After completing this note you will be able to assess a patient, choose an appropriate antimicrobial regimen, apply basic stewardship principles and recognise early signs of resistance. Always verify doses and local protocols against the Kenya Ministry of Health guideline and your hospital formulary.
Definition
Antimicrobial selection is the process of matching a pathogen’s susceptibility profile with a drug that achieves therapeutic concentrations at the site of infection while minimising toxicity and collateral damage.
Stewardship is the coordinated effort to promote the optimal use of antimicrobials—right drug, right dose, right route, right duration—to improve patient outcomes, curb resistance, and preserve future efficacy.
Resistance refers to the ability of microorganisms to survive and multiply despite exposure to an antimicrobial that would normally inhibit or kill them.
Anatomy and physiology you need
| System | Relevant structures | Key physiological concepts |
|---|---|---|
| Respiratory | Upper airway, trachea, bronchi, alveoli | Mucociliary clearance, surfactant, gas exchange |
| Cardiovascular | Endocardium, valvular tissue, myocardium | Endothelial integrity, blood flow dynamics |
| Gastro‑intestinal | Stomach, small intestine, colon | Acidic barrier, gut microbiota, absorption |
| Urinary | Renal pelvis, ureter, bladder, prostate | Urine flow, urothelial defence |
| Skin & soft tissue | Epidermis, dermis, subcutaneous fat | Barrier function, lymphatic drainage |
| Central nervous system | Meninges, blood‑brain barrier | Limited drug penetration, CSF turnover |
| Hepatic & biliary | Hepatocytes, bile ducts | Biliary excretion, first‑pass metabolism |
Understanding these sites helps predict drug distribution, required penetration, and potential toxicities.
Causes and risk factors
- Prior antimicrobial exposure (especially broad‑spectrum agents)
- Inadequate dosing or premature discontinuation
- Hospitalisation (ICU stay, invasive devices)
- HIV infection (CD4 < 200 cells/µL, opportunistic infections)
- Tuberculosis (multidrug‑resistant TB, treatment failure)
- Malaria endemicity (co‑infection, use of antimalarials with antibacterial activity)
- Sickle cell disease (functional asplenia, repeated pneumococcal infections)
- Rheumatic disease (immunosuppressive therapy)
- Chronic lung disease (COPD, bronchiectasis)
- Diabetes mellitus (hyperglycaemia impairing neutrophil function)
- Malnutrition (immune compromise)
- Travel to high‑resistance regions
Pathophysiology
- Colonisation → 2. Selection pressure from antimicrobial use → 3. Survival of resistant sub‑populations → 4. Horizontal gene transfer (plasmids, transposons) → 5. Clonal expansion of resistant strains → 6. Infection with resistant organism → 7. Treatment failure or need for broader‑spectrum agents
Clinical features
| Domain | Key questions / findings | Rationale |
|---|---|---|
| Onset & chronology | When did the symptoms start? Was the onset sudden or gradual? | Sudden onset suggests toxin‑mediated or acute bacterial infection; gradual rise favours opportunistic or chronic infections (e.g., TB, fungal). |
| Fever pattern | Peak temperature, chills, rigors, diurnal variation? | High, sustained fevers with rigors point to invasive bacterial sepsis; intermittent fevers are classic for malaria or TB. |
| Localising symptoms | Cough, sputum, dyspnoea, chest pain, dysuria, abdominal pain, diarrhoea, skin lesions, joint swelling? | Guides organ system involved; e.g., productive cough with purulent sputum → lower respiratory infection; dysuria with suprapubic pain → urinary tract infection. |
| Risk‑factor exposure | Recent travel, animal contact, sick contacts, hospitalisation, surgery, indwelling catheters, recent antibiotics, HIV status, CD4 count, TB exposure, malaria prophylaxis, sickle‑cell crises, rheumatic disease, immunosuppressants? | Identifies predisposition to specific pathogens (e.g., HIV → opportunistic fungi; sickle‑cell → encapsulated bacteria). |
| Medication history | Current antibiotics, antiretrovirals, antimalarials, immunosuppressants, recent drug allergies? | Prior antibiotics select resistant flora; drug interactions affect choice of agents. |
| Vaccination status | Pneumococcal, Hib, influenza, typhoid, yellow fever, BCG? | Lack of vaccine protection raises likelihood of vaccine‑preventable organisms. |
| Systemic review | Weight loss, night sweats, fatigue, myalgia, headache, neurological signs? | Constitutional symptoms suggest disseminated infection or TB; neurological signs may indicate meningitis or cerebral malaria. |
| Examination – General | Temperature, pulse, blood pressure, respiratory rate, mental status, skin colour, jaundice, lymphadenopathy, rash, petechiae? | Fever, tachycardia, hypotension = systemic inflammatory response; rash/petechiae may indicate meningococcemia or drug reaction. |
| HEENT | Conjunctival injection, oropharyngeal erythema, tonsillar exudate, sinus tenderness? | Upper respiratory sources; sinusitis can seed lower tract. |
| Chest | Breath sounds (crackles, bronchial breath sounds), pleural rub, egophony, percussion dullness? | Consolidation → bacterial pneumonia; pleural rub → pleuritis or TB pleuritis. |
| Cardiovascular | Murmurs, signs of endocarditis (Osler nodes, Janeway lesions), peripheral pulses? | New murmur or peripheral stigmata suggest infective endocarditis, especially in HIV or IV drug users. |
| Abdomen | Tenderness, guarding, organomegaly, hepatosplenomegaly, ascites? | Hepatosplenomegaly common in malaria, disseminated TB, or opportunistic fungal infection. |
| Genitourinary | Costovertebral angle tenderness, suprapubic tenderness, discharge? | CVA tenderness → pyelonephritis; discharge → STI‑related urethritis. |
| Skin | Lesions (ulcers, pustules, necrotic eschars), cellulitis, erythema nodosum? | Necrotic eschar → cutaneous anthrax; cellulitis → Staphylococcus/Streptococcus; erythema nodosum → TB or sarcoidosis. |
| Neurological | Neck stiffness, photophobia, focal deficits, altered consciousness? | Meningeal signs → meningitis; focal deficits → brain abscess or cerebral malaria. |
| Peripheral | Joint swelling, warmth, limited ROM? | Septic arthritis, especially in sickle‑cell disease or HIV. |
Differential diagnosis
| Condition | Points toward it | Distinguishing features |
|---|---|---|
| Bacterial pneumonia | Sudden fever, productive purulent sputum, pleuritic chest pain, lobar consolidation on exam | Focal crackles, lobar infiltrate, rapid response to β‑lactams |
| Pulmonary TB | Chronic cough >2 weeks, night sweats, weight loss, HIV+, prior TB exposure | Upper‑lobe cavitary lesions, positive GeneXpert, slower symptom progression |
| Malaria (falciparum) | Recent travel to endemic area, cyclic fever, chills, splenomegaly, anaemia | Peripheral smear shows parasites, rapid diagnostic test positive |
| Bacterial sepsis (Gram‑negative) | Hypotension, tachycardia, warm extremities, recent abdominal source or catheter | High lactate, neutrophilia, source identified (e.g., urinary tract) |
| Opportunistic fungal infection (e.g., Cryptococcus) | Advanced HIV (CD4 < 100), headache, meningismus, papilledema | India‑Ink stain positive, CSF cryptococcal antigen |
| Viral hepatitis (A/E) | Jaundice, malaise, recent contaminated water/food, HIV co‑infection | Elevated transaminases, serology positive, no bacterial growth |
| Acute rheumatic fever | Recent streptococcal pharyngitis, migratory arthritis, carditis, chorea | Jones criteria, elevated ASO titre, no bacterial culture |
| Sickle‑cell vaso‑occlusive crisis with infection | Known sickle cell, bone pain, fever, splenic sequestration | Positive sickle‑cell screen, pain pattern, possible osteomyelitis on imaging |
Investigations
| Test | What it answers | Interpretation |
|---|---|---|
| Full blood count | Leukocyte response, anaemia, thrombocytopenia | Neutrophilia → bacterial; lymphopenia → viral/HIV; anaemia with schistocytes → malaria |
| Blood culture (2 sets) | Presence of bacteremia/fungemia | Growth of organism guides definitive therapy; no growth after 48 h suggests non‑bacterial or prior antibiotics |
| Urine microscopy & culture | Urinary tract infection | Pyuria + ≥10⁵ CFU/mL of a single organism = significant UTI |
| Sputum Gram stain & culture | Lower respiratory pathogens | Gram‑positive cocci in chains → Streptococcus pneumoniae; Gram‑negative rods → H. influenzae, Klebsiella |
| Chest X‑ray | Lung infiltrates, effusion, cavitation | Lobar consolidation → typical pneumonia; cavitation → TB or necrotising infection |
| Rapid malaria test (HRP‑2) | Presence of Plasmodium falciparum | Positive = treat for malaria; negative → consider microscopy |
| Thick & thin blood smear | Species identification, parasite density | Ring forms, gametocytes confirm falciparum; high density predicts severe disease |
| HIV test (4th generation) | HIV status | Positive → need opportunistic infection work‑up, CD4 count |
| CD4 count & viral load (if HIV+) | Immune competence | CD4 < 200 cells/µL = high risk for opportunistic pathogens |
| GeneXpert MTB/RIF (sputum or CSF) | Mycobacterium tuberculosis & rifampicin resistance | Positive = TB; rifampicin resistance alters regimen |
| CSF analysis (cell count, protein, glucose, Gram stain, culture, cryptococcal antigen) | Meningitis aetiology | Neutrophilic pleocytosis → bacterial; lymphocytic + low glucose → TB/fungal |
| Liver function tests | Hepatic involvement, drug safety | Elevated transaminases may limit hepatotoxic agents |
| Renal function (creatinine, electrolytes) | Kidney involvement, dosing considerations | Rising creatinine → adjust nephrotoxic drugs |
| Procalcitonin | Bacterial vs viral infection | High level supports bacterial sepsis; low level suggests viral or non‑infective inflammation |
| C‑reactive protein | Inflammatory burden | Very high values correlate with severe bacterial infection |
Diagnosis and severity
- Integrate history, exam and investigations
Identify the primary syndrome (e.g., community‑acquired pneumonia, severe malaria, septic shock, meningitis).
Confirm aetiology when microbiology is available; otherwise, use syndromic diagnosis guided by local epidemiology (e.g., high malaria prevalence in coastal districts).
- Severity assessment tools (use locally validated scores where available)
- Pneumonia: CURB‑65 (confusion, urea, respiratory rate, BP, age ≥ 65).
- Sepsis: qSOFA (altered mentation, RR ≥ 22, SBP ≤ 100 mmHg).
- Malaria: WHO criteria for severe malaria (cerebral involvement, severe anaemia, renal failure, acidosis, hyperparasitaemia).
- Meningitis: Glasgow Coma Scale, presence of seizures, focal deficits.
- Classification
- Uncomplicated: No organ dysfunction, stable vitals, able to take oral therapy.
- Complicated/Severe: Organ dysfunction (hypotension, hypoxia, renal impairment, altered mental status), high inflammatory markers, or evidence of resistant pathogen.
- Management pathway
- Immediate empiric therapy based on severity and likely pathogens, using broad‑spectrum agents (e.g., third‑generation cephalosporin for severe pneumonia, artesunate for severe malaria, ceftriaxone plus vancomycin for suspected meningitis in HIV).
- Definitive therapy once culture/diagnostic results return; de‑escalate to narrow‑spectrum agents (e.g., amoxicillin for susceptible Streptococcus pneumoniae).
- Adjuncts: fluid resuscitation, oxygen, antipyretics, organ‑support (dialysis, ventilation) as indicated.
- Monitoring & safety
- Vital signs q4‑6 h (or continuous in ICU).
- Daily labs: CBC, renal & liver panels, electrolytes, inflammatory markers.
- Therapeutic drug monitoring for agents with narrow therapeutic index (e.g., aminoglycosides, vancomycin).
- Watch for adverse effects: nephrotoxicity, hepatotoxicity, ototoxicity, Clostridioides difficile.
- Stewardship actions
- Review antimicrobial choice at 48–72 h with microbiology input.
- Stop therapy if non‑infective cause identified.
- Switch to oral route when clinically stable and pathogen susceptible.
- Document indication, duration, and de‑escalation steps in the patient chart.
- Complications to anticipate
- Sepsis: multi‑organ failure, disseminated intravascular coagulation.
- Malaria: cerebral malaria, acute respiratory distress, renal failure.
- TB: drug‑induced hepatitis, treatment failure due to resistance.
- Fungal meningitis: increased intracranial pressure, hydrocephalus.
- Antimicrobial‑related: C. difficile colitis, allergic reactions, drug interactions (especially with antiretrovirals).
Prompt recognition, appropriate empiric therapy, rapid de‑escalation based on diagnostics, and vigilant monitoring constitute the core of antimicrobial stewardship in the Kenyan clinical setting.
Management
Immediate Stabilisation
Prioritise the ABCDE approach. Identify septic shock or severe sepsis early using qSOFA or SIRS criteria. Resuscitate with intravenous crystalloids, secure oxygenation, obtain blood and site-specific cultures before giving antimicrobials, and administer the first dose of an appropriate broad-spectrum empiric agent within the first hour of recognition ("golden hour"). Concurrently identify and manage correctable sources of infection (source control: drain abscesses, remove infected lines, debride necrotic tissue, relieve urinary or biliary obstruction).
Definitive Treatment and Stewardship Strategy
Apply the core principles of antimicrobial stewardship (AMS) throughout therapy:
- Syndromic Empiric Selection: Match local resistance antibiograms and host risk factors (e.g., advanced HIV, neutropenia, recent hospitalisation). Cover likely pathogens without excessive broad-spectrum redundancy.
- Microbiological De-escalation: Review culture and susceptibility reports at 48 to 72 hours. Narrow the spectrum to the most targeted, least toxic agent (e.g., switch from a carbapenem to an aminopenicillin once susceptibility confirms an ampicillin-sensitive Enterococcus or switch from ceftriaxone to crystalline penicillin for sensitive Streptococcus pneumoniae).
- IV-to-Oral Switch: Transition to oral therapy once the patient is clinically stable, afebrile for 24–48 hours, tolerating oral intake, and has an intact gastrointestinal tract with a bioequivalent oral option (e.g., fluoroquinolones, co-trimoxazole, metronidazole, or amoxicillin-clavulanate).
- Fixed Duration: Use the shortest validated curative duration (e.g., 5–7 days for uncomplicated community-acquired pneumonia, 7 days for uncomplicated pyelonephritis) to minimise selective pressure. Stop antibiotics if a non-infectious aetiology is confirmed.
| Drug Class | Common Agents | Primary Clinical Indication | Stewardship Rationale |
|---|---|---|---|
| Penicillins | Crystalline penicillin, Ampicillin | Streptococcal, enterococcal infections | Narrowest spectrum; saves broad agents |
| Antipseudomonal β-lactam | Piperacillin-tazobactam | Severe nosocomial sepsis, intra-abdominal | Sparing carbapenems; covers P. aeruginosa |
| Cephalosporins (3rd/4th gen) | Ceftriaxone, Cefepime | Severe CAP, meningitis, pyelonephritis | High ESBL induction risk; de-escalate early |
| Carbapenems | Meropenem | Documented ESBL, multidrug-resistant sepsis | "Watch/Reserve" class; restricted use |
| Glycopeptides | Vancomycin | Documented or high-risk MRSA | Guided by levels; avoid in MSSA |
| Oxazolidinones | Linezolid | VRE, MRSA pneumonia/soft tissue | Reserve oral/IV agent; avoid prolonged use |
| Polymyxins | Colistin | Extensively drug-resistant Gram-negatives | Last-line resort; requires renal monitoring |
Monitoring and Safety
- Clinical Response: Track temperature curve, heart rate, respiratory rate, resolution of local signs, and clearance of organ dysfunction daily.
- Laboratory Parameters: Monitor full blood count trends, renal and hepatic profiles, and dynamic inflammatory markers (C-reactive protein or procalcitonin) to assist discontinuation decisions.
- Drug-Specific Toxicities:
- Aminoglycosides (gentamicin, amikacin): Nephrotoxicity and irreversible ototoxicity; monitor trough levels and serum creatinine.
- Glycopeptides (vancomycin): Nephrotoxicity and "red man syndrome" (histaminergic reaction prevented by slow infusion); monitor trough levels.
- Fluoroquinolones (ciprofloxacin, levofloxacin): QT-interval prolongation, dysglycaemia, tendon rupture.
- Co-trimoxazole: Hyperkalaemia, bone marrow suppression in HIV/malnourished patients, severe cutaneous adverse reactions (Stevens-Johnson syndrome).
- Polymyxins (colistin): High incidence of acute tubular necrosis and neuromuscular blockade.
Complications and Prognosis
- Individual Complications: Treatment failure, breakthrough bacteraemia, progression to septic shock and multi-organ failure. Drug-induced organ injury (acute kidney injury, drug-induced liver injury, cytopenias). Secondary superinfections, particularly Clostridioides difficile colitis and invasive candidiasis due to disruption of the protective host microbiome.
- Public Health Complications: Selection and dissemination of multidrug-resistant organisms (MDROs)—including Extended-Spectrum Beta-Lactamase (ESBL) producers, Methicillin-Resistant Staphylococcus aureus (MRSA), Carbapenem-Resistant Enterobacterales (CRE), and Vancomycin-Resistant Enterococci (VRE)—leading to exhausted therapeutic options.
- Prognosis: Favourable if early, targeted therapy and source control are achieved. Mortality rises significantly with inappropriate initial empiric therapy, delayed de-escalation, high baseline host frailty (uncontrolled retroviral disease, severe malnutrition), and infection with MDROs.
High-Yield Exam Points
- The Blood Culture Rule: Examiners will fail candidates who prescribe empiric antibiotics before ordering and collecting diagnostic blood cultures, unless the delay directly threatens life in extreme septic shock.
- Colonisation vs. Infection: A tracheal aspirate, asymptomatic catheter urine, or superficial chronic ulcer swab growing an organism (even an MDRO) does not automatically equal an infection; treating asymptomatic bacteriuria or surface colonisation drives resistance without clinical benefit.
- The "Vancomycin for MSSA" Trap: Vancomycin is inferior to antistaphylococcal penicillins (e.g., flucloxacillin or cloxacillin) or first-generation cephalosporins for Methicillin-Susceptible Staphylococcus aureus bacteraemia in terms of bacterial clearance and mortality.
- Look-Alikes for Treatment Failure: Non-infectious causes of persistent fever include drug-induced fever, pulmonary embolism, deep vein thrombosis, and underlying connective tissue disease or malignancy.
- Common Wrong First Steps: Continuing empiric broad-spectrum combination therapy (e.g., ceftriaxone + metronidazole + gentamicin) past 72 hours despite clean cultures and clinical recovery, instead of formal de-escalation or cessation.
- The Bedside Antibiotic "Time-Out": Examiners expect you to state the three key review questions at day 3: Is an infection truly present? Is the pathogen identified? Can we narrow the spectrum or switch to the oral route?
Clinical Case
A 58-year-old male with poorly controlled type 2 diabetes mellitus is admitted from a peripheral health facility with a 5-day history of right lower limb swelling, blistering, and confusion. Examination reveals temperature 38.9°C, blood pressure 86/50 mmHg, pulse 124 bpm, respiratory rate 26 breaths/min. The right leg shows extensive dusky erythema, skin necrosis, foul-smelling seropurulent discharge, and marked subcutaneous crepitus extending to the mid-thigh.
Question 1
What is the most urgent intervention required alongside resuscitation and empiric broad-spectrum antibiotics? Model Answer: Immediate emergent surgical consultation for operative debridement and source control of necrotising fasciitis. Antibiotics alone cannot penetrate non-perfused, necrotic tissue.
Question 2
Which empiric antimicrobial regimen is most appropriate to cover the likely mixed flora pending theatre cultures? Model Answer: Broad-spectrum coverage against Gram-positive, Gram-negative, and anaerobic pathogens, including MRSA: a combination such as piperacillin-tazobactam plus vancomycin, or a carbapenem plus vancomycin, often with clindamycin added to suppress bacterial toxin production.
Question 3
On day 4, operative tissue cultures yield pure Streptococcus pyogenes sensitive to penicillin. The patient has improved clinically. What is the next antibiotic stewardship step? Model Answer: De-escalate therapy immediately by discontinuing broad-spectrum agents and switching to intravenous crystalline penicillin, alongside clindamycin if toxin-mediated shock persists, thereby narrowing the spectrum and minimising selection pressure.
Practice Questions
Question 1
A 34-year-old female living with HIV (CD4 count 88 cells/µL) is admitted with septic shock secondary to acute pyelonephritis. She received intravenous ceftriaxone 2 weeks ago for an outpatient urinary tract infection. Which of the following is the most appropriate empiric antimicrobial selection?
A. Intravenous Ciprofloxacin B. Intravenous Meropenem C. Intravenous Amikacin monotherapy D. Intravenous Ampicillin-Sulbactam
Answer: B. Intravenous Meropenem Explanation: Prior recent broad-spectrum cephalosporin exposure and severe presentation place this immunosuppressed patient at high risk for Extended-Spectrum Beta-Lactamase (ESBL)-producing Enterobacterales, making a carbapenem the drug of choice until susceptibility is confirmed.
Question 2
A 65-year-old man completes 48 hours of intravenous ceftriaxone for right middle lobe community-acquired pneumonia. He is now afebrile, respiratory rate is 16 breaths/min, oxygen saturation is 96% on room air, and he is eating comfortably. Sputum culture has no growth. What is the best next step?
A. Add intravenous vancomycin to cover hidden resistant organisms B. Continue intravenous ceftriaxone for a total of 14 days C. Switch to oral amoxicillin-clavulanate to complete a 5-day total course D. Change to intravenous meropenem to ensure complete pathogen eradication
Answer: C. Switch to oral amoxicillin-clavulanate to complete a 5-day total course Explanation: The patient meets criteria for clinical stability, allowing a prompt IV-to-oral switch and a short total duration (5 days), which reduces line-associated infection risks and suppresses antimicrobial resistance.
Question 3
An inpatient with an indwelling urinary catheter for 10 days has cloudy urine. The patient feels well, has stable vital signs, no suprapubic or flank tenderness, and normal blood counts. Catheter urine culture grows >10^5 CFU/mL of Klebsiella pneumoniae resistant to third-generation cephalosporins. What is the correct management?
A. Prescribe intravenous meropenem according to the susceptibility report B. Exchange the urinary catheter and do not initiate antimicrobials C. Administer oral nitrofurantoin for 7 days D. Initiate intravenous colistin immediately
Answer: B. Exchange the urinary catheter and do not initiate antimicrobials Explanation: The patient has asymptomatic bacteriuria associated with an indwelling catheter; treating colonisation without clinical signs of infection breeds multi-drug resistance without conferring patient benefit.
Question 4
A bedside culture report for a patient with deep osteomyelitis grows Staphylococcus aureus that is sensitive to oxacillin, cefazolin, erythromycin, and vancomycin. Why is cefazolin or flucloxacillin preferred over vancomycin?
A. Vancomycin lacks tissue penetration into bone cortex B. Beta-lactam agents achieve superior, faster bactericidal killing in MSSA than vancomycin C. Vancomycin causes immediate induction of ESBL enzymes D. Flucloxacillin has a lower incidence of hypersensitivity reactions
Answer: B. Beta-lactam agents achieve superior, faster bactericidal killing in MSSA than vancomycin Explanation: For Methicillin-Susceptible Staphylococcus aureus, targeted beta-lactams demonstrate faster bacterial clearance and lower relapse and mortality rates compared to glycopeptides, which are reserved for MRSA.
Question 5
A 42-year-old man being treated with broad-spectrum antimicrobials for intra-abdominal sepsis develops profuse, watery, non-bloody diarrhoea, abdominal cramping, and a new leukocytosis on hospital day 6. What is the most likely iatrogenic complication?
A. Entamoeba histolytica colitis B. Clostridioides difficile infection C. Small intestinal bacterial overgrowth D. Non-typhoidal Salmonella gastroenteritis
Answer: B. Clostridioides difficile infection Explanation: Antibiotic therapy disrupts the indigenous protective colonic microflora, permitting the overgrowth of C. difficile and toxin-mediated pseudomembranous colitis.
Drafted with AI assistance from standard references and reviewed for structure. Check details against your lecture notes and the Kenya MoH guideline.