key: cord-0005379-hg5l7k0p
authors: Heald, Alison; Auckenthaler, Raymond; Borst, Francois; Delaspre, Olca; Cermann, Daniel; Matter, Lukas; Kaiser, Laurent; Stalder, Hans
title: Adult bacterial nasopharyngitis: A clinical entity?
date: 1993-12-03
journal: J Gen Intern Med
DOI: 10.1007/bf02598283
sha: 6e1c41f42300b4c328b7686b4fe370aa55681bcc
doc_id: 5379
cord_uid: hg5l7k0p

Objective: To investigate bacterial nasopharyngitis as a cause of adult upper respiratory infection. Design: Prospective case series. Setting: Walk-in medical clinic of a university hospital. Patients: 507 patients with cold or flu symptoms, sore throat, or recent cough; 21 control subjects without symptoms of upper respiratory infection. Measurements and main results: After thorough history and physical examination, the patients underwent nasopharyngeal aspiration and throat culture. Nasopharyngeal specimens were cultured for both bacteria and viruses; antigens for influenza, parainfluenza, and respiratory syncytial virus were sought by enzyme-linked immunosorbent assay (ELISA); serum antibodies to viral respiratory pathogens were determined. Group A beta-hemolytic streptococci grew from the throat specimens of 39 of the 507 patients (8%) or 38 of 3 34 patients (11%) who had clinical diagnoses of pharyngitis. Thirty-three cases of influenza A, 20 cases of influenza B, and seven cases of parainfluenza infections were diagnosed. Bacteria were cultured from the nasopharyngeal secretions of 284 patients (56%). In contrast to pharyngeal culture, commensal mixed flora were rarely found in nasopharyngeal culture. Nasopharyngeal culture of bacteria usually considered to be respiratory pathogens was significantly associated with the presence of leukocytes.Streptococcus pneumoniae (odds ratio 6.0, 95% confidence interval 2.6–14.2),Moraxella catarrbalis (odds ratio 12.9, 95% confidence interval 3.1–79.5), andHemophilus influenzae (odds ratio 3.0, 95% confidence interval 1.2–7.4) were all associated with the presence of leukocytes. In contrast, nasophaiyngeal culture of coagulase-negative staphylococci, mixed flora, and the documentation of a viral infection were not associated with the presence of leukocytes. For none of 21 control subjects were “pathogenic” bacteria found. Conclusions: These data suggest that potentially pathogenic bacteria may have a causal role in adult nasopharyngitis, although further data are needed to confirm this hypothesis.

tory infection such as acute bronchitis, pneumonia, sinusitis, and otitis media are recognized to have a bacterial origin and warrant treatment with antibiotics. Nonetheless, many practicing physicians prescribe antibiotics for uncomplicated upper respiratory infections. [7] [8] [9] In adults investigations of the etiology of upper respiratory infection have not included bacterial culture of nasopharyngeal secretions. Instead, researchers have focused on throat culture for group A streptococci, viruses, and mycoplasma and on nasopharyngeal sampling for viral detection and culture. 3, 5, 10 In children, however, investigations of the etiology of upper respiratory infections have frequently included bacterial culture of nasopharyngeal secretions, and bacterial nasopharyngitis is considered to be both a distinct entityt 1, 12 and a contributing factor to complications such as otitis media and pneumonia) 3, 14 In a prospective case series of adult patients with upper respiratory infection, we were surprised to find an increased number of leukocytes in nasopharyngeal secretions associated with the presence of bacteria considered to be pathogens only in the lower respiratory tract. This suggests that bacterial infection of the upper respiratory tract may occur in adults.

From March 1, 1988 , to February 28, 1990 , patients who presented to the walk-in medical clinic of the University Hospital of Geneva, Switzerland, with complaints of cold or flu symptoms, sore throat, or recent cough were eligible for the study. Patients were excluded from the study if they showed any clinical or radiologic evidence of pneumonia. Twenty-one patients with no recent history of upper respiratory infection were included as control subjects. All patients gave informed consent to participate in the study.

A thorough history was taken and a physical examination was performed for each study participant by one of several participating housestaff physicians using a specific questionnaire. History of exposure to schoolage and preschool children, other sick people at home or at work, cigarette use, and relevant past medical problems was obtained. The presence and duration of 667 symptoms such as fever, headache, rhinitis, sore throat, cough, hoarseness, myalgias, arthralgias, and photophobia were noted. General physical status, temperature, pulse, and results of physical examination of the oropharynx, tympanic membranes, sinuses, and lungs were recorded. Repeat physical examination was performed at a follow-up visit two weeks later and total duration of symptoms and use of medications were noted.

Aspiration of the nasopharynx was performed at the initial clinical visit by inserting a 5-mm soft plastic catheter from a Lukens specimen container (Argyle, Sherwood Medical, Tullamore, Ireland) into the posterior nasopharynx and using simple wall suction to aspirate the secretions. The secretions were then rinsed from the plastic catheter using 6 mL of sterile saline and processed within one hour in the laboratory. The secretions and rinse solution were vortexed for one minute and were processed as outlined below.

A throat culture was also obtained by rubbing a Culturette II swab stick (Marion Scientific, Kansas City, MO) firmly against the tonsilar fossa. This was sent to the microbiology laboratory for analysis within six hours.

Two hundred to four hundred microliters of the nasopharyngeal secretions were cytocentrifuged and stained with Gram and Giemsa stains. All smears were analyzed by the same technician. The nasopharyngeal secretions and the throat specimens were cultured on sheep blood agar, chocolate agar, colistin-nalidixic acid agar, and Thayer-Martin agar for 48 hours for aerobic organisms. Anaerobic organisms were cultured on Centers for Disease Control agar and on sheep blood agar with a disk of bacitracin and trimethoprimsulfamethoxazole in the primary streaking. Mycoplasma was cultured on biphasic medium. Chlamydia was not cultured. Bacteria were identified using standard methods.

Two milliliters of the vortexed nasopharyngeal secretions was transferred to 1 mL of viral transport medium (L- 15 

Acute and convalescent serum specimens were obtained at the initial and follow-up visits. Complement fixation was used to test for antibodies to adenovirus, respiratory syncytial virus, parainfluenza viruses types 1, 2, and 3, influenza viruses types A and B, and Chlamydiapneumoniae. Immunofluorescence was used to test for IgM antibodies to Epstein-Barr virus (Savyon, Tel Aviv, Israel). An ELISAwas used for the determination of IgM antibodies to cytomegalovirus (Medac, Hamburg, Germany) and to rubella virus (Abbott Laboratories, North Chicago, IL). Microimmunofluorescence was used to test for IgG and IgM antibodies to C. pneumoniae. ~6

Statistical comparisons were performed using Statcalc, a statistics program available through Epi Info. 17 All p-values reported are two-sided.

Of 12,384 patients seen in the outpatient medical clinics, 507 (4.1%) met selection criteria and were enrolled in the study. The average age of the patient at the time of entry was 33.3 years (range 15.2 to 83.3 years), and 276 (54%) were men. One hundred ninetyeight (39%) were smokers, and 167 (33%) had contact with preschool or school-age children. Three hundred thirty-four (66%) patients came to their follow-up visits an average of 13 days after the initial visit. Of those, 312 had blood samples drawn at the second visit for convalescent serologic study.

At the initial clinical visit, the patients were given one or more clinical diagnoses by the housestaff physician. The diagnoses given were: pharyngitis (n = 334, 66%), rhinitis (n = 221, 44%), bronchitis (n----123, 24%), laryngitis (n = 53, 10%), sinusitis (n----44, 9%), conjunctivitis (n----23, 5%), otitis media (n----11, 2%), and mononucleosis (n----5, 1%). More than one diagnosis was given in 234 (46%) of the cases.

Cytologic examination was performed on 453 of the 507 nasopharyngeal specimens. Two hundred thirty-five patients (52%) had ten or more leukocytes per high-powered field in their nasopharyngeal secre- tions, 55 (12%) fewer than ten leukocytes, and 163 (36%) no leukocyte. Epithelial cells were noted in the nasopharyngeal secretions of 317 patients (70%) and ciliated cells in the secretions of 136 (30%) patients. One or more kinds of cells were seen in 407 (90%) of the specimens. Epithelial cells were present in the secretions of 153 of 235 patients (65%) with ten or more leukocytes, and in the secretions of 164 of 218 patients (75%) with fewer than ten leukocytes (p = 0.029). Ciliated cells were present in the secretions of 121 of 235 patients (51%) with ten or more Ieukocytes, but in the secretions of only 15 of 218 patients (7%) with fewer than ten leukocytes (p<O.O01). Bacteria were present on Gram stain in the secretions of 123 of 235 patients (52%) with ten or more leukocytes, but in the secretions of only seven of 218 patients (3%) with fewer than ten leukocytes (p <0.001).

Results of nasopharyngeal and pharyngeal cultures are summarized in Table 1 . The most frequently cultured organisms from the nasopharynx were: coagulase-negative staphylococci, Corynebacterium species, Streptococcus pneumoniae, Staphylococcus aureus, Hemophilus influenzae, and Moraxella catarrhalis. Only 9% of the patients grew "mixed flora," a mixture of light growth of Corynebacteria, streptococci, Neisseria species, and anaerobes. Forty-four percent of the cultures were sterile. In contrast, the most frequently cultured organisms from the pharynx were Hemophilus parainfluenzae, group A streptococci, H. influenzae, S. pneumoniae, Enterobacteriaceae, and S. aureus. Only three cultures were sterile, and 99% grew "mixed flora."

Growth of group A fl-hemolytic streptococci from the pharynx was considered to indicate streptococcal pharyngitis, occurring in 38 of 334 (11%) patients with a clinical diagnosis of pharyngitis and in one of 173 (0.6%) patients without a clinical diagnosis of pharyngitis. Nine of the patients with pharyngitis and a positive pharyngeal culture also grew group A streptococci from the nasopharynx. One patient with pharyngitis grew group A streptococci from the nasopharynx but not the pharynx.

The results of virologic studies of the 312 patients who had two serum specimens drawn are summarized in Table 2 . The most frequent pathogens documented 

No infection with C. pneumoniae was demonstrated by a fourfold rise in IgG titer detected by complement fixation for the 312 patients with two serum specimens available. In addition, no infection was demonstrated by microimmunofluorescence to IgG or IgM antibodies for 55 patients tested at random.

The association of culture of bacteria from the nasopharynx, streptococcal pharyngitis, and viral infection (influenza A, influenza B, parainfluenza) with ten or more leukocytes per high-powered field in nasopharyngeal secretions is summarized in Table 3 . Analysis was performed for 416 patients; 54 patients for whom leukocytes were not counted and 37 patients who had already been treated with antibiotics were not included. Streptococcal pharyngitis and influenza A and B and parainfluenza infection were not associated with increased leukocytes in the nasopharyngeal secretions. However, S. pneumoniae, M, catarrhaHs, H. influenzae, group A streptococci, and $. aureus were associated with ten or more leukocytes per high-powered field in nasopharyngeal secretions. The number of colony-forming units of the organism isolated was independent of the number of leukocytes in nasopharyngeal secretions (data not shown).

The difference in the numbers of leukocytes associated with bacterial and viral infections is more clearly illustrated in Figure 1 . An increased number of leukocytes was found in 73% of the patients with only bacteria cultured from the nasopharynx and in 62% of the patients with both bacteria cultured and virus detected from the nasopharynx. In contrast, only 37% of the patients with a viral infection and sterile nasopharyngeal secretions had ten or more leukocytes in nasopharyngeal secretions. This is not statistically different from the results for patients with sterile nasopharyngeal secretion and no viral infection.

To examine the association of clinical parameters with ten or more leukocytes per high-powered field in the nasopharyngeal secretions, we performed univarlate and multivariate analysis of all the clinical information obtained for the 416 patients who had not already received antibiotic treatment and for whom leukocytes were counted. Results are summarized in Table 4 . History of runny nose (p = 0.002) and rhinitis on physical examination (p = 0.02) occurred significantly more frequently in patients with an increased number of leukocytes in the nasopharyngeal secretions. There was no association with several clinical parameters that might alter the nasopharyngeal flora and therefore increase the number of leukocytes in nasopharyngeal secretions. These include age, history of tobacco abuse, duration of illness prior to seeking medical attention, history of sinusitis, asthma or chronic bronchitis, and clinical diagnosis of sinusitis or otitis media. Multivariate analysis did not change the interpretation of the data (not shown).

Of the nasopharyngeal aspirates of the 21 control subjects, ten were sterile; S. aureus was cultured in two; Corynebacterium in seven; and coagulase-negative staphylococci in five. An increased number of leukocytes was seen in two (9%) on direct examination.

In our study, more than half of the patients with upper respiratory infections had an increased number of leukocytes in the nasopharyngeal secretions associated with the culture of S. pneumoniae, group A streptococci, S. aureus, H. influenzae, and M. catarrhalls from the nasopharynx. An increased number of leukocytes was not associated with diagnosis of viral infection or with the diagnosis of streptococcal pharyngitis. These results raise the possibility of bacterial infection or superinfection of the nasopharynx ("bacterial nasopharyngitis").

Univariate analysis of clinical signs and symptoms revealed that only rhinitis was associated with an increased number of leukocytes in the nasopharyngeal secretions. On the other hand, we did not detect any clinical parameter that might alter the nasopharyngeal flora and/or the inflammatory reaction during upper respiratory infection. In particular, there was no association with a history or current diagnosis of sinusitis, otitis media, tobacco abuse, or chronic respiratory infection.

Methodologically, there are a few factors that may have confounded the correlation of increased leukocytes with the culture of pathogens. First, the nasopharynx may not have been accurately sampled in all cases. However, 90% of specimens contained some sort of cellular material. Furthermore, the presence of epithe- lial cells was inversely correlated with the recovery of leukocytes, suggesting that the absence of leukocytes and bacteria was not due to a sampling error. The presence of ciliated cells was strongly correlated with the presence of leukocytes. It is possible that inflammation, reflected as an increased number of leukocytes, leads to sloughing of ciliated cells.

Other problems with specimen collection and handling include difficulty in homogenizing nasopharyngeal secretions. The specimens analyzed microscopically and cultured for bacteria and viruses may not have been comparable. However, if homogenization had been more uniform, the association between bacteria and leukocytes would have become even stronger. Another difficulty is that differing amounts of nasopharyngeal secretions were aspirated and diluted with the same amount of saline, resulting in variable concentrations of microorganisms and leukocytes.

In addition, relatively few viral infections were diagnosed in our study. Almost all cases were diagnosed by serologic means, precluding diagnosis in the 38% of patients who did not have a second serologic examination. Very few infections were diagnosed by antigen detection or by viral culture. No rhinovirus or coronavirus infection was cultured at all. However, the rate of viral diagnosis in patients with two sera examined was 21%, comparable to the rate of 25% obtained by Huovinen et al. in a recent study of patients with pharyngitis. 5 In this study, as in ours, the bulk of the diagnoses were made by serologic means, with very few made by antigen detection or culture.

The overall rate of viral diagnosis was well below the rate of 23% obtained by Eggenberger 18 in a recent study of upper respiratory infections in children using only antigen detection at the same viral laboratory after a similar transport time. Antigen detection may be less successful in adults than in children for a couple of reasons. The immune response of adults may be more swift and effective than that of children, neutralizing the viral antigen and making diagnosis by this method more difficult. Furthermore, adults may wait longer to seek medical attention than children do, rendering the detection of viral antigen in nasopharyngeal secretions less likely.

Most viral upper respiratory infections are felt to be caused by rhinovirus. 1' 2 Because rhinovirus was not successfully cultured, we cannot eliminate the possibility that this virus is associated with an increased number of leukocytes. However, this seems unlikely since none of the other viral infections was associated with a significant number of leukocytes.

Chlamydia pneumoniae has recently gained recognition as a cause of respiratory tract infection, especially of the lungs) 9, 2o In our study, no infection with C. pneumoniae was demonstrated. This may be because patients with pneumonia were excluded.

In children, purulent bacterial nasopharyngitis is recognized and has been studied extensively. 11"13 It is felt to be caused by ~8-hemolytic streptococci, H. infuenzae, and pneumococci and should be managed with antibiotics. 12 Hypothesizing the existence of bacterial nasopharyngitis in adults, the most likely bacteria would be those that are not part of the normal nasopharyngeal flora and those that are known to cause infection in the lower respiratory tract. Jousimies-Somer et al. compared the nasal swab cultures of 183 healthy military recruits with those of 18 5 military recruits who had acute maxillary sinusitis. 21 The culture of S. pneumoniae increased from 1% to 25% and that of H. influenzae increased from 4% to 61% between the healthy military recruits and the recruits with sinusitis. In contrast, the culture of Corynebacteria decreased from 43% to 19% and the culture ofS. aureusdecreased from 36% to 18%. The cultures of coagulase-negative staphylococci and M. catarrhalis remained about the same in both groups studied. In our study, potentially pathogenic bacteria were not cultured for any of the control subjects.

On the other hand, it is possible that the presence of pathogenic bacteria and increased leukocytes in the nasopharnx may be secondary to colonization of already inflamed nasal mucosa, rather than the pathogenic bacteria causing inflammation and an increased number of leukocytes in the nasopharynx. It is also possible that certain bacteria, such as S. aureus, may have been introduced into the nasopharyngeal aspirate as the sampling catheter passed through the anterior nares.

Our data suggest that S. pneumoniae, M. catarrhalls, and H. influenzae may be a cause of bacterial infection in the nasopharynx, whereas S. aureus is only weakly associated with the presence of leukocytes. Group A streptococci have been shown to be pathogenic in the nasopharynx of young children, tl but have so far not been cultured in adults.

More investigation is required to determine whether the presence of bacteria and leukocytes in the nasopharynx in adults really means bacterial nasopharyngitis. If it exists, recognition and treatment would be important. Bacteria in the nasopharynx may lead to descending infections, such as bronchitis and pneumonia. Antibiotic treatment could shorten the duration of upper respiratory infections caused or exacerbated by bacteria and possibly prevent more serious lower respiratory tract infections. Although many physicians already treat adults who have uncomplicated upper respiratory tract infections with antibiotics, only a controlled prospective study using placebo and antibiotics could resolve the issue.

Viral respiratory illnesses

Epidemiology of community-acquired respiratory tract infections in adults: incidence, etiology, and impact

Acute respiratory illness in an American community: the Tecumseh study

Clinical syndromes in adults caused by respiratory infection

Pharyngitis in adults: the presence and coexistence of viruses and bacterial organisms

Diagnostic methods in respiratory infections

A new look at respiratory illness in general practice: a reclassification of respiratory illness based on antibiotic prescribing

A controlled trial of erythromycin in adults with nonstreptococcal pharyngitis

Broad and persistent effects of benzathine penicillin G in the prevention of febrile, acute respiratory disease

Isolation of viruses from nasopharyngeal secretions: comparison of aspiration and swabbing as means of sample collection

Aerobic and anaerobic bacteriology of purulent nasopharyngitis in children

Can nasal bacteria flora be predicted from clinical findings?

The nasopharyngeal microflora of otitis-prone children, with emphasis on H. influenzae

Bacterial colonization of the upper respiratory tract and its association with acute lower respiratory tract infections in highland children of Papua New Guinea

Identification of respiratory virus antigens in middle ear fluids of children with acute otitis media

Microimmunofluorescence serological studies with the TWAR organism

Version 5: a word processing, database, and statistics program for epidemiology on micro-computers

Donn~es ~pid~miologiques des maladies infectieuses respiratoires provenant d'un cabinet de p6diatrie ambulatoire

Seroprevalence of Chlamydia pneumontae infections in otolaryngeal diseases

Comparisonofthe nasal bacterial floras in two groups of healthy subjects and in patients with acute maxillary sinusitis

The authors thank the patients who participated in the study, the physicians and nurses of the Policlinique de M~decine who treated the patients, the laboratory technicians who assisted with the study, and Drs. Bernadette Mermillod and Alfredo Morabia, who helped perform the statistical analysis.