Cytomegalovirus infection in immunocompetent critically ill adults: literature review

Al-Omari, Awad; Aljamaan, Fadi; Alhazzani, Waleed; Salih, Samer; Arabi, Yaseen

doi:10.1186/s13613-016-0207-8

Annals of Intensive Care

Table 2 Summary of studies assessing CMV disease in ICU patients

From: Cytomegalovirus infection in immunocompetent critically ill adults: literature review

Year of publication	Study	Study design	Patient population	Patients no.	Method and specimen	Frequency of monitoring	Incidence (%)	Mortality (%)
Year of publication	Study	Study design	Patient population	Patients no.	Method and specimen	Frequency of monitoring	Incidence (%)	CMV positive^a	CMV negative^b
1990	Domart et al. [31]	Prospective, single center	Mediastinitis, post-cardiac surgery Patients in whom viral cultures could be done within 10 days of surgical debridement	115	Serology for CMV IgG Viral culture blood and urine. Positive cases: positive CMV culture	Within first 10 days of debridement then every 3 weeks	25	55*	37*
1994	Docke et al. [50]	Unidentified	Septic patients	60	1—CMV culture in blood. 2—Immunocytological detection of CMV antigens in blood. 3—PCR amplification in blood. 4—TNF and interleukin six assays. Positive cases: any positive PCR or culture or antigen detection	Once	97.7	NA
1996	Stephan et al. [51]	Prospective, single center	Mechanically ventilated	23	Culture, PCR Blood and BAL	Unclear	0	0
1996	Papazian et al. [39]	Retrospective Single center	Patients with ventilator-associated pneumonia	86	Histopathology Autopsies and open lung biopsy	Once 22.4 ± 8.8 days after admission to the intensive care unit	29	NA	NA
1998	Kutza et al. [29]	Prospective, single center	SICU Septic patients with positive CMV IgG serology	34	CMV IgG serology CMV antigenemia CMV DNA PCR in blood Serum cytokines: TNF alpha, IL-1b, and IL-6 measured by ELISAs. Positive cases: positive CMV antigenemia and/or CMV DNA PCR in blood	1—Blood samples were collected on day 1 of sepsis, then twice weekly during ICU stay, then once weekly after release from the ICU, until recovery or death	32	73.9*	63.6*
1998	Cook et al. [27]	Prospective, case–control single center	Postoperative general SICU. Septic patients with no identifiable bacterial or fungal source. Positive BAL or blood or sputum CMV culture	12	CMV and HSV viral culture from BAL, blood or sputum. All cases included had positive CMV culture	CMV was cultured in diploid human foreskin fibroblast culture for 6 weeks Plasma was evaluated by shell vial technique to IE antigen at 24 h. HSV cultures	100	65^α	35^α
2001	Heininger et al. [24]	Prospective, single center	SICU Patients with SAPS II >40 and positive serology	56	CMV DNA PCR and/or viral culture Leukocytes, plasma, and lower respiratory tract secretions Positive cases: positive PCR	Once weekly	35.6	55*	36.2*
2002	Razonable et al. [52]	Prospective Case–control Single center	Mixed ICU	120	CMV and HHV-6 and HHV-7 DNA by PCR in blood Positive cases: positive PCR	4th days after ICU admission	<1	NA
2003	Cook et al. [23]	Prospective Single center	SICU Patients staying for 5 days or more in SICU	104	Serology in blood CMV and HSV cultures in blood and sputum Positive cases: positive CMV culture	Once weekly until discharge from SICU	9.6	50*	26.5*
2005	Jaber et al. [28]	Retrospective, matched case–control, single center	Medical, surgical, and transplant unit Non-immune-compromised patients	237	PP65 antigen Blood Positive cases: positive CMV antigenemia	1—Clinical judgment. 2—The diagnosis of CMV antigenemia was defined by a positive CMV pp65 antigenemia assay result	16.8	50^α	28^α
2006	von Muller et al. [53]	Prospective observational single center	Anesthesiological intensive care unit. Non-immunocompromized CMV IgG-seropositive patients with septic shock with ICU stay for at least 7 days	23	Serology CMV antigenemia Blood. CMV reactive T helper 1 lymphocytes Positive cases: positive CMV antigenemia	Twice during 1st week then weekly until discharge Positive cases: positive antigenemia	30.4	57*	38*
2008	Ziemann et al. [2]	Retrospective, single center	Mixed ICU Patients treated for at least 14 days in ICU	99	CMV DNA PCR Blood. Positive cases: at least two positive samples	Based on the decision of the treating team	35^∑	28.6^α	10.9^α
2008	Limaye et al. [1]	Prospective, multicenter	Mixed ICU, positive anti-CMV IgG	120	PCR Blood Positive cases: positive blood CMV PCR	Thrice weekly until death or discharge	33	CMV disease was significantly associated with death or continued hospitalization after 30 days
2009	Chiche et al. [26]	Prospective, single center	MICU Ventilated patients for at least 2 days	242	CMV serology and antigenemia. CMV culture on BAL if VAP suspected, antigenemia on the day of BAL. Other organ Virologic studies based on clinical suspicion. Positive cases: positive antigenemia or BAL CMV culture	Within 48 h of ICU admission and once weekly until discharge	16.1	54*	37*
2010	Chilet et al. [54]	Prospective observational Single center	Anesthesiological ICU Single center CMV-seropositive, ICU stay longer than 5 days	53	CMV PCR Tracheal aspirate and plasma Plasma tumor necrosis factor alpha	Once a week	39.7	61*	46*
2010	Smith et al. [55]	Prospective single center	Tertiary ICU Mechanically ventilated patients	174	Respiratory secretions CMV PCR Thrice weekly		19	NA
2011	Iahangard	Prospective	ICU CMV-seropositive patients	132	CMV IgG serology PCR in blood	Weekly	34	The overall mortality rate associated with active CMV infection was 1.93 times higher than that without CMV infection
2011	Bordes et al. [56]	Prospective Single center	Severe burn unit Burn surface area more than 15%	29	CMV DNA Blood	First sample on admission then one to twice weekly until discharge	55	33*	20*
2011	Uegaki	Retrospective Single center	ICU	67	CMV antigenemia	After 7 days of admission if intensivists suspected CMV	52	NA
2011	Heininger et al. [38]	Prospective, observational, single center	Severe sepsis, positive anti-CMV IgG	86	Viral culture from tracheal secretions. Qualitative CMV DNA PCR from leukocytes, plasma, tracheal secretions Quantitative CMV DNA PCR from positive plasma and tracheal secretions HSV DNA PCR from tracheal secretions Positive cases: positive PCR from any source	Once weekly until discharge from hospital or death	40.7	37.1*	35.3*
2012	De Vlieger et al. [57]	Prospective, MICU and SICU, single center (Van Den Berge study)	Admitted for at least 3 days in ICU Mechanically ventilated in SICU MICU regardless of mechanical ventilation	1504	CMV IgG serology	Within first 2 days of admission	64	19.2*	17.1*
2012	Chiche et al. [10]	Prospective Single center	MICU CMV-seropositive patients	82	CMV serology CMV antigenemia Lymphocyte subset Interferon-γ	Within 48 h of admission then once weekly until discharge	27	40*	13.3*
2012	Coisel et al. [37]	Prospective single center	MICU Mechanically ventilated suspected of having pneumonia 10% were previously immunocompromized	93	1—Serology (IgM and IgG) for cytomegalovirus (CMV) and herpes simplex (HSV) using (ELISA) Blood PCR was not routinely done 2—CMV antigen detection in blood 3—CMV and HSV DNA PCR on BAL Positive cases: positive CMV PCR in BAL or positive antigenemia or positive IgM	Within 12 h of pneumonia diagnosis	24	55^α	20^α
2013	Clari et al. [9]	Prospective single center	SICU Mechanically ventilated patients CMV seropositive	31	CMV serology at baseline CMV-specific interferon-γ-producing CD8, CD4 T lymphocytes CMV PCR in blood and tracheal aspirate	2–8 samples per patient were analyzed for T lymphocytes subset and CMV PCR	54.8	47*	35*
2014	Ishioka et al. [58]	Prospective Single center	Cardiac ICU Post-surgery	100	CMV PP65 antigenemia Serum	On admission, day 7 and day 14	4	0*	1*
2014	Osman	Prospective Single center	Respiratory and geriatric ICU	51	CMV PCR Blood	NA	68.6	74.3^α	31.3^α
2014	Walton et al. [59]	Prospective Single center	MICU and SICU Critically ill septic and non-septic patients versus healthy volunteers	560	CMV IgG CMV PCR Blood	Daily Starting within 24–72 h of admission	24.2	Significant increase in 90 days mortality in CMV-positive patients compared to CMV-negative ones
2015	Ong et al. [40]	Multicenter prospective cohort	Mixed ICU (tertiary care referral centers) ARDS patients on mechanical ventilation for at least 4 days	271	CMV IgG if positive CMV PCR in blood	Weekly for maximum 30 days	27	46^α	28^α
2015	Frantzeskaki et al. [12]	Prospective, observational two centers	Mixed ICU, mechanically ventilated, seropositive anti-CMV IgG	80	CMV DNA PCR Blood	At admission, then weekly until day 28 or discharge from ICU or death	13.75	18*	22*
2015	Ong et al. [60]	Multicenter prospective cohort	Mixed ICU (tertiary care referral centers) ARDS patients on mechanical ventilation for at least 4 days	209	CMV IgG between days 5 and 14 of admission If positive CMV DNA PCR in plasma	CMV DNA PCR on day 14 or ICU discharge date (whichever first) then weekly	26	28*^,δ	16*

Positive serology: positive anti-CMV IgG or IgM
ELISA enzyme-linked immunosorbent assay, PCR polymerase chain reaction, CMV cytomegalovirus, ARDS acute respiratory distress syndrome, BAL bronchoalveolar lavage, MICU medical intensive care unit, SICU surgical intensive care unit, SAPS simplified acute physiology score, ICU intensive care unit, ELISA enzyme-linked immunosorbent assay
^aCMV positive based on study methodology
^bCMV negative based on study methodology
* Nonsignificant difference in mortality
^αStatistically significant difference in mortality between groups
^δ24% in seropositive without reactivation
^∑Considered infected if at least two positive results

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