F. International Nosocomial Infection Control Consortium report, data summary for 2002-2007, issued January 2008. Am J Infect Control. 2008 Nov. 36(9):627-37. [Medline].

  23. Aiken AM, Mturi N, Njuguna P, Mohammed S, Berkley JA, Mwangi I, et al. Risk and causes of paediatric hospital-acquired bacteraemia in Kilifi District Hospital, Kenya: a prospective cohort study. Lancet. 2011 Dec 10. 378(9808):2021-7. [Medline].

  24. Gastmeier P, Geffers C, Brandt C, Zuschneid I, Sohr D, Schwab F. Effectiveness of a nationwide nosocomial infection surveillance system for reducing nosocomial infections. J Hosp Infect. 2006 Sep. 64(1):16-22. [Medline].

  25. Klevens RM, Edwards JR, Richards CL, et al. Estimating healthcare-associated infections in US hospitals, 2002. Public Health Rep. Mar 2007. 122(2):160-6.

  26. Scott RD. The direct medical costs of healthcare-associated infections in US hospitals and the benefits of prevention, 2008. CDC. Available at Accessed: 7/1/2009.

  27. Vital signs: central line-associated blood stream infections--United States, 2001, 2008, and 2009. MMWR Morb Mortal Wkly Rep. 2011 Mar 4. 60(8):243-8. [Medline].

  28. Richards MJ, Edwards JR, Culver DH, Gaynes RP. Nosocomial infections in pediatric intensive care units in the United States. National Nosocomial Infections Surveillance System. Pediatrics. 1999 Apr. 103(4):e39. [Medline].

  29. Lessa FC, Mu Y, Ray SM, Dumyati G, Bulens S, Gorwitz RJ, et al. Impact of USA300 Methicillin-Resistant Staphylococcus aureus on Clinical Outcomes of Patients With Pneumonia or Central Line-Associated Bloodstream Infections. Clin Infect Dis. 2012 May 21. [Medline].

  30. Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control. 2008 Jun. 36(5):309-32. [Medline].

  31. Craven DE, Chroneou A, Zias N, Hjalmarson KI. Ventilator-associated tracheobronchitis: the impact of targeted antibiotic therapy on patient outcomes. Chest. 2009 Feb. 135(2):521-8. [Medline].

  32. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005 Feb 15. 171(4):388-416. [Medline].

  33. Chastre J, Wolff M, Fagon JY, et al. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA. 2003 Nov 19. 290(19):2588-98. [Medline].

  34. Siegel JD, Rhinehart E, Jackson M, Chiarello L, and the Healthcare Infection Control Practices Advisory Committee. 2007 Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Healthcare Settings. CDC. Available at Accessed: 7/9/2009.

  35. Committee on Infectious Diseases, American Academy of Pediatrics. Pickering LK. Red Book 2006. 27th ed. American Academy of Pediatrics; 2006. 153-160.

  36. [Guideline] Centers for Disease Control and Prevention. Guidelines for the prevention of intravascular catheter-related infections, 2011. Centers for Disease Control and Prevention. Available at Accessed: January 31 2013.

  37. Piper HG, Wales PW. Prevention of catheter-related blood stream infections in children with intestinal failure. Curr Opin Gastroenterol. 2013 Jan. 29(1):1-6. [Medline].

  38. Sanders J, Pithie A, Ganly P, et al. A prospective double-blind randomized trial comparing intraluminal ethanol with heparinized saline for the prevention of catheter-associated bloodstream infection in immunosuppressed haematology patients. J Antimicrob Chemother. 2008 Oct. 62(4):809-15. [Medline].

  39. Hand L. Catheter disinfection caps cut infection rates. Medscape Medical News. Jan 4, 2013. Available at Accessed: Jan 16, 2013.

  40. Wright MO, Tropp J, Schora DM, Dillon-Grant M, Peterson K, Boehm S, et al. Continuous passive disinfection of catheter hubs prevents contamination and bloodstream infection. Am J Infect Control. 2013 Jan. 41(1):33-8. [Medline].

  41. Loftus RW, Brindeiro BS, Kispert DP, et al. Reduction in intraoperative bacterial contamination of peripheral intravenous tubing through the use of a passive catheter care system. Anesth Analg. 2012 Dec. 115(6):1315-23. [Medline].

  42. Tablan OC, Anderson LJ, Besser R, Bridges C, Hajjeh R. Guidelines for preventing health-care--associated pneumonia, 2003: recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee. MMWR Recomm Rep. 2004 Mar 26. 53:1-36. [Medline].

  43. Wong ES, Hooton TM. Guideline for prevention of catheter-associated urinary tract infections. CDC. Available at Accessed: 7/7/2009.

  44. Passaretti CL, Otter JA, Reich NG, Myers J, Shepard J, Ross T, et al. An evaluation of environmental decontamination with hydrogen peroxide vapor for reducing the risk of patient acquisition of multidrug-resistant organisms. Clin Infect Dis. 2013 Jan. 56(1):27-35. [Medline].

  45. Pullen LC. H2O2 Vapor Technology Improves Hospital Infection Control. Available at Accessed: March 13, 2013.

  46. Maziade PJ, Andriessen JA, Pereira P, et al. Impact of adding prophylactic probiotics to a bundle of standard preventative measures for Clostridium difficile infections: enhanced and sustained decrease in the incidence and severity of infection at a community hospital. Curr Med Res Opin. 2013 Oct. 29(10):1341-7. [Medline].

  47. Nierengarten M. Ultraviolet Disinfection Cuts Hospital-Acquired Infections. Medscape Medical News. Available at Accessed: June 9, 2014.

  48. Haas JP, Menz J, Dusza S, Montecalvo MA. Implementation and impact of ultraviolet environmental disinfection in an acute care setting. Am J Infect Control. 2014 Jun. 42(6):586-90. [Medline].

Medscape Consult
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.