Gramegative diplococci include several Neisseria species, such as meningococci and gonococci; and Branhamella catarrhalis. Branhamella catarrhalis (formerly Neisseria catarrhalis) is a member of the genus Moraxella but closely resembles neisseriae in many respects, including microscopic appearance. B. catarrhalis, as well as some of the neisseriae, is normally found in the upper respiratory tract. Although usually nonpathogenic, it occasionally can produce pneumonia (especially in patients with chronic lung disease) and very uncommonly has caused bacteremia.

Meningococci

Meningococcal infection is still the most common type of meningitis, although the incidence varies with age (Chapter 19). Meningococci are present in the nasopharynx of approximately 5%-15% (range, 0.9%-40%) of clinically normal persons, and it takes special subculturing to differentiate these from nonpathogenic Neisseria species that are normal common inhabitants of the nasopharynx. In rare instances one of the (usually) nonpathogenic Neisseria species may be associated with serious disease, such as septicemia or meningitis.

Gonococci

Neisseria gonorrhoeae causes gonorrheal urethritis and initiates the majority of cases of acute salpingitis, so-called pelvic inflammatory disease (PID). Gonorrhea is not symptomatic in about 75%-80% (range, 60%-83%) of infected females and in about 10%-15% (range, 5%-42%) of infected males. Currently, about 2% of gonococcal strains are resistant to penicillin (range, 0%-6%, depending on the location in the United States; rates of 10%-30% have been reported in parts of the Far East and Africa). A presumptive diagnosis of gonorrhea can often be made by a Gram-stained smear of discharge from the male urethra. Gonococci appear as bean-shaped gramegative intracellular diplococci, located within the cytoplasm of polymorphonuclear neutrophils. Extracellular organisms are not considered reliable for diagnosis. Acinetobacter calcoaceticus (formerly Mima polymorpha) and Moravella osloensis look somewhat like gonococci in urethral gram stain; these bacteria are usually extracellular but can be intracellular. S. aureus sometimes may simulate Diplococcus, although it is rounder than typical gonococci organisms and is gram positive rather than gram negative. Finally, rare urethral infections by Neisseria meningitidis have been reported. Nevertheless, consensus is that diagnosis of gonorrhea can be made from a male urethral smear with reasonable confidence if there are definite gramegative diplococci having characteristic Neisseria morphology within neutrophils. In males with a urethral exudate, a smear is usually all that is required. The patient can wait while the smear is processed, and if the smear is negative or equivocal, culture can be done. In females, an endocervical Gram-stained smear is positive in only 50% of gonorrhea cases (literature range, 20%-70%). Cultures should therefore be done, both to supplement the smear as a screening technique and to provide definitive diagnosis. In females, the endocervical canal is the single best site for culture, detecting about 82%-92% of cases that would be uncovered by culture from multiple sites. About 30%-50% of patients have positive rectal cultures (swab cultures using an anoscope, taking care to avoid contamination with feces). Rectal culture adds an additional 5%-10% of cases to endocervical culture. Cultures repeated on specimens obtained 1 week later will uncover an additional 5%-10% of cases. In males, a rectal culture is positive much less frequently except in male homosexuals, with one study finding approximately 30% of cases positive only by rectal culture. Pharyngeal gonorrhea is usually asymptomatic, self-limited (10-12 weeks), and visible in less than 50% of cases. Gonococcal penicillin resistance occurs in 2% (0%-6%) of cases; some are resistant to certain other antibiotics.

Certain technical points deserve mention. Gonococci should be cultured on special media, such as Thayer-Martin or NYC, rather than on the traditional less selective media like chocolate agar, and need a high carbon dioxide atmosphere for adequate growth. Speculum instruments should not be lubricated with material that could inhibit gonococcal growth (which includes most commercial lubricants). Specimens should be inoculated immediately into special transport media. There are several commercial transport systems available specifically for gonococci, most of them based on modified Thayer-Martin medium and incorporating some type of carbon dioxide source. Some authors state that the medium on which the specimen is to be inoculated should be warmed at least to room temperature before use, since gonococci may not grow if the medium is cold. However, others obtained similar results with cold or room temperature media. To make matters more confusing, some investigators report that vancomycin used in gonococcal selective media to prevent bacterial contaminant overgrowth may actually inhibit gonococcal growth if the gonococcal strain is sensitive to vancomycin (about 5%-10% of strains, range, 4%-30%). Due to the 24- to 48-hour delay in obtaining culture results and lack of adequate Gram stain sensitivity in female infection, additional rapid tests to detect gonococcal infection have been introduced. One of these is Gonozyme, an immunologic enzyme-linked immunosorbent assay (ELISA) procedure that takes 3 hours to perform. Sensitivity (compared to culture) in males is reported to be about 97% (range, 93%-100%, similar to Gram stain results) and about 93% (range, 74%-100%) in females. Disadvantages are that Gram stain is faster and less expensive in males, the test cannot be used for rectal or pharyngeal specimens due to cross-reaction with other Neisseria species, there is an inability to determine if a positive result is a penicillin-resistant infection, and there are a significant number of false negative results in females. At present, the test is not widely used. Gonorrhea precedes the majority of cases of acute and chronic salpingitis (PID). However, gonococci can be isolated from endocervical culture in only about 40%-50% of patients with proved PID (literature range, 5%-80%). Chlamydia trachomatis apparently is also an important initiator of PID— or at least associated with it in some way—with acute infection with Chlamydia being present in a substantial minority of patients, either alone or concurrently with gonorrhea (combined infection of the endocervix is reported in 25%-50% of cases). The organisms most frequently recovered from infected fallopian tubes or from tuboovarian abscesses include gonococci, group D streptococci, anaerobes such as Bacteroides or anaerobic streptococci, and gramegative rods. Infection is often polymicrobial.

Nongonococcal urethritis and the acute urethral syndrome. In men, nongonococcal urethritis reportedly constitutes about 40% of urethritis cases, and some believe that it is more frequent than gonorrhea. The most common symptom is a urethral discharge. Chlamydia trachomatis is the most commonly reported organism, identified in 30%-50% of male nongonococcal urethritis patients. Chlamydia has also been found in some female patients with nongonococcal cervicitis, and Chlamydia may coexist with gonococci in other patients. Ureaplasma urealyticum (formerly called T mycoplasma) is frequently cultured in male nongonococcal urethritis, but its relationship to disease is not proved. Reiter’s syndrome might also be mentioned as an occasional cause of nongonococcal urethritis. Chlamydia organisms have been found in some cases of Reiter’s syndrome. In females, nongonococcal urethritis is usually called the acute urethral syndrome. Symptoms are most commonly acute dysuria and frequency, similar to those of acute cystitis. In females with these symptoms, about 50% have acute cystitis, and about 25%-30% (range, 15%-40%) are due to the acute urethral syndrome. Some of the remainder are due to vaginitis. Differentiation between acute cystitis and the acute urethral syndrome is made through urine culture. A urine culture with no growth or quantitative growth less than 100,000/mm3 suggests acute urethral syndrome. Diagnosis of urethral infection usually requires the following steps:

1. Symptoms of urethritis (urethral discharge or dysuria).
2. Objective evidence of urethritis. In men, a urethral Gram-stained smear demonstrating more than four segmented neutrophils per oil immersion field or (alternatively) 10 or more leukocytes per high-power field (some require 15 rather than 10) in the centrifuged sediment from the first portion (first 10-30 ml collected separately) of a clean-catch (midstream) voided urine specimen is required. In women, a urine culture without growth or growing an organism but quantitatively less than 100,000 (105) organisms/ml is required.
3. Exclusion of gonococcal etiology (urethral smear or culture in men, urethral culture in women). Culture or direct identification (e.g., fluorescent antibody or nucleic acid probe methods) would be needed to detect Chlamydia or Mycoplasma organisms.