Final Year CUCMS Teaching Module

Dr Nor Shuhaila Shahril

BACTERIA!!

Gram staining method

If stained dark blue or violet = gram positive

Due to high amount of peptidoglycan in cell wall

If cannot retained crystal violet but takes up counterstain (safranine or fuchsine), and appear pink or red = gram negative

coccus (sing.), cocci (pl.): are spherical (coccus = a berry), bacillus (sing.), bacilli (pl.): are rod-shaped (bacill(um) = a little stick) spirillum (sing.), spirilla (pl.): are spiral (spiro = spiral, coil).

Streptococcus in chains (strepto = bent, twisted, pliable) Staphylococcus in clusters (staphylo = a bunch of grapes Diplococcus in sets of two (diplo = double)

Gram-positive bacteria, stained purple, of both the bacillus (rod-shaped) and coccus (spherical) forms. A few Gram-negative bacteria are also present, stained pink. Numbered ticks are eleven (11) microns apart.

Cocci (sphere-shaped bacteria)

Streptococcus spp.

Staphylococcus spp.

Bacilli (rod-shaped bacteria)

Subdivided based on their ability to form spores: Non-spore formers are Corynebacterium and Listeria (a coccobacillus) Spore-formers: Bacillus and Clostridium (anaerobes)

E.coli

Coxiella burnetti (coccobacilli) Coccobacillus intermediate between cocci and bacilli shape

Enzymes produced by some bacteria Responsible for their resistance to beta lactam antibiotics like penicillins and carbapenems. These antibiotics have a common element in their molecular structure: a four-atom ring known as a beta-lactam. The lactamase enzyme breaks that ring open, deactivating the molecule's antibacterial properties.

Beta-lactam antibiotics are typically used to treat a broad spectrum of Gram-negative bacteria. Beta-lactamases produced by Gram-negative organisms are usually secreted.
Enterobacteriaceae, Pseudomonas aeruginosa,

Haemophilus influenzae, and Neisseria gonorrhoeae

Cephalosporins (except for 1st generation) are relatively resistant to beta-lactamase.

cephalosporins with an oxyimino side chain, such

as cefotaxime, ceftazidime, ceftriaxone, or cefepime.

Consequently, when these antibiotics were first introduced, they were effective against a broad group of otherwise resistant bacteria.

Enzyme not only chops apart penicillins, but also cephalosporin antibiotics.

Many different species of bacteria can produce the ESBL enzyme, including both gram positive and gram negative bacteria.
The most common ESBL bacteria are E. coli and Klebsiella species.
Surgical site infections and blood infections, and are

commonly responsible for urinary tract infections (UTIs).

Clavulanic acid + amoxicillin = Augmentin Sulbactam+ ampicillin= Unasyn Tazobactam+ piperacillin= Tazosin

GOOD NEWS! Beta-lactamase inhibitors inhibit the beta lactamase thereby not allowing the molecule to hydrolyze the antibiotic. Most ESBLS remain susceptible to Beta-lactamase inhibitors BAD NEWS! Some ESBL producing bacteria produce large amounts of betalactamase thereby overwhelming the beta-lactamase inhibitors.

Antibiotics may need dosage adjustment in patients with renal impairment.

Calculate creatinine clearance

Some antiBx do not need adjustement for patients with renal insufficiency
e.g. amphotericin B, azithromycin, ceftriaxone,

clindamycin, doxycycline, pyrimethamine, rifampicin.

A group of antibiotics derived from Penicillium fungi

1. Natural penicillins: Pen G and V indicated against streptococci, anaerobes (above the diaphragm), syphilis, Listeria monocytogenes (high dose), dog and cat bites (Pasteurella multocida ). Does not cover S. aureus.

2. Penicillinase-Resistant Penicillins (PRSP): Methicillin / cloxacillin indicated against penicillinase producing S.aureus (MSSA not MRSA) for endocarditis, osteomyelitis.
3. Aminopenicillins: Ampicillin / Amoxicillin: G(+) coverage similar to above, covers many G(-) in GI tract (Salmonella, Shigella, E. coli, Proteus), N. meningitidis, 70% of H. influenza, Listeria, Nocardia.

Amoxicillin + clavulanate = Augmentin.

Covers most G(+) except MRSA, and many G(-). Anaerobe coverage ((B. fragilis, C. difficile )

Ampicillin + sulbactam = Unasyn.

Coverage to G(+) similar to above and G(-) all

except Serratia, Enterobacter, Pseudomonas, Legionella. Anaerobe coverage (B. fragilis, C. difficile ) Indication: GYN, GI and skin.

4. Anti-pseudomonal penicillins:
CarboxyPCN e.g. ticarcillin UreidoPCN e.g. piperacillin

Cover most streptococci, and most G(-) with variable coverage for Klebsiella, M. catarrhalis, Serratia, Legionella. NO coverage for Staphylococcus (except for Piperacillin+Tazobactam). Good anaerobic coverage (B. fragilis, C. difficile ). Main indication is Pseudomonas aeuroginosa.
For serious Pseudomonas infections an aminoglycoside should be

added for synergism.

A class of -lactam antibiotics originally derived from the fungus Acremonium, which was previously known as "Cephalosporium. First-generation cephalosporins are active predominantly against Gram-positive bacteria Successive generations have increased activity against Gram-negative bacteria (albeit often with reduced activity against Gram-positive organisms).

Infrequent ADRs (0.11% of patients) include: nausea, vomiting, rash, headache, dizziness, oral and vaginal candidiasis, pseudomembranous colitis, eosinophilia, and/or fever. The cross reactivity with penicillin (5-10%) is a concern especially if pt had anaphylaxis cephalosporins should be completely avoided.

Cephalexin , Cefazolin.

Covers all streptococci, S. aureus (not MRSA) and S. epidermis. Also cover G (-) bacteria: N. gonorrhea, M. catarrhalis, H. influenza , E. coli, Klebsiella. Main indications are surgical prophylaxis and Strep. / Staph. (not MRSA)

Subdivided into: "good for H. influenza" cefuroxime and "good for anaerobes" cefoxitin, cefotetan.

Similar G(+) coverage as 1ST generation and better G(-) coverage including N. meningitis (not the drug of choice for meningitis), Salmonella / Shigella / Proteus and +/Yersenia. Main indications are GI (colorectal surgery and appendicectomy), and Ob-Gyn procedures.

Ceftriaxone (Rocephin) & ceftazidime (Fortum) two most commonly used. Others: cefotaxime (Claforan), cefoperazone (Cefobid) G(+) coverage is similar to 1ST and 2ND generation.

Bacterial meningitis
Has activity against H. influenza (resistant to PCN), N.

gonorrhea and N. meningitidis Good CSF penetration. Dose 2g bd

Pneumonia
CAP (1-2g od, together with macrolide) Mild-to-mod health-care associated pneumonia

Typhoid fever (3g od) Gonorrhoea (125mg IM stat)

Anaerobic coverage varies from one drug to the other. G(-) are generally covered well except for atypicals (e.g. Legionella). Cephalosporins DO NOT cover Listeria or Enterococcus.

Ceftazidime: indicated against Pseudomonas. Older 3RD generation include cefotaxime (Claforan), similar to ceftriaxone, and cefoperazone (Cefobid), similar to ceftazidime.

Cefepime (Maxipine)

Similar to 3rd generation but with better G(-) coverage (P. aeruginosa, Enterobacter, Serratia, C. freundii) and better G(+) coverage (S. aureus ).

Erythromycin Clarithromycin Azithromycin

Clarithromycin and azithromycin have similar antimicrobial profiles, providing enhanced activity against H. influenza as compared with erythromycin and retaining good efficacy against G+ organisms.

Cover Streptococcus, Staphylococcus (not MRSA), +/- N. gonorrhea, H. influenza, M. catarrhalis, Legionella, M. pneumonia and Chlamydia.

Cross-resistance is seen among all macrolides, particularly in Gram positive bacteria. Because azithromycin has the best activity against Chlamydia trachomatis
1 gm PO single dose for the treatment of non-

gonococcal urethritis and cervicitis.

An alternative to penicillin in allergic patients

Non-gonococcal urethritis / cervicitis Upper respiratory tract infections

Pneumonia (atypical) secondary to Legionella or Mycoplasma.

Gastrointestinal complaints, particularly nausea, abdominal pain and diarrhea Headache Abnormal LFT's Reversible hearing loss. Azithromycin and clarithromycin lowest S/E. Clarithromycin - taste disturbance, Archilles tendon rupture

More significant with clarithromycin and erythromycin, as they both increase serum concentrations of drugs metabolized by the P-450 system in the liver. May increase the levels of warfarin, digoxin, carbamezapine May cause arrhythmias when used with some anti-histamines.

Most common is imipenam + cilastatin (Imipenem)

given with cilastatin to inhibit renal breakdown.

Wide spectrum antibiotic Covers most G (+) except MRSA and most G (-) except Legionella and some strains of Pseudomonas (maltophilia, cepacia ).

Also covers all anaerobes and has activity against Listeria and Nocardia.

Seizures are reported particularly in patients with history of seizures or renal failure. Main indication is multidrug resistant bacteria and should NOT be a first choice.

Good activity against G(-) such as Proteus mirabilis and E. coli. Good for GI pathogens such as Vibrio cholera, Campylobacter jejuni, Yersinia, Salmonella and Shigella (drug of choice for traveler's diarrhoea) Most active fluoroquinolone against the Pseudomonas species. Good against bacteria that depend on the production of beta lactamase for survival, thus it covers H. influenza and S. aureus But surprisingly weak against streptococci (including S. pyogenes and S. pneumonia)

NO activity against anaerobic bacteria, including B. fragilis. (not a good choice for PID - weak against chlamydia and enterococci. NOT used in children impair proper growth of cartilage.

Levofloxacin
Better activity against Gram (+) cocci and perhaps

less toxicity. Main advantage: daily dose (250-500mg po qd)

Moxifloxacin (Avelox)
Main indication: community acquired pneumonia

Used as monotherapy

Gentamycin, netilmicin and amikacin are the most common. BEWARE! All aminoglycosides have the potential to cause nephrotoxicity and ototoxicity.

They cover many G(-) including Pseudomonas aeruginosa (but not cepacia or maltophilia) and they do not cover Neisseria (gonorrhea or meningitidis).

DO NOT cover anaerobes, Legionella or atypicals. G(+) coverage is poor, but they will cover S. aureus (MSSA only) and Listeria monocytogenes.

As volume of distribution increases (CHF, ascites, third spacing) the dosage of the drug must be increased. NO CSF penetration. TDM: Peaks and troughs should be measured, although other dosing alternatives are now being used, such as once-daily 7 mg/kg/day of gentamycin. Divided dosing in endocarditis.

Gram negative sepsis, endocarditis (in combination with penicillin), and for synergism against P. aeruginosa infections.

Indicated mainly for anaerobic coverage

Good activity against C. difficile (given PO), Trichomonas, Giardia and B. fragilis.

E.g Tetracycline, doxycycline, minocycline Indication:

Infection due to Rickettsiae, Chlamydia, Nocardia, Lyme's

Minocycline is more effective against staph and used for the treatment of acne. Drugs should be taken on empty stomach since milk, Fe, Ca and antacids interfere with absorption. Photosensitivity reported. Not given to pregnant women or children < 10 years old.

disease (early) Patients allergic to PCN that requires treatment for syphilis

Wide spectrum including activity against streptococci and H. influenza. Indicated PO for uncomplicated UTI, COPD/bronchitis, otitis media and PCP prophylaxis. Indicated IV for active PCP with pO2 < 70 mmHg or if unable to tolerate PO.

TMP/SMX (TMP 20mg/kg/day divided into 4 doses).

In HIV (+) pt allergic effects are as high as 50%. Avoid in G6PD deficiency.

Excellent against anaerobes, including such below the diaphragm pathogens as B. fragilis. Covers streptococci and S. aureus (not MRSA). Well absorbed orally Most frequent cause of C. difficile pseudomembranous colitis.

Glycopeptide antibiotics Covers all G(+) including MRSA, C. difficile, Diphtheria, Enterococcus. Indications: alternative to PCN / Cephalosporin in the allergic patient, C. difficile (oral preparation) and MRSA.

Red-man syndrome is seen following rapid administration and is believed to be histamine mediated.
Vancomycin has good CSF penetration and is used as a secondary drug in meningitis to cover resistant Streptococcus. Because of emerging patterns in drug resistance, Vancomycin should be reserved for specific situations and not be used as a first line agent.

30 yr old Malay man Gardener Left lower limb swelling and redness X 5/7 Fever+ Diagnosis? What is the offending organism? What antibiotics do you want to initiate?

Uncomplicated /Immunocompetent
Staphylococcus aureus

Streptococcus pyogenes (Group A)

Streptococcus agalactiae (Group B)

Complicated (burns, diabetes, infected pressure ulcers, traumatic/ surgical wounds)

Gram negative bacilli (Escherichia coli,

Pseudomonas aeruginosa)

Group A streptococci or Clostridium species, with or without other anaerobes, can cause fulminant soft tissue infection and necrosis, especially in diabetic patients.

Anti-staphylococcal penicillin
Cloxacillin/ flucoxacillin Amoxicillin plus clavulanic acid (Augmentin)

1st gen. Cephalosporin (Cephalexin)

If allergic to penicillin
Fluroquinolones with good activity against gram

positive organism (levofloxacin, moxifloxacin, gatifloxacin) Clindamycin

Reasonable empiric monotherapy

Piperacillin/tazobactam (Tazocin)

Carbapenem (imipenem/ meropenem)

Methicillin-resistant Staphylococcus aureus (MRSA)

Vancomycin

Alternatives: Linezolid

21 yr old female Monoarthritis of the left knee Sexually active

Possible diagnosis?
Septic arthritis

Reactive arthritis

What investigation would you do to confirm your suspicion?

Joint aspiration and send synovial fluid for FEME/

C&S

Gonococcal septic arthritis

Neisseria gonorrhoeae

Non-gonoccal septic arthritis

S. aureus (60-70%) Strep species (15-20%) Gram negative bacilli (haemophilus) 5-25% Anaerobes (bacteroides/ Prophionibacterium acnes) 1-5% Brucella/ mycoplasma (rare)

Gonococcal

Non-gonococcal Small children, elderly, immunocompromised Monoarthritis Rare Rare > 95% 40-50% Poor in 30-50%

Host Pattern Tenosynovitis Dermatitis Positive joint cultures Positive blood cultures Outcome

Young, healthy adults Migratory, polyarthralgias/ arthritis Common Common < 25% Rare Good in > 95%

Ceftriaxone
Covers for S. aureus, Strep and N.gonorrhoeae.

50 yr old Malay man Diabetes Type 2 Swelling of right big toe X 3/52
Associated with redness,

yellowish pus discharge+ x 1/52 Fever X 1/52

What investigations would you do?

WCC 15 X 109/L RBS 20 mmol/l Blood C&S: gram positive cocci X-ray as shown: What is the diagnosis? What antibiotic of choice would you commence?

Hallmark characteristics: Bone destruction Periosteal new bone formation

Location:
Lower extremities (most common)
Over pressure areas in diabetics

Spine
Lumbar > thoracic > cervical

Radial styloid Sacroiliac joint

S.aureus (most common) Streptococcus pyogenes Pseudomonas, Klebsiella (drug addicts) Salmonella spp (in sickle cell disease patients) Gram negative bacilli (E.coli, Pseudomonas) post-orthopaedic procedures
Infections of the feet in diabetic patients often involve both bone and soft tissue and are usually POLYMICROBIAL both aerobic and anaerobic bacteria.

REMEMBER!

Gram positive cocci

Group A Strep (may cause acute

sepsis) Enterococcus (may be most common) S. aureus

Enterobactericaeae

Streptococcus spp
IV Penicillin IV Ceftriaxone

Gram negative
IV Ceftriaxone IV Ceftazidime IV Ciprofloxacin

IV Vancomycin/ Linezolid if MRSA

22 yr old male student Fever and headache of 2/7 Vomiting 10X today

What other information do you require?

Nature of headache
Headache worse with coughing, sneezing,

bending over, defaecation raised ICP

Photophobia ENT symptoms ENT region entry point to meninges Reason for immunocompromised state
TB, cryptococcal

Travel history Contact history

Orientated to time/ place/ person Photophobic++ Kernigs positive Tone generally increased bilaterally Power 5/5 both UL and LL Plantars downgoing Unable to perform fundoscopy severe photophobia. No rash

What is the most likely diagnosis?

List the investigations that you would do in this case with justification.

FBC Hb 14, WCC 23, Plt 290 BU 9.0, Na 135, K 3.4, Cl 91, Creat 120 INR 1.05 , PTT 33s (n < 33) RBS 6.8 Blood C&S prior to empirical antiBx Rx CT brain - normal

What do you want to send for:

CSF biochemistry protein, glucose CSF FEME/ Gram stain CSF Indian ink CSF culture and sensitivity CSF AFB smear CSF AFB stain CSF virology CSF cryptococcal antigen

LP results are as follows:

Opening pressure 20 cmH2O Appearance cloudy CSF protein 1.0 g/L CSF glucose 1.5 mmol/l CSF FEME: numerous polymorphonuclear neutrophils, RBC 0.2 X 106/L

COMMENT!

Value
Appearance White Cells Red Cells Protein Glucose pH Pressure

Normal Range
Clear & colourless 0 - 5 x 106 /L (all lymphocytes with no neutrophils) 0 - 10 x 106 /L 0.2 - 0.4 g/L (or less than 1% of the serum protein concentration)

3.3 - 4.4 mmol/L (or 60% of a simultaneously derived plasma glucose concentration)
7.31 7 18 cmH2O

Condition

Appearance

White Cells

Red Cells N N N VH

Protein H or VH N or H H or VH N or H H (only after 1 week)

Glucose VL N or L VL N or L

Bacterial Meningitis

Cloudy & Turbid

Raised neutrophils
Raised lymphocytes

Viral Meningitis N

Tuberculous Meningitis
Subarachnoid Haemorrhage Guillan-Barr Syndrome

N or slightly cloudy
Usually blood stained N N

Raised lymphocytes
N

N or L N

Multiple Sclerosis

Raised N H lymphocytes N= normal, L= low, H = high, VH = very high, VL = very low

Streptococcus pneumoniae (pneumococcus) Neisseria meningitidis H. influenza type b

usually children, but now decreased incidence due to

immunization

Enteric gram negative bacteria

neonates, elderly, recent neurosurgery, immunosuppressed

Group B strep
neonates

Listeria monocytogenes
pregnant women, newborns, elderly, immunosuppressed

Pending culture results High-dose IV Ceftriaxone or Cefotaxime If suspect Cephalosporin-resistant pneumococci, add vancomycin (usually very high doses needed to reach CSF [may need up to 4g/day) needs very careful monitoring!)
STOP if organism known susceptible to cephalosporin/

penicillin

Nosocomial meningitis
Make sure cover for Pseudomonas IV Vancomycin and a cephalosporin with good

activity against Pseudomonas e.g. IV Ceftazidime If confirmed Pseudomonas, add an aminoglycoside e.g. gentamicin or amikacin.

Listeria meningitis
IV Ampicillin +/- gentamicin IV Bactrim if allergic to penicillin

45 year old lady c/o fever and dysuria X 3/7 Chills and rigors Nausea+, poor appetite Vomiting 2-3X per day What is the diagnosis? Lethargic+ BP 110/70 PR 96/min PA: soft, tender Rt loin with positive renal punch, no ballotable kidneys.

UTI
Uncomplicated: Cystitis/ urethritis

Pathogens
Enterobacteriacae (E.coli, Serratia, Klebsiella, Enterobacter, Citrobacter) Staph saprophyticus Enterococci

Antibiotics
Augmentin Fluroquinolones (ciprofloxacin, levofloxacin) Bactrim

Recurrent cystitis (> As above 3 episodes per year) Complicated UTI: Indwelling cathter, obstruction, pyelonephritis As above Possible pseudomonas

As above with prophylaxis Bactrim Beta-lactam plus aminoglycoside Fluroquinolones Piperacillin-tazobactam Imipenem

65 year old lady, non-smoker Diabetic Type 2 for 2 years Fever and cough X 4/7 Productive cough of yellowish sputum No haemoptysis Right-sided pleuritic chest pain Poor appetite No history of recent travel No contact with persons with respiratory illness.

Pink on air, spO2 93%, alert Dyspnoeic RR 32/min Febrile T 38C BP 100/70 mmHg PR 115/ min reg Lungs: dull percussion note with coarse crepitations at right lower zone, bronchial breath sounds.
Diagnosis? Investigation?

FBC Hb 14 Hct 50% Plt 239 TWC 20 BU 16 Na 134 K 4.2 Creat 140 RBS 15 UFEME gluc 1+, ketones nil, prot 1+ ABG pH 7.49 pO2 76 pCO2 29 HCO3 19 What other Investigations would you like to do?

Rt lower lobe pneumonia

(urea > 7 mmol/l)

Streptococcus pneumoniae
Adults with risk factors for drug-resistant Strep pneumoniae (DRSP):

Hemophilus influenzae

older than 65, having exposure to children in day care, having alcoholism or other severe underlying disease, or recent treatment with antibiotics damage from viral pneumonia.

commonly causes CAP in people who have suffered recent lung

Enteric Gram negative bacteria

Escherichia coli and Klebsiella pneumoniae (bacteria in human

Pseudomonas aeruginosa

intestines) Risk factors for infection including residence in a nursing home, serious cardiac and pulmonary disease, and recent antibiotic use.
An uncommon cause of CAP Risk factors: malnourished, bronchiectasis, on corticosteroids , or have

recently had strong antibiotics for a week or more.

Mycoplasma pneumoniae

Chlamydophila pneumoniae Legionella pneumophilia (less common)

Atypical organisms are more difficult to grow.

Healthy outpatients without risk factors

No risk factors for DRSP, enteric Gram negative

bacteria, Pseudomonas Usually caused by viruses, atypical bacteria, penicillin sensitive Streptococcus pneumoniae, and Hemophilus influenzae. Recommended management is with a macrolide antibiotic such as azithromycin/ clarithromycin/ erythromycin for 7 10 days.
IDSA 2007

Outpatients with underlying illness and/or risk factors but do not require hospitalization
underlying cardiac (e.g. CCF) or pulmonary

disease (COPD) or is at risk for DRSP and/or enteric Gram negative bacteria. Treatment:
Fluroquinolone active against Streptococcus pneumoniae such as levofloxacin or moxifloxacin, or A beta-lactam antibiotics (e.g. cefuroxime, augmentin) plus a macrolide (azithromycin, clarithromycin) for 7 10 days.

Hospitalized individuals NOT at risk for Pseudomonas

Beta lactam antibiotics (cefotaxime, ceftriaxone,

ampicillin/sulbactam, ertapenem for selected patients), plus IV macrolide antibiotic (azithromycin) for 7 - 10 days (alternative to azithromycin is doxycycline) Or IV fluroquinolones active against Streptococcus pneumoniae such as levofloxacin or moxifloxacin (if penicillin-allergy)

Hospitalized, ICU treatment NOT at risk for Pseudomonas

Beta lactam antibiotics (cefotaxime, ceftriaxone,

ampicillin/sulbactam, ertapenem for selected patients), plus IV macrolide antibiotic (azithromycin) or fluroquinolones (levofloxacin)

Individuals requiring intensive care at risk for Pseudomonas 2 regimes:

IV anti-pseudomonal beta-lactam (cefipime, imipenem,

Or

meropenem, piperacillin/ tazobactam) plus IV antipseudomonal fluoroquinolone (levofloxacin)

IV anti-pseudomonal beta-lactam (cefepime, imipenem,

meropenem, or piperacillin/ tazobactam) plus IV aminoglycoside (gentamicin) and IV macrolide (azithromycin) or IV anti-pneumococcal fluroquinolone.

72 year old man Recent admission to a private hospital for upper GIT bleed due to duodenal ulcer. Discharged 5/7 ago. c/o cough and dyspnoea for 2/7 OE: temp 37.5C, BP 110/78 PR 100/min Lungs: creps left lower zone with reduced air entry What is the diagnosis?

Early onset
Occurring < 5 days after hospital admission Commonly associated with antibiotic-sensitive bacteria :

H.influenzae, oxacillin-sensitive S. aureus, and S. pneumoniae No risk factors for infection due to potentially antibiotic-resistant bacteria : antibiotic treatment or prior health care facility exposure

Late onset
Occurring 5 days after hospital admission Usually antibiotic-resistant bacteria: MRSA, P. aeruginosa,

Acinetobacter spp., and Enterobacter spp.

ATS. Am J Respir Crit Care Med. 171;388, 2005 Ibrahim EH, et al. Chest. 117:1434, 2000 ; Trouillet JL, et al. Am J Respir Crit Care Med. 157;531, 1998

Antimicrobial therapy in preceding 90 days Current hospitalization of 5 days High frequency of antibiotic resistance in the community or in the specific hospital unit Presence of risk factors for HCAP :

Immunosuppressive disease and/or therapy

hospitalization for 2 days in the preceding 90 days residence in a nursing home home infusion therapy chronic dialysis within 30 days home wound care family member with MDR pathogens

57 year old man Fever X 1/12 Lethargy+ O/E: febrile 38C Lungs: clear PA soft, hepatosplenomegaly Petechiae rashes on lower limbs

Hb 5.6 Plt 27 TWC 2.0 ANC 0.4

Fever in the presence of neutropenia Neutropenia:

ANC of <500 cells/mm3 or ANC that is expected to decrease to < 500 cells/mm3

during the next 48 h.

Profound is sometimes used to describe neutropenia in which the ANC is < 100 cells/mm3
a manual reading of the blood smear is required to

confirm this degree of neutropenia.

Infections (more commonly viral infections, but also bacterial or parasitic infections).

E.g HIV, TB, malaria, EBV

Medications that may damage the bone marrow or neutrophils, including cancer and chemotherapy

Vitamin deficiencies (megaloblastic anaemia B12 and folate)

Diseases of the bone marrow such as leukaemias, myelodysplastic syndrome, aplastic anaemia, myelofibrosis,

Radiation therapy
Congenital (inborn) disorders of bone marrow function or of neutrophil production Autoimmune destruction of neutrophils (either as a primary condition or associated with another disease such as Feltys syndrome) or from drugs stimulating the immune system to attack the cells Hypersplenism, which refers to the increased sequestration and/or destruction of blood cells by the spleen

RP LFT FBP 2 sets of blood culture Culture from any suspected sites of infection CXR

Monotherapy with:
an anti-pseudomonal beta-lactam agent, such as

cefepime, or carbapenem (meropenem or imipenemcilastatin), or piperacillin-tazobactam

IDSA 2011

Other antimicrobials (aminoglycosides, fluoroquinolones, and/or vancomycin) may be added to the initial regimen for management of complications (eg, hypotension and pneumonia) or if antimicrobial resistance is suspected or proven. Vancomycin (or other agents active against aerobic grampositive cocci) is not recommended as a standard part of the initial antibiotic regimen for fever and neutropenia
To be considered for specific clinical indications including

If MRSA: Consider early addition of vancomycin, linezolid, VRE: Consider early addition of linezolid

suspected catheter-related infection, skin or soft-tissue infection, pneumonia, or hemodynamic instability.

Empirical antifungal therapy and investigation for invasive fungal infections should be considered for patients with persistent or recurrent fever after 47 days of antibiotics and whose overall duration of neutropenia is expected to be > 7 days

Hand hygiene is the most effective means of preventing transmission of infection in the hospital. Standard barrier precautions should be followed for all patients, and infection-specific isolation should be used for patients with certain signs or symptoms. Plants and dried or fresh flowers should not be allowed in the rooms of hospitalized neutropenic patients. Avoid attending to patient if health care workers are ill.