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Vol. 41. Issue 8.
Pages 468-484 (October 2023)
Vol. 41. Issue 8.
Pages 468-484 (October 2023)
Original article
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Clinical significance of isolation of Haemophilus no ducreyi in genital samples. Systematic review
Importancia clínica del aislamiento de Haemophilus spp. (excluyendo H. ducreyi) en muestras genitales. Revisión sistemática
Marta Ruiz del Pinoa, Antonio Rosales-Castillob,d,
Corresponding author

Corresponding author.
, José María Navarro-Maríc,d, José Gutiérrez-Fernándeza,d
a Departamento de Microbiología, Facultad de Medicina, Universidad de Granada-ibs, Granada, Spain
b Servicio de Medicina Interna, Hospital Universitario Virgen de las Nieves-ibs, Granada, Spain
c Departamento de Microbiología, Hospital Universitario Virgen de las Nieves-ibs, Granada, Spain
d Programa de Doctorado en Medicina Clínica y Salud Pública, Universidad de Granada, Granada, Spain
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Tables (3)
Table 1. Studies reporting the isolation of Haemophilus spp. in genital samples.
Table 2. Antibiotic susceptibility (%) of Haemophilus spp. isolates.
Table 3. Rates of antibiotic susceptibility and presence of β-lactamases separated by species (%).
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Introduction and objectives

Currently, the microbiological diagnosis of genital infections is carried out with molecular methods, which allow the detection of less frequent etiological agents but with potential pathogenic importance, such as Haemophilus spp. The objective of this review is to analyse and highlight the clinical importance of the isolation of Haemophilus spp. in genital and rectal infections, excluding Haemophilus ducreyi.

Material and methods

A systematic review was carried out based on an exhaustive search of the publications included in the MEDLINE database up to August 5, 2021, on the presence of Haemophilus spp. in genital and rectal infections, excluding H. ducreyi.


After reviewing what was described in the literature, Haemophilus spp. (excluding H. ducreyi: HSNOD) was detected in 2397 episodes of genital infection, the most frequently isolated species being H. influenzae and H. parainfluenzae. Most of the episodes (87,6%) are constituted by single isolation. There is a slight predominance in women (48,3%) where it can cause vaginitis, salpingitis, endometritis or complications during pregnancy. In men, the clinical picture usually corresponds to urethritis. Most of the samples correspond to vaginal and urethral exudates, with a minority representation at the rectal level (2.3%).


HSNOD plays a relevant pathogenic role in episodes of genital infection, so microbiological diagnostic protocols must include methods that allow their detection, as well as include them in the etiological spectrum of this type of clinical picture.

Sexually transmitted infections
Introducción y objetivos

Actualmente el diagnóstico microbiológico de las infecciones genitales se realiza con métodos moleculares, los cuales permiten detectar agentes etiológicos menos frecuentes, pero con potencial importancia patogénica, como Haemophilus spp. El objetivo de esta revisión es analizar y resaltar la importancia clínica del aislamiento de Haemophilus spp. en infecciones genitales y rectales, excluyendo H. ducreyi.

Material y métodos

Se ha realizado una revisión sistemática en base a una búsqueda exhaustiva de las publicaciones incluidas en la base de datos MEDLINE hasta el 5 de agosto de 2021, sobre la presencia de Haemophilus spp. en infecciones genitales y rectales, excluyendo H. ducreyi.


Tras revisar lo descrito en la literatura, las especies de Haemophilus (excluyendo H. ducreyi: HSNOD) se detectaron en 2397 episodios de infección genital, siendo las especies más frecuentemente aisladas H. influenzae y H. parainfluenzae. La mayoría de los episodios (87,6%) están constituidos por aislamiento único. Existe un ligero predominio en mujeres (48,3%) donde puede producir cuadros de vaginitis, salpingitis, endometritis o complicaciones durante el embarazo. En hombres, el cuadro clínico suele corresponder a una uretritis. La mayoría de las muestras corresponde a exudados vaginales y uretrales, con una representación minoritaria a nivel rectal (2,3%).


HSNOD desempeña un papel patogénico relevante en episodios de infección genital, por lo que los protocolos de diagnóstico microbiológico deben incluir métodos que permitan su detección, así como incluirlos en el espectro etiológico de este tipo de cuadros clínicos.

Palabras clave:
Infecciones de transmisión sexual
Full Text

Genital tract infections are common entities that share a clinical presentation but can be caused by myriad aetiological agents apart from the microorganisms commonly regarded as pathogens1. In addition, there is a large diversity of microbiota and significant inter-individual variability that makes it even more difficult to distinguish between a possible pathogenic role or not2. These less common agents that play a possibly pathogenic role include the species of the genus Haemophilus, excluding Haemophilus ducreyi (HSNOTD). The genus Haemophilus, belonging to the Pasteurallaceae family, is made up of small non-sporulating, pleomorphic, non-motile, facultative anaerobic gram-negative bacilli. It is characterised by having demanding nutritional requirements and requires chocolate agar medium for proper growth and identification. The species of HSNOTD most frequently involved are Haemophilus influenzae (H. influenzae), Haemophilus parainfluenzae (H. parainfluenzae) and Haemophilus haemolyticus (H. haemolyticus). The first one is well-known, it is a colonising agent of the upper respiratory and genital tract and can behave as an opportunistic pathogen. In recent years, more and more cases of urethritis associated with H. influenzae, and more recently its association with non-gonococcal urethritis, have been described both in men who have sex with men (MSM) and women3. In addition, it is the second most common cause of vulvovaginitis in girls not linked to sexual transmission4. H. parainfluenzae predominantly colonises the oropharynx and can lead to infections through contiguity, bacteraemia, endocarditis and genital infections5. H. haemolyticus is difficult to distinguish from the non-encapsulated species of H. influenzae due to its morphological, biochemical and genetic similarities, and it is sometimes difficult to distinguish between them by conventional microbiological methods, hence some authors advocate the combination of conventional methods and polymerase chain reaction (PCR) analysis; 6 mass spectrometry (MALDI-TOF) has also shown good results in differentiation capacity7. It rarely has pathogenic potential.

In addition, there are the biotype IV cryptic genospecies, genetically related to H. haemolyticus, but with a different phenotype and location, such as "Haemophilus quentini", whose presence has been described in the genitourinary tract and can cause genital infections in pregnant women, chorioamnionitis and preterm delivery, and even pneumonic or septic conditions in newborns8.

The objective of this study is to analyse the presence of HSNOTD species in the development of genital infections through a systematic literature review.

Materials and methods

A search was made in the MEDLINE database, through PubMed, for studies that describe the presence of Haemophilus spp. in genital (vaginal, endocervical and urethral) and rectal exudates (in MSM). The following search terms were used: "Haemophilus and urethritis", "Haemophilus and proctitis", "Haemophilus and vaginitis", "Haemophilus and cervicitis", "Haemophilus and salpingitis", "Haemophilus and endometritis", "Haemophilus and bartholinitis", "Haemophilus and tubo-ovarian abscess", "Haemophilus and septic abortion", "Haemophilus and chorionamnionitis". The inclusion criteria were: studies published up until 1 September 2021; and studies published in English or Spanish. The exclusion criteria were: studies referring to the H. ducreyi or Haemophilus vaginalis species; and studies that analysed samples from sources other than genital or rectal. The references listed in the studies were also reviewed to reduce the number of losses.


145, 3, 583, 595, 21, 73, 14, 6, 16 and 30 publications were obtained for the criteria "Haemophilusand urethritis", "Haemophilusand proctitis", "Haemophilusand vaginitis", "Haemophilusand cervicitis", "Haemophilusand salpingitis", "Haemophilusand endometritis", "Haemophilusand bartholinitis", "Haemophilusand tubo-ovarian abscess", "Haemophilusand septic abortion", "Haemophilus and chorionamnionitis", respectively, which were subsequently submitted to the inclusion and exclusion criteria, yielding 117 studies. Of these, 13 could not be located (Northwest Med. 1955;54(9):992−3, J Pathol Bacteriol. 1967;93(1):109−18, Am J Vet Res. 1971;32(12):2067−9, Am J Clin Pathol. 1980;73(2):285−7, Med J Aust. 1985;143(5):223, Med J Aust. 1985;142(9):531, J Infect Dis. 1986;153(1):165−7, Acta Paediatr Scand. 1987;76(2):363−4, Med Clin (Barc). 1989;92(9):335−7, Med Clin (Barc). 1989;93(19):758−9, Pediatr Infect Dis J. 1994;13(3):243, Am J Obstet Gynecol. 1994;170(4):1008−17, J Am Board Fam Pract. 1994;7(4):335−41). Table 1 shows 104 works, which group together a total of 2397 episodes of genital infection caused by Haemophilus spp. The most frequently isolated species were H. influenzae (57.7%; 1383/2397) and H. parainfluenzae (35.7%; 855/2397). No species was identified in 6.7% (159/2397) of the episodes. In most episodes (87.6%; 2099/2397), Haemophilus was isolated in monomicrobial culture. Otherwise, it was often detected along with Chlamydia trachomatis, Neisseria gonorrhoeae, Ureaplasma spp. or Mycoplasma spp.

Table 1.

Studies reporting the isolation of Haemophilus spp. in genital samples.

Author (year of publication)  No. of episodes  Microorganisms  Age/sex  Possible predisposing factors  Clinical manifestations  Clinical sample  Microbiological diagnosis reflected  Treatment 
Skirrow MB (1970)9  H. influenzae  48/F  NP  Tubo-ovarian abscess  Abscess exudate  Culture  Surgery and ampicillin 
Hurley R (1970)10  H. influenzae  29/F  Intrauterine device  Endometritis  Vaginal exudate  Culture  Removal of device 
Farrand RJ (1971)11  H. influenzae  4/ F  NP  Vaginal dischargeand irritation Inflamed vagina with purulent exudate  Vaginal exudate  Culture  Ampicillin 
  H. influenzae  35/ F  Tubal ligation surgery 7 years previously.  Right tubal abscess  Puncture-aspiration of the abscess  Culture  Ampicillin+cloxacillin 
Berczy J (1973)12  H. influenzae  27/F  NP  Septic abortion  Vaginal exudate  Culture  NP 
Khuri-Bulos N (1975)13  H. influenzae  NP/F  NP  Neonatal sepsis  Vaginal and/or cervical exudate  NP  NP 
Herva E (1975)14  H. influenzae  NP/F  NP  Salpingitis  Tubal exudate  Culture  NP 
Nicholls S (1975)15  H. influenzae  31/ F  NP  Neonatal sepsis  Vaginal exudatePlacental biopsy  Culture  Penicillin+kanamycin (NR)Ampicillin 
  H. influenzae  18/ F  NP  Antepartum haemorrhage and vaginal discharge.Neonatal sepsis and death  Vaginal exudate and respiratory samples from the newborn  Culture  Penicillin+kanamycin 
Bowie WR (1977)16  10  7 H. parainfluenzae4 + C. trachomatis3 H. influenzae  NP/M  NP  4 urethritis and3 asymptomatic3 asymptomatic  Urethral exudate  Culture (Virginia Polytechnic Institute)  NP 
Albritton WL (1978)17  H. influenzae  18F, 20F, 22F 30F,33/F  2 Pregnancy  1 vulvovaginitis, 2 septic abortion, 1 acute salpingitis  Vaginal exudate, blood cultures  Culture  Ampicillin, kanamycin 
Gibson M (1978)18  H. influenzae  NP/F  28 weeks pregnant. Premature rupture of membranes  Amnionitis  Amniotic fluid  Culture  NP 
Ogden E (1979)19  H. influenzae  NP/F  16 weeks pregnant  Amnionitis  Amniotic fluid  Culture  NP 
Simon HB (1980)20  H. influenzae  36/F  NP  Salpingitis/endometritis  Vaginal exudate  Culture  NP 
Arias JW (1981)21  H. parainfluenzae  18/F  29 weeks pregnant  Chorioamnionitis  Placenta  Culture  NP 
De Pass EE (1982)22  H. influenzae  22/F  NP  Bilateral salpingitis and abscess  Tubal exudate  Culture  Bilateral salpingo-oophorectomy, hysterectomy and ampicillin 
Pastorek J (1982)23  H. influenzae  26F and 17F  Pregnant (37 and 40 weeks)  ChorioamnionitisEndometritis  Placenta and cervical exudate  Culture  Ampicillin, gentamicin 
Chowdhury MN (1983)24  H. parainfluenzae  NP/M  NP  Urethritis, urethral discharge  Urethral exudate  NP  Amoxicillin 
Hall GD (1983)25  11  11 H. influenzae  NP/F2 M  NP  4 vaginitis, 2 IUD-associated endometritis, 1 incomplete septic abortion, 1 urethral syndrome and 1NP2 urethritis  Vaginal, cervical or urethral exudate  Biochemical tests  NP 
Messing M (1983)26  H. parainfluenzae  NP/M  NP  Nongonococcal urethritis: genital erythema and urethral discharge  Urethral exudate  Culture and biochemical tests  NP 
  H. parainfluenzae    NP  Ulcerative lesions on the genitals       
  H. parainfluenzae    Secondary syphilis  Genital erythema and inguinal adenopathy       
  H. parainfluenzae    Pubic folliculitis  Erythematous genital lesions       
  H. parainfluenzae    Gonorrhoea and condyloma acuminata  Urethral discharge and genital lesion       
  H. influenzae    NP  Dysuria and urethral discharge       
  H. influenzae    Primary syphilis  Ulcerative lesions on the genitals       
  H. influenzae    NP  Nongonococcal urethritis: dysuria and urethral discharge       
Tebbutt GM (1984)27  H. influenzae1 + N. gonorrhoeae  NP/F  NP  3 girls with vaginal discharge2 postnatal infection1 pelvic inflammatory disease  Vaginal exudate  Culture and biochemical tests  NP 
Nakamura KT (1984)28  H. parainfluenzae  24/F  28 weeks pregnant.  Premature rupture of membranes  Placenta and cervical exudate  Culture  Ampicillin and gentamicin 
Paavonen J (1985)29  H. influenzae  22/F, 29/F  1 Previous risky sexual relationship  1 pyosalpinx1 tubo-ovarian abscess  Tubal and abscess exudate  Culture  Doxycycline and metronidazolePenicillin G and metronidazole 
Campognone P (1986)30  17  H. influenzae  17 F  17 pregnant. 1 diabetic  Chorioamnionitis  Placenta and maternal blood  Culture  NP 
Crowe HM (1987)31  H. influenzae  NP/F  1 Crohn's disease  2 tubo-ovarian abscesses  Abscess exudate  Culture  Chloramphenicol and tobramycin 
LW Davis (1987) 32  H. influenzae  NP/F  NP  Tubo-ovarian abscess  NP  NP  NP 
Winn HN (1987)33  H. influenzae  25/F  22 weeks pregnant.  Chorioamnionitis  Maternal blood and amniotic fluid  Culture  Ampicillin 
Casin I (1988)34  60  60 H. influenzae52 solitarily3 + C. albicans3 + T. vaginalis1 + N. gonorrhoeae1 + C. trachomatis  NP/37M, 20F and 3 NP  NP  NP  37 Urethral exudate19 Vaginal and/or cervical exudate3 urine1 Bartholin's gland  Culture and biochemical tests  NP 
Andreu A (1989)35  10  7 H. parainfluenzae3 H. influenzae7 solitarily3 + other*  NP/M  NP  7 urethritis  Urethral exudate  NP  NP 
  20  15 H. influenzae5 H. parainfluenzae + others*  NP/F  5 IUD carriers  8 vaginitis, 3 salpingitis and 9 NP  Vaginal or endocervical exudate  NP  NP 
Drouet EB (1989)36  244  216 H. parainfluenzae28 H. influenzae  NP  NP  NP  NP  NP  NP 
Houang E (1989)37  73  H. parainfluenzae  NP/71M and 2 F  NP  NP  71 urethral exudate2 vaginal exudate  MicroScan  NP 
Martel AY (1989)38  103  Haemophilus spp.  NP/56M, 33F and 14 NP  NP  NP  55 genital exudate48 rectal exudate  Biochemical tests  NP 
Leiberman JR (1989)39  H. influenzae  35/F  16 weeks pregnant.  Amnionitis  Amniotic fluid  Culture  NP 
van Bosterhaut B (1990)40  H. influenzae  NP/F  NP  3 bartholinitis  Gland exudate  Culture  NP 
Christensen JJ (1990)41  17  Haemophilus spp.  NP/F  NP  Bartholinitis, salpingitis and/or vaginal discharge  NP  NP  NP 
Quentin R (1990)42  H. influenzae  NP/F  Bartholin's gland cyst or abscess surgery  Bartholinitis  Aspirated cyst or abscess  NP  NP 
Silverberg K (1990)43  H. influenzae  17/F  29 weeks pregnant.  Chorioamnionitis  Amniotic fluid and placenta  Culture  Ampicillin, gentamicin, clindamycin 
Pinhas-Hamiel O (1991)44  H. influenzae  28/F  13 weeks pregnantPrevious risky sexual relationship  Septic abortion  Blood cultures  Culture  NP 
Facinelli B (1991)45  H. parainfluenzae  NP  Risky sexual relationship  Urethritis  NP  NP  NP 
Bendig JW (1991)46  H. influenzae  35/F, 29/F  1 IUD  2 purulent salpingitis  Peritoneal and tubal exudate  Culture  Drainage, ceftriaxone, metronidazole 
Lefevre JC (1991)47  21  H. parainfluenzae  NP/M  NP  Urethritis  Urethral exudate  NP  NP 
Bosch J (1991)48  H. influenzae  NP/F  NP  7 Bartholin's gland abscesses1 post-caesarean section endometritis1 chorioamnionitis  Vaginal and gland exudate  NP  Ampicillin 
Rusin P (1991)49  13  H. influenzae  NP/F  NP  13 endometritis/chorioamnionitis  NP  NP  NP 
Mazor M (1991)50  H. influenzae  28/F  29 weeks pregnant.Premature rupture of membranes  Amnionitis  Amniotic fluid and neonatal blood  Culture  Ampicillin and gentamicin 
Kragsberg P (1993)51  H. influenzae  NP/F  6 pregnancies1 Recurrent endometritis  3 tubo-ovarian abscesses2 septic abortions1 postpartum sepsis  Abscess exudateVaginal exudate  Culture  Cephalosporin, ampicillin, metronidazole, doxycycline 
Ault KA (1993)52  H. influenzae  18F, 22F, 29F  3 Pregnancies (29, 31 and 31 weeks)  Amnionitis  Placenta and maternal blood  Culture  Vancomycin and gentamicinAmpicillin and gentamicinCeftizoxime 
Kinney JS (1993)53  H. influenzae  NP/F  Pregnant 24–40 weeks  Chorioamnionitis  Placenta and neonatal blood  Culture  1 Ampicillin, 1 cephalosporin 
Gill MV (1995)54  H. influenzae  36/F  35 weeks pregnant, placenta percreta  Chorioamnionitis  Blood cultures and cervical exudate  Culture  Ceftazidime and aztreonam 
Llanes Caballero R (1996)55  H. influenzae  NP/M  Previous schistosomiasis  Discomfort while urinating and purulent urethral discharge  Urethral exudate  NP  Norfloxacin 
Pena MJ (1996)56  20  H. influenzae  NP/F  Prepubescent girls  Vulvovaginitis  Vaginal exudate  NP  NP 
Vázquez F (1996)57  155  100 H. parainfluenzae45 H. influenzae10 Haemophilus spp.21 solitarily134 + others*  2 M, 11F and 142 NP  Female sex workers and men with urethritis  8 urethritis2 epididymo-orchitis9 cervicitis and/or vaginitis2 Bartholin's gland abscesses134 NP  NP  Culture  NP 
Carmeci C (1997)58  H. influenzae  48/F  NP  Acute salpingitis and septic shock  Peritoneal exudate and blood cultures  Culture  Salpingo-oophorectomy and ceftriaxone 
Cox RA (1997)4  11  H. influenzae  <14/ F  NP  Vulvovaginitis  Vaginal and vulvar exudate  Culture  Amoxicillin 
García E (1997)59  30  18 H. influenzae  NP/F  Pregnant, parturient, puerperal  1 abortion2 antepartum deaths1 postpartum death14 live newborns (5 confirmed infection and 5 suspected infection and 4 healthy)  Vaginal exudate taken intrapartum or in the immediate postpartum  NP  NP 
    12 H. parainfluenzae      1 antepartum death12 live newborns (10 suspected infection)       
Aydin MD (1998)60  19  11 H. parainfluenzae8 H. influenzae  NP/M  NP  Urethritis  Urethral exudate  Biochemical tests  NP 
Rodríguez-Guardado (2000)61  H. influenzae  36/F  NP  Bilateral salpingitis  Peritoneal exudate  Culture  Salpingectomy, clindamycin, gentamicin 
Cherpes TL (2002)62  H. influenzae  39/F  8 weeks pregnant  Septic abortion. Acute chorioamnionitisLow-grade fever, vaginal bleeding, and headache  Blood culturePlacental biopsy  NP  Ampicillin+gentamicin+clindamycinCeftriaxoneLevofloxacin 
Cox RA (2002)63  39  38 H. influenzae1 H. parainfluenzae8 + mixed anaerobic flora  18 months -11 years/ F  14 recurrent vulvovaginitis5 two previous episodes of vulvovaginitis due to H. influenzae, 1 three previous episodes  Vulvovaginitis: vaginal discharge and irritation  Vaginal and vulvar exudate  Culture  19 amoxicillin9 amoxicillin/clavulanic acid6 trimethoprim6 miconazole2 metronidazole2 clarithromycin, erythromycin 
Campos J (2003)64  H. influenzae serotype e  NP/F  NP  Vaginitis  NP  NP  NP 
Cuadros J (2004)65  12  H. influenzae  2−12/ F  NP  Vulvovaginitis  Vaginal exudate  NP  NP 
Mikamo H (2005)66  H. influenzae  NP/F  NP  Bartholinitis  Gland exudate  Culture  Cefteram pivoxil 
Tanaka K (2005)67  H. influenzae  NP/F  NP  Bartholin's gland abscess  Gland exudate  Culture and PCR  NP 
Iser P (2005)68  H. influenzae  NP/M  Heterosexual  Nongonococcal urethritis  Urethral exudate  Culture  NP 
Tsai HY (2006)69  H. influenzae  NP/F  Prepubescent girl. No sexual relations, no abuse.  Vulvovaginitis, profuse vaginal discharge  Vaginal exudate  NP  NP 
Varela JA (2006)70  12  Haemophilus spp.  NP/M  HeterosexualCouple with cervical intraepithelial neoplasia (CIN)  Asymptomatic  Urethral exudate  Culture  NP 
Kohlberger P (2007)71  11  H. influenzae  NP/F  Girls with a history of sexual abuse  NP  Vaginal exudate  NP  NP 
Santiago JL (2008)72  H. parainfluenzae  41/M  HeterosexualUnprotected oral sex with a sex worker  Dysuria, urethral discharge and inguinal adenopathy.Conjunctival hyperemia with purulent exudate, tarsal follicular reaction, blepharitis and palpebral oedema  Urethral and conjunctival exudate  Culture and biochemical tests  Ceftriaxone+doxycycline 
Orellana MA (2009)73  36  22 H. parainfluenzae14 H. influenzae  NP/M  NP  NP  Urethral exudate  API NH® test  NP 
Sikanić-Dugić N (2009)74  H. influenzae  2−8/ F  NP  Vulvovaginitis  Vaginal exudate  Culture  NP 
Kakisi (2010)75  H. influenzae  42F  NP  Tubo-ovarian abscess  Abscess exudate  Culture  Surgery and cefoxitin/metronidazole 
Glover WA (2011)8  H. quentini  28/M  Previous episodes of urethritis and prostatitis.Unprotected sex  Scarce urethral discharge, painful ejaculation  Urethral exudate  16S rRNA sequencing  Ceftriaxone+azithromycin 
  H. quentini  30/M  NP  NP      NP 
  H. quentini +N. gonorrhoeae  32/M  NP  NP      NP 
Mc Kechnie ML (2011)76  11  H. influenzae  2<25,5 25−29,4>35/ F  NP  7 symptomatic4 asymptomatic  Vaginal exudate Endocervical exudateUrine  PCR  NP 
Orellana MA (2011)77  77  45 H. parainfluenzae32 H. influenzae4 + C. trachomatis2 + U. urealyticum  >15/M  NP  Urethritis  Urethral exudate  API NH® test  NP 
Calner PA (2012)78  H. influenzae  36/F  16 weeks pregnant  Septic abortion  Blood cultures  Culture  Curettage, ampicillin, gentamicin, clindamycin 
Ranđelović G (2012)79  H. influenzae  2−12/ F  NP  Vulvovaginitis  Vaginal exudate  NP  NP 
Martin D (2013)80  H. influenzae  48/ F  Uterine leiomyoma. No IUD  Acute endometritisLower abdominal pain and fever  Endometrial biopsy  PCR  NP 
Tinguely R (2013)81  H. parainfluenzae +N. gonorrhoeae  NP/M  Homosexual.Recently treated syphilis  Urethritis  Urethral exudate  16S rRNA sequencing  Ciprofloxacin 
      Homosexual      PCR  Ciprofloxacin+doxycycline (NR)Ceftriaxone+azithromycin 
Mendz GL (2014)82  H. parainfluenzae +C. curvus  29/ F  Pregnant (25 weeks)  Chorioamnionitis, premature rupture of membranes, neonatal sepsis  Vaginal exudate  16S rRNA sequencing  Penicillin+gentamicin+metronidazole 
Cardines R (2015)83  46  37 H. parainfluenzae7 H. pittmaniae2 H. parahaemolyticus  32.5/ F  Pregnant (25−38 weeks)  Asymptomatic  Vaginal exudate  16S rRNA sequencing  NP 
Hsu MS (2015)84  H. parainfluenzae + Enterococcus spp.  29/M  Homosexual, unprotected sex  Dysuria, purulent urethral discharge  Urethral exudate  16S rRNA sequencing  Ceftriaxone+doxycycline 
  H. parainfluenzae +N. gonorrhoeae +M. morganii  32/M    Dysuria, frequency, purulent urethral discharge      Ceftriaxone+doxycycline 
  H. parainfluenzae + Enterococcus spp.  27/M    Dysuria, purulent urethral discharge, inguinal adenopathy      Clarithromycin 
Deza G (2016)85  52  45 H. parainfluenzae7 H. influenzae24 + other microbes10 + N. gonorrhoeae8 + C. trachomatis3 + C. albicans2 + G. vaginalis1 + U. urealyticum  31.8/M  31 (60%) homosexual and 21 (40%) heterosexual4 (8%) HIV9 (17%) previous STI52 (100%) unprotected oral sex29 (55%) anal sex, 44% unprotected19 (36%) vaginal sex, 31% unprotected  37 (71%) purulent urethral discharge13 (25%) non-purulent urethral discharge2 (4%) dysuria without urethral discharge  Urethral exudate  API20E  48 (92%) ceftriaxone+azithromycin/doxycycline2 (4%) doxycycline1 (2%) azithromycin1 (2%) ciprofloxacin 
    28 solitarily23 H. parainfluenzae5 H. influenzae  33.7/M  15 (54%) homosexual and 13 (46%) heterosexual.3 (11%) HIV5 (18%) previous STI28 (100%) unprotected oral sex (5 (18%) only sexual practice)13 (46%) anal sex, 39% unprotected11 (39%) vaginal sex, 32% unprotected  18 (64%) purulent urethral discharge9 (32%) non-purulent urethral discharge1 (4%) dysuria without urethral discharge      28 (100%) ceftriaxone+azithromycin/ doxycycline 
Frølund M (2016)86  6 H. influenzae solitarily2 + adenovirus1 + M. genitalium  NP/M  NP  Acute urethritisDysuria and urethral discharge  First morning urine  PCR  NP 
Ito S (2016)87  22  21 H. influenzae solitarily1 + U. urealyticum  7<31 and14>31/M  11 married and 10 single.12 prior urethritis.21 unprotected oral sex(12 exclusively).9 unprotected oral and vaginal sex.13 sex worker partner  21 urethral discharge (13 moderate and 8 scant) in 10 serous,6 mucoid and 5 mucopurulent15 urethral irritation12 moderate dysuria3 meatitis and/or balanitis3 pharyngeal discomfortIncubation < 7 days  Urethral exudate  NP  NP 
Kim H (2016)88  H. influenzae  0−9/ F  Prepubescent girl  Vulvovaginitis  Vaginal or vulvar exudate  Culture  NP 
You C (2016)89  H. influenzae  NP/M  NP  Urethritis  First morning urine  16S RNA sequencing  NP 
Porter M (2016)90  31  H. influenzae  21−29/F  31 pregnancies  31 Chorioamnionitis  Placenta  Culture  NP 
Baba H (2017)91  H. influenzae  31/ F  17 weeks pregnant.History of upper respiratory infection with cough.  Septic abortion.High fever, vaginal bleeding, and abdominal pain  Vaginal exudateBlood culture  Culture, MALDI-TOF, PCR.  Piperacillin/tazobactamCefotaxime+metronidazole 
Chen X (2017)92  H. influenzae  6/ F  History of a foreign body in the vagina.Recurrent and chronic rhinitis. In nasal exudate, H. influenzae is isolated, derived from the same clone as the one detected in the vagina  Vulvovaginitis associated with rhinitis  Vaginal exudate  NP  NP 
Deguchi T (2017)93  73  H. influenzae  NP/M  NP  67 acute urethritis4 acute epididymitis2 urethritis and epididymitis  Urethral exudate  NP  NP 
Ito S (2017)1  68  54 H. influenzae solitarily5 + U. urealyticum4 + U. urealyticum + M. hominis2 + U. parvum1 + C. trachomatis1 + N. gonorrhoeae  35/M    Urethritis  Urethral exudate  HN-20 Rapid system identification test  43 azithromycin (5 NR)20 sitafloxacin3 levofloxacin2 ceftriaxone 
  H. influenzae  NP/M  NP  Epididymitis      NP 
        Acute prostatitis       
Li JP (2017)94  110  H. influenzae  NP/F  Prepubescent girls  Vulvovaginitis  Vaginal exudate  Culture  55 ofloxacin49 β-lactams6 NP 
Caballero Mateos AM (2018)95  H. parainfluenzae + C. trachomatis L2 (lymphogranuloma venereum)  34/M  Homosexual, unprotected sexHepatitis B previously treated. Secondary syphilis.Drug addict.  Proctalgia, constipation, rectal bleeding, fever.Rectal ulcer  Rectal biopsy  NP  Doxycycline 
Horie K (2018)96  H. quentini + Streptococcus spp. +M. hominis +U. urealyticum  34/M  Heterosexual. SinglePrevious urethritis (no other previous STIs)Casual partners  Moderate mucoid urethral dischargeIncubation 12 days  Urethral exudate  16S rRNA sequencing  Azithromycin 
  H. quentini  24/M  Heterosexual SingleNo previous STIsHIV negativeUnprotected oral sex with a sex worker  Scant mucoid urethral discharge, dysuriaIncubation 4 days      Sitafloxacin 
  H. quentini + Streptococcus spp. +  30/M  Heterosexual SingleNo previous STIsHIV negativeUnprotected oral and vaginal sex with a stable partner and other partners  Condyloma acuminatum on the glansScant serous urethral discharge, urethral irritation, dysuria      Levofloxacin 
Kondo H (2018)97  H. influenzae + Streptococcus spp. +U. urealyticum  32/M  Heterosexual Married4 previous episodes of urethritis (no other STIs)Multiple sexual partners  Urethral irritation, mucopurulent urethral discharge  Urethral exudate    AzithromycinND 
  H. influenzae  27/M  Heterosexual MarriedNo previous STIsStable sexual partner  Urethral irritation, scant mucoid urethral dischargeIncubation 16 days       
  H. influenzae +S. agalactiae  30/M  Heterosexual SingleNo previous STIsUnprotected oral sex with a sex worker  Urethral irritation, scant mucoid urethral dischargeIncubation 5 days       
  H. influenzae  29/M  Heterosexual Married1 previous episode of urethritis (no other STIs)Unprotected oral sex with a sex worker  Dysuria, scanty mucoid urethral dischargeIncubation 12 days       
  H. influenzae  21/M  Heterosexual Married1 previous episode of urethritis (no other STIs)Unprotected oral and vaginal sex with a sex worker  Urethral irritation, mucopurulent urethral dischargeIncubation 5 days       
  H. influenzae  25/M  Heterosexual MarriedNo previous STIsUnprotected oral sex with a sex worker  Dysuria, urethral irritation, mucopurulent urethral dischargeIncubation 9 days       
Saxena A (2018)98  H. parainfluenzae  33/M  No previous STIsHIV negativeUnprotected oral sex with a sex worker  Urethral pruritus, urethral discharge  Urethral exudate  MALDI-TOF  Norfloxacin+amoxic-clav+fluconazole (NR)Azithromycin+ciprofloxacin 
Cevik M (2019)99  H. influenzae  35/ F  14 weeks pregnant  Septic abortion. Acute chorioamnionitisAbdominal pain, vaginal discharge/bleeding, fever.  Placental biopsyBlood cultureCervical exudate  NP  β-lactams 
    22/ F  14 weeks pregnant         
    33/ F  20 weeks pregnant.Premature rupture of membranesPrevious abortion. History of chorioamnionitis         
Magdaleno Tapial J (2019)100  38  32 H. parainfluenzae5 H. influenzae1 H. haemolyticus15 Haemophilus spp. solitarily9 + M. hominis/ Ureaplasma spp7 + Chlamydia6 + Neisseria2 + M. genitalium  30.5/35 (92%) M3 (8%) F  21 (55%) M homosexual13 (34%) M heterosexual3 (8%) F heterosexual1 (3%) NP5 (13%) HIV20 (57%) previous STI38 (100%) unprotected oral sex  22 (58%) purulent urethral discharge6 (16%) dysuria10 (26%) asymptomatic, risky sexual contact  Urethral exudate  NP  17 (45%) ceftriaxone+azithromycin12 (31%) ceftriaxone+doxycycline5 azithromycin4 doxycycline6NR 
Wang HJ (2019)101  230  H. influenzae  NP/F  Prepubescent girls  Vulvovaginitis  Vaginal exudate  Vitek culturesystem NH  NP 
Alsuhaibani MA (2019)102  H. parainfluenzae  26/F  Pregnant  Chorioamnionitis  Placenta and neonatal blood  Culture  Cefotaxime+gentamicin 
Ducours M (2020)103  H. parainfluenzae +S. hominis+E. faecalis+S. anginosus+p. harei  20/M  HeterosexualUnprotected vaginal sex  Urethral discharge  Urethral exudate  MALDI-TOF  Ceftriaxone+azithromycin 
  H. parainfluenzae +N. gonorrhoeae +S. epidermidis +S. anginosus+S. mitis  31/M  HomosexualUnprotected anal sex  Dysuria, urethral discharge      Ceftriaxone+azithromycin 
  H. parainfluenzae +M. genitalium +E. faecalis+S. mitis  37/M  Heterosexual  Dysuria, urethral discharge      Minocycline+pristinamycin 
  H. parainfluenzae +N. gonorrhoeae +S. haemolyticus+Corynebacterium sp.  43/M  HomosexualHIVUnprotected oral and anal sex  Dysuria, urethral discharge      Ceftriaxone+doxycycline 
  H. parainfluenzae +S. haemolyticus +E. faecalis  30/M  Homosexual. PrEPUnprotected oral and anal sex  Dysuria, urethral discharge      Cotrimoxazole (NR)Gentamicin +ciprofloxacin 
  H. parainfluenzae +S. haemolyticus+S. mitis  28/M  HomosexualUnprotected anal sex  Dysuria, urethral discharge      Ceftriaxone+doxycycline 
  H. parainfluenzae +S. haemolyticus  27/M  NP  NP      NP 
  H. influenzae  55/M  Homosexual. PrEPUnprotected oral and anal sex  Urethral discharge      Ceftriaxone+azithromycin 
  H. parainfluenzae +N. gonorrhoeae+E. coli  33/M  Homosexual. PrEPUnprotected oral and anal sex  Dysuria, urethral discharge      Ceftriaxone 
Nishimura Y (2020)104  H. influenzae  51/ F  Polypoid adenomyomaEarly stage endometrioid adenocarcinoma  Microabscesses in adenomyoma.  Vaginal exudateBlood culture  MALDI-TOF  Ceftriaxone+hysterectomy 
Sierra Y (2020)105  175  H. parainfluenzae ± NP125 NOT multiresistant50 multiresistant30 H. parainfluenzae +C. trachomatis/N. gonorrhoeae/T. pallidum10 NP10 H. parainfluenzae solitarily  37.8/97 (55%) M78 (45%) FNPNPNPNP42/M  NPNPNPNPNP4 homosexuals, 4 heterosexuals and 2 NP.4 HIV6 previous STI8 unprotected sex with a stranger, 1 unprotected sex with a stable partner and 1 NP  NPNP26 urethritis and 24 NP16 urethritis and 14 NP5 asymptomatic and 5 NP10 (100%) urethritis  79 (45%) urethral exudate62 (35%) vaginal13 (7%) preputial9 (5%) cervical6 (3%) rectal3 (2%) genital ulcer1 (1%) pharyngeal1(1%) semen1 (1%) urineNPNPNPNP10 urethral exudate  MALDI-TOF  NPNPNPNPNP5 ceftriaxone+azithromycin2 ceftriaxone+doxycycline1 ceftriaxone+azithromycin+doxycycline1 amox-clav 
Snirivasan S (2020)3  40  H. influenzae  NP/M  23 heterosexual17 homosexual  16 urethritis and 7 asymptomatic16 urethritis and 1 asymptomatic  First morning urine  16S rRNA sequencing  NP 
Vives A (2020)106  30  19 H. parainfluenzae10 H. influenzae1 Haemophilus sp.25 solitarily5 + other microbes4 + C. trachomatis1 + N. gonorrhoeae  36.6/M  17 (57%) heterosexual, 8 (27%) homosexual, 2 (7%) bisexual and 3 (10%) NP3 (10%) HIV with no detectable viral load13 (43%) previous STI21 (75%) oral sex, 15 (54%) vaginal sex, and 10 (36%) anal sex.N.o sexual partners 3.5 [1–20]  13 (43%) urethral discharge7 (23%) dysuria5 (17%) testicular pain2 (7%) genital ulcer1 (4%) hematospermia1 (4%) painful ejaculation1 (4%) lower abdominal pain  Urethral exudate  API NH® test  Ceftriaxone+azithromycin/doxycyclineAzithromycin±ciprofloxacinCiprofloxacinDoxycycline8 NR 
Hu BF (2021)107  140  H. influenzae  5.8/F  NP  Symptomatic vulvovaginitis  Vaginal exudate  Vitek  Ampicillin 
Bruins MJ (2021)108  127  H. influenzae  37 (<12 y)/F2(12−17 y)/F45(18−51 y)/F43(>51)/F  NP  Symptomatic vulvovaginitis  Vaginal exudate  Culture  NP 

F: woman; M: male; NP: not provided; NR: no response to treatment.


+ others: these studies do not describe which other microorganisms are isolated concomitantly.

Most of the studies adequately described the method used in the laboratory for the isolation of Haemophilus. Until 2011, mainly culture techniques and biochemical tests were used. From 2011 onwards, molecular biology techniques, such as PCR or the sequencing of the 16S subunit of rRNA, became more prominent. More recently, mass spectrophotometry has been used (MALDI -TOF).

Regarding patient gender, 34.8% (835/2397) were men; 48.3% were women (1158/2397) and 16.9% (404/2397) were not reported. Only half of the studies provided data on patient age. The men were all adults with a mean age of 30 years20–55. The women were divided into two groups, one of children under 14 years of age (53.9%; 624/1158) and another of adults (14 years of age or older, 28.4%; 329/1158). The age was not recorded in 17.7% of women (205/1158).

In the group of men, H. parainfluenzae (44.1%; 367/835) and H. influenzae (42.6%; 356/835) were detected with almost equal frequency. The vast majority were diagnosed with urethritis. The most frequent clinical manifestations were urethral discharge, purulent or not, dysuria and urethral pruritus or irritation. Regarding sample type, in the vast majority of cases it was urethral exudates. The most frequently administered treatment was ceftriaxone with azithromycin and/or doxycycline, although the treatment was only specified in 40% (15/37) of the publications referring to men.

We subdivided the group of adult women according to whether the infection occurred during pregnancy (52.9%; 174/329) or not (47.1%; 155/329). In the latter, there were episodes of vaginitis, bartholinitis, salpingitis, endometritis or tubal abscesses. The absence of a significant portion of data prevents us from drawing conclusions about the prevalence of a specific species of Haemophilus. In pregnant women, almost all the studies refer to septic abortion, acute chorioamnionitis, premature rupture of membranes and neonatal sepsis. H. influenzae was detected more frequently (64.9%; 113/174) than H. parainfluenzae (30.5%; 53/174). H. influenzae was isolated in all the samples from girls (vaginal or vulvar exudates). Most of them presented vaginal discharge, vulvar irritation or pruritus and did not have predisposing factors. Antibiotic treatment included β-lactams or quinolones.

Samples of rectal origin only represented 2.3% (55/2397). The clinical and epidemiological information available on these patients was very scant, with the exception of one reported case7.

Table 2 summarises the information on the susceptibility ofHaemophilus to different groups of antibiotics (penicillin, carbapenems, tetracycline, quinolones, first-, second- and third-generation cephalosporins) contributed by 21 of the 67 studies. Four of these were excluded because they did not disaggregate the results by sample origin, as were those with fewer than five reported cases to avoid bias. Overall susceptibility of Haemophilus spp. to penicillins was 78.9%, and the overall rate of β-lactamase production was 26.4%. It should be remembered that although the production of β-lactamases is the main mechanism of resistance in this genus, there are also strains that do not produce β-lactamases but have alterations in the penicillin-binding proteins with a low affinity for β-lactams and even a combination of both mechanisms109.

Table 2.

Antibiotic susceptibility (%) of Haemophilus spp. isolates.

Author (year of publication)  Species  No. cases  Prod. βL  Pen  CFZ  Ceph 2nd  Ceph 3rd  Ceph 4th  Carba  Macr  Quin  TC  RIF  FOS 
Campognone P (1986)30  Hi  17  –  100  100          100    100     
Casin I (1988)34  Hi  60  16.7  83.3  –  –  –  –  –  100  100  85.8  –  – 
Houang E (1989)37*  Hp + Hi  73                         
Bosch J (1991)  Hi    100                     
Vázquez F (1996)57  HpHiH  1004510  2926.7–  7173.3–  –––  –––  –––  –––  –––  –––  –––  –––  –––  ––– 
Kragsberg P (1993)51  Hi  100  100              100     
Cox RA (1997)4  Hi  11  –  100  –  –  –  –  –  –  –  –  –  – 
García E (1997)59  Hi  18  27  –  –  –  –  –  –  –  –  –  –  – 
Cox RA (2002)63  Hi + Hp  39  10  95  –  100  –  –  –  95  –  –  –  – 
Tanaka K (2005)67  Hi  37.5  37.5                     
Orellana MA (2009)73  Hp + Hi  36  –  76.5  –  94.1  100  –  –  64.7  91.1  –  –  – 
Orellana MA (2011)77  Hp + Hi  77  34.2  75.9  –  92.4  100  –  –  73  87.8  76.8  –  – 
Cardines R (2015)83  HpH. pittmaniaeH. haemolyticus  3772  13.5––  85.1100100  –––  –––  97.3100100  –––  100100100  –––  91.9100100  –––  –––  ––– 
Deguchi T (2017)93  Hi  73  27.4  67.1  –  58.9  82.6  –  99.5  95.2  100  98.6  –  – 
Li JP (2017)94*  Hi  110                         
Kondo H (2018)97  Hi  16.7  16.7  –  –  –  –  –  –  33.3  –  –  – 
Magdaleno Tapial J (2019)100  Hp + Hi +H. haemolyticus  38  –  79  –  92.1  94.8  –  –  65.8  90.8  73.7  –  – 
Wang HJ (2019)101*  Hi  230                         
Ducours M (2020)103  Hp + Hi  –  10  –  –  25  –  100  –  22.2  –  – 
Sierra Y (2020)105  Hp  175  –  87.1  –  92.3  99.4  –  –  88.2  78.6  53.7  –  – 
Hu BF (2021)107  Hi  136  35  –  –  81.6  98.5  –  100  91.9  100       

Amin: aminoglycosides; ATM: aztreonam (monobactam); Carba: carbapenems; Ceph 2nd: 2nd-generation cephalosporins; Ceph 3rd: 3rd-generation cephalosporins; Ceph 4th: 4th-generation cephalosporins; CFZ: cefazolin (1st-generation cefalosporin); CHL: chloramphenicol; FOS: fosfomycin; Hi: Haemophilus influenzae; Hp: Haemophilus parainfluenzae; Macr: macrolides; Pen: penicillins; Prod. βL: β-lactamase production; Quin: quinolones; RIF: rifampicin; SXT: trimethoprim-sulfamethoxazole; TC: tetracyclines.


The data provided by these studies are not included because they include samples of a different origin to the genital apparatus.

In addition, susceptibility to these antibiotics was determined separately for each species. These data are shown in Table 3.

Table 3.

Rates of antibiotic susceptibility and presence of β-lactamases separated by species (%).

Species  Prod. βL  Pen  CFZ  Ceph 2nd  Ceph 3rd  Carba  Macr  Quin  TC 
H. influenzae  27.97  76.14  100  73.7  92.9  99.7  94.9  98.5  93.9 
H. parainfluenzae  24.81  81.66    92.3  99  100  88.2  80.9  53.7 

Carba: carbapenems; Ceph 2nd: 2nd-generation cephalosporins; Ceph 3rd: 3rd-generation cephalosporins; CFZ: cefazolin (1st-generation cephalosporin); Macr: macrolides; Pen: penicillins; Prod. βL: β-lactamase production; Quin: quinolones; TC: tetracyclines.


It is difficult to demonstrate the pathogenic role of microorganisms that can be colonisers and present together with other species, as in the case of HSNOTD and in particular Haemophilus influenzae. There are few studies with a control group on the prevalence of the latter in men with urethritis, although in one of them3, an association is demonstrated with non-gonococcal urethritis in both MSM and heterosexuals, which would support its aetiological and pathogenic role in urethritis. Doubts remain as to the pathogenic role of the rest of the HSNOTD species since there are no rigorous studies with valid methodology, and most of them are case series.

The acquisition mechanism varies depending on the characteristics of the patient. For example, in girls with no history of sexual intercourse or abuse, there could be an auto-inoculation mechanism from the nasal location to the vaginal area. In contrast, in adults, the transmission route is predominantly sexual. One of the most relevant data items we can extract from this bibliographical review is the high frequency with which urethritis caused by HSNOTD is associated with the practice of unprotected oral sex, which in many cases is the only form of exposure reported. Genital infection by HSNOTD seems to be associated with sexual contact with multiple sexual partners and with the domain of prostitution. However, it is important to be cautious when drawing conclusions about possible predisposing factors to genital infection by HSNOTD, since the information provided by the different publications is scant. Regarding the sexual orientation of male patients, 53.3% were heterosexual and 46.7% homosexual, but the information available is very limited and does not allow us to conclude that the risk of infection is related to sexual orientation. The same occurs with previous having had sexually transmitted infections (urethritis, HIV, syphilis, etc.) as a risk factor. We found the same number of patients with a history of STIs as without them, although once again we cannot draw definitive conclusions due to the general lack of information. The low number of publications in which HSNOTD is considered a pathogenic agent causing proctitis is striking.

The susceptibility rates of Haemophilus against cephalosporins, especially third-generation, are very high, which together with amoxicillin/clavulanic acid are the treatments of choice. Taking into account the antibiotic susceptibility profile of all the species described above, we can deduce that the empiric treatment administered for STIs could be more effective against H. influenzae than against H. parainfluenzae, since the latter presents lower rates of susceptibility to macrolides, tetracyclines and quinolones.

Traditionally, vulvovaginitis in girls has been treated with penicillins, and a great tendency to a recurrence of these episodes has been described3, which could be due to the ineffectiveness of empiric treatment, since the susceptibility rate of H. influenzae to these antibiotics is only 72.3%. This hypothesis is reinforced by the fact that the recurrence rate is higher in girls who had received penicillins in the preceding months to treat infections in other locations. One alternative to penicillins are cephalosporins, which show good susceptibility rates and do not have the possible side effects of other antibiotics, such as quinolones, in children. Finally, one of the works reviewed46 demonstrates the frequency with which Haemophilus spp. is detected in the vaginal exudate of asymptomatic pregnant women, with percentages close to 10%. This could entail a greater risk of vertical transmission and infectious complications both at maternal level and regarding neonatal sepsis, and prophylactic eradication may be considered as a strategy. However, a deeper analysis of the risk-benefit ratio of this intervention, which could increase antibiotic pressure, is necessary.

This review has several limitations. An extensive search was carried out. However, articles in Spanish and English were included and we did not have access to a series of published studies, listed at the beginning of the article, meaning that not all published studies may not have been included. In addition, the wide variability of data published between articles regarding epidemiological, microbiological and antibiotic susceptibility data makes it difficult to analyse the data homogeneously and therefore draw conclusions. Furthermore, the methodology of most of the included studies is outmoded and the aetiological role of these microorganisms cannot therefore be firmly established.

Following the review, we can highlight, in HSNOTD, the role ofHaemophilus influenzae as an aetiological agent in cases of non-gonococcal urethritis in men, both MSM and heterosexuals, and therefore the usefulness of systematically searching for this microorganism in this entity, as it can explain a significant percentage of urethritis without microbiological isolation. It proved impossible to find consistently described epidemiological risk factors and/or an acquisition mechanism, hence more studies are needed. On the other hand, taking the antibiotic resistance profile into account, third-generation cephalosporins, amoxicillin-clavulanic acid and quinolones are postulated as the most successful eradication options. With regard to azithromycin and doxycycline, which are widely used in the empiric treatment of STIs, we did not find significant resistance rates in the review, although we are seeing a growing trend of strains with a higher resistance profile and higher minimum inhibitory concentrations for doxycycline110.

Conflicts of interest

The authors declare that they have no conflicts of interest.

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