• Summary
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• Background
• Clinical Diagnosis
• Investigation
• Treatment
• Non-Antimicrobial Treatment
• Empirical Antimicrobial Treatment
• Directed Antimicrobial Treatment (when microbiology results are known)
• Duration of Treatment
• Switch to oral agent(s)
• Treatment Failure

Diagnosis

The diagnosis of appendicitis is primarily clinical and based on a history of acute abdominal pain. In children, the classical presentation of central abdominal pain radiating to the right iliac fossa is less common than in adults. Malaise, nausea and a low grade fever are common. Evaluating a child for peritonism relies on careful examination and this may include observing the child sit up, walk or hop. Children under the age of 5 are particularly hard to assess and the threshold for admission for repeated assessment should be low. Similarly peripubertal girls require particular care to ensure there are no gynaecological causes.

Investigations

• Urine for dipstick test, microscopy/culture if <3 years or if urinalysis positive for nitrites or leukocyte esterase (>3years).
• Pregnancy test: all post menarcheal girls
• Abdominal imaging – Do not perform ultrasound scan routinely but consider USS particularly for post menarcheal girls and be aware of false negatives.
• No routine microbiological sampling at uncomplicated appendicectomy.
• Sample pus/fluid at operation if a complex appendicitis or if reoperation is required.

Non-Antimicrobial Management

Screen for severe sepsis and manage accordingly if present.
If appendicitis strongly suspected, the child should be fluid resuscitated, adequacy of analgesia should be confirmed and appendicectomy should be performed once the child is “optimised”. Antibiotics should be prescribed at the time of diagnosis, initial doses should be prescribed in the single dose section and the prescriber should ensure that these are administered immediately.

Empirical (initial) antimicrobial treatment

I.V Cefuroxime plus I.V Metronidazole (see main guideline) unless perforation thought clinically to have already occurred (see complicated appendicitis below).

Duration/subsequent antimicrobial therapy is determined by operative findings:

Allergy to penicillins and cephalosporins:
Clindamycin (IV, Child 1 month–16 years 10 mg/kg 6-hourly plus Gentamicin (once daily regime) (max 1.2g)

Previous MRSA infection or colonization:
Add single dose Teicoplanin 10mg/kg IV (Max 400mg) to above regimens pre-operation.

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Appendicitis is the most common cause of acute abdominal pain requiring surgical intervention. The aetiology of appendicitis has not been established. However, inflammation of the appendix is thought to occur when its lumen is obstructed for example by lymphoid hyperplasia or faecolith. Bacterial invasion and infection of the obstructed appendix results in an inflammatory process. Subsequent oedema is hypothesized to increase intraluminal pressure and cause transmural tissue necrosis.  Rupture of the appendix may result in peritonitis and local abscess formation may occur.

Definitions

In this guideline a case is defined as simple appendicitis when there is no abscess formation or generalised peritonitis and any systemic signs of infection resolve rapidly after appendicectomy.

A case is defined as complicated appendicitis when there is abscess formation or generalised peritonitis or systemic signs of infection that persist after appendicectomy.

Differential diagnosis

Although appendicitis is the only common cause of abdominal pain in childhood requiring surgery, it may easily be confused with a number of other intra-abdominal pathologies. In 75% of children, admitted to hospital with abdominal pain, no specific cause can be identified. Potential causes of abdominal pain other than appendicitis include acute non specific abdominal pain (ANSAP) which may in turn be associated with mesenteric adenitis, non-specific colic or a viral illness. Typically ANSAP improves spontaneously within 24 to 36 hours.

Other causes include urinary tract infection (especially in girls), intussusception in children younger than 3 years old, Meckel’s diverticulitis, ovarian torsion, appendicular colic and in post menarcheal girls Mittelschmerz or, in sexually active girls, pelvic inflammatory disease (PID) or pregnancy. Thread worms (Enterobium vermicularis) have been identified in histologically normal appendices and seem to produce right lower quadrant symptoms that are similar to appendicitis but more colicky in nature and often associated with an elevated eosinophil count. In tropical countries round worms (Ascaris lumbricoides) are rife.
 
If inflammation extends to the ureter or bladder, sterile pyuria may be noted on urinalysis. A torted ovary tends to lead to acute severe pain of sudden onset. Acute salpingitis with a tubo-ovarian abscess or impaction of a stone in the right ureter can be confused with acute appendicitis.

Appendicitis is rare in infants but the incidence rises during childhood, peaking age 15-25 (Sifri & Madoff, 2010).

Bacteriologic studies in appendicitis usually show mixed intestinal flora. Enteric bacteria e.g. Escherichia coli and other Enterobacteriaceae (coliforms), Enterococcus sp., Streptococcus anginosus group (sometimes called “milleri”), Bacteroides spp. and other anaerobes are the most common organisms associated with appendicitis (Sifri & Madoff, 2010).

Care pathways and guidelines have been shown to reduce the complication rates from peritonitis in multiple studies (Bakker et al.; Collins et al.; Smink et al., 2004).  Acute appendicitis complicated by perforation with generalised peritonitis or abscess formation requires a different therapeutic approach to localised appendiceal infection.

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Despite advances in imaging and laboratory studies in recent years, patient history and physical examination remains the cornerstone of diagnosis.

History

Diagnosis of acute appendicitis may be a challenging task for any clinician. Despite technological advances in imaging modalities and laboratory investigations, no specific investigation exists which can identify acute appendicitis with sufficient specificity. Furthermore, clinical evaluation may be more difficult than in adults, particularly in preschool children who cannot verbalise their symptoms. Careful history taking, considerate physical examination and active observation are particularly important to allow safe clinical decision-making.

A classical history of acute onset of colicky periumbilical abdominal pain migrating over several hours (6-24) to the right lower quadrant is encountered less frequently in children in comparison to adults and is almost never seen in preschool children. For this reason, the diagnosis may be delayed or even missed. Anatomical differences (narrow appendiceal lumen) and the potential for rapid physiological deterioration in this age group means presentation with collapse and generalized peritonitis is relatively common.

In the consultation, the importance of privacy, ample time and a sympathetic approach to the child and family can not be over-stated; a rushed evaluation on a ward round is unlikely to produce the required information and may do harm. Some personal questions from parents and child may help to build an atmosphere of trust. Details about the onset of pain, lack of activity and disinterest in toys, associated symptoms of vomiting, fever, coryzal symptoms and refusal to feed are good pointers to the presence of pathology.

If the appendix lies in a position away from the anterior parietal peritoneum, pain may remain poorly localized. A history of previous pain, long duration of symptoms (> 1week) in an otherwise ‘well’ child and lack of migration to the right lower quadrant mitigate against a diagnosis of appendicitis.

Abdominal pain in adolescent females deserves special consideration; the most important diagnoses to exlclude are a torted ovary (pain is often severe and of very sudden onset so presentation is therefore early in the process), pregnancy (ectopic or otherwise) and PID. A gynaecological history should never be forgotten for this group of children.

Examination

Again, an unrushed, considered approach is the key to a successful abdominal examination and is likely to produce valuable information. Distracting the child with conversation during the examination is also very useful. A gentle approach will make ongoing management easier if it is deemed that a repeat examination or even an ultrasound scan is necessary. Occasionally, in a screaming infant the only time for abdominal palpation is a split second during inspiration, when the abdominal wall relaxes.

Guarding and tenderness over McBurney's point is typical but may not be always present. Signs of generalised peritonitis may be present. Systemic signs of infection e.g. tachycardia are more pronounced in those with perforated appendix. Assessment of dehydration should always be performed by assessment of oral intake, urine output, weather, fever, tachycardia, capillary refill time and pulse volume.

A particular difficulty is encountered in diagnosing a pelvic appendix as abdominal symptoms and signs are often attenuated. Patients often present with symptoms of diarrhoea and may therefore be misdiagnosed as gastroenteritis. In contrast to patients with gastroenteritis, diarrhoea may be described as low volume and less offensive than in a purely infective cause. The presence of mucus may also be noted. Similarly, patients with retrocaecal appendicitis may also have a paucity of signs on abdominal palpation unless the loins are careful examined and other techniques such as the psoas stretch test employed. Special attention is required in assessing a child with abdominal pain who has been given antibiotics for some other recent problem e.g otitis media, acne or an unproven UTI. This underlines the importance of avoiding the administration of empirical antibiotics in children with abdominal symptoms and signs without a specific diagnosis.
 
Active observation

Frequently, even with a careful clinical examination, the diagnosis is not certain. In these circumstances, if the child has convincing history but vague clinical signs, they should be observed in hospital. The objective of observation is to assess the child’s symptoms and physical findings every 2-3 hours actively and not wait for new symptoms to appear or pain to subside (Jones, 1976). This way one can frequently differentiate a surgical patient from non-surgical ones. A child, who is otherwise well and lives not far from hospital may be able to go home provided parents can observe for any adverse change in symptoms and agree to return to A&E promptly if necessary.

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Recommended: Urine dipstick followed by microscopy and culture in children suspected of UTI on history and physical examination.
[Evidence level A]

Recommendation: Serum concentration of β-human chorionic gonadotropin should be measured in all post-menarcheal girls to rule out a uterine or ectopic pregnancy.
[Evidence level C]

Recommendation: routine measurement of full blood count, urea and electrolytes and C-reactive protein is not recommended within the first 24 hours of onset of symptoms. Subsequent to this, where there is diagnostic uncertainty, a neutrophilia associated with a raised CRP may indicate an increased likelihood of appendicitis
[Evidence level C]
Most patients have a mild leukocytosis and elevated C-reactive protein but no laboratory tests can distinguish between the different causes of acute abdominal pain.

Recommendation: Routine ultrasonography is recommended in post menarcheal girls and in cases where there is diagnostic uncertainty.
[Evidence level B]
Ultrasonography (US) is rapid and noninvasive, requires no contrast material, it uses no ionizing radiation, and is excellent at visualizing gynecologic abnormalities. Routine use in children with suspected appendicitis showed a 96% negative predictive value (Cappell & Friedel, 2003; Dilley et al., 2001)  N.B. Dutch college of surgeons recommends US in all cases (Bakker et al.)

Recommendation: Routine Computed Tomography (CT) scanning is not indicated in suspected acute appendicitis but may be required when intra-abdominal abscess is suspected and in cases where there is diagnostic uncertainty despite detailed clinical assessment and ultrasound.
[Evidence level B]
Routine CT scanning is unnecessary but the high positive and negative predictive values justify use in selected cases (Toorenvliet et al., 2010). CT should be avoided in children wherever possible because of risks such as increased rate of malignancy according to Brenner et al.

Recommendation: Routine microbiological sampling at the time of appendicectomy is not recommended in acute localised appendicitis in children.
[Evidence level B].

The routine collection of samples for microbiology is common place, but may not influence management and is therefore of questionable clinical value (Foo et al., 2008).  Sampling in more complex cases should be undertaken at the discretion of the surgeon.  N.B pus samples are preferable to wound swabs.

Recommendation: Microbiological sampling (ideally a peritoneal pus sample) is recommended when a child needs to be taken back to theatre for a second procedure.
[Evidence level D].

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Screen for severe sepsis and manage accordingly if present.
If appendicitis strongly suspected, the child should be fluid resuscitated, adequacy of analgesia should be confirmed and appendicectomy should be performed. The aim of surgery is primarily to reduce the septic burden and operating in a timely fashion on an appropriately resuscitated child is more likely to be associated with a good outcome. Early discussion with anaesthetic colleague may facilitate this process.

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Recommendation: When appendicitis is diagnosed commence Cefuroxime and Metronidazole
[Evidence level D]

- Cefuroxime
By intravenous injection:
Child 1 month–16 years 50 mg/kg (max. 1.5g) up to 2 further doses of 30mg/kg (max. 750mg) may be given in simple appendicitis by intravenous injection every 8 hours.

- Metronidazole
By intravenous infusion:
1 month - 16 years 7.5mg/kg/dose (max 500mg) 8-hourly up to 7 days

Recommendation: In children with a history of previous MRSA infection or colonization, add single dose Teicoplanin 10mg/kg IV (Max 400mg) to antimicrobial regimens to be given in the hour pre-operation.
[Evidence level D]

Recommendation: amend antimicrobial duration when operative findings are known as below.
[Evidence level D]

Recommendation: patients with a normal appendix at operation and no other focus of infection identified should discontinue antimicrobials after appendicectomy.
[Evidence level D]

Recommendation: patients without abscess formation, generalized peritonitis at operation OR severe systemic sepsis should normally receive 2 further doses of antimicrobials after appendicectomy.
[Evidence level D]

Recommendation: patients with abscess formation, or generalized peritonitis at operation OR severe systemic sepsis should be changed to Amoxicillin , Gentamicin and Metronidazole . See above
[Evidence level D]

-Amoxicillin
By intravenous injection or infusion:
Child 1 month–16 years 30mg/kg (max. 500mg) every 8 hours

-Gentamicin
Once daily dose regimen by intravenous infusion
Child 1 month–16 years initially 7mg/kg, then adjusted according to serum-Gentamicin concentration

Metronidazole -
Child 1 month–16 years 7.5 mg/kg (max 500mg); up to 7 days treatment (7.5 mg/kg every 8 hours)

Recommendation: patients with abscess formation, or generalized peritonitis at operation OR severe systemic sepsis AND a true allergy to penicillins or cephalosporins should be changed to Clindamycin plus Gentamicin. See above
[Evidence level D]

Clindamycin
By intravenous infusion
Child 1 month–16 years 10 mg/kg 6-hourly (max 1.2g)

Rationale.
Antimicrobial therapy for appendicitis is usually empirical (i.e. without prior knowledge of the microbial cause). Empirical regimens should have activity against the organisms that commonly complicate appendicitis i.e. Faecal flora.

Acute appendicitis complicated by perforation with generalised peritonitis or abscess formation requires a different therapeutic approach to localized appendiceal infection.  The former requires a period of antimicrobial therapy in conjunction with surgery to effect a cure, while the latter may require no further antimicrobial therapy after appendicectomy (Andersen et al., 2005).

Metronidazole and Cefuroxime were previously used for many children with appendicitis. The Trust is trying to reduce the incidence of C. difficile infections and is therefore trying to move away from routine use of cephalosporins. As a result we have been asked to change our practice.  It seems reasonable to continue to use short course (<24 hours) cephalosporin therapy for patients with uncomplicated appendicitis but to change regimen when operative and clinical parameters suggest a more severe infection or that more prolonged therapy is required.  Aminoglycoside-based regimens have broader Gram negative cover than the second generation cephalosporin used previously and, in combination with Amoxicillin and Metronidazole provide an appropriate spectrum of antimicrobial activity.  It is noteworthy that some centres are choosing to add aminoglycosides to their usual regimen because of concerns about antimicrobial resistance (Chan et al., 2010).

There is good evidence supporting the safety of Gentamicin in children and the improved stability of serum drug concentration with once-daily dosing regime (Bass et al., 1998; Contopoulos-Ioannidis et al., 2004; McGlone & Cranswick, 2008; Tonz et al., 2000) [Evidence level A]. This has been seen in all age ranges from pre-term neonates through to adults. Meta-analyses show a trend towards improved clinical efficacy in once-daily dosing regimens (ODR) of Gentamicin compared to multi-dose regimens (MDR; clinical failure rates: 6.7% ODR versus 10.4% MDR; microbiology failure rates: 1.8% ODR versus 4.0% MDR). No difference has been demonstrated in the incidence of ototoxicity or nephrotoxicity between ODR and MDR. Authors also support the use of ODR since it reduces the need for venepunture, accessing of central lines (and therefore the rate of Healthcare Associated Infection). It also reduces cost and leads to greater consistency in practice by simplifying administration, thereby improving patient safety. Local experience has demonstrated a significant proportion of children on a TDS regimen having subtherapeutic levels with may have compromised efficacy.

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Recommendation: Amend antimicrobial therapy according to microbiology results in those complicated cases where samples have been taken.
[Evidence level D]
There is no evidence to guide practice in this area, so this statement represents local consensus.  NB In cases of treatment failure where broad spectrum antimicrobial therapy has already been given, resistant organisms may be cultured and may need alternative therapy.

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Recommendation: In localized appendicitis without abscess formation or generalised peritonitis antimicrobial therapy can stop after appendicectomy after 2 further post operative doses of antibiotic.
[Evidence level D]

Recommendation: In appendicitis with abscess formation or generalised peritonitis or severe systemic sepsis antimicrobial therapy should continue for 5 days.  Occasionally more prolonged therapy may be required.
[Evidence level D]

Variability in antibiotic regimens and the duration of antibiotic therapy has thus-far disabled meta-analyses from giving guidance on this matter.  Recommendations are based on local consensus.

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Recommendation: Children who require antimicrobial therapy for peritonitis or abscess should be treated with IV antibiotics until fever resolves, the white blood cell count normalises and bowel function returns.
[Evidence level D]
There is no evidence to guide practice in this area, so this statement represents local consensus.

Recommendation: Co-amoxiclav is an appropriate empirical choice for oral step down in a NON-penicillin allergic patient.
[Evidence level D]

-Co-amoxiclav
Child 1 month–1 year 0.25mL/kg of 125/31 suspension 3 times daily
Child 1–6 years 5mL of 125/31 suspension 3 times daily or 0.25mL/kg of 125/31 suspension 3 times daily
Child 6–12 years 5mL of 250/62 suspension 3 times daily or 0.15mL/kg of 250/62 suspension 3 times daily
Child 12–18 years one 250/125 strength tablet 3 times daily

Recommendation: In children with a true allergic reaction to pencillins and/or  cephalosporins – give Clindamycin plus Metronidazole .
[Evidence level D]

Clindamycin
By mouth
Child 1 month–12 years 3-6mg/kg 6-hourly (body weight <10kg then minimum dose 37.5 mg 8-hourly)
Child 12-18 years 150-300mg 6-hourly

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Recommendation:  Patients who require a second trip to theatre because of uncontrolled infection should have pus or fluid sent for microbiological investigation.
[Evidence level D]

Recommendation: Patients failing therapy with ongoing clinical signs of infection in spite of antimicrobial therapy as recommended should be discussed with microbiology.
[Evidence level D]

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