infectious

16 Pages·2017·1.02 MB·English

Volume 19. Nº 2. March - April 2018
d
e
erv
es
hts r
g
All ri
9.
2
1
3
6-
7
5
1
N
S
S
0. I
0
0
2
9-
9
E-
S
osit
p
e
d
al
g
e
L
Advances in
INFECTIOUS
DISEASES
Journal of independent publications and comments
about advances in infectious diseases
Published by the Andalusian Association of Infectious Diseases
www.saei.org
START Volume 19. Nº 2. March - April 2018
CONTENTS
EDITOR´S CHOICE
THE BENEFITS OF A GLOBAL EDUCATIONAL PROGRAM FOR THE PRESCRIPTION OF ANTIMICROBIALS.
COMMENT: Dr. Manuel Torres Tortosa
Pág 3
GUEST COLLABORATOR
WHAT IS THE OPTIMAL DOSE OF DAPTOMYCIN FOR THE TREATMENT OF AN MRSA BACTEREMIA?
COMMENT: Dra. Mireia Puig-Asensio
Pág 3
2017 IDSA GUIDELINES UPDATE FOR THE MANAGEMENT OF TRAVELER´S DIARRHEA.
COMMENT: Dr. Angel Dominguez Castellano
Pág 4
THE BACTEREMIA CONTROL TEAM: A NECESSITY IN CLINICAL DAILY ASSISTANCE.
COMMENT: Dr. Alfonso del Arco
Pág 6
OPENING HIDDEN DOORS.
COMMENT: Dr. Jesús Canueto Quintero
Pág 6
IS IT POSSIBLE TO DISREGARD RIFAMPICIN IN THE TREATMENT OF INTERVENED STAPHYLOCOCCAL
PROSTHETIC ENDOCARDITIS?
COMMENT: Dr. Luis Eduardo López Cortés
Pág 7
THE SAFETY OF THE HPV VACCINE IN PREGNANT WOMEN… PARADIGM SHIFT IN THE TREATMENT?
COMMENT: Dr. Marcos Guzmán
Pág 8
LTBI IN HIV: WHO ALGORITHM VS SCORE... WHEN DO WE TREAT?
COMMENT: Dra. M. Luisa Fernández Ávila
Pág 9
PROS AND CONS OF SURGICAL PROPHYLAXIS WITH BETA LACTAMS, VANCOMYCIN OR A COMBINATION OF
BOTH.
COMMENT: Dr. Alberto Romero Palacios
Pág 9
KEY REFERENCES IN PROSTHETIC JOINT INFECTION IN RECENT YEARS
COMMENT: Dra. Maria Dolores del Toro
Pág 10
COHORT NESTED CASE-CONTROL STUDIES.
COMMENT: Dr. Antonio Gutiérrez-Pizarraya
Pág 12
NOTICIAS
Pág 14
IMÁGENES CLÍNICAS
Pág 15
COMITÉ DE REDACCIÓN
CONTENTS
Pág 16
Advances in Infectious Diseases 2
BACK Volume 19. Nº 2. March - April 2018 CONTENS
EDITOR´S CHOICE
Dr. Manuel Torres Tortosa
THE BENEFITS OF A GLOBAL EDUCATIONAL PROGRAM FOR THE PRESCRIPTION OF ANTIMICRO-
BIALS.
Referencia Original: Molina J, Peñalva G, Gil-Navarro MV et al. PRIOAM team. Long-term impact of an educational
antimicrobial stewardship program on hospital-acquired candidemia and multidrug-resistant bloodstream infections: a
quasi-experimental study of interrupted time-series analysis. Clin Infect Dis 2017: 65: 1992-1999.

This study analyzed the results of an antimicrobial prescription advice program (APAP) from a period of 5 years at the Virgen
del Rocío Hospital, Seville. Different interventions were used, including direct interviews between the consultant and prescribers from
all the departments of the hospital (also ICU and Pediatrics). Throughout the study period, the methodology of the program was the
same, without the introduction of other measures that would influence the prescription. The effect of the APAP was measured through
antibiotic consumption (AC), incidence density of bloodstream infections (BI) caused by multiresistant bacteria (MR) or Candida spp,
and crude mortality per 1000 stays (CM/1000) caused by these infections. Six months after the introduction of the APAP, an intense and
significant decrease in AC was observed, which continued in the following years. There was also a decrease in bacteraemia caused
by MR germs or candidemias and a significant decrease of CM/1000. It was interesting that the mortality associated with BI caused by
non-MR bacteria also decreased with the APAP without this affecting its incidence.
COMMENT: Dr. Manuel Torres Tortosa
The results of this study evidence that when antibiotic pressure is reduced in a hospital, the diversity of MR bacterial strains
decreases, along with the incidence of infections caused by them. It is a pioneer investigation in several aspects, reinforced by the
strength with which the authors defend their conclusions. The antibiotic treatment (AT) is prescribed by any specialist of any field, and
this fact is not going to change in the future. Probably related to this, about half of the antimicrobial prescriptions given in a hospital are
inappropriate; hence the importance of an educational program (considered secondary in other advice programs), its prevalence in time
and its implementation in different ways, in which the personal advisor-prescriber peer-to-peer interview is a key element. According to
the authors, the decrease of mortality in BI caused by non-MR germs is explained by the improvement in the prescription of antimicro-
bials produced by the APAP. Clearly, the remarkable results of this inventive study, conducted in a public hospital of Andalusia, induce
some reflections. The reduction in expenses produced by the application of the program should be analyzed with a potential increase
of infectologists in other centers that would allow to carry out similar programs. This could be beneficial, considering only the economic
aspects. On the other hand, these results (along with others) are a strong evidence to carry out studies about the duration of the AT of
specific infections that are performed within the hospital. As we can see, it would be very appropriate to shorten the current standards
of AT in specific processes, if this is convincingly demonstrated.
GUEST COLLABORATOR
Dra. Mireia Puig-Asensio
WHAT IS THE OPTIMAL DOSE OF DAPTOMYCIN FOR THE TREATMENT OF AN MRSA BACTEREMIA?
Referencia Original: Timbrook TT, Caffrey AR, Luther MK, et al. Association of Higher Daptomycin Dose (7 mg/kg or
Greater) with Improved Survival in Patients with Methicillin-Resistant Staphylococcus aureus Bacteremia. Pharmacothe-
rapy. 2017 Dec 13. d

Advances in Infectious Diseases 3
BACK Volume 19. Nº 2. March - April 2018 CONTENS
Retrospective, multicentre study conducted in the American centres of Veteran Affairs that compares the effectiveness of conventio-
nal doses of daptomycin (6mg/kg/day) with higher doses (≥7mg/kg) for the treatment of Methicillin-resistant Staphylococcus aureus
(MRSA) bacteremia. To be included in the study, the patients had to start an empirical treatment with vancomycin within the first 24 hours
and shift to daptomycin within the first week after obtaining a positive blood culture. The doses of daptomycin were calculated based
on the actual weight of the patient, and patients that needed dialysis were excluded. The main variable of the study was mortality at 30
days. The study included a total of 371 adult patients who had an episode of MRSA bacteremia between the year 2002 and 2015: 233
(62.8%) in the group of conventional doses and 138 (37.2%) in the group of high doses. In the latter, 42.8% received 7 mg/kg, 50%
received 8-9 mg/kg and 7.2% received ≥10mg/kg. The average until the start of daptomycin treatment, the average of Charlson´s index
and the presence of a source of endocarditis were similar between the two groups. However, the percentage of obese patients was
larger in the group of daptomycin at conventional doses (39.9% vs 29%). Mortality at 30 days, adjusted by confounding factors using
the propensity score method, was similar in both groups: 8.6% in the group of ≥7mg/kg compared to 18.6% in the group of conventio-
nal doses of 6mg/Kg (0.31 Hazard ratio, confidence interval: 0.10-0.94). No significant differences were observed in other secondary
variables, such as the need for hospital readmission at 30 days and reinfection by S. aureus. The CART analysis (Classification And
Regression Trees) showed that the higher doses of daptomycin (≥7mg/kg) were more effective than the conventional doses for those
patients with an estimated probability of success above 51% at 30 days.
COMMENT: Dra. Mireia Puig-Asensio
University Hospital Vall d´Hebron, Autonomous University of Barcelona.
This study aims to give an answer to a very important question: what is the optimal dose of daptomycin for the treatment of
MRSA bacteremia. Since it reached the market, the doses of daptomycin have increased progressively from 6 to 10mg/kg. In fact, it
has been suggested that complex infections like endocarditises, and those caused by strains with a MIC to vancomycin >1.5mg/L by
E-test would be the ones to benefit the most from a high daptomycin dose of 8-10mg/kg. The hypothesis is that this dosage could
prevent the emergence of resistant strains and it would be associated with a better patient survival rate. However, these points have
not been clearly demonstrated. In fact, the IDSA guidelines of 2011 continue to recommend 6mg/kg in patients with MRSA bacteremia
in the absence of endocarditis and with negative control blood cultures; hence the importance of this study, which is the first to de-
monstrate globally the benefit of daptomycin doses above 6mg/kg for this type of infections. Unfortunately, there are still matters to be
solved. The study does not show whether the doses or the effectiveness of daptomycin could vary depending on the early management
of the source of infection, the MIC to vancomycin or in the presence of a high bacterial inoculum. Nevertheless, in the face of such a
serious disease like MRSA bacteremia, and in the absence of a clinical trial, surely this level of evidence could be enough to favor the
generalized clinical use of high doses of daptomycin, as already suggested by the Spanish guidelines of the SEIMC (Spanish Society
of Infectious Diseases and Clinical Microbiology).
2017 IDSA GUIDELINES UPDATE FOR THE MANAGEMENT OF TRAVELER´S DIARRHEA.
Referencia Original: Shane AL, Mody RK, Crump JA, et al. 2017 Infectious Diseases Society of America Clinical Prac-
tice Guidelines for the Diagnosis and Management of Infectious Diarrhea. Clin Infect Dis 2017; 65(12):1963-1973.
COMMENT: Dr. Angel Dominguez Castellano
Infectious Diseases Unit. University Hospital Virgen Macarena. Seville. Spain.
GEPISI: Study Group on Imported Pathology and International Health.
The CID has recently published an update on the management of traveler´s diarrhea. This guide has 36 pages. I summarise
here the most important recommendations:
1.- People with fever or bloody diarrhea must be examined to discard enteropathogens, for which antimicrobial agents can confer cli-
nical benefit. These include: Salmonella enterica, Shigella and Campylobacter.
2.-. Enteric fever must be taken into account when a febrile person (with or without diarrhea), with a travelling history in areas where the
Advances in Infectious Diseases 4
BACK Volume 19. Nº 2. March - April 2018 CONTENS
causal agents are endemic, has consumed foods prepared by people with recent endemic exposure or laboratory exposure to Salmo-
nella enterica subspecies enterica serovar Typhi and Salmonella enterica subspecies enterica serovar Paratyphi.
3.- Diagnostic tests are not recommended in most cases of non-complicated traveler´s diarrhea, unless treatment is indicated. Travelers
with diarrhea that persists 14 days or more must be assessed for intestinal parasitic infections. The tests for C. difficile must be perfor-
med in travelers treated with antimicrobial agents within the previous 8-12 weeks. Moreover, digestive tract diseases, including intestinal
inflammatory disease (IID) and the post-infectious irritable bowel syndrome (PI-IBS), must be considered for full evaluation.
4.- In immunocompetent children and adults, the empiric antimicrobial therapy is not recommended for bloody diarrhea before obtaining
the microbiological results, with the exception of: A) babies <3 months of age with suspicion of a bacterial etiology; B) immunocompe-
tent people with documented fever in a medical environment, abdominal pain, bloody diarrhea and bacillary dysentery (faeces with little
and frequent blood, fever, abdominal colic, tenesmus) presumably caused by Shigella; C) people who have recently travelled to other
countries with body temperature ≥ 38.5 °C and/or other signs of sepsis.
More information: https://wwwnc.cdc.gov/ travel / yellowbook / 2016 / the-pre-travel-consultation / travelers-diarrhea.
5.- The empiric antimicrobial therapy in adults must be performed with a fluoroquinolone, such as ciprofloxacin, or azithromycin, depen-
ding on the local susceptibility patterns and/or travel route. The empiric therapy for children includes a third generation cephalosporin for
babies <3 months of age and those with neurological involvement, or azithromycin, also depending on the local susceptibility patterns
and/or travel route.
6.- The empiric antimicrobial treatment must be considered in immunocompromised patients with severe disease and bloody diarrhea.
7.- In most patients with acute watery diarrhea and no recent international trips, the empiric antimicrobial therapy is not recommended.
An exception could be made for immunocompromised patients or young babies in a poor general condition. The empiric antimicrobial
treatment must be avoided in patients with persistent watery diarrhea that continues for 14 days or more.
8.- The antimicrobial treatment must be modified or suspended when a clinically plausible microorganism has been identified.
9.- Antimotility drugs (e.g. loperamide) must not be administered to children <18 years of age with acute diarrhea. Loperamide may be
administered to immunocompetent adults with acute watery diarrhea; however, it must be avoided at any age in suspicious or proven
cases in which toxic megacolon may cause inflammatory diarrhea or diarrhea with fever.
10.- Two typhoid vaccines (oral and injectable) are licensed in the United States, but they are not recommended on a routine basis.
Typhoid vaccination is recommended as a complement of hand hygiene and avoidance of high-risk foods and drinks, for people who
travel to areas where there is a moderate to high risk of exposure to Salmonella enterica subspecies enterica serovar Typhi, people with
intimate exposure (by contact) to a documented chronic carrier or microbiologists and other laboratory professionals routinely exposed
to cultures of Salmonella enterica subspecies enterica serovar Typhi. Booster doses are recommended for patients who remain under
risk.
11.- A live attenuated vaccine against cholera, which is available as a single-dose oral vaccine in the United States, is recommended
for adults between 18 and 64 years of age who travel to areas affected by cholera.
More information at: https://www.cdc.gov/colera/vacunas.html.
THE BACTEREMIA CONTROL TEAM: A NECESSITY IN CLINICAL DAILY ASSISTANCE.
Referencia Original: Del Arco A, Olalla J, de la Torre J, et al. Results of an early intervention programme for patients with
bacteraemia: analysis of prognostic factors and mortality. BMC Infect Dis 2017; 17(1):360.
[1] Del Arco-Jiménez A, Olalla-Sierra J, de la Torre-Lima J, Prada-Pardal JL, et al. Results of an early intervention program
for patients with bacteremia discharged from the emergency department. Med Clin 2014;142(3):107–10.
Advances in Infectious Diseases 5
BACK Volume 19. Nº 2. March - April 2018 CONTENS
This two-year prospective study analysed 773 cases of bacteremia attended to by a multidisciplinary team and assessed the
epidemiological and microbiological characteristics, modifications of the antibiotic treatment, prognostic indicators (McCabe, Charlson
and Pitt score) and the impact on mortality within the first 7 days and after 28 days. Male patients represented 61.6% of the sample,
and the average age was 65.2 years. Community acquisition was 41.1%, the most frequent source was urologic (30%) and the most
frequent microorganism was E. coli (31.6%). Fifty-one percent of the patients had their treatment modified (spectrum, length or Pk/Pd
optimization). Mortality within the first 7 days was 8.2%, and 4.5% of the patients had passed away prior to the intervention. The bivariate
analysis showed significant differences (p<0.001) between mortality by bacteremia and the following: age (higher in elderly patients),
McCabe index with ultimately fatal disease and rapidly fatal disease, Charlson and Pitt score ≥ 3, the absence of original source and
no treatment modification. There were no statistically significant differences in the distribution by sex, isolated microorganism or place
of disease acquisition, although nosocomial acquisition showed a higher percentage (18%) comparted to community infection (13.2%)
and acquisition related to healthcare assistance (14.6%). Each of the multivariate logistic regression models performed, which were
differenciated according to the comorbidity adjustment introduced, had this included as a variable associated to higher risk of mortality,
with the model with rapidly fatal McCabe index adjustment being the one with the highest adjusted risk of mortality at seven days (RR
7.616, IC95%: 3.81-15.221). In the multivariate model with Pitt score adjustment ≥3, the RR is 7.014 (IC95%: 4.345-11.,321) compa-
red to the 2.678 RR (IC95%: 1.706-4.204) in the model with Charlson adjustment ≥3. In the three multivariate models, age, absence
of source and keeping the same treatment are mortality risk factors, including in the model with Charlson comorbidity adjustment the
presence of nosocomial infection. In the substudy conducted in patients who had been discharged from the emergency department
[1], 90 patients were assessed, with an average age of 67 years and 60% women. Fifty-one percent had been community-infected, E
coli was the most frequent microorganism and the most frequent source was urologic. The variables associated to the need of hospital
admission, once the patients were contacted, were the need to modify the antimicrobial treatment and Pitt score >1. One patient had
passed away during the contacting procedures.
COMMENT: Dr. Alfonso del Arco
Facultative of Infectious Diseases. Hospital Costa del Sol. Malaga.
The presence of multidisciplinary teams integrated in the daily healthcare activity, with expert clinicians specialised in the early
diagnosis of bacteremia, in the stratification of the prognosis identifying patients with more advanced stages of the disease and in the
prescription of the optimal treatment, can have a very favourable impact on the decrease of morbimortality. Moreover, it allows to recover
those patients that were discharged from the emergency department and who require their treatment to be modified or to be admitted
in the hospital due to poor evolution.
OPENING HIDDEN DOORS.
Referencia Original: George Sakoulas, Warren Rose, Andrew Berti, et al. Classical β-Lactamase Inhibitors Potentiate
the Activity of Daptomycin against Methicillin-Resistant Staphylococcus aureus and Colistin against Acinetobacter bau-
mannii. Antimicrob. Agents Chemother 2017; 61: e01745-16

“Gandalf told his friend Frodo about the art of the Dwarves in the building of secret doors that not only required a spell to be
opened, but even to discover their presence”.
The proposal of this complex and excellent study was to determine whether the association of classic beta lactam inhibitors (cBLI) with
polypeptide antibiotics improves the efficacy of the former against multi-resistant bacteria, specifically, whether cBLI increase the activity
of Daptomycin (DAP) against methicillin-resistant Staphylococcus aureus (MRSA), of Colistin (COL) against Acinetobacter baumannii,
and of the human antimicrobial peptide y del péptido antimicrobiano humano Cathelicidin LL-37 agains both pathogens. To demons-
trate this hypothesis, the authors carried out in vitro bacterial death curves for DAP and Cathelicidin LL-37 with and without cBLI with
MRSA, VISA and hVISA. They used the same technique again with COL and Cathelicidin LL-37 with and without cBLI in the presence
of A. baumannii. Microscopy analyses were conducted with labelled DAP to observe the effect of adding TAZ in the capacity of DAP
to bind the cell membrane of strains of MRSA and hVISA. Lastly, the combination of COL plus TAZ was analysed in a murine model of
A. baumannii pneumonia. TAZ increased the activity of COL against multiple strains of A. baumannii in vitro. The synergy observed in
Advances in Infectious Diseases 6
BACK Volume 19. Nº 2. March - April 2018 CONTENS
the bacterial death curves was confirmed using other methods of PK/PD modeling and simulation. TAZ improved the capacity of the
human peptide Cathelicidin LL-37 to eliminate A. baumannii. Finally, TAZ improved the activity of COL in a murine model of A. baumannii
pneumonia. The activity of DAP against MRSA, hVISA and VISA was enhanced by TAZ, as demonstrated by the analysis of the bacterial
death curves, PK/PD models and the improved binding of DAP to the cell membrane shown through microscopy. Similarly to what was
observed with A. baumannii, the activity of the human peptide Cathelicidin LL-37 against MRSA was also increased with the addition
of TAZ. The association of Sulbactam (SUL) with antimicrobial peptides was partially analysed in the case of Cathelicidin LL-37, and
thus it was more difficult to interpret. The authors concluded that cBLI increase the activity of polypeptide antibiotics, both exogenous
and endogenous, against MRSA and A. baumannii. cBLI have very low antimicrobial activity; therefore, it could be considered as an
advantage the fact that they produce a very low ecological pressure. This synergistic activity between cBLI and polypeptide antibiotics
could pose a new starting point for the design of future therapeutic strategies. The exact mechanism by which cBLI improve the activity
of DAP and LL-37 against MRSA, VISA and hVISA is still unknown, but it is more likely to be related to the interference in the synthesis
of the cell wall through its binding to PBP rather than to direct inhibition by beta lactams.
COMMENT: Dr. Jesús Canueto Quintero (con la colaboración de JRR Tolkien)
The crisis related to bacterial resistance forces researchers to look for new strategies using available antibiotics and not only
synthesising new molecules. Based on previous studies about the activity of SUL against A. baumannii, and the potentiating effect of
the association of carbapenems and penicillins (with chemical structures similar to that of cBLI), but not of cephalosporins with DAP
against MRSA, the authors investigated whether cBLI -which are beta lactam structured molecules- could also enhance the activity of
polypeptide antibiotics like COL and DAP and even human antibacterial peptides. It is an innovative idea about complex interactions at
the bacterial cell wall that were little known until now. As it is an experimental study, more solid results will have to be produced before
drawing conclusions and assessing the in vivo applicability of this strategy. Nevertheless, it is an original development that stands out
of the usual line and paves the way for new possibilities.

IS IT POSSIBLE TO DISREGARD RIFAMPICIN IN THE TREATMENT OF INTERVENED STAPHYLOCOC-
CAL PROSTHETIC ENDOCARDITIS?
Referencia Original: Shrestha NK, Shah SY, Wang H, et al. Rifampin for surgically treated staphylococcal infective
endocarditis: A propensity score-adjusted cohort study. Ann Thorac Surg 2016; 101(6):2243-50.

This is a retrospective observational study that included adult patients with confirmed prosthetic staphylococcal endocarditis,
who had been intervened between the years 2008 and 2014 at Cleveland Clinic (Ohio, USA), which is a reference hospital in the field
of cardiovascular surgery. The authors compared the relapse frequency and mortality of those patients that received rifampicin for at
least 3 days after surgery with that of those who did not receive rifampicin for various reasons (physician´s decision, interactions, etc.).
The study included 273 patients (65 treated without rifampicin) with the following characteristics: 50% had prosthetic endocarditis
(89% in the left side), 60% were caused by S. aureus or lugdunensis, and 57% had extravalvular involvement. Although no significant
differences were observed regarding the scales of severity and prediction of mortality between the patients of both groups, the basal
characteristics were not exactly the same. The patients who received rifampicin showed greater frequency of left-side endocarditis, as
well as extravalvular involvement and greater frequency of cases caused by MRSA. A propensity score was calculated for the probability
of receiving rifampicin, which suitably adjusted the variables in which the two groups differed, and it was added to the multivariate analy-
sis. The model presented for the variable “death and/or need for reintervention” did not show significant differences (HR 0.76, IC95%
0.44 – 1.32, p=0.34). The Kaplan-Meier curves regarding the variable “time until reintervention” were superimposable. In the analysis
conducted exclusively for the prosthetic endocarditises, there were no significant differences (HR 0.69, IC95% 0.34 – 1.38, p=0.29).
Lastly, a sensitivity analysis was carried out as a function of the period in which rifampicin had been used (prior to surgical intervention,
after it or both), without significant differences in any case.
Advances in Infectious Diseases 7
BACK Volume 19. Nº 2. March - April 2018 CONTENS
COMMENT: Dr. Luis Eduardo López Cortés
GEICV - Andalusian Group for the Study of Cardiovascular Infections.
The last guidelines published (both European and American) recommend a treatment based on the combination of cloxacillin
or vancomycin, along with gentamicin (the first two weeks) and rifampicin in the treatment of staphylococcal prosthetic endocarditis. As
was already demonstrated for staphylococcal native endocarditis, there are experts who suggest that gentamicin could be disregarded,
since it does not seem to improve the prognosis and it produces a greater frequency of nephrotoxicity. Once the prosthetic material
has been replaced and, subsequently, the biofilm has been removed, it seems logic to think that it would be possible to disregard
rifampicin. This is not a minor issue, since, quite frequently, this drug is not well tolerated and it also interacts with other drugs used in
this type of patient. Although the authors performed a sensitivity analysis as a function of the period in which rifampicin was used, the
manuscript does not include information that allows to know the time elapsed between diagnosis and surgery. Likewise, there is no
information about the dosage used for this drug, which is an aspect that could potentially affect the prognosis of the patients. It could
be considered as a limitation the fact that the series included patients with both prosthetic and native endocarditis, although when this
article was published (June 2016) there were still no conclusive results about the usefulness of the combined treatment (Thwaites GE,
et al. Lancet 2017. Published) and, moreover, such situation was taken into account in the propensity analysis. The commented study,
although with limitations, paves the way for the possibility to disregard rifampicin once the prosthetic material has been replaced. There
seems to be no more clinical trials in this regard at present, thus we will wait for similar analyses in the different existing series.
THE SAFETY OF THE HPV VACCINE IN PREGNANT WOMEN… PARADIGM SHIFT IN THE TREAT-
MENT?
Referencia Original: Scheller NM, Pasternak B, Mølgaard-Nielsen D et al. Quadrivalent HPV Vaccination and the Risk
of Adverse Pregnancy Outcomes. N Engl J Med 2017; 376(13):1223-1233.

Prescribing the vaccination against the human papillomavirus (HPV) is still a controversial topic. Danish researchers, using the
National Registry, analysed the information obtained from 540,805 pregnant women between the 1st of October 2006 and the 30th
of November 2013. The study linked the information about vaccination, adverse results of the pregnancy and possible confounding
factors between the women of the cohort. Those who were vaccinated during the periods pre-specified were paired in a propensity
score through matching in a ratio of 1:4 with those who were not vaccinated during the same periods. The results included spontaneous
abortion, intrauterine fetal death, major congenital malformations, small for gestational age, low birth weight and premature birth. The
analysis excluded the women who had a spontaneous abortion within the first 6 weeks of gestation. In the combined analysis, vacci-
nation against HPV did not show higher risk of adverse results among pregnant women with respect to those who were not vaccinated
during the same period. Between the two groups, the prevalence odds ratio (OR) for major congenital malformations was 1.19 [confi-
dence interval (CI) of 95%, 0.90 to 1.58, 65/1665 vaccinated and 220/6660 not vaccinated]. For premature birth, the prevalence OR
was 1.15 (95% CI, 0.93-1.42, 116/1774 vaccinated and 407/7096 not vaccinated). For low birth weight, the prevalence OR was 1.10
(95% CI, 0.85 – 1.43, 76/1768 vaccinated and 277/7072 not vaccinated). For the result of small for gestational age, the prevalence
OR was 0.86 (95% CI, 0.72 a 1.02, 171/1768 vaccinated and 783/7072 not vaccinated). The authors demonstrated risk quotients of
0.71 (95% CI, 0.45-1.14) for spontaneous birth (20/463 vaccinated and 131/1852 not vaccinated) and 2.43 (95% CI, 0.45 – 13.21)
for intrauterine fetal death (2/501 vaccinated and 4/2004 not vaccinated). However, the authors pointed out that since there were only
two cases of fetal death in the analysis, no clinically significant conclusions can be drawn with respect to this result.
COMMENT: Dr. Marcos Guzmán

The Danish researchers present a thorough revision of the adverse results of pregnancy, well described in this article, found
in women who received the tetravalent vaccine against HPV. These very promising data strongly support the safety of HPV vaccines if
administered inadvertently during pregnancy. This study complements the previous safety reports of the HPV vaccine in non-pregnant
women and opens the door to a new possible generalised vaccination for young women. Currently, the inclusion of pregnant women
in trials related to drugs may be controversial, since this stratum of the population is considered vulnerable and their participation in cli-
nical studies is very debatable due to the ethical dilemma that it poses, which hinders the gathering of relevant information about these
Advances in Infectious Diseases 8
BACK Volume 19. Nº 2. March - April 2018 CONTENS
patients in many cases. This study raises several controversial situations that continue to be an issue nowadays and in the near future,
such as the role of administering the tetravalent vaccine in patients with known previous unsafe sexual relations or the lack of serious
studies that suggest their real benefit in patients with previous exposure to different strains of HPV. Another controversial aspect is focu-
sed on the beginning of prescription for male patients by the public health administration, which is currently contradictory according to
the opinion of some social strata; this may make increasingly less sense if we consider the possible “herd immunity” effect in massive
vaccinations. A wide range of questions arises, which may change the paradigm of the treatment of certain tumours… Could systematic
vaccination against HPV be the key to the eradication of these pathologies?
LTBI IN HIV: WHO ALGORITHM VS SCORE... WHEN DO WE TREAT?
Referencia Original: Griesel R, Stewart A, van der Plas H, et al: Optimizing Tuberculosis Diagnosis in HIV-Infected
Inpatients Meeting the Criteria of Seriously Ill in the WHO Algorithm. Clin Infect Dis 2017. En prensa.

This article aims to develop a clinical predictive model for the diagnosis of LTBI in severely immunodepressed HIV positive
patients, including the study of 6 variables and the use of Xpert MTB/RIF as a diagnostic tool. In addition to this, the authors compared
their data with the algorithm published by the WHO for the diagnosis of LTBI in this patient profile. To this end, they conducted a pros-
pective cohort study with inpatients from two South African hospital centres infected by HIV, with cough of any duration and at least one
of the symptoms of serious illness indicated by the WHO. The study included 484 participants, with an average CD4 of 89 cell/mcl and
35.2% of them under antiretroviral treatment. Of the data gathered, 52.7% were diagnosed with LTBI through standardised methods.
The variables of the study were: cough >14 days (1 point), inability to walk (1 point), fever >39º (1 point), chest X-ray suggestive of LTBI
(with alterations, 1 point; suggestive of LTBI, 5 points), hemoglobin (<8.3 g/dL, 3 points; >8.4 g/dL, 2 points) and WBC count (<6.5
x109/L, 1 point; > 11.2 x109/L, -2 points). Furthermore, the Xpert MTB/RIF showed 86.3% sensitivity and 96.1% specificity (higher
than others described in previous studies due to the fact that these were samples obtained through the induced sputum procedure).
The study concluded that its clinical prediction model can be useful in severely immunodepressed HIV patients and that Xpert MTB/RIF,
recently incorporated in the WHO´s algorithm of 2016, has high sensitivity and specificity in this patient profile.
COMMENT: Dra. M. Luisa Fernández Ávila
Specialist Physician. Internal Medicine Department of the San Juan de la Cruz Hospital (Úbeda, Spain).

In 2016, the WHO published an update of the document about the use of antiretroviral drugs that included a diagnostic algo-
rithm for LTBI in severely immunodepressed HIV patients, including the classic symptoms of LTBI and, for the first time, Xpert MTB/RIF
as a diagnostic tool in these patients. The presented study aims to develop a clinical prediction model of LTBI based on 6 variables,
among which the most significantly associated to the diagnosis of LTBI are the development of alterations in chest X-rays and anemia,
with leukocytosis being a negative prediction factor of LTBI. A score of 3-4 in this model could be used as an indicator to initiate anti-
tuberculosis treatment in these patients, with over 90% sensitivity and over 45% specificity, according to the data provided. The 2016
update corrects many of the flaws of the first algorithm published in 2007 and includes the use of Xpert MTB/RIF, adapting to the cu-
rrent practice. The idea of developing a LTBI risk score in these patients can be very useful, especially in centres where it is not easy to
conduct quick tests and decisions must be made based on limited resources in many cases. However, I consider that further research
must be done to correct and overcome the limitations of this study.

PROS AND CONS OF SURGICAL PROPHYLAXIS WITH BETA LACTAMS, VANCOMYCIN OR A COMBI-
NATION OF BOTH.
Referencia Original: Branch-Elliman W, Ripollone JE, O’Brien WJ, et al. Risk of surgical site infection, acute kidney
injury, and Clostridium difficile infection following antibiotic prophylaxis with vancomycin plus a beta- lactam versus either
drug alone: A national propensity-score-adjusted retrospective cohort study. PLoS Med 2017, 14(7): e1002340.
This retrospective, multicentre study, conducted with a cohort of US veterans, compared the pros and cons of surgical pro-
phylaxis based on beta lactams (BL), vancomycin (V) or a combination of the two (BL+V). The study included all the patients of this
Advances in Infectious Diseases 9
BACK Volume 19. Nº 2. March - April 2018 CONTENS
cohort, who, between the 1st of October 2008 and the 30th of September 2013, underwent heart surgery (by-pass, valvular, structural
disease repair), joint substitution (pelvis or knee), vascular surgery (arterial and venous resections, by-pass, peripheral and central
shunts, endarterectomies), colorectal surgery or hysterectomy, and received BL, V or BL+V as prophylaxis. The main objective was to
identify the relationship between the antibiotic guideline used in the surgical prophylaxis and the post-surgery infection rate at 30 days
after operation (SI) and, as secondary objectives, the authors proposed to determine the relationship between the guideline used and
the development of diarrhea by C. difficile (CDD) and the deterioration of kidney functionality at 7 days after operation according to
the criteria of the AKI scale (from the “Acute Kidney Injury Network”). Data were analysed from 70.101 patients who met the inclusion
criteria, calculating in each surgical intervention group the crude and adjusted relative risk through propensity score (which included
age, diabetes, smoking, ASA surgical risk, previous colonization by methicillin-resistant S. aureus (MRSA) and treatment with mupiro-
cin). The patients that underwent heart surgery were the only ones in whom the combined prophylaxis (BL+V) was associated with a
lower SI rate (66/6,953, 0.95%) compared to those who received a prophylaxis guideline with either of the two antibiotics alone (BL or
V) (190/12,834, 1.48%; crude RR 0.64 [95% CI, 0.49-0.85]; adjusted RR 0.61 [95%CI, 0.46-0.83]). This difference was three times
greater in MRSA carrier patients than in those whose carrier state was negative or unknown (NNT to prevent a SI of 53 among carriers
and 176 among non-carriers or unknown), regardless of whether or not they had received treatment with mupirocin. The CDD rate was
similar in all groups, whereas the combined guideline was significantly associated with a higher risk of post-surgical kidney damage (any
AKI state, from 1 to 3) in all surgeries, with a risk increase that ranged from 11% (AKI 1 in orthopedic surgery) to 89% (AKI 2 in vascular
surgery).
COMENTARIO: Dr. Alberto Romero Palacios
The question on which the authors focused this research is a topic that continues to generate controversy in the field of
post-surgical infection control: what is better as antibiotic prophylaxis guideline in surgery, one or two antibiotics? After analysing more
than 70,000 patients, they concluded that: 1) the combined guideline (BL+V) prevented more infections in patients who underwent
heart surgery; 2) in this group, the infection risk was even lower if the patient was previously colonised by MRSA (regardless of whether
or not such colonisation was treated with mupirocin); 3) the combined guideline did not determine higher rate of diarrhea by C. difficile,
although it was associated with a variable decrease of kidney function depending on the type of surgery.
However, and despite the effort of the researchers to achieve an optimal validity of their study (considerably large sample, propensity
score, etc.), I have several questions after a critical reading: a) what specific antibiotic guidelines were analysed? They mention BL and
V, but they neither specify which BL they used, the dose of any of them nor the duration; b) what microorganisms cause the infections
detected? It would be appropriate to know against which microorganism this preventive measure would be most effective, MSSA,
MRSA or CNS?; c) what effect did the application of mupirocin have on the patients who were decolonised? It would have been useful
to know if there were differences between the patients who were colonised and successfully treated and those who were unsuccess-
fully treated; d) would it not be necessary to analyse other data that might have influenced the decrease in kidney function beyond the
mere combination of antibiotics? Perhaps there are confounding factors, such as the duration of surgery or the administration of other
potentially nephrotoxic drugs, that should be weighted before relating this kidney deterioration directly to the combination of antibiotics.
KEY REFERENCES IN PROSTHETIC JOINT INFECTION IN RECENT YEARS.
AUTOR: Dra. Maria Dolores del Toro.
University Hospital Virgen Macarena, Seville.
ARTICLE EVALUATION: *Relevant/ **Indispensable
1. Referencia Original: Ariza J, Cobo J et al and Spanish Network for the Study of Infectious Diseases and the Socie-
dad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC). Executive summary of management of pros-
thetic joint infections. Clinical practice guidelines by the Spanish Society of Infectious Diseases and Clinical Microbiology
(SEIMC). Enferm Infecc Microbiol Clin 2017;35(3):189-195.
Advances in Infectious Diseases 10