Outbreak of Bacterial Conjunctivitis at a College—New Hampshire, January-March, 2002 FREE

MMWR. 2002;15:205-207

2 figures omitted

During February 1-14, 2002, approximately 100 students presented to a New Hampshire college's student health service with clinical signs of conjunctivitis. The cause of conjunctivitis was initially thought to be viral. However, because of the high number of cases, eye cultures were collected from 12 consecutive students; Streptococcus pneumoniae was isolated from cultures of all 12 students. The medical director of the student health service notified the New Hampshire Department of Health and Human Services about the outbreak and on February 22, the state health department requested assistance from CDC. This report summarizes preliminary results of the investigation of this outbreak, which indicate that an uncommon strain of pneumococcus caused this outbreak and that health-care providers should consider pneumococcus as a cause of conjunctivitis among college students.

Students at the college are entitled to medical care at the student health service, and school officials estimate that approximately 95% of students use the health service for nonemergency health care. Discharge diagnoses of visits to the student health center were reviewed to identify episodes of conjunctivitis. A case of probable pneumococcal conjunctivitis was defined as a diagnosis of conjunctivitis-unspecified (International Classification of Diseases, Ninth Revision code 372.30), pink eye or mucopurulent conjunctivitis (ICD-9 code 372.03), or viral conjunctivitis (ICD-9 code 077.99) in a student who presented to the student health service during January 15–March 7, 2002. A case of confirmed pneumococcal conjunctivitis was defined as a diagnosis of conjunctivitis with S. pneumoniae isolated from eye secretions.

Among 5,060 students enrolled for the winter term, 493 (9.7%) students had probable pneumococcal conjunctivitis, and 81 (1.6%) had confirmed pneumococcal conjunctivitis. The attack rate was highest among freshmen (18.0%) followed by sophomores (14.9%), juniors (12.8%), seniors (12.0%), and graduate students (1.7%). A survey of college faculty and interviews with local child care centers, schools, ophthalmologists, and primary-care physicians did not identify excessive episodes of conjunctivitis in persons other than college students.

A systematic clinical examination of 80 students with conjunctivitis found that most reported eye crusting on awakening. The findings of eye examinations were variable, ranging from mildly inflamed conjunctiva with a clear watery discharge to severe conjunctival inflammation with purulent discharge and preauricular adenopathy. Students examined by an ophthalmologist showed a papillary rather than follicular conjunctival response. Giemsa stains of conjunctival discharge from seven students showed lancet-shaped diplococci in a preponderance of neutrophils. No smears showed a predominantly lymphocytic response or viral inclusions. Students were treated with topical antibiotics.

Of eye specimens cultured from 189 students, 81 (42.9%) grew bacteria identified as S. pneumoniae by optochin sensitivity and bile solubility tests. Strains were resistant to erythromycin but susceptible to balcitracin, sulfonamides, and quinolones. Thirty strains were sent to CDC for serotyping but could not be typed using the Quellung reaction. Viral cell cultures of specimens from 70 students were negative for adenovirus (no cytopathic effect after 10 days' incubation).

School health officials used campus-wide e-mail, posters, and the college newspaper to notify students, faculty, and staff about the outbreak and ways to reduce transmission. The messages instructed students to wash their hands frequently; to avoid sharing towels, drinking glasses, or other utensils; and to make an appointment with the student health service if they developed signs or symptoms of conjunctivitis.

The student health service provided topical antibiotic therapy to students presenting with signs or symptoms of conjunctivitis. In addition, bottles of alcohol-based anti-septic gel were provided to all undergraduate students along with an information sheet that provided instructions on proper hand antisepsis using the gel. Local primary-care physicians and ophthalmologists were notified about the outbreak and asked to obtain cultures from patients presenting with conjunctivitis and to report cases to the investigating team. A student health service listserv was used to notify other student health services in the United States about the outbreak.

The college's winter term ended March 14, 2002, and students will be departing for spring break. As of March 13, the student health service was still reporting new cases of conjunctivitis.

JH Turco, MD, JH Pryor, MA, YY Baumgartner, MBA, Dartmouth College Health Svc; ME Zegans, MD, P Sanchez, Dartmouth Medical School; A Bashir, MD, JD Schwertzman, MD, Dartmouth Hitchcock Medical Center, Hanover; J Puffer, JT Montero, MD, New Hampshire Dept of Health and Human Svcs. S Sodha, J Elliott, PhD, CG Whitney, MD, Div of Bacterial and Mycotic Diseases, National Center for Infectious Diseases; M Martin, MD, EIS Officer, CDC.

This report describes an outbreak of conjunctivitis attributed to an unusual nontypeable strain of S. pneumoniae. Outbreaks caused by nontypeable pneumococci have been reported previously.^1,2 Person-to-person transmission of the outbreak strain may be occurring from eye secretions, respiratory droplets, or hands. Prevention messages were intended to reduce contact that would encourage transmission. The use of alcohol-based antiseptic gel improves hand hygiene in the hospital setting³; however, its benefit in the setting of a community outbreak is unknown.

Some of the college's students will have left campus for spring break with active S. pneumoniae conjunctivitis. Others will have left during the incubation period of the infection or might be asymptomatic carriers of the epidemic strain of S. pneumoniae. Some students will be traveling to popular college student vacation spots. Crowding and limited access to handwashing facilities might result in further transmission of this highly infectious strain of S. pneumoniae.

Students who develop symptoms of conjunctivitis (e.g., red eyes, crusting of eyes in the morning, or increased eye discharge) should seek medical care. Health-care providers who see college students with conjunctivitis should suspect a bacterial etiology, and consider obtaining a culture of eye secretions, treating with a topical antibiotic, and ensuring that standard infection-control practices are followed.⁴ Outbreaks of conjunctivitis attributed to S. pneumoniae should be reported to state health departments, and state health department personnel should notify CDC, telephone (404) 639-2215.

Acknowledgements

This report is based on data contributed by J Greenblatt, MD, S Macrae, MS, M Sweeney, MS, New Hampshire Dept of Health and Human Svcs. M Richardson, MS, C Bradley, S Power, D Fisk, D Cook, S Robinson, L Clancy, J Karlen, C Henderson, and clinicians and staff, Dartmouth College Health Svc; Nathan Smith Pre-Med Society, Dartmouth College, Hanover, New Hampshire. A Schuchat, MD, RR Facklam, PhD, DM Jackson, MS, Div of Bacterial and Mycotic Diseases; N Khetsuriani, MD, U Parashar, MPH, DD Erdman, DrPH, Div of Viral and Rickettsial Diseases; SK Fridkin, MD, Div of Healthcare Quality Promotion, National Center for Infectious Diseases, CDC.

References: 4 available

MMWR. 2002;51:207-210

Tissue allografts are commonly used in orthopedic surgical procedures; in 1999, approximately 650,000 musculoskeletal allografts were distributed by tissue processors.¹ A rare complication of musculoskeletal allografts is bacterial infection.^2- 3 After the reported death of a recipient of an allograft contaminated with Clostridium spp. (an anaerobic spore and toxin-forming organism),³ CDC investigated this case and solicited additional reports of allograft-associated infections; 26 cases have been identified. This report summarizes the investigation of these cases and describes additional steps given to a tissue processor to enhance tissue transplant safety.

On November 7, 2001, a man aged 23 years underwent reconstructive knee surgery at a hospital in Minnesota using a femoral condyle (bone-cartilage) allograft. On November 10, he developed pain at the surgical site, which rapidly progressed to shock; the patient died the following day.³ Blood cultures obtained premortem grew Clostridium sordellii.

On November 13, a man aged 17 years underwent reconstructive knee surgery in Illinois using a femoral condyle (fresh) and a meniscus (frozen). The next day, the patient developed fever, which did not respond to first-generation cephalosporin antibiotics. Eight days after surgery, he was admitted to a local hospital for septic arthritis; his temperature on admission was 103.5° F (39.7° C). The patient received ampicillin-sulbactam, and the fever subsided within 24 hours. The patient is recovering. Cultures for anaerobic bacteria, including C. sordellii, were not obtained.

The three allografts received by these two patients came from the same cadaveric donor (donor A) and were supplied by tissue processor A (TP-A). Based on records from the medical examiner, no evidence indicated that donor A was septic or had risk factors for Clostridium spp. infection (e.g., injecting drug use or abdominal trauma). The body of donor A was refrigerated 19 hours after death; tissue was procured 23.5 hours after death. One tissue-procurement organization recovered the tissue and sent all tissue to TP-A for processing.

Including the two cases described above, 10 tissues from donor A were transplanted into nine patients located in eight states. No additional infections were identified. CDC obtained 19 nonimplanted tissues from donor A and identified C. sordellii in two tissues (fresh femoral condyle and frozen meniscus) and from the fluid bathing the tissues.

TP-A used aseptic processing of harvested tissues. Companion tissue (e.g., a sliver of cartilage from a femoral condyle) was processed alongside the allograft. After suspension of the allograft and companion tissue in an antibiotic/antifungal solution, the companion tissue was cultured. The aerobic and anaerobic cultures of the companion tissues from donor A were reported as negative at TP-A. No other cultures were taken before tissue processing. No swab cultures were taken; all cultures were destructive (i.e., performed on tissue that had been ground up).

To identify additional cases of allograft-associated infections, CDC solicited case reports through electronic listservers and MMWR^2- 3 and by contacting the Food and Drug Administration (FDA) and state regulatory authorities.² A case of allograft-associated infection was defined as any surgical site infection (SSI) at the site of allograft implantation occurring within 12 months of allograft implantation in an otherwise healthy patient with no known risk factors for SSI (e.g., diabetes). Cases could be culture-negative if diagnosed by infectious diseases physicians or surgeons and diagnostic (e.g., knee aspirate) or operative findings supported SSI diagnosis. If only Staphylococcus aureus or Staphylococcus spp. were isolated, patients were excluded unless additional epidemiologic or microbiologic evidence suggested allograft contamination.

As of March 11, 2002, CDC has received 26 reports of bacterial infections associated with musculoskeletal tissue allografts including the previously reported cases.^2- 3 Thirteen (50%) of the 26 patients were infected with Clostridium spp. (C. septicum, C. sordellii ); 11 (85%) of these patients received tissue processed by TP-A. Allografts that were implicated in Clostridium spp. infections were tendons used for anterior cruciate ligament (ACL) reconstruction (eight), femoral condyles (two), bone (two), and meniscus (one). Eleven (85%) of the allografts were frozen and two (15%) were fresh (femoral condyles). All allografts were processed aseptically but did not undergo terminal sterilization. In 11 of these 13 cases, additional evidence (e.g., common donors or cultures of nonimplanted tissue) implicated the allograft as the source of the infection. CDC has requested additional information for the other two cases. The median age of these 13 patients was 35 years (range: 15-52 years); onset of symptoms occurred at a median of 8.5 days (range: 2-85 days) following allograft implantation. One patient died.

Eleven patients were infected with gram-negative bacilli; five had polymicrobial infection. Cultures from two patients were negative: the Illinois patient and a patient with necrotizing soft tissue infection treated with multiple debridements, hyperbaric oxygen, and intravenous antibiotics that covered anaerobes. The transplanted tissues included ACL,¹⁰ femoral condyle (one), meniscus (one), and bone (one). One tissue was fresh (femoral condyle), one was freeze dried (bone), and the rest were frozen. For eight (62%) of these 13 cases, additional evidence implicated the allograft (e.g., common donors or positive pre-implantation or processing cultures with matching microorganisms).² CDC continues to investigate these cases. Eight patients received allografts that had undergone aseptic processing but no terminal sterilization. Three patients received allografts that were reported to have undergone gamma irradiation.

In response to the initial case investigation and the subsequent reports of Clostridium spp. infections, CDC provided to TP-A some additional steps to reduce the risk for allograft associated infections.

When possible, a method that can kill bacterial spores should be used to process tissue. Existing sterilization technologies used for tissue allografts such as gamma irradiation, or new technologies effective against bacterial spores should be considered. Unless a sporicidal method is used, aseptically processed tissue should not be considered sterile, and health-care providers should be informed of the possible risk for bacterial infection.

If no sporicidal method is available (e.g., for certain tissues such as fresh femoral condyles), efforts should be made to minimize the potential for Clostridium spp. and other bacterial contamination. First, tissue should be cultured before suspension in antimicrobial solutions,⁴ and if Clostridium spp. or other bowel flora are isolated, all tissue from that donor that cannot be sterilized should be discarded. Second, culture methods should be validated to ensure that residual antimicrobials do not result in false negative culture results.⁵ Performing both destructive and swab cultures should be considered. Third, recommended time limits for tissue retrieval should be followed.⁴

After receiving a report of potential allograft-associated infection, remaining tissue from that donor should not be released until it is determined that the allograft is not the source of infection.⁴ Tissue processors should contact health-care providers of recipients of tissue from the same donor implicated in an allograft-associated infection. In these cases, a sample of nonimplanted tissues that underwent the same processing method should be cultured by an independent laboratory using a validated method. CDC has recommended that TP-A perform a one-time audit of its unreleased tissue inventory to estimate the proportion of unreleased tissue that might be contaminated with microorganisms or spores.

LK Archibald MD, DB Jernigan MD, Div of Healthcare Quality Promotion, National Center for Infectious Diseases; MA Kainer, MD, EIS Officer, CDC.

Tissue allografts can improve substantially the quality of life for many patients. However, infections associated with bacterial contamination of allografts can result in serious morbidity and death.^2- 3 As of March 11, 26 patients with allograft-associated infections have been identified: 13 with Clostridium spp. infection and 14 associated with a single tissue processor. The findings in this report have important implications for patient safety and indicate that current federal regulations and industry standards on processing and quality control methods need to be enhanced and implemented to prevent Clostridium spp. and other allograft-associated infections.

At CDC, destructive cultures of nonimplanted tissues from donor A were positive for C. sordellii. In contrast, destructive cultures of the companion tissue from donor A were reported to be negative at TP-A. Two factors might explain this discrepancy. First, because tissues were cultured at TP-A only after suspension in the antibiotic/antifungal solution, residual antibiotics on the tissues might have caused a false-negative culture result because of bacteriostasis. Second, cultures of the smaller companion tissues might not have been representative of the allografts. Although American Association of Tissue Banks standards recommend that cultures be obtained before and after processing, these standards do not address the potential problem of bacteriostasis after processing or specify a culture method.⁴ Although destructive cultures used by TP-A are very sensitive, a combination of swab and destructive cultures would be most sensitive in detecting bacterial contamination.⁶

Donor A tissue probably became hematogenously seeded by bowel flora, including Clostridium spp., before harvesting.⁷ Factors that may contribute to contamination with bowel flora include time interval between death and tissue retrieval and delays in refrigeration and mode of death (e.g., trauma).⁷ Aseptic processing does not eradicate contamination with organisms,² and antibiotic/antifungal solutions will not eliminate spores of organisms such as Clostridium spp.

Sterilization of tissue that does not adversely affect the functioning of tissue when transplanted into patients is the best way to reduce the risk for allograft-associated infections. However, two sterilization methods (ethylene oxide and gamma irradiation) that would eliminate spores have associated technical problems that limit their use in processing of tissues for transplantation.² New low-temperature chemical sterilization technologies that kill spores⁸ but preserve the biomechanical integrity and function of some allografts are being evaluated.^9- 10

FDA regulations state that each tissue bank is required to have written procedures for prevention of infectious disease contamination or cross-contamination by tissue during processing. In response to these cases reports, FDA has released new guidelines for tissue processors (http://www.fda.gov/cber/guidelines.htm#tissval).

CDC, in collaboration with state health departments, tissue processors, and clinicians, continues to solicit and investigate case reports to identify risk factors associated with acquisition of infection following receipt of an allograft. When septic arthritis occurs after use of an allograft, contamination should be suspected, and diagnostic work-up should include obtaining anaerobic cultures. Clinicians should consider expanding empiric antibiotic therapy to include agents effective against gram-negative organisms and anaerobes. Clinicians should report infections involving allograft tissue to tissue processors, FDA's Medwatch System, and CDC, telephone (800) 893-0485.

Acknowledgements

This report is based on data contributed by JC Davis, MD, Alabama Sportsmedicine and Orthopedic Center, Birmingham, Alabama. SA Barbour, MD, Warren King Sports Medicine Fellowship; W King, MD, Palo Alto Medical Foundation, Palo Alto, California; J Rosenberg, MD, Div of Communicable Disease Control, California Dept of Health Svcs. DC Bartley, MD, St Vincents Medical Center, Jacksonville; D Dodson, MD, West Palm Beach; JM Malecki, MD, Palm Beach County Health Dept; AC Morse, Div of Sports Medicine, Florida Orthopedic Institute, Tampa; OV Martinez, PhD, Univ of Miami, Miami; S Wiersma, MD, Florida Dept of Health. HJ Cohen, MD, Northside Hospital; G Cierney III, MD, St Joseph's Hospital; MA Blass, MD, Georgia Infectious Diseases; EW Carson, MD, Resurgens Orthopaedics; DL Dickensheets, MD, JC Garrett, MD, Atlanta, Georgia. DJ Raab, MD, Illinois Bone and Joint Institute, Des Plaines; MJ Joyce, MD, American Academy of Orthopaedic Surgeons, Rosemont, Illinois. T Tibbot, Indiana Cardiac Retrieval, New Haven, Indiana. B Lutz, MD, Memorial Medical Center-Baptist Campus, New Orleans; R Ratard, MD, Lousiana Dept of Health and Hospitals. BS Wolock MD, Orthopedic Associates, Towson office, Baltimore; RJ Brechner, MD, Maryland Dept of Health and Mental Hygiene. SM Mulawka, MD, DJ Whitlock, MD, SJ Petrowski, MF Buhl, St. Cloud Hospital, St. Cloud; PM Hoeft, MD, Rice Memorial Hospital, Willmar; KH LeDell, MPH, R Lynfield, MD, RN Danila, PhD, HF Hull, MD, Minnesota Dept of Health. EA Bresnitz, MD, New Jersey Dept of Health and Senior Svcs. SG Jenkins, PhD, Mt Sinai Medical Center, New York; J Linden, MD, Blood and Tissue Resources, New York State Dept of Health. D Perrotta, PhD, Texas Dept of Health. DA Deneka, MD, Middle Tennessee Orthopedics and Sports Medicine, Murfreesboro; TF Jones, MD, AS Craig, MD, Tennessee Dept of Health. J Mowe, SH Doppelt, MD, RE Stevenson, PhD, American Association of Tissue Banks, McLean, Virginia. RD Noyce, MD, Midelfort Clinic, Eau Claire; TA Israel, MD, Sports Medicine, Luther/Midelfort, Mayo Health Systems, Eau Claire; JP Davis, MD, Wisconsin Div of Public Health. BJ Jensen, MS, MJ Arduino, DrPH, DN Whaley, HT Holmes, PhD, Div of Healthcare Quality Promotion, National Center for Infectious Diseases; DL Kirschke MD, ML Castor MD, EIS officers, CDC.