Category Archives: Infectious disease

Macrolides

Erythromycin, clarithromycin, azithromycin.

Bacteriostatic not bacteriocidal, but doesn’t necessarily mean inferior.

Broad spectrum, including things that aren’t even bacterial! eg Bordetella pertussis, syphilis.

Diarrhoea and vomiting as main side effects, not an allergy as such. True allergy is virtually unheard of! Other important issues:

  • Risk of pyloric stenosis in neonates
  • Prolong QT, so beware other things that also prolong QT including electrolyte disturbance

Schistosomiasis

Egg in freshwater taken up by snails.  Cercariae released into water and penetrate skin.  With this first infection, urticaria, discrete raised lesions 1-3cm and immune response (to dying larvae, rather than living!).  These then migrate into lungs, so acute schistosomiasis causing immune complex deposition, lymphadenopathy, eosinophilia, pulmonary infiltrates. 

Larvae mature in liver.  Adult worms migrate to mesenteric vessels of bowel, where eggs are laid.  Chronic blood loss from gut lesions. Hepatomegaly, splenomegaly, eventually varices if fibrotic. 

Worms can live 3-10 years.  Immunity only really develops where lots of dead worms, not necessarily high worm burden!  Eggs only start appearing 8 weeks after infection, and multiple samples required (intermittent excretion, perhaps every few days). 

Serology only really useful in travellers as persists? Praziquantel often causes abdo pain, rash, headache.  Only acts on adult worms.   

Campylobacter

Common cause of bloody diarrhoea. As with other causes of bloody diarrhea, often associated with fever and abdominal cramps.

Usually self resolving within a week. Antibiotics help if symptoms severe enough.

Excretion continues for a number of weeks, although risk of spreading infection after diarrhoea has settled of course much less, assuming decent hygiene.

Chronic excretion can occur with continuous symptoms rarely, certainly in immunosuppressed patients. Asymptomatic carriers exist, although seems to be more common in developing countries (so malnutrition probably a factor) and reinfection can also occur, of course.

About 1 in 1000 cases develop Guillain Barre syndrome after the infection. Inflammatory bowel disease seems more common after campylobacter infection?

Epstein Barr virus

One of the Herpes virus family, and like other herpesviruses (herpes, varicella) becomes latent in the body after infection, in the case of EBV in B-lymphocytes. Immune system has developed specific strategies over the course of human evolution to control it – hence specific immunodeficiencies such as Duncan’s syndrome where EBV appears to be the only infection that becomes problematic (even catastrophic).

Associated with a number of tumours, including non-Hodgkin’s lymphoma, Burkitt Lymphoma (especially in Africa), nasopharyngeal carcinoma.

In most children, a mild febrile illness, with lymphadenopathy (“glandular fever” or infectious mononucleosis), sore throat (can be severe). Failure to improve with antibiotics is a clue! Peak age for severe presentations is teenagers – “kissing disease” (sexually transmitted!? Edinburgh students study found lower rates if routine barrier methods used). Prolonged incubation period of 30-50 days!

Classically rash triggered by amoxicillin (which is why amoxicillin isn’t recommended for sore throats, but rash can be seen with penicillin too) – maculopapular, sometimes petechial and/or urticarial, which is rather more suggestive.

On examination, hepatosplenomegaly can be seen.

Blood film characteristically shows atypical lymphocytosis. Monospot test (for heterophile antibodies) 70-90% sensitive so has false negatives as well as false positives so may need to proceed to PCR if important to know.

Mild hepatitis and cholestasis pretty common.

Rarer features are dacrocystitis, pneumonia, myocarditis, low platelets and neutrophils, interstitial nephritis, encephalitis. Haemophagocytic syndrome. 20x higher risk of Guillain Barre syndrome after EBV

Management

Supportive.

Splenic rupture after EBV has been reported but is very rare. Advice usually given to avoid contact sports. In ultrasound studies, peak spleen size is typically noted within the first 2 weeks of illness, but may extend to 3.5 weeks. The majority of spleen injuries occur within the first 21 days of illness and are exceedingly rare at >28 days, so one month avoidance probably sufficient.

A minority develop chronic fatigue type symptoms.

[Sports health 2014]

Meningococcal disease

Gram negative diplococci, causing meningitis and septicaemia. Sometimes bone/joint infection. Neisseria (not meningitidis) responsible for ophthalmia neonatorum.

Main serogroups:

  • A – responsible for epidemics of meningitis across “Meningitis belt” of Sub-Saharan Africa, until Men A monovalent vaccine introduced in 2010 (still epidemics, but due to other serotypes). Hajj also triggers outbreaks.
  • B – 4 component vaccine introduced in 2015 to deal with B being the most common cause of invasive meningococcal disease since introduction of MenC vaccine. Based on vaccine developed for New Zealand epidemic.
  • C – used to be most common cause of invasive meningococcal disease in UK until vaccine introduced. So successful that early dose was dropped from routine schedule, although later resurgence in older children and young people, so teenage booster and university catch up programme introduced.

Clinically, notorious for rapidly evolving, often fatal septicaemia with non blanching rash and limb ischaemia. Curiously, meningococcal meningitis, on the other hand, is the most benign of the various causes of bacterial meningitis. Can be mixed picture, ranging from a few petechial spots only with an otherwise typical meningitis presentation, or else meningococcal septicaemia with neck stiffness, where presence of meningitis is actually a good prognostic sign.

Exquisitely sensitive to antibiotics. Meningitis epidemics in Africa treated with single IM dose ceftriaxone!!! Nasal carriage is the reason for spread, so prophylaxis for close contacts important.

Uveitis

The Uvea is the term for the whole eye (uvea=peeled grape). Whereas conjunctivitis looks like a red eye, it’s only really the surface that is inflamed. With uveitis, all the different tissues of the eye are inflamed. Acutely, might not look that different to conjunctivitis but painful, whereas latter usually just itchy. Anterior chamber starts to fill up with inflammatory cells so vision starts to deteriorate. An irregular pupil due to synechiae can eventually be seen, with hypopyon. Cataracts and scarring can follow.

Chronic on the other hand can be subclinical but potential for visual loss so screening important in associated conditions.

Usually idiopathic, otherwise:

  • Juvenile idiopathic arthritis – about 10% of patients with non-oligoarthritis, and 30% of ANA positive oligo so pretty common
  • HLA-B27 – with or without other B27 conditions such as Ankylosing spondylitis
  • Behcet’s disease (so do HLA B51)
  • Crohns disease and other IBD
  • Granulomatosis with polyangitis (ex-Wegeners)
  • Sarcoidosis (so do chitotriosidase)
  • Tubulointerstitial nephritis and uveitis (TINU) syndrome

Some infections can cause it:

Quinolones

eg ciprofloxacin.

Broad spectrum antibiotics.

Block DNA synthesis by bacteria (uniquely among antibiotics).

Good against gram negatives, including Salmonella, Shigella, Neisseria, Pseudomonas (one of the few oral antipseudomonals).

Good intracellular penetration so active against organisms such as Chlamydia, Mycoplasma, Legionella and some Mycobacteria.

Good tissue penetration including central nervous system. 80% of orally administered drug is bioavailable so the IV route is only used when absorption impaired.

But no anti-anaerobic activity, and not very good against common gram positives eg Pneumococcus, Enterococcus, Staphylococcus (in fact, use is associated with MRSA). The newer types (Gatifloxacin, Moxifloxacin, Levofloxacin) have better gram positive activity but would still not be your first line choice, and have less anti-pseudomonal activity.

Not licensed under 1yr.

Only contraindication is previous tendon problem caused by it!

Adverse Effects:

  • Disabling, long-lasting (even irreversible) musculoskeletal and neurological problems reported, v rarely. So only use for severe infections, unless no other antibiotic appropriate. And stop ASAP if symptoms (muscle pain, joint pain, weakness, neuropathy etc)
  • Seizures (+/- predisposing condition)
  • Tendonitis – rupture can occur within 48hrs of starting, but can also be months later! Steroids at same time may increase risk, as may renal impairment and solid organ transplants
  • Arthropathy in immature animals – so avoided in children (except Nalidixic acid) unless extenuating circumstances (only reversible musculoskeletal symptoms have been reported). Arthropathy occurs in CF anyway.
  • Can prolong QT
  • Photosensitivity
  • Valve regurgitation – so caution if preceding valve disease or other risk factor eg connective tissue disorder (Ehlers-Danlos, Marfans), hypertension (!), Turners (!)

SARS-CoV-2 vaccine

Multiple vaccines in the pipeline, mostly against spike (S) protein in SARS-CoV-2 that facilitates host cell entry.

Pfizer vaccine is mRNA vaccine, completely in vitro derived, uses nanoparticles to aide absorption into host cells which then produce the S protein themselves from the mRNA. AstraZeneca vaccine is chimp adenovirus vector for genetic sequence – mRNA produced once virus taken up by host cell.

Single dose IM injection.

Staphylococcal bacteraemia

7-14 days IV recommended if uncomplicated. Higher relapse rate with shorter course.

Uncomplicated viz

  • Negative repeat blood cultures
  • Defervescence within 72 hours of treatment
  • No evidence of endocarditis
  • No prosthesis or venous catheter
  • No evidence of metastatic infection

I wonder about PVL positive though.

Should echo if high risk for endocarditis or persistent fever.

Consider removing catheters

Neonates should get 14 days IV.

If endocarditis, then 4-6 weeks IV treatment.

If osteoarthritis, then 3-6 weeks IV/oral treatment.

[Peds 2020]