Infectious Disease Compendium

Neisseria

Microbiology

Gram negative diplococci. N. cinerea, N. gonorrhea, N. lactamica, N. meningitis (Serogroups A,B,C,W135 in US X in Africa), N. subflava, N. sicca.

On gram stain Neisseria are side to side footballs, streptococci tend to be end to end footballs.

Some gonorrhea lack the prolyliminopeptidase and as a result may not have a positive antigen test (PubMed).

Epidemiologic Risks

N. gonorrhoeae: sex with infected partner. If you blame acquisition on a toilet seat, that's a hell of a place to have sex. Neonates can acquire it at birth. Getting ready for a date? Listerine (which does NOT contain Listeria) can kill oral GC (PubMed). Men who have sex with men have markedly more transmission; perhaps they should use Listerine? (PubMed).

N. meningitidis: can be part of normal flora, especially in the winter and during times of crowding. Carriage rates depends on age: "Carriage prevalence increased through childhood from 4·5% in infants to a peak of 23·7% in 19-year olds and subsequently decreased in adulthood to 7·8% in 50-year olds. The odds of testing positive for carriage decreased if swabs were not plated immediately after being taken compared with if swabs were plated immediately (PubMed)"

MSM have increased rates of N. meningitidis and HIV positive MSM even more (PubMed).

N. lactamica, N. sicca, N. subflava, N. cinerea: part of normal human flora.

Syndromes

N. gonorrhoeae: urethritis, cervicitis, disseminated disease with a migratory tenosynovitis followed by oligoarticular arthritis (with and without a purpuric rash), PID, occasionally pharyngitis (not uncommon in men who have sex with men but 95% are asymptomatic (PubMed)), and proctitis.

In men who have sex with men, it can be often found in the pharynx and routine therapy for urethral diseases may not eradicate it (PubMed).

N. meningititis: meningitis and sepsis with and without purpura. About 8% will develop arthritis (clinically making you wonder if GC) that will respond to antibiotics and a tap without taking to the OR, although the fact that many needed steroids to get better suggests better debridement may have been in order (PubMed). HIV have 10 x the incidence of disease (Pubmed).

And N. meningititis can cause urethritis (PubMed) and proctitis (PubMed) .

N. lactamica, N. sicca, N. subflava, N. cinerea: will be isolated in sputum, blood and other body fluids on occasion, significance depends on the patient and the body fluid. I see the occasional endocarditis with these Neisseria.

Treatment

N. gonorrhoeae is well on its way to becoming the first completely resistant common pathogen (Pubmed). I bet it beats S. aureus to the punch.

N. gonorrhoeae: All from the CDC STD Guidelines of 2010 except as noted (CDC).

Given resistance rates, YOU CANNOT USE quinolones for GC and rely on it (PubMed). GC can become resistant to azithromycinin as little as 12 days after exposure. And azithromycin resistance is increasing as well (PubMed). Antibiotic resistance by STD always seems to be reported in areas where people like to go for vacation like Hawaii. Must be intense evolutionary pressure.

As of Oct 2011, the CDC recommends dual therapy with a cephalosporin (ceftriaxone; 250 mg) plus either azithromycin (preferred) or doxycycline because of increasing resistance including resistance of cefixime; there is now a strain resistant to all antibiotics except the carbapenems (PubMed).

Uncomplicated Gonococcal Infections of the Cervix, Urethra, and Rectum
Recommended Regimens (CDC)*

ceftriaxone 250 mg IM in a single dose. Preferred.

cefixime 400 mg orally in a single dose. As of Aug 2012, no more po cephs to treat GC. Too much resistance.

PLUS TREATMENT FOR CHLAMYDIA IF CHLAMYDIAL INFECTION IS NOT RULED OUT

azithromycin 1g orally in a single dose

OR

doxycycline 100 mg a day for 7 days

As back up, but not CDC approved, consider gentamicin 240 mg intramuscularly plus azithromycinin 2 g orally (100% cure), OR gemifloxacin 320 mg orally plus azithromycinin 2 g orally (98.5% cure) (PubMed).

Uncomplicated Gonococcal Infections of the Pharynx

ceftriaxone 250 mg IM in a single dose. Preferred.

PLUS

azithromycin 1g orally in a single dose

OR

doxycycline 100 mg a day for 7 days. However the doxycycline option may have a higher failure rate (PubMed).

* Quinolones should not be used for infections in MSM or in those with a history of recent foreign travel or partners’ travel, infections acquired in California or Hawaii, or infections acquired in other areas with increased QRNG prevalence.

Recommended Regimens for MSM or Heterosexuals with a History of Recent Travel*

Ceftriaxone 250 mg IM in a single dose

OR

cefixime 400 mg orally in a single dose. As of Aug 2012, no more po cephs to treat GC. Too much resistance.

PLUS

TREATMENT FOR Chlamydia IF Chlamydia INFECTION IS NOT RULED OUT

* Quinolones should not be used for infections in MSM or in those with a history of recent foreign travel or partners’ travel, infections acquired in California or Hawaii, or infections acquired in other areas with increased QRNG prevalence.

As of 2003, 14% are resistant to penicillin and 6.5% are resistant to tetracycline (PubMed).

As of 2010, there is decreased susceptibility to azithromycin reported in SoCal (PubMed).

Disseminated Gonococcal Infection (DGI) Recommended Regimen:

Ceftriaxone 1 g IM or IV every 24 hours

Alternatives

Cefotaxime 1 g IV every 8 hours

OR

Ceftizoxime 1 g IV every 8 hours

All of the preceding regimens should be continued for 24--48 hours after improvement begins, at which time therapy can be switched to cefixime 400 mg orally twice daily to complete at least 1 week of antimicrobial therapy. No treatment failures have been reported with the recommended regimens.

Whenever you treat GC, you treat chlamydia and vice versa.

- one alternative for GC is gentamicin 240 mg intramuscularly plus azithromycin 2 g orally, or gemifloxacin 320 mg orally plus azithromycin 2 g orally (PubMed).

N. meningitidis: Penicillin (although resistance is starting to creep up in some parts of the world) OR a third generation cephalosporins or, if not meningitis, quinolones. While we usually treat for 10 days, 5 may be sufficient.

Do not forget steroids if meningitis

Prophylaxis: if they were sharing air with the index case for greater than 4 hours or exchanging body fluids (saliva) or a roommate in a crowded situation (prison or dorms) up to 10 days from onset of index case disease. Rifampin 600 mg po q 12 x 2 d OR ciprofloxacin 500 mg po x 1 OR ceftriaxone 250 mg im x 1 (pregnancy).

BEWARE: there has been quinolone resistance in the US as of 2008 (MMWR) and it may not be the right drug in your area.

Here is my 'take':

Meningococcal Post-Exposure Prophylaxis

There is apparently some misunderstanding about the necessity of post exposure prophylaxis for health care providers exposed to a real or potential cases of Meningococcal meningitis or bacteremia. Exposure to colonized patients is not a risk and can be present in 2%–10% of children and

“In Europe, as much as 35% of young adults are carriers at a given time.”

Family members exposed to an index case of invasive disease are transiently at increased risk for disease with an attack rate of .3 to 1%. This is likely partly due genetic/hereditary variations in the immune system that predispose the patient and their family in invasive disease. It is likely as much the patient and as the organism that leads to infection.

For family members, greater than 4 hours exposure or contact with respiratory secretions antibiotic prophylaxis is recommended. And no physician has EVER spent 4 hours in a room with a patient.

In contrast, despite studies, there is no benefit to be found in treating colonized people or their contacts outside of invasive disease as nicely summed up by UpToDate:

“There are no recommendations for eradicating nasopharyngeal carriage in the community outside of an outbreak or a patient with invasive meningococcal disease. There are three problems with attempting to eliminate nasopharyngeal carriage in the community:

Spontaneous loss and acquisition of carriage is common. This was illustrated in a study in military recruits in which 34 percent experienced one or more change in carrier status over time.

Recurrent colonization may occur after prophylaxis. In a community-wide prophylaxis program in a semi-closed kibbutz population in Israel, the colonization rate of group B meningococcus dropped from 4.6 percent at baseline to 0 percent at three weeks; it then rose to 0.5 percent at six months and 3.9 percent (similar to the baseline level) at one year.

Antimicrobial prophylaxis has no proven clinical efficacy outside of an outbreak. The meta-analysis cited above included trials in healthy carriers [48]. Clinical efficacy of eradication could not be assessed since there were no cases of disease following antibiotics or placebo.”

How about health care providers? There are at best a half dozen cases of secondary spread to HCWs ever reported and they all had one factor in common: exposure to respiratory secretions without proper PPE:

“Transmission of N. meningitidis to health-care personnel has occurred after unprotected exposure to infected patients during endotracheal intubation, airway suctioning, and oxygen administration (6–8), but more than one occupationally acquired infection from the same index patient has not been reported. Findings from this investigation indicate that breaches in infection control…likely contributed to secondary cases of meningococcal disease (1).”

And the first step when the issue of meningitis is raised should be to put on a mask.

Unless exposed to direct secretions, no antibiotic prophylaxis is warranted, only driving cost, toxicity, and resistance without benefit.

“To be on the safe side, any person directly exposed to the case’s nasopharyngeal secretions (e.g., through kissing or mouth-to-mouth resuscitation) is also advised to take prophylaxis. On the other hand, health care workers who haven’t had contact with secretions are not at risk and do not benefit from prophylaxis (Pubmed).”

Here is a suggested algorithm

1) Meningitis is suspected.

Droplet Isolation i.e. surgical masks. Viola. Everyone safe.

2) LP shows meningitis by cell count, protein, glucose.

Wait. No hurry for prophylactic antibiotics, Meningococcus is not like lice, jumping off the patient on to you.

3) Gram stain is negative or has gram negative rods or gram positive cocci.

Meningococcus is gram negative diplococci. Wait. It isn’t Meningococcus; prophylactic antibiotics will not be needed.

4) Gram stain has gram negative diplococci.

Wait. No hurry.

5) Cultures grow N. meningitis.

Prophylaxis for those who were directly exposed to respiratory secretions: mouth to mouth, suctioning, intubation or other respiratory procedures without PPE.

Other health care providers do not need prophylaxis and to do so would be, and I have to be careful of the adjective I use in an official communication, lets say ill advised.

However, everyone who has even the remotest contact with a meningococcal disease freaks out and wants prophylaxis. In a recent case I had an anesthesiologist place a line in a patient with meningococcal disease, actually followed all isolation procedures, and still thought they have an exposure that warranted the use of ciprofloxacin, What are you gonna do? It is a battle that is probably not worth fighting; I figure the ciprofloxacin is more of an anxiolytic.

Prevention:

There is a vaccine that is cover A, C, and W-135. It's an OK vaccine; my children got it when they went off to college; it does not cover serotype B, for which a separate vaccine became available in 2015. As of July 2007, the CDC recommends the vaccine for all children ages 11 to 18.

As of 2007, serotype X (yes X, it infects the Mac OS) is on the rise in Africa (PubMed).

For those at high risk, the vaccine should be given every 5 years: persistent complement component deficiencies (such as C3, properdin, Factor D, and late complement component deficiencies), anatomic or functional asplenia, and prolonged exposure (eg, microbiologists routinely working with Neisseria meningitidis, or travelers to or residents of countries where meningococcal disease is hyperendemic or epidemic).

N. lactamica, N. sicca, N. subflava, N. cinerea: penicillin OR a third generation cephalosporins OR quinolones.

Notes

The meningococcal vaccine may partially protect against gc(PubMed).

Recurrent, and probably any, Neisseria bacteremia except gonorrhea, should raise suspicion of a terminal complement deficiency. So anyone with non gonococcal Neisseria in their blood should get a CH50. Just do not get it during active illness as complement levels are wonky during disease.

W-135 may have worse disease (PubMed).