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ICMR Antimicrobial guidelines in immunecompromised hosts and solid organ transplant recipients

ICMR Antimicrobial guidelines in immunecompromised hosts and solid organ transplant recipients

With advances in treatment of organ failure, auto-immune diseases and malignancies, an increasing population of immune compromised hosts and transplant recipients will develop infections and require care by the medical system. Such patients present unique challenges with regard to diagnosis and treatment, which often differ from the immune competent host. Moreover, these patients are likely to suffer repeated episodes of infections and consequently receive repeated courses of antimicrobial agents leading to higher level of antimicrobial resistance in pathogens.

Indian Council of Medical Research, Department of Health Research has issued the ICMR Antimicrobial guidelines in immunecompromised hosts and solid organ transplant recipients. Following are the major recommendations :

Case definition

An immune compromised host includes the following:

  • recipients of solid and stem cell organ transplants
  • congenital immune deficiency disorders
  • patients on medications that compromise cell mediated immunity eg corticosteroids, calcineurin inhibitors, mTOR pathway inhibitors, TNF-alpha antagonists, anti-thymocyte globulin and monoclonal antibodies like rituximab, adalimumab, etc.
  • Patients suffering from cancer, cystic fibrosis

Common pathogens

Immunocompromised hosts are at risk of developing opportunistic infections but also remain exposed to normal community acquired pathogens. Clinical presentation can be subtle and often difficult to diagnose in these hosts. The pathogens involved are by and large the same as those affecting immune competent hosts. Some specific pathogens unique to patients with compromised cell mediated immunity include Listeria monocytogenes, Nocardia spp, Pneumocystis jiroveci, Cytomegalovirus (CMV), Cryptococcus, Aspergillus spp, Strongyloides stercoralis

BMW

Prevalent AMR status in common pathogens

Table 1. Enterobacteriaceae isolates from blood. ICMR AMR data 2014.

Note : Ec : Escherichia coli; Ks : Klebsiella spp.; Es : Enterobacter spp

Table 2. Salmonella Typhi isolates from blood ICMR AMR Data 2014

AMA PGIMER, Chandigarh ‘n’ 109


No. R (%)

AIIMS, New Delhi ‘n’ 22        


No. R

CMC, Vellore ‘n’ 71                                     


No. R (%)

JIPMER, Puducherry ‘n’ 7


No. R

National ‘n’ 209                      


No.R %)

Ampicillin 9 (8.3) 0 2 (2.8) 0 11 (5.3)
Cefixime 0 (0) 0 0 (0) 0 0 (0)
Ceftriaxone 0 (0) 0 0 (0) 0 0 (0)
Chloramphenicol 3 (2.8) 0 1 (1.4) 0 4 (1.9)
Ciprofloxacin 56 (51.4) 15 67 (94.4) 7 145 (69.4)
Trimethoprim-sulphamethoxazole 0 (0) 0 3 (4.2) 0  3 (1.4)

Note : If No. Tested is ≥30, No. R (%) given. If No. tested <30, only No. R given.

Table 3. Staphylococcus aureus ICMR AMR Data 2014

*The 4 numbers listed as Vancomycin Resistant (R) are VISA isolates.

No VRSA was isolated during the year 2014 at JIPMER.

Cefoxitin : Surrogate marker for Methicillin.

Table 4. Enterococcus faecalis ICMR AMR Data 2014

Table 5. Enterococcus faecium ICMR AMR Data 2014.

Table 6. Pseudomonas aeruginosa ICMR AMR Data 2014

AMA PGIMER, Chandigarh ‘n’ 75 R (%) AIIMS, New Delhi ‘n’ 102 R (%) JIPMER, Puducherry ‘n’ 113 R (%) CMC, Vellore ‘n’ 84 R (%) National ‘n’ 374 R %
Amikacin 27 49 38 21 35
Aztreonam 62 55 30 48
Cefepime 52 57 20 41
Cefoparazone -sulbactam 39 41 30 38
Ceftazidime 64 51 51 23 47
Colistin 34 2 10
Imipenem 17 54 48 25 37
Levofloxacin 44 42 23 36
Meropenem 74 41 23 47
Netilmicin 66 45 22 45
Piperacillin-tazobactam 44 67 25 46
Tobramycin 56 43 18 33

Table 7. Acinetobacter baumannii susceptibility pattern 2014

AMA PGIMER, Chandigarh ‘n’ 209 R (%) AIIMS, New Delhi ‘n’ 143 R (%) JIPMER, Puducherry ‘n’ 157 R (%) CMC, Vellore ‘n’ 90 R (%) National ‘n’ 599 R %
Amikacin 77 83 59 84 75
Aztreonam 87 93 84 87
Cefepime 98 86 75 61 81
Cefoparazone -sulbactam 89 23 22 47 57
Ceftazidime 99 86 68 68 84
Colistin 1 64 22 22
Imipenem 52 83 62 64 63
Levofloxacin 86 68 60 73
Meropenem 50 86 59 61 62
Netilmicin 79 56 69
Piperacillin-tazobactam 73 86 71 83
Tobramycine 61 52 55
Tobramycin 54 64 58 58
Trimethoprim-sulphamethoxa zole 46 63 55

Table 8 Central nervous system infections

Clinical condition Common pathogens Empiric antimicrobial agents Alternative antimicrobial agents Comments
Acute bacterial meningitis Pneumococcus, Listeria monocytogenes, H.influenzae, Meningococcus Ceftriaxone 2 gm IV q 12h/ Cefotaxime 2 gm IV q 4-6h

+

Ampicillin 2gm IV q4h

Moxifloxacin 400mg IV q 24h

or

Meropenem 2gm IV q 8h

Exclude TB, Cryptococcus

Vancomycin not required due to low level of penicillin resistance in Pneumococcus

If penicillin allergic, use cotrimoxazole 15 mg/kg/day (TMP component) or meropenem 2gm IV q 8h to cover for Listeria

Duration: 10-14 days, 21 days for Listeria or Gram negative infection

Brain abscess, subural empyema

 

 

 

 

 

 

Streptococci, Bacteroides, Enterobacteriace -ae, Staph aureus

 

 

 

 

 

 

Nocardia spp

 

 

 

Ceftriaxone 2 gm IV q12h/ Cefotaxime 2 gm IV q 4-6h

+

Metronidazole 1 gm IV q 12h

Duration based upon clinical & radiological response, minimum 8 weeks

 

Co-trimoxazole 15 mg/kg/dose (trimethoprim component) IV or PO, plus imipenemcilastatin 500 mg q6h

Meropenem 2gm IV q 8h

 

 

 

 

 

 

 

 

 

Linezolid 600 mg IV or PO q12h

 

 

Exclude TB, Nocardia, Aspergillus

Aspiration/surgical drainage required unless abscess <2.5cm & patient neurologically stable

 

 

 

 

Duration: 3-6 weeks of IV therapy, followed by 12 months of oral therapy

 

Table 9 Respiratory tract infections

Condition Organisms Empiric antibiotics Alternative antibiotics Comments
Pneumonia

 

 

 

 

 

 

 

 

 

 

 

 

 

S. pneumoniae, H.influenzae, Legionella,

E.coli,

Klebsiella, Pseudomonas, S.aureus

 

 

 

 

Pneumocystis

 

 

 

Ceftriaxone 2 g IV od or

Piperacillin-tazobactam 4.5 gm IV q 6h plus either

azithromycin 500 mg PO/IV OD or doxycycline 100 mg PO BD Duration 5-8 days

 

Cotrimoxazole (trimethoprim component 15 mg/kg /day) Duration: 14 days, 21 days in patients with HIV

Imipenem- cilastatin 500 mg q6h

 

 

 

 

 

 

Clindamycin 600 mg IV q8h+ Primaquine 15 mg q12h(if sulpha allergy)

 

 

If MRSA is a concern,

add linezolid 600 mg IV/PO BD

Avoid fluoroquinolones unless

TB excluded

Exclude TB, influenza, Nocardia, fungi (Aspergillus,

Mucor, Cryptococcus), Strongyloides

hyperinfection

De-escalate to

narrow spectrum agent on

receipt of senstivity report

 

Lung abscess, empyema

 

Pneumococcus, Strep milleri group, E.coli, Klebsiella, Pseudomonas, S.aureus, anaerobes Piperacillin-tazobactam 4.5 gm IV q 6h Duration: 3-4 weeks

 

Cefoperazone-sulbactam 3 gm IV q 12h + clindamycin 600-900 mg IV q 8h Drainage of pleural space essential for empyema

 

 

Acute bacterial pharyngitis Group A ß- hemolytic streptococci (GABHS) Benzathine penicillin 12 laks units IM or amoxicillin 500 mg PO q8h for 10 days Most cases viral, confirm GABHS on culture before treating
Head and neck space infections Polymicrobial (Str pyogenes, Staph aureus, oral anaerobes) Clindamycin 600 mg IV q8h or Amox-clav 1.2 gm IV/PO q8h Piperacillin-tazobactam 4.5 gm IV q 6h Duration: At least 1 week

 

Acute sinusitis Viral, S.pneumoniae, H.influenzae,      M. catarrhalis Amox-clav 1.2 gm IV/PO q8hfor 7 days Piperacillin-tazobactam 4.5 gm IV q 6h Exclude fungi

(Aspergillus, Mucor)

Acute bronchitis Viral Antibiotics not required

Table 10 Gastrointestinal & intra-abdominal infections

Condition Organisms Empiric antibiotics Alternative antibiotics Comments
Acute gastroenteritis

 

 

Food poisoning

 

Viral, entero toxigenic & entero pathogenic

E. coli

S. aureus, B. cereus, C. botulinum

none

 

 

 

 

none

 

 

 

 

Rehydration (oral/IV) essential

 

 

 

 

Cholera

 

 

 

V.cholerae

 

 

 

Doxycycline 300 mg PO stat

 

 

Azithromycin 1 gm PO stat

or

Ciprofloxacin 500 mg BD for 3 days

Rehydration (oral/IV) essential

 

Antibiotics are adjuvant therapy

Bacterial dysentery

 

 

Shigella, Campylobacter, non typhoidal salmonellosis, Shiga toxin producing E. coli Ceftriaxone 2 gm IV OD for 5 days

 

Azithromycin 1 gm od x 3d

 

Amoebic dysentery E. histolytica Metronidazole 500 to 750 mg IV q8h for 7-10 days Tinidazole 2 gm PO OD for 3 days Add diloxanide furoate 500 mg tds for 10d
Enteric fever S.Typhi, S.Paratyphi A Outpatients: TMP-SMX4 1 DS tablet BD for 2 weeks or azithromycin 500 mg BD for 7 days Inpatients: Ceftriaxone 2 g IV OD for 2 weeks
Biliary tract infections (cholangitis, cholecystitis)

 

 

 

Enterobacteriacea (E.coli, Klebsiella)

 

 

 

 

Piperacillin-tazobactam 4.5 gm IV q 6h or Cefoperazone-sulbactam 3 gm IV q 12h or Ertapenem 1 gm IV OD

 

 

Imipenem-cilastatin 500 mg q6h or meropenem 1 gm IV q8h

 

 

Surgical or endoscopic intervention to be considered if there is biliary obstruction. De-escalate to narrow spectrum agent on receipt of sensitivities.
Hospital acquired diarrhea C. difficile

 

Mild-moderate: Metronidazole 400 mg po qid for 10 days Severe: vancomycin 250 mg po q 6h empirically Confirm by PCR or GDHEIA test

 

Spontaneous bacterial peritonitis

 

Enterobacteriaceae (E.coli, Klebsiella) Piperacillin-tazobactam 4.5 gm IV q 6h or Cefoperazone-sulbactam 3 gm IV q 12h or Ertapenem 1 gm IV OD Duration: 7-10 days Imipenem-cilastatin 500 mg IV q6h or meropenem 1 gm IV q8h De-escalate to narrow spectrum agent on receipt of sensitivities.
Secondary peritonitis, intra-abdominal abscess Enterobacteriaceae (E.coli, Klebsiella), Bacteroides

 

Piperacillin-tazobactam 4.5 gm IV q 6h or Cefoperazone-sulbactam 3 gm IV q 12h or Ertapenem 1 gm IV OD Imipenem-cilastatin 500 mg IV q6h or meropenem 1 gm IV q8h Source control is important. De-escalate to narrow spectrum agent on receipt of sensitivities.

Table 11 Skin & soft tissue infections

Condition Organisms Empiric antibiotics Alternative antibiotics Comments
Cellulitis Strep. pyogenes, S.aureus Cefazolin 2 gm IV q8h. Clindamycin 600-900 mg IV q8h Duration: 5-7 days. Can switch to oral therapy once improving
Abscess, carbuncle S.aureus Cefazolin 2 gm IV q8h Clindamycin 600-900 mg IV TDS or Linezolid 600 mg q 12h Get pus cultures. MRSA coverage advisable for children <5 or severe infections
Necrotizing fasciitis

 

 

Strep. pyogenes, Staph aureus (monomicrobial), Anaerobes, Enterobacteriaceae (polymicrobial) Piperacillin-tazobactam 4.5 gm IV q 6h or Cefoperazone-sulbactam 3 gm IV q 8h plus Clindamycin 600-900 mg IV q8h Imipenem-cilastatin 500 mg IV q6h or meropenem 1 gm IV q8h + Clindamycin 600-900 mg IV q8h Early surgical intervention crucial. De-escalate to narrow spectrum agent on receipt of sensitivities.

Table 12 Urinary tract infections

Condition Organisms Empiric antibiotics Alternative antibiotics Comments
Cystitis Enterobacteriaceae (E.coli, Klebsiella) Nitrofurantoin 100 mg BD for 5 days Co-trimoxazole DS BD or ciprofloxacin 500 mg BD for 3 days Obtain urine cultures before antibiotics & modify therapy based on senstivity report
Acute pyelonephritis Enterobacteriaceae (E.coli, Klebsiella) Piperacillin-tazobactam 4.5 gm IV q 6h or Cefoperazone-sulbactam 3 gm IV q 12h or Ertapenem 1 gm IV OD. Treat for 10-14 days. Imipenem-cilastatin 500 mg IV q6h or meropenem 1 gm IV q8h Obtain urine cultures before antibiotics & switch to a narrow spectrum agent based on senstivity report
Acute prostatitis

 

 

 

 

 

Chronic bacterial prostatitis

 

 

Enterobacteriaceae (E.coli, Klebsiella)

 

 

 

 

 

Enterobacteriaceae (E.coli, Klebsiella)

 

 

Piperacillin-tazobactam 4.5 gm IV q 6h or Cefoperazone-sulbactam 3 gm IV q 12h or Ertapenem 1 gm IV OD or

 

 

Ciprofloxacin 750 mg po bid

 

 

TMP/SMX DS PO q12h

 

 

 

 

 

 

 

Obtain urine and blood cultures before antibiotics & switch to narrow spectrum agent based on sensitivities. Treat for 4 weeks.

Therapy based on urine and prostatic massage cultures obtained before antibiotics. Treat for 4-6 weeks

Table 13 Bone & joint infections

Condition Organisms Empiric antibiotics Alternative antibiotics Comments
Acute osteomyelitis, septic arthritis

 

 

 

S.aureus, Strep. pyogenes, Enterobacteriaceae

 

 

 

 

Cefazolin 2 g IV q8h

or

Ceftriaxone 2 g IV od

 

 

Piperacillin-tazobactam 4.5 gm IV q 6h or Cefoperazone-sulbactam 3 gm IV q 12h plus Clindamycin 600-900 mg IV TDS

 

Treat based on culture of blood/synovial fluid/bone biopsy. Surgical debridement essential. Duration: 3-4 weeks (from initiation or last major debridement)
Chronic osteomyelitis, chronic infective arthritis No empiric therapy

 

Definitive treatment guided by bone/synovial biopsy culture.

Table 14 Severe sepsis and septic shock of undetermined source

Condition Organisms Empiric antibiotics Comments
Community acquired Enterobacteriace ae, Pseudomonas, Staph aureus Imipenem- cilastatin 1 g IV q8h or meropenem 1 g IV q8h Add vancomycin if Staph aureus is a concern. Add colistin if high local prevalence of carbapenem resistant organisms or previously colonized.
Hospital acquired Entero-bacteriaceae, Pseudomonas, Acinetobacter, Staph aureus Imipenem 1g IV q8h or meropenem 1g IV q8h plus Vancomycin 1g IV q12h plus Colistin 9 mu IV stat then 4.5 mu IV q12h Broaden spectrum if prior antibiotic exposure. De-escalate to narrow spectrum agent on receipt of sensitivities.

Table 15 Post-op infections following solid organ transplant (kidney, liver, heart, lung)

Condition Organisms Empiric antibiotics Alternative antibiotics Comments
Post-op fever with hemodynamic stability Usually not due to infection None

 

Look for hematoma, DVT, transfusion related fever, rejection
Surgical site infection Staph aureus, Entero-bacteriaceae, Pseudomonas Treat based on culture and sensitivities
VAP/HAP

 

 

 

 

Entero-bacteriaceae, Pseudomonas, Acinetobacter

 

 

Piperacillin-tazobactam 4.5 g IV q6h or Cefoperazone-sulbactam 3 g IVq8h. Add colistin if high local prevalence of carbapenem resistant organisms. Imipenem-cilastatin 1g IV q8h or meropenem 1g IV q8h

 

De-escalate to narrow spectrum agent on receipt of sensitivities.

 

 

CLABSI

 

 

 

 

Entero-bacteriaceae, Pseudomonas, Acinetobacter, Staph aureus

 

 

Piperacillin-tazobactam 4.5 g IV q6h or cefoperazone-sulbactam 3 g IVq8h plus vancomycin 1g IV q12h. Add colistin if high local prevalence of carbapenem resistant organisms. Imipenem-cilastatin 1g IV q8h or meropenem 1g IVq8h

 

 

Obtain blood cultures before starting antibiotics. Deescalate to narrow spectrum agent on receipt of sensitivities.

 

CA-UTI

 

 

ntero-bacteriaceae, enterococci

 

Piperacillin-tazobactam 4.5 g IV q6h or cefoperazone-sulbactam 3 g IVq12h Imipenem-cilastatin 1g IV q8h or meropenem 1g IV q8h Obtain blood and urine cultures before starting antibiotics. Deescalate to narrow spectrum agent on receipt of sensitivities.

Guidelines by Indian Council of Medical Research :

Dr Soumya Swaminathan, Director General, Indian Council of Medical Research Secretary, Department of Health Research

Source: self
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