ICMR Antimicrobial guidelines in immunecompromised hosts and solid organ transplant recipients

Published On 2017-03-18 08:47 GMT | Update On 2017-03-18 08:47 GMT

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

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

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