David H. Spach

Transmission of Infection by Gastrointestinal Endoscopy and Bronchoscopy

Spurred in part by the acquired immunodeficiency syndrome (AIDS) epidemic, both health care workers and the lay public have become keenly interested in preventing the iatrogenic transmission of infections. Recently, reports of the transmission of infections via contaminated endoscopes have generated concern. We review the reported evidence of infections transmitted by flexible gastrointestinal and pulmonary endoscopes, the circumstances surrounding transmission of these infections, and recommended means to prevent such transmission. Methods We identified all relevant English-language articles published between 1966 and July 1992 through prominent review articles and a MEDLINE search (keywords: endoscopy, bronchoscopy, infections, transmission, and disinfection). We also manually searched bibliographies of identified articles to find additional sources. The entire search yielded 265 articles, all of which were reviewed in depth. General Considerations Flexible endoscopy is a common clinical procedure; an estimated 8.7 million gastrointestinal and 580 000 pulmonary flexible endoscopies were done in the United States in 1989 [1]. The risk for transmitting infections via these procedures depends on three factors: exposure of the endoscope to microorganisms, cleaning and disinfection procedures, and instrument design. Depending on the origin of the contaminating microorganisms, transmission of infection can be categorized as either patient-to-patient or environment-to-patient (Figure 1). During a procedure, an endoscope can be contaminated with whatever organisms are contained in patient secretions. Environmental contamination typically results from flushing or cleaning the endoscope with contaminated solutions. Whether contamination of the endoscope persists depends on the quantity and nature of the microorganisms. Some microbes are inherently more resistant to disinfectants (Figure 2), the efficacy of which depends on type, concentration, and duration of exposure. If patient material, such as blood, feces, or secretions, remains on or in the endoscope after cleaning, the effectiveness of subsequent disinfection diminishes. Figure 1. Nosocomial transmission of microorganisms via endoscopes. Figure 2. Resistance of microorganisms to disinfectants. Because endoscopes are made of fragile, heat-sensitive materials, they are routinely decontaminated by high-level disinfection, not sterilization [2]. Gastrointestinal endoscopes, with their multiple internal channels and valves (Figure 3), are more complex than the single-channeled bronchoscopes. In general, the more complex the instrument, the more crevices, joints, or surface pores there are and, hence, the more problematic cleaning and disinfection becomes [2]. Figure 3. Cross-section of typical gastrointestinal endoscope. Transmission of Specific Microorganisms Salmonella Infections Salmonella infections occur frequently in the United States; for example, more than 41 000 culture-positive patients were reported to the Centers for Disease Control (CDC) in 1989[3]. A chronic asymptomatic carrier state, defined by the continued fecal excretion of Salmonella organisms for more than 1 year, develops in approximately 3% of persons after S. typhi infection (typhoid fever) [4] and in fewer than 1% of persons after nontyphoidal Salmonella infection [5]. Both acutely infected persons and chronic carriers are thus potential sources of endoscopic contamination. Many disinfectants, including glutaraldehyde, phenolics, and iodophors, effectively kill salmonellae [2]. Transmission of Salmonella infections by endoscopy has occurred with many serotypes, including S. agona, S. kedougou, S. newport, S. oranienburg, S. oslo, S. typhi, and S. typhimurium [6-14]. Of the 84 patients reported to have developed such infections, 6 patients developed septicemia and 1 patient died. In most cases, the disinfectant (hexachlorophene, cetrimide, chlorhexidine, or quaternary ammonium compounds) used to clean the endoscopes had relatively little microbiocidal activity against salmonellae. In one outbreak, investigators identified inadequately disinfected colonic biopsy forceps as the source of infection [9]. Pseudomonas Infections Pseudomonas aeruginosa flourishes in warm, damp environments. Typical environmental reservoirs include respiratory equipment, sinks, and water bottles [15]. Most acute P. aeruginosa infections, which often involve the lungs, are nosocomially acquired. Among healthy adults, P. aeruginosa can colonize many body sites, as evidenced by isolation from throat (0% to 7%), sputum (2%), and stool (3% to 24%). Hospitalized patients, as well as patients with certain chronic lung diseases, have higher colonization rates [16]. Potential sources of endoscope contamination with Pseudomonas species thus include environmental reservoirs, acutely infected patients, and colonized patients. Like Salmonella species, P. aeruginosa is susceptible to glutaraldehyde, phenolics, and iodophors [2]. Most P. aeruginosa infections transmitted by endoscopy occurred after endoscopic retrograde cholangiopancreatography and resulted from environment-to-patient transfer of organisms. In all cases, the investigators isolated P. aeruginosa from some part of the endoscope. These infections resulted in bacteremia in 45 patients, of whom 4 died [17-26]. Most infections were caused by the use of an inadequate disinfectant [21, 22], contamination of an inner channel [18, 20], or incomplete drying of the endoscope channels before overnight storage [23, 26]. One epidemic, however, occurred despite the use of glutaraldehyde after each procedure and ceased only after replacement of the endoscope [19]. The first reports of bronchoscopic transmission of P. aeruginosa involved patients who developed Pseudomonas pneumonia [27, 28]. In a subsequent report, investigators cultured P. aeruginosa from the bronchoscopic washings of 11 patients; 1 patient, who was immunosuppressed, developed severe pneumonia [29]. The investigators isolated P. aeruginosa from the aspiration-irrigation channel of the bronchoscope, and the outbreak continued until they sterilized the bronchoscope with ethylene oxide. Mycobacteria Approximately 22 000 new cases of active tuberculosis occur in the United States each year [30], and an estimated 10 to 15 million persons carry Mycobacterium tuberculosis in its dormant phase [31]. After many years of decline, the incidence of tuberculosis in the United States began increasing dramatically in 1986 [30], predominantly because of an increasing number of cases in HIV-infected patients [32]. Infections with mycobacteria commonly found in the environment, such as M. avium-intracellulare complex, M. chelonae, and M. fortuitum, have also recently increased [33]. Unfortunately, studies determining the sensitivity of mycobacteria to various disinfectants are conflicting. In general, cetrimide, chlorhexidine, and iodophors are considered unreliable. Glutaraldehyde is widely accepted as a mycobactericidal agent, but the time required for disinfection remains undefined [34-36]. In the first reports of the bronchoscopic transmission of M. tuberculosis, the investigators, who disinfected the bronchoscopes with iodophor, advocated using a more effective disinfectant such as glutaraldehyde [37, 38]. In three subsequent cases, the patients developed clinically apparent M. tuberculosis infection despite rigorous cleaning and disinfection of the bronchoscope; the suction valve, with its spring-operated sleeve, seemed the most likely source of contamination [39]. The investigators tested this hypothesis by contaminating bronchoscopes with M. fortuitum; after they routinely cleaned and disinfected the instrument, M. fortuitum remained in all valves. Among other mycobacteria, M. chelonae has most commonly been associated with endoscopic transmission. In a large outbreak, M. chelonae was isolated from bronchial washings, brushings, or sputum in 72 patients [40]. Two patients developed clinical disease and one patient died. After recognizing the outbreak, the investigators changed from glutaraldehyde disinfection of the bronchoscopes to ethylene oxide sterilization. Nevertheless, they continued to isolate M. chelonae from clinical specimens until they discovered punctured suction channels in two of the bronchoscopes; M. chelonae was isolated from slimy material in the interior of both instruments. Hepatitis B Virus On average, more than 300 000 cases of primary hepatitis B virus (HBV) occur each year in the United States [41], and approximately 5% to 10% of patients develop persistent HBV infection. The estimated number of chronic HBV carriers in the United States ranges from 750 000 to 1 000 000 [42]. In infected persons, hepatitis B surface antigen (HBsAg) has been found in various body fluids, including serum, feces, bile, and saliva [43]. The inability to culture HBV has limited the evaluations of its environmental stability and its susceptibility to disinfectants. Alternative approaches include measuring the presence of HBsAg or inoculating chimpanzees. A study in chimpanzees showed that HBV-contaminated inanimate objects, if not properly cleaned and disinfected, can harbor and transmit the virus for up to 1 week [44]. Most of the commonly used disinfectant and sterilization procedures, however, inactivate HBV [45, 46]. Two studies have shown the potential for the endoscopic transmission of HBV. In one study, iodophor-isopropyl alcohol removed HBsAg from surfaces of endoscopes used in four HBsAg-positive patients, but not from the cytology brushes or biopsy forceps [47]. In the other study, an endoscope and a biopsy forceps were immersed for 15 minutes in gastric juice containing 1.0% serum and Iodine-125-HBsAg, and, despite subsequent disinfection with chlorhexidine and cetrimide for 15 to 20 minutes, they were both positive for Iodine-125-HBsAg [48]. One group of investigators documented the endoscopic transmission of HB

Bartonella (Rochalimaea) quintana Bacteremia in Inner-City Patients with Chronic Alcoholism

BACKGROUND Bartonella (Rochalimaea) quintana is a fastidious gram-negative bacterium known to cause trench fever, cutaneous bacillary angiomatosis, and endocarditis. Between January and June 1993 in Seattle, we isolated B. quintana from 34 blood cultures obtained from 10 patients not known to be infected with the human immunodeficiency virus (HIV). METHODS After identifying the isolates as B. quintana by direct immunofluorescence and DNA-hybridization studies, we determined strain hybridization with studies of restriction-fragment-length polymorphisms (RFLPs) of the intergenic spacer (noncoding) region of ribosomal DNA amplified by the polymerase chain reaction (PCR). To characterize the epidemiologic and clinical features of bartonella infections in these patients, we performed a retrospective case-control study using as controls 20 patients with blood cultures obtained at approximately the same time as those obtained from the index patients. RESULTS B. quintana isolates from the 10 patients were indistinguishable by PCR-RFLP typing. All 10 patients had chronic alcoholism, and 8 were homeless (P = 0.001 for both comparisons with controls). The six patients who underwent HIV testing were seronegative. At the time of their initial presentation, seven patients had temperatures of at least 38.5 degrees C. Six patients had three or more blood cultures that were positive for B. quintana, and in four of these patients B. quintana was isolated from blood cultures obtained 10 or more days apart. Subacute endocarditis developed in two patients and required surgical removal of the infected aortic valve in one of them. Nine patients recovered; one died of sepsis from Streptococcus pneumoniae infection. CONCLUSIONS B. quintana is a cause of fever, bacteremia, and endocarditis in HIV-seronegative, homeless, inner-city patients with chronic alcoholism.

Babesiosis in Washington State: A New Species of Babesia?

Babesiosis is an intraerythrocytic protozoan infection, transmitted by ticks, and characterized by malaria-like symptoms and hemolytic anemia. The first reported zoonotic cases in Europe and the United States occurred in 1956 [1] and 1966 [2], respectively. In Europe, cases of this infection have generally been in splenectomized persons infected with the cattle parasites Babesia divergens and Babesia bovis [3, 4], which are thought to be maintained by Ixodes ricinus ticks. No national surveillance system for babesiosis exists in the United States, but hundreds of cases have been reported [4, 5]. Most have been attributed to infection with Babesia microti, a rodent parasite maintained by Ixodes dammini ticks, the primary vector of the agent of Lyme disease (Borrelia burgdorferi). Human babesiosis is endemic on various coastal islands in the northeastern United States, such as Nantucket Island and Marthas Vineyard, Block Island, Long Island, and Shelter Island, and in mainland Connecticut [6]. Cases acquired in Wisconsin have been reported as well [7, 8]. Asplenic, immunocompromised, and elderly persons infected with B. microti are at greatest risk for clinical illness [5, 7, 9-13], which may be severe, whereas other infected persons commonly are asymptomatic or only mildly symptomatic. Only three human cases of babesiosis acquired in the western United States have been reported previously, all of which occurred in splenectomized patients in California [2, 14, 15]; the infecting species was not definitively identified for any of these cases. In September 1991, the first recognized case of babesiosis acquired in Washington State was diagnosed. We present the clinical details of this case, which occurred in an apparently immunocompetent person, and provide evidence that it was not caused by B. microti. We also provide results of 1) serologic testing that was done in an attempt to identify the species of the patients Babesia isolate [referred to as WA1]; 2) experimental inoculations of various mammalian species to determine WA1s host specificity; 3) a comparison of the DNA hybridization patterns of WA1, B. microti, and B. gibsoni using a Babesia-specific, ribosomal-DNA (rDNA) probe [16]; 4) a serosurvey of the patients family members and neighbors for antibody to WA1; and 5) attempts to identify WA1s reservoir host and tick vector. Case Report A 41-year-old man from a rural forested area in south-central Washington State went to a local emergency room on 15 September 1991 because of a 1-week history of fever, rigors, anorexia, rhinorrhea, cough, and headache. He had previously been in good health, was not taking any medications, and had never had a blood transfusion. He had a dog, two cats, and two head of cattle and was exposed daily to tick habitats, but he did not recall any tick bites. He had not been outside the Washington-Oregon border region in many years and had never been in areas reported to be endemic for babesiosis or malaria. On evaluation, he had a few rales in his left-lung field and a platelet count of 48 109/L. He was treated for a presumed bronchopneumonia, with intravenous cefazolin to be followed with oral cefixime, and was sent home. He was hospitalized the next day (September 16) because of persistent fever, severe rigors, and dark-colored urine. He had a temperature of 39.5 C, tenderness in both upper quadrants of his abdomen without hepatosplenomegaly, a normal hematocrit (0.44) and leukocyte count, a platelet count of 46 109/L, 1+ occult blood on urine-dipstick analysis with no cells detected microscopically, a normal chest radiograph, and blood and urine culture results that were negative for bacteria. He was treated with cefazolin and gentamicin without improvement. On September 18, his temperature peaked at 40.4 C; his hematocrit was 0.36, his serum lactate dehydrogenase level was 21.34 kat/L (1280 U/L), and his total bilirubin level was 20.5 mol/L (1.2 mg/dL). Intraerythrocytic ring forms attributed to Plasmodium falciparum malaria were noted on his peripheral blood smear. He was treated with mefloquine and sent home at his request. He was rehospitalized the next day (September 19) with a temperature of 40 C, rigors, and vomiting. On re-examination of his blood smears from September 15 and 18, intraerythrocytic ring forms (in 1.2% and 3.0% of the erythrocytes) were noted as well as tetrad forms characteristic of Babesia (Figure 1). Therapy with oral quinine (650 mg, three times daily) and intravenous clindamycin (600 mg, four times daily) was begun on September 20, with symptomatic improvement by the next day. By September 23, he was afebrile, his hematocrit was 0.35, the parasitemia had decreased from 3.7% (September 20) to 0.4%, and his platelet count had increased to 143 109/L. On September 24, he was sent home on oral quinine and clindamycin (600 mg, three times daily) to complete a 10-day course of therapy. Figure 1. Photographs of Giemsa-stained peripheral blood smears from a patient who acquired babesiosis in Washington State. Left. Right. On September 30, he was evaluated because of a diffuse urticarial rash. His blood smear was normal, and he was treated with a 12-day tapering course of prednisone for a presumed hypersensitivity reaction. On November 3, when he felt feverish and had a headache, his temperature was 37.5 C, his hematocrit 0.34, and he had a detectable parasitemia of <1%. Urticaria recurred after a dose of quinine (650 mg). Although he appeared to be improving without further therapy for babesiosis, he was treated with intravenous clindamycin (1.2 grams, twice daily for 10 days). His hematocrit decreased to 0.28 on November 7; his anemia had resolved by December 12. Because of slowly resolving fatigue, he did not return to work until 6 January 1992. No parasites were detected on his blood smear in December 1991 or on smears in January, March, July, and September 1992, during which time he remained asymptomatic. Evaluation of his immunologic status with a Western-blot test for human immunodeficiency virus; a liver-spleen scan; quantitative immunoglobulins (including immunoglobulin-G subtypes); and serologic testing for antibody to tetanus toxoid, rubella virus, and streptolysin O, indicated normal results. Methods Serologic Studies Serum specimens from the patient were tested at the Centers for Disease Control and Prevention (CDC) in serial fourfold dilutions by indirect immunofluorescent antibody (IFA) testing [17] for antibody to B. microti and the patients isolate (WA1), which was propagated in hamsters inoculated with his blood (see below). A titer of at least 64 to B. microti was considered positive. Stored serum specimens from patients in the northeastern United States with B. microti-antibody titers ranging from 64 to greater than 4096 and blood smears with intraerythrocytic ring forms were assayed for IFA reactivity with WA1. In another laboratory (University of California at Davis [UCD]) with a different IFA protocol [18], serum from the patient was assayed in serial twofold dilutions for reactivity with various Babesia isolates maintained by passage in animals (Table 1). A titer of at least 320 to B. microti was considered positive. Fluorescein-labeled, affinity-purified antibody to human IgG (Kirkegaard & Perry, Gaithersburg, Maryland) was used as the secondary antibody. Blood smears from the patient were examined for B. bovis, Babesia equi, and Babesia bigemina antigens by direct immunofluorescence testing with monoclonal antibodies specific for these species [24-26]. Table 1. Indirect Immunofluorescent Antibody Reactivity of Serum from November 1991 from a Patient Who Acquired Babesiosis (Isolate WA1) in Washington State* Animal Inoculations Whole blood specimens from the patient were inoculated intraperitoneally (1-mL inocula) into at least two hamsters (Mesocricetus auratus) or jirds (Mongolian gerbils; Meriones unguiculatus). Giemsa-stained thin smears of blood from the inoculated animals were examined (at least 25 oil-immersion fields per slide) weekly for 6 to 8 weeks. Erythrocytes from hamsters infected with WA1 were washed in Pucks Saline G and were inoculated into a splenectomized 1-year-old female golden Labrador retriever (5.6 109 parasitized erythrocytes were administered intravenously and an equal number, subcutaneously) and into a hamster (9 106 parasitized erythrocytes, intraperitoneally). During the 34-day monitoring period, the dogs clinical status and hematocrit were checked daily for 20 days and then 3 times weekly, and thin smears were examined (>5000 erythrocytes/slide) daily through day 20 and then twice weekly. Pre-and postinoculation serum samples from the dog were assayed for IFA reactivity (UCD) with WA1, B. microti (GI [20] and P20 isolates), and B. gibsoni. Southern-Blot Analysis Babesia-infected erythrocytes (P1 pellets) were obtained as previously described [16]; erythrocytes infected with WA1, a human isolate of B. microti (2Bm) [16], and a canine isolate of B. gibsoni (6Bg) were used. Control mammalian leukocytes were separated from uninfected blood of a hamster and a dog by differential centrifugation (400 x g, 4 C, 20 min) on Ficoll-paque (Pharmacia LDB Biotechnology, Piscataway, New Jersey) gradients. After Babesia and leukocyte DNA samples were prepared [27], approximately 1 g of each DNA sample was digested with restriction endonucleases (HindIII or HaeIII; Boehringer Mannheim, Indianapolis, Indiana), as previously described [16]. DNA fragments were separated by electrophoresis in horizontal 0.8% (weight/volume) agarose gels in 45 mM Tris-borate and 1 mM ethylenediaminetetraacetic acid at 40 V for 16 to 18 hours. A Babesia-specific rDNA probe was hybridized to Southern blots of the restriction-endonuclease- digested DNAs; the probe had been produced by polymerase chain reaction amplification of sequences from B. microti DNA, with universal primers directed against highly conserved portions of the nuclear sma

BARTONELLA-ASSOCIATED INFECTIONS

Bartonella-associated infections occur in immunocompetent and immunocompromised patients. The spectrum of diseases caused by Bartonella species has expanded and now includes cat-scratch disease, bacillary angiomatosis, bacillary peliosis, bacteremia, endocarditis, and trench fever. Most Bartonella-associated infections that occur in North America and Europe are caused by B. henselae or B. quintana. The domestic cat serves as the major reservoir for B. henselae; the reservoir for the modern day B. quintana infection remains unknown. Methods used to diagnose Bartonella-associated infections include histopathologic analysis of biopsy specimens, culture of tissue samples, blood culture, and serology. Available data on treatment of Bartonella-associated infections remain relatively sparse but would suggest that erythromycin or doxycycline provide the best responses.

Bartonellosis (Carrión's Disease) in the Modern Era

Bartonellosis remains a major problem in Peru, but many contemporary aspects of this disease have not been adequately described. We examined the cases of 145 symptomatic patients in Lima, Peru, in whom bartonellosis was diagnosed from 1969 through 1992, including 68 patients in the acute (hematic) phase and 77 patients in the eruptive (verruga) phase. In modern Peru, symptomatic patients who have acute-phase bartonellosis typically present with a febrile illness and systemic symptoms caused by profound anemia; most patients respond successfully to treatment with chloramphenicol. Patients who have eruptive-phase bartonellosis most often present with cutaneous verrugas but may have less specific symptoms, such as fever and arthralgias; diagnosis can be confirmed in such patients by Western immunoblotting, and most patients appear to respond to treatment with rifampin.

HIV-specific cytotoxic T lymphocytes traffic to lymph nodes and localize at sites of HIV replication and cell death

We have tracked the in vivo migration and have identified in vivo correlates of cytotoxic T-lymphocyte (CTL) activity in HIV-seropositive subjects infused with autologous gene-marked CD8(+) HIV-specific CTL. The number of circulating gene-marked CTL ranged from 1.6 to 3.5% shortly after infusion to less than 0.5% 2 weeks later. Gene-marked CTL were present in the lymph node at 4.5- to 11-fold excess and colocalized within parafollicular regions of the lymph node adjacent to cells expressing HIV tat fusion transcripts, a correlate of virus replication. The CTL clones expressed the CCR5 receptor and localized among HIV-infected cells expressing the ligands MIP-1alpha and MIP-1beta, CC-chemokines produced at sites of virus replication. Aggregates of apoptotic cells and cells expressing granzyme-B localized within these same sites. In contrast, lymph node sections from untreated HIV-seropositive subjects, all with significant viral burden (> 50,000 HIV RNA copies/mL plasma), showed no CC-chemokine expression and exhibited only sporadic and randomly distributed cells expressing granzymes and/or apoptotic cells. These studies show that the infused CTL specifically migrate to sites of HIV replication and retain their antigen-specific cytolytic potential. Moreover, these studies provide a methodology that will facilitate studies of both the magnitude and functional phenotype of Ag-specific CD8(+) T cells in vivo.

Septic arthritis of the temporomandibular joint: review of the literature and report of two cases in children.

Septic arthritis of the temporomandibular joint (TMJ) has a high morbidity, is infrequently reported, and has been described almost exclusively in adults. We present two cases of septic arthritis of the TMJ that occurred in children after minor blunt trauma. Literature related to septic arthritis of the TMJ was reviewed, and a composite list of cases was constructed. The most common causes were various infections of the head and neck, rheumatic joint disease, and iatrogenesis. Pathogens may gain access to the TMJ by several routes. Patients typically present with an acute, tender, monarticular arthritis with associated swelling and erythema. Malaise, nausea, and vomiting may also be present. Traumatic effusions, fractures, and neoplasms may present in a similar fashion, and mimic TMJ septic arthritis. Staphylococcus aureus is the most commonly reported pathogen and often causes permanent joint damage. Aspiration and analysis of joint fluid, as well as blood chemistry, imaging studies, and clinical impression, may assist in the diagnosis. Timely diagnosis and treatment are essential for a successful outcome; therapy should include antimicrobial agents, adequate drainage, and resting of the joint. Complications include spread of infection, postinfectious bony changes, and fibrous (or bony) ankylosis of the temporomandibular joint.

Intracerebral Bacillary Angiomatosis in a Patient Infected with Human Immunodeficiency Virus

Excerpt Bacillary angiomatosis is a recently described illness that results from infection with a novel, rickettsia-like, gram-negative bacillus (1, 2). This disorder occurs predominantly in patien...

Effect of trimethoprim-sulfamethoxazole as Pneumocystis carinii pneumonia prophylaxis on bacterial illness, Pneumocystis carinii pneumonia, and death in persons with AIDS

To measure the effect of trimethoprim-sulfamethoxazole (TMP-SMX) in preventing bacterial illness, Pneumocystis carinii pneumonia (PCP), and death in people with AIDS, we conducted a retrospective medical record review of 1078 persons who were observed for 3 years on average who attended nine outpatient facilities in Seattle, Washington between January 1990 and April 1996. We calculated relative risk estimates to measure the protective effect of TMP-SMX on the development of major bacterial illnesses, PCP, and death. Use of TMP-SMX decreased the risk of PCP (relative risk [RR] = 0.23; 95% confidence interval [CI], 0.14-0.36) and deaths not attributable to PCP (RR = 0.59; 95% CI, 0.47-0.73). Prevention of major bacterial illnesses of known etiology was of borderline significance (RR = 0.77; 95% CI, 0.57-1.05) and became statistically significant with the addition of patients with infections of unknown etiology (RR = 0.77; 95% CI 0.61-0.97). Use of TMP-SMX PCP prophylaxis significantly reduced the risks of death and of PCP and was associated with a trend toward reduced risk of major bacterial infections.

Antibiotic Resistance in Community-Acquired Respiratory Tract Infections: Current Issues

OBJECTIVE In recent years, antibiotic resistance has emerged as an important global problem. The major goal of this review is to update important issues pertaining to antibiotic resistance, with an emphasis on antibiotic resistance involving community-acquired respiratory pathogens. In addition, this review examines potential reasons why antibiotic resistance has increased in recent years, how clinicians can better understand commonly used laboratory antibiotic resistance tests, and possible solutions to the increasing problem of antibiotic resistance. The article emphasizes the diagnosis, therapy, and prevention of antibiotic-resistant infections. DATA SOURCES We identified relevant English-language articles through MEDLINE search (1966 to March 1998). All articles related to antibiotic resistance and the scope of the articles included original investigative articles, reviews, letters, and editorials. In addition, we selected additional references from the bibliographies of the identified articles. STUDY SELECTION We selected articles for detailed review if they provided direct insight into the cause of antibiotic resistance, testing for antibiotic resistance, or the treatment of antibiotic resistance. Most, but not all, of the articles selected pertained to antibiotic resistance and respiratory tract infections. We performed a detailed review on approximately 40% of the originally selected articles. RESULTS Multiple factors that play a significant role in the development of antibiotic resistance include the overuse of antibiotics in both humans and animals, situations such as day care that enhance transmission via frequent close personal contact, and widespread dissemination of resistant strains via global travel. Most respiratory pathogens have developed resistance to commonly used antibiotics either by producing beta-lactamase or by altering binding site proteins. CONCLUSIONS In many regions of the United States, the level of antibiotic resistance has impacted the clinical management of common respiratory pathogens. Future efforts to curtail antibiotic resistance will require a concerted effort in multiple areas, particularly enhanced epidemiologic surveillance to better detect resistance trends, judicious use of antibiotics, and new drug development.